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For MD-IQ on Family Practice News, but a regular topic for Rheumatology News
Denosumab may halt erosive hand OA progression
But pain outcomes questionable
PHILADELPHIA – A double dose of the antiosteoporosis biologic denosumab (Prolia) slowed progression and repaired joints in erosive hand osteoarthritis (OA) but showed no impact on pain levels until 2 years after patients received the first dose, the lead investigator of a Belgium-based randomized clinical trial reported at the annual meeting of the American College of Rheumatology.
“This is the first placebo-controlled, randomized clinical trial showing the efficacy of denosumab double-dosing regimen in structural modification of erosive hand osteoarthritis,” Ruth Wittoek, MD, PhD, a rheumatologist at Ghent (Belgium) University, said in presenting the results.
“Our primary endpoint was confirmed by a more robust secondary endpoint, both showing that denosumab stopped erosive progression and induced remodeling in patients with erosive hand OA,” she added. “Moreover, the double-dosing regimen was well-tolerated.”
However, during the question-and-answer period after her presentation, Dr. Wittoek acknowledged the study didn’t evaluate the impact denosumab had on cartilage and didn’t detect a signal for pain resolution until 96 weeks during the open-label extension phase. “I’m not quite sure if denosumab is sufficient to treat symptoms in osteoarthritis,” she said. “There were positive signals but, of course, having to wait 2 years for an effect is kind of hard for our patients.”
The trial randomized 100 adult patients 1:1 to denosumab 60 mg every 12 weeks – double the normal dose for osteoporosis – or placebo. The primary endpoint was changes in erosive progression and signs of repair based on x-ray at 48 weeks, after which all patients were switched to denosumab for the open-label study. To quantify changes, the investigators used the Ghent University Scoring System (GUSS), which uses a scale of 0-300 to quantify radiographic changes in erosive hand OA.
Dr. Wittoek said that the average change in GUSS at week 24 was +6 vs. –2.8 (P = .024) in the treatment and placebo groups, respectively, widening at week 48 to +10.1 and –7.9 (P = .003). By week 96, the variation was +18.8 for denosumab and +17 for placebo with switch to denosumab (P = .03).
“During the open-label extension the denosumab treatment group continued to increase to show remodeling while the former placebo treatment group, now also receiving denosumab, also showed signs of remodeling,” she said. “So, there was no more erosive progression.”
The secondary endpoint was the percentage of new erosive joint development at week 48: 1.8% in the denosumab group and 7% in placebo group (odds ratio, 0.23; 95% confidence interval, 0.10-0.50; P < .001). “Meaning the odds of erosive progression is 77% lower in the denosumab treatment group,” Dr. Wittoek said.
By week 96, those percentages were 0% and 0.7% in the respective treatment groups. “During the open-label extension, it was clear that denosumab blocked all new development of erosive joints,” she said.
Pain was one of the study’s exploratory endpoints, and the mean numeric rating scale showed no difference between treatment arms until the 96-week results, with a reduction by almost half in the denosumab group (from 4.2 at week 48 to 2.4) and a lesser reduction in the placebo-switched-to-denosumab arm (from 4.2 to 3.5; P = .028) between arms.
The placebo group was more susceptible to adverse events, namely musculoskeletal complaints and nervous system disorders, Dr. Wittoek noted. Infection rates, the most common adverse event, were similar between the two groups: 41 and 39 in the respective arms. Despite the double dose of denosumab, safety and tolerability in this trial was comparable to other trials, she said.
In comments submitted by e-mail, Dr. Wittoek noted that the extension study results will go out to 144 weeks. She also addressed the issues surrounding pain as an outcome.
“Besides disability, pain is also important from the patient’s perspective,” Dr. Wittoek said in the e-mailed comments. “However, pain and radiographic progression are undeniably coupled, but it’s unclear how.”
In erosive hand OA, structural progression and pain may not be related on a molecular level, she said. “Therefore, we don’t deny that pain levels should also be covered by treatment, but they should not be confused with structural modification; it is just another domain, not more nor less important.
The second year of the open-label extension study should clarify the pain outcomes, she said.
In an interview, David T. Felson, MD, MPH, professor and director of clinical epidemiology research at Boston University, questioned the delayed pain effect the study suggested. “It didn’t make any sense to me that there would be because both groups at that point got denosumab, so if there was going to be a pain effect that would’ve happened,” he said.
The pain effect is “really important,” he said. “We don’t use denosumab in rheumatoid arthritis to treat erosions because it doesn’t necessarily affect the pain and dysfunction of rheumatoid arthritis, and I’m not sure that isn’t going to be true in erosive hand osteoarthritis, but it’s possible.”
To clarify the pain outcomes, he said, “They’re going to have to work on the data.”
Amgen sponsored the trial but had no role in the design. Dr. Wittoek and Dr. Felson reported no relevant disclosures.
But pain outcomes questionable
But pain outcomes questionable
PHILADELPHIA – A double dose of the antiosteoporosis biologic denosumab (Prolia) slowed progression and repaired joints in erosive hand osteoarthritis (OA) but showed no impact on pain levels until 2 years after patients received the first dose, the lead investigator of a Belgium-based randomized clinical trial reported at the annual meeting of the American College of Rheumatology.
“This is the first placebo-controlled, randomized clinical trial showing the efficacy of denosumab double-dosing regimen in structural modification of erosive hand osteoarthritis,” Ruth Wittoek, MD, PhD, a rheumatologist at Ghent (Belgium) University, said in presenting the results.
“Our primary endpoint was confirmed by a more robust secondary endpoint, both showing that denosumab stopped erosive progression and induced remodeling in patients with erosive hand OA,” she added. “Moreover, the double-dosing regimen was well-tolerated.”
However, during the question-and-answer period after her presentation, Dr. Wittoek acknowledged the study didn’t evaluate the impact denosumab had on cartilage and didn’t detect a signal for pain resolution until 96 weeks during the open-label extension phase. “I’m not quite sure if denosumab is sufficient to treat symptoms in osteoarthritis,” she said. “There were positive signals but, of course, having to wait 2 years for an effect is kind of hard for our patients.”
The trial randomized 100 adult patients 1:1 to denosumab 60 mg every 12 weeks – double the normal dose for osteoporosis – or placebo. The primary endpoint was changes in erosive progression and signs of repair based on x-ray at 48 weeks, after which all patients were switched to denosumab for the open-label study. To quantify changes, the investigators used the Ghent University Scoring System (GUSS), which uses a scale of 0-300 to quantify radiographic changes in erosive hand OA.
Dr. Wittoek said that the average change in GUSS at week 24 was +6 vs. –2.8 (P = .024) in the treatment and placebo groups, respectively, widening at week 48 to +10.1 and –7.9 (P = .003). By week 96, the variation was +18.8 for denosumab and +17 for placebo with switch to denosumab (P = .03).
“During the open-label extension the denosumab treatment group continued to increase to show remodeling while the former placebo treatment group, now also receiving denosumab, also showed signs of remodeling,” she said. “So, there was no more erosive progression.”
The secondary endpoint was the percentage of new erosive joint development at week 48: 1.8% in the denosumab group and 7% in placebo group (odds ratio, 0.23; 95% confidence interval, 0.10-0.50; P < .001). “Meaning the odds of erosive progression is 77% lower in the denosumab treatment group,” Dr. Wittoek said.
By week 96, those percentages were 0% and 0.7% in the respective treatment groups. “During the open-label extension, it was clear that denosumab blocked all new development of erosive joints,” she said.
Pain was one of the study’s exploratory endpoints, and the mean numeric rating scale showed no difference between treatment arms until the 96-week results, with a reduction by almost half in the denosumab group (from 4.2 at week 48 to 2.4) and a lesser reduction in the placebo-switched-to-denosumab arm (from 4.2 to 3.5; P = .028) between arms.
The placebo group was more susceptible to adverse events, namely musculoskeletal complaints and nervous system disorders, Dr. Wittoek noted. Infection rates, the most common adverse event, were similar between the two groups: 41 and 39 in the respective arms. Despite the double dose of denosumab, safety and tolerability in this trial was comparable to other trials, she said.
In comments submitted by e-mail, Dr. Wittoek noted that the extension study results will go out to 144 weeks. She also addressed the issues surrounding pain as an outcome.
“Besides disability, pain is also important from the patient’s perspective,” Dr. Wittoek said in the e-mailed comments. “However, pain and radiographic progression are undeniably coupled, but it’s unclear how.”
In erosive hand OA, structural progression and pain may not be related on a molecular level, she said. “Therefore, we don’t deny that pain levels should also be covered by treatment, but they should not be confused with structural modification; it is just another domain, not more nor less important.
The second year of the open-label extension study should clarify the pain outcomes, she said.
In an interview, David T. Felson, MD, MPH, professor and director of clinical epidemiology research at Boston University, questioned the delayed pain effect the study suggested. “It didn’t make any sense to me that there would be because both groups at that point got denosumab, so if there was going to be a pain effect that would’ve happened,” he said.
The pain effect is “really important,” he said. “We don’t use denosumab in rheumatoid arthritis to treat erosions because it doesn’t necessarily affect the pain and dysfunction of rheumatoid arthritis, and I’m not sure that isn’t going to be true in erosive hand osteoarthritis, but it’s possible.”
To clarify the pain outcomes, he said, “They’re going to have to work on the data.”
Amgen sponsored the trial but had no role in the design. Dr. Wittoek and Dr. Felson reported no relevant disclosures.
PHILADELPHIA – A double dose of the antiosteoporosis biologic denosumab (Prolia) slowed progression and repaired joints in erosive hand osteoarthritis (OA) but showed no impact on pain levels until 2 years after patients received the first dose, the lead investigator of a Belgium-based randomized clinical trial reported at the annual meeting of the American College of Rheumatology.
“This is the first placebo-controlled, randomized clinical trial showing the efficacy of denosumab double-dosing regimen in structural modification of erosive hand osteoarthritis,” Ruth Wittoek, MD, PhD, a rheumatologist at Ghent (Belgium) University, said in presenting the results.
“Our primary endpoint was confirmed by a more robust secondary endpoint, both showing that denosumab stopped erosive progression and induced remodeling in patients with erosive hand OA,” she added. “Moreover, the double-dosing regimen was well-tolerated.”
However, during the question-and-answer period after her presentation, Dr. Wittoek acknowledged the study didn’t evaluate the impact denosumab had on cartilage and didn’t detect a signal for pain resolution until 96 weeks during the open-label extension phase. “I’m not quite sure if denosumab is sufficient to treat symptoms in osteoarthritis,” she said. “There were positive signals but, of course, having to wait 2 years for an effect is kind of hard for our patients.”
The trial randomized 100 adult patients 1:1 to denosumab 60 mg every 12 weeks – double the normal dose for osteoporosis – or placebo. The primary endpoint was changes in erosive progression and signs of repair based on x-ray at 48 weeks, after which all patients were switched to denosumab for the open-label study. To quantify changes, the investigators used the Ghent University Scoring System (GUSS), which uses a scale of 0-300 to quantify radiographic changes in erosive hand OA.
Dr. Wittoek said that the average change in GUSS at week 24 was +6 vs. –2.8 (P = .024) in the treatment and placebo groups, respectively, widening at week 48 to +10.1 and –7.9 (P = .003). By week 96, the variation was +18.8 for denosumab and +17 for placebo with switch to denosumab (P = .03).
“During the open-label extension the denosumab treatment group continued to increase to show remodeling while the former placebo treatment group, now also receiving denosumab, also showed signs of remodeling,” she said. “So, there was no more erosive progression.”
The secondary endpoint was the percentage of new erosive joint development at week 48: 1.8% in the denosumab group and 7% in placebo group (odds ratio, 0.23; 95% confidence interval, 0.10-0.50; P < .001). “Meaning the odds of erosive progression is 77% lower in the denosumab treatment group,” Dr. Wittoek said.
By week 96, those percentages were 0% and 0.7% in the respective treatment groups. “During the open-label extension, it was clear that denosumab blocked all new development of erosive joints,” she said.
Pain was one of the study’s exploratory endpoints, and the mean numeric rating scale showed no difference between treatment arms until the 96-week results, with a reduction by almost half in the denosumab group (from 4.2 at week 48 to 2.4) and a lesser reduction in the placebo-switched-to-denosumab arm (from 4.2 to 3.5; P = .028) between arms.
The placebo group was more susceptible to adverse events, namely musculoskeletal complaints and nervous system disorders, Dr. Wittoek noted. Infection rates, the most common adverse event, were similar between the two groups: 41 and 39 in the respective arms. Despite the double dose of denosumab, safety and tolerability in this trial was comparable to other trials, she said.
In comments submitted by e-mail, Dr. Wittoek noted that the extension study results will go out to 144 weeks. She also addressed the issues surrounding pain as an outcome.
“Besides disability, pain is also important from the patient’s perspective,” Dr. Wittoek said in the e-mailed comments. “However, pain and radiographic progression are undeniably coupled, but it’s unclear how.”
In erosive hand OA, structural progression and pain may not be related on a molecular level, she said. “Therefore, we don’t deny that pain levels should also be covered by treatment, but they should not be confused with structural modification; it is just another domain, not more nor less important.
The second year of the open-label extension study should clarify the pain outcomes, she said.
In an interview, David T. Felson, MD, MPH, professor and director of clinical epidemiology research at Boston University, questioned the delayed pain effect the study suggested. “It didn’t make any sense to me that there would be because both groups at that point got denosumab, so if there was going to be a pain effect that would’ve happened,” he said.
The pain effect is “really important,” he said. “We don’t use denosumab in rheumatoid arthritis to treat erosions because it doesn’t necessarily affect the pain and dysfunction of rheumatoid arthritis, and I’m not sure that isn’t going to be true in erosive hand osteoarthritis, but it’s possible.”
To clarify the pain outcomes, he said, “They’re going to have to work on the data.”
Amgen sponsored the trial but had no role in the design. Dr. Wittoek and Dr. Felson reported no relevant disclosures.
AT ACR 2022
Randomized trial finds community-based weight-loss programs ease knee OA pain
PHILADELPHIA – What works in the clinic can also work in community settings: Patients who are overweight or obese with knee osteoarthritis can find relief from pain through diet and exercise programs conducted in recreation centers, local gyms, fitness centers, and other places close to home, according to investigators in a pragmatic randomized trial.
The Weight Loss and Exercise for Communities With Arthritis in North Carolina (WE-CAN) study was modeled after the successful Intensive Diet and Exercise for Arthritis trial, which showed that adults randomized to 18 months of either a diet and exercise program or diet alone had more weight loss and larger reductions in levels of the inflammatory cytokine interleukin-6 than patients randomized to exercise alone, and that diet alone was associated with greater reductions in knee compressive force than exercise alone.
That study was conducted by Stephen P. Messier, PhD, and colleagues at Wake Forest University, Winston-Salem, N.C.. As previously reported, the investigators also saw continued benefits for participants years after the original trial.
With the WE-CAN trial, results of which were reported at the annual meeting of the American College of Rheumatology, Dr. Messier and colleagues took the intervention one step further, randomizing 823 community-dwelling adults who were overweight or obese (body mass index [BMI], ≥ 27 kg/m2) with knee OA to either an 18-month diet and exercise intervention or attention control group consisting of five 1-hour face-to-face meetings over 18 months, plus information packets and phone sessions during alternate months.
“Compared to the control group, diet plus exercise had a statistically significant but modest reduction in pain. Diet plus exercise was 20% more likely to attain a clinically important 2-point improvement in pain,” Dr. Messier said in an oral abstract session at ACR.
Real-world setting
The primary goal of WE-CAN was to “determine whether adaptation of a diet and exercise academic center–based efficacy trial to community settings results in a statistically significant reduction in pain relative to an attention control.”
A total of 3,751 potential candidates were screened, and 823 were randomized and assigned to either a diet and exercise arm (414) or attention control arm (409). Of the patients randomized, 336 in the diet/exercise arm and 322 in the control arm attended the final 18-month follow-up visit.
The exercise component consisted of a 15-minute walking period, followed by a 20-minute weight-training period, and ending with a second 15-minute walking period. The diet goal was 10% or greater weight loss, aided by a distribution of low-calorie recipes to produce a reduced-calorie diet of the patient’s choice, with the option to include nutritional powder to make low-calories shakes as meal replacements, one or two per day for the first 6 months, with the option of one per day for the remaining months.
The pragmatic components included the use of established community facilities in both urban and rural counties in North Carolina, broad inclusion criteria, patient-centered outcomes, use of community-based staff to deliver the treatment, nonphysicians trained by study physicians to perform knee exams, and various means of communication, Dr. Messier said.
Participants in each arm were closely matched by demographic and clinical characteristics, with a mean age of 64.5 years in the diet/exercise group and 64.7 years in the attention control group, respective mean weight of 100.7 kg and 101.1 kg, and respective BMI of 36.7 and 36.9. Women comprised about 77% of participants in each group.
Endpoints met
The trial met its primary endpoint of a significantly greater reduction in pain at 18 months in the diet and exercise group as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and scored on a scale of 0 (no pain) to 20 (worst pain).
In an analysis adjusted for sex, BMI, and baseline values, there was a 32% reduction in pain scores from baseline in the active intervention arm versus 24% in the control arm (P = .02).
In all, 60.2% of participants assigned to diet and exercise had a minimum reduction in pain scores of at least 2 points at 18 months, compared with 49.7% of participants assigned to the attention control group. This translated into a relative risk for achieving at least a 2-point improvement with diet and exercise was 1.20 (P = .01).
Among participants who remained in the study for the entire 18 months, there were significant improvements in the diet and exercise group compared with controls in the prespecified secondary endpoints of weight change (–8 kg vs. –2 kg), waist circumference, WOMAC function, 6-minute walk distance, and mean Short Form–36 health-related quality of life subscale (P < .001 for all comparisons).
Dr. Messier acknowledged that the diagnosis of knee OA was based only on ACR clinical criteria and was not confirmed with imaging. In addition, offering patients the option of free meal replacement limited the pragmatic nature of the intervention.
He also noted that the 24% reduction in pain seen in the control group suggests that interacting with patients can improve clinical outcomes.
‘Tour de force’
In the question-and-answer session following Dr. Messier’s presentation, David T. Felson, MD, a rheumatologist at Boston Medical Center, called in and said the study was “a tour de force” and congratulated Dr. Messier and colleagues on “a lovely study.”
Dr. Felson asked whether the investigators had conducted a mediation analysis to determine what proportion of the improvement was attributable to weight loss, and whether patients assigned to exercise were sticking with it throughout the study.
Dr. Messier replied that they had not yet done a mediation analysis but were continuing to examine the data. Regarding the exercise question, he noted that “the adherence was over 80% for 6 months and over 70% for the whole 18 months, so they did a really nice job.”
In an interview, session moderator Anne Davidson, MBBS, director of the rheumatology program at Northwell Health in Manhasset, N.Y., commented that the investigators managed to accomplish a very challenging task.
“In terms of recruitment of patients with engagement of community facilities and quality of data, I would say that, as far as an osteoarthritis study goes, this was really a tremendous effort on the part of all people involved,” she said.
She noted that, while the WE-CAN program may work in North Carolina, there may be barriers to implementing it elsewhere, such as large suburban areas where some patients experience food insecurity and others have difficulty with transportation and access to treatment facilities.
“The question here that remains is, as Dr. Felson asked, what is the contribution of weight loss and what is the contribution of exercise? Because if it’s just weight loss, we have a whole lot of new things coming to help with that,” she said.
The WE-CAN study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Messier disclosed that GNC, a health food and nutrition chain, donated the meal replacements used by patients. Dr. Davidson reported no relevant conflicts of interest.
PHILADELPHIA – What works in the clinic can also work in community settings: Patients who are overweight or obese with knee osteoarthritis can find relief from pain through diet and exercise programs conducted in recreation centers, local gyms, fitness centers, and other places close to home, according to investigators in a pragmatic randomized trial.
The Weight Loss and Exercise for Communities With Arthritis in North Carolina (WE-CAN) study was modeled after the successful Intensive Diet and Exercise for Arthritis trial, which showed that adults randomized to 18 months of either a diet and exercise program or diet alone had more weight loss and larger reductions in levels of the inflammatory cytokine interleukin-6 than patients randomized to exercise alone, and that diet alone was associated with greater reductions in knee compressive force than exercise alone.
That study was conducted by Stephen P. Messier, PhD, and colleagues at Wake Forest University, Winston-Salem, N.C.. As previously reported, the investigators also saw continued benefits for participants years after the original trial.
With the WE-CAN trial, results of which were reported at the annual meeting of the American College of Rheumatology, Dr. Messier and colleagues took the intervention one step further, randomizing 823 community-dwelling adults who were overweight or obese (body mass index [BMI], ≥ 27 kg/m2) with knee OA to either an 18-month diet and exercise intervention or attention control group consisting of five 1-hour face-to-face meetings over 18 months, plus information packets and phone sessions during alternate months.
“Compared to the control group, diet plus exercise had a statistically significant but modest reduction in pain. Diet plus exercise was 20% more likely to attain a clinically important 2-point improvement in pain,” Dr. Messier said in an oral abstract session at ACR.
Real-world setting
The primary goal of WE-CAN was to “determine whether adaptation of a diet and exercise academic center–based efficacy trial to community settings results in a statistically significant reduction in pain relative to an attention control.”
A total of 3,751 potential candidates were screened, and 823 were randomized and assigned to either a diet and exercise arm (414) or attention control arm (409). Of the patients randomized, 336 in the diet/exercise arm and 322 in the control arm attended the final 18-month follow-up visit.
The exercise component consisted of a 15-minute walking period, followed by a 20-minute weight-training period, and ending with a second 15-minute walking period. The diet goal was 10% or greater weight loss, aided by a distribution of low-calorie recipes to produce a reduced-calorie diet of the patient’s choice, with the option to include nutritional powder to make low-calories shakes as meal replacements, one or two per day for the first 6 months, with the option of one per day for the remaining months.
The pragmatic components included the use of established community facilities in both urban and rural counties in North Carolina, broad inclusion criteria, patient-centered outcomes, use of community-based staff to deliver the treatment, nonphysicians trained by study physicians to perform knee exams, and various means of communication, Dr. Messier said.
Participants in each arm were closely matched by demographic and clinical characteristics, with a mean age of 64.5 years in the diet/exercise group and 64.7 years in the attention control group, respective mean weight of 100.7 kg and 101.1 kg, and respective BMI of 36.7 and 36.9. Women comprised about 77% of participants in each group.
Endpoints met
The trial met its primary endpoint of a significantly greater reduction in pain at 18 months in the diet and exercise group as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and scored on a scale of 0 (no pain) to 20 (worst pain).
In an analysis adjusted for sex, BMI, and baseline values, there was a 32% reduction in pain scores from baseline in the active intervention arm versus 24% in the control arm (P = .02).
In all, 60.2% of participants assigned to diet and exercise had a minimum reduction in pain scores of at least 2 points at 18 months, compared with 49.7% of participants assigned to the attention control group. This translated into a relative risk for achieving at least a 2-point improvement with diet and exercise was 1.20 (P = .01).
Among participants who remained in the study for the entire 18 months, there were significant improvements in the diet and exercise group compared with controls in the prespecified secondary endpoints of weight change (–8 kg vs. –2 kg), waist circumference, WOMAC function, 6-minute walk distance, and mean Short Form–36 health-related quality of life subscale (P < .001 for all comparisons).
Dr. Messier acknowledged that the diagnosis of knee OA was based only on ACR clinical criteria and was not confirmed with imaging. In addition, offering patients the option of free meal replacement limited the pragmatic nature of the intervention.
He also noted that the 24% reduction in pain seen in the control group suggests that interacting with patients can improve clinical outcomes.
‘Tour de force’
In the question-and-answer session following Dr. Messier’s presentation, David T. Felson, MD, a rheumatologist at Boston Medical Center, called in and said the study was “a tour de force” and congratulated Dr. Messier and colleagues on “a lovely study.”
Dr. Felson asked whether the investigators had conducted a mediation analysis to determine what proportion of the improvement was attributable to weight loss, and whether patients assigned to exercise were sticking with it throughout the study.
Dr. Messier replied that they had not yet done a mediation analysis but were continuing to examine the data. Regarding the exercise question, he noted that “the adherence was over 80% for 6 months and over 70% for the whole 18 months, so they did a really nice job.”
In an interview, session moderator Anne Davidson, MBBS, director of the rheumatology program at Northwell Health in Manhasset, N.Y., commented that the investigators managed to accomplish a very challenging task.
“In terms of recruitment of patients with engagement of community facilities and quality of data, I would say that, as far as an osteoarthritis study goes, this was really a tremendous effort on the part of all people involved,” she said.
She noted that, while the WE-CAN program may work in North Carolina, there may be barriers to implementing it elsewhere, such as large suburban areas where some patients experience food insecurity and others have difficulty with transportation and access to treatment facilities.
“The question here that remains is, as Dr. Felson asked, what is the contribution of weight loss and what is the contribution of exercise? Because if it’s just weight loss, we have a whole lot of new things coming to help with that,” she said.
The WE-CAN study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Messier disclosed that GNC, a health food and nutrition chain, donated the meal replacements used by patients. Dr. Davidson reported no relevant conflicts of interest.
PHILADELPHIA – What works in the clinic can also work in community settings: Patients who are overweight or obese with knee osteoarthritis can find relief from pain through diet and exercise programs conducted in recreation centers, local gyms, fitness centers, and other places close to home, according to investigators in a pragmatic randomized trial.
The Weight Loss and Exercise for Communities With Arthritis in North Carolina (WE-CAN) study was modeled after the successful Intensive Diet and Exercise for Arthritis trial, which showed that adults randomized to 18 months of either a diet and exercise program or diet alone had more weight loss and larger reductions in levels of the inflammatory cytokine interleukin-6 than patients randomized to exercise alone, and that diet alone was associated with greater reductions in knee compressive force than exercise alone.
That study was conducted by Stephen P. Messier, PhD, and colleagues at Wake Forest University, Winston-Salem, N.C.. As previously reported, the investigators also saw continued benefits for participants years after the original trial.
With the WE-CAN trial, results of which were reported at the annual meeting of the American College of Rheumatology, Dr. Messier and colleagues took the intervention one step further, randomizing 823 community-dwelling adults who were overweight or obese (body mass index [BMI], ≥ 27 kg/m2) with knee OA to either an 18-month diet and exercise intervention or attention control group consisting of five 1-hour face-to-face meetings over 18 months, plus information packets and phone sessions during alternate months.
“Compared to the control group, diet plus exercise had a statistically significant but modest reduction in pain. Diet plus exercise was 20% more likely to attain a clinically important 2-point improvement in pain,” Dr. Messier said in an oral abstract session at ACR.
Real-world setting
The primary goal of WE-CAN was to “determine whether adaptation of a diet and exercise academic center–based efficacy trial to community settings results in a statistically significant reduction in pain relative to an attention control.”
A total of 3,751 potential candidates were screened, and 823 were randomized and assigned to either a diet and exercise arm (414) or attention control arm (409). Of the patients randomized, 336 in the diet/exercise arm and 322 in the control arm attended the final 18-month follow-up visit.
The exercise component consisted of a 15-minute walking period, followed by a 20-minute weight-training period, and ending with a second 15-minute walking period. The diet goal was 10% or greater weight loss, aided by a distribution of low-calorie recipes to produce a reduced-calorie diet of the patient’s choice, with the option to include nutritional powder to make low-calories shakes as meal replacements, one or two per day for the first 6 months, with the option of one per day for the remaining months.
The pragmatic components included the use of established community facilities in both urban and rural counties in North Carolina, broad inclusion criteria, patient-centered outcomes, use of community-based staff to deliver the treatment, nonphysicians trained by study physicians to perform knee exams, and various means of communication, Dr. Messier said.
Participants in each arm were closely matched by demographic and clinical characteristics, with a mean age of 64.5 years in the diet/exercise group and 64.7 years in the attention control group, respective mean weight of 100.7 kg and 101.1 kg, and respective BMI of 36.7 and 36.9. Women comprised about 77% of participants in each group.
Endpoints met
The trial met its primary endpoint of a significantly greater reduction in pain at 18 months in the diet and exercise group as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and scored on a scale of 0 (no pain) to 20 (worst pain).
In an analysis adjusted for sex, BMI, and baseline values, there was a 32% reduction in pain scores from baseline in the active intervention arm versus 24% in the control arm (P = .02).
In all, 60.2% of participants assigned to diet and exercise had a minimum reduction in pain scores of at least 2 points at 18 months, compared with 49.7% of participants assigned to the attention control group. This translated into a relative risk for achieving at least a 2-point improvement with diet and exercise was 1.20 (P = .01).
Among participants who remained in the study for the entire 18 months, there were significant improvements in the diet and exercise group compared with controls in the prespecified secondary endpoints of weight change (–8 kg vs. –2 kg), waist circumference, WOMAC function, 6-minute walk distance, and mean Short Form–36 health-related quality of life subscale (P < .001 for all comparisons).
Dr. Messier acknowledged that the diagnosis of knee OA was based only on ACR clinical criteria and was not confirmed with imaging. In addition, offering patients the option of free meal replacement limited the pragmatic nature of the intervention.
He also noted that the 24% reduction in pain seen in the control group suggests that interacting with patients can improve clinical outcomes.
‘Tour de force’
In the question-and-answer session following Dr. Messier’s presentation, David T. Felson, MD, a rheumatologist at Boston Medical Center, called in and said the study was “a tour de force” and congratulated Dr. Messier and colleagues on “a lovely study.”
Dr. Felson asked whether the investigators had conducted a mediation analysis to determine what proportion of the improvement was attributable to weight loss, and whether patients assigned to exercise were sticking with it throughout the study.
Dr. Messier replied that they had not yet done a mediation analysis but were continuing to examine the data. Regarding the exercise question, he noted that “the adherence was over 80% for 6 months and over 70% for the whole 18 months, so they did a really nice job.”
In an interview, session moderator Anne Davidson, MBBS, director of the rheumatology program at Northwell Health in Manhasset, N.Y., commented that the investigators managed to accomplish a very challenging task.
“In terms of recruitment of patients with engagement of community facilities and quality of data, I would say that, as far as an osteoarthritis study goes, this was really a tremendous effort on the part of all people involved,” she said.
She noted that, while the WE-CAN program may work in North Carolina, there may be barriers to implementing it elsewhere, such as large suburban areas where some patients experience food insecurity and others have difficulty with transportation and access to treatment facilities.
“The question here that remains is, as Dr. Felson asked, what is the contribution of weight loss and what is the contribution of exercise? Because if it’s just weight loss, we have a whole lot of new things coming to help with that,” she said.
The WE-CAN study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Messier disclosed that GNC, a health food and nutrition chain, donated the meal replacements used by patients. Dr. Davidson reported no relevant conflicts of interest.
AT ACR 2022
Total replacement and fusion yield similar outcomes for ankle osteoarthritis
Ankle osteoarthritis remains a cause of severe pain and disability. Patients are treated nonoperatively if possible, but surgery is often needed for individuals with end-stage disease, wrote Andrew Goldberg, MBBS, of University College London and colleagues in the Annals of Internal Medicine.
“Most patients with ankle arthritis respond to nonoperative treatments, such as weight loss, activity modification, support braces, and analgesia, [but] once the disease has progressed to end-stage osteoarthritis, the main surgical treatments are total ankle re-placement or ankle arthrodesis,” Dr. Goldberg said, in an interview.
In the new study, patients were randomized to receive either a total ankle replacement (TAR) or ankle fusion (AF).
“We showed that, in both treatment groups the clinical scores improved hugely, by more than three times the minimal clinically important difference,” Dr. Goldberg said in an interview.
“Although the ankle replacement arm improved, on average, by more than an extra 4 points over ankle fusion, this was not considered clinically or statistically significant,” he said.
The study is the first randomized trial to show high-quality and robust results, he noted, and findings support data from previous studies.
“Although both TAR and ankle fusion have been shown to be effective, they are very different treatments, with one fusing the bones so that there is no ankle joint movement, and the other replacing the joint with the aim of retaining ankle joint movement. It is difficult for a patient to know which treatment is more suitable for them, with most seeking guidance from their surgeon,” he said.
Generating high-quality evidence
The study, a randomized, multicenter, open-label trial known as TARVA (Total Ankle Replacement Versus Ankle Arthrodesis), aimed to compare the clinical effectiveness of the two existing publicly funded U.K. treatment options, the authors wrote.
Patients were recruited at 17 U.K. centers between March 6, 2015, and Jan. 10, 2019. The study enrolled 303 adults aged 50-85 years with end-stage ankle osteoarthritis. The mean age of the participants was 68 years; 71% were men. A total of 137 TAR patients and 144 ankle fusion patients completed their surgeries with clinical scores available for analysis. Baseline characteristics were mainly similar between the groups.
Blinding was not possible because of the nature of the procedures, but the surgeons who screened the patients were not aware of the randomization allocations, the researchers noted. A total of 33 surgeons participated in the trial, with a median number of seven patients per surgeon during the study period.
For TAR, U.K. surgeons use both two-component, fixed-bearing and three-component, mobile-bearing implants, the authors write. Ankle fusion was done using the surgeon’s usual technique of either arthroscopic-assisted or open ankle fusion.
The primary outcome was the change in the Manchester–Oxford Foot Questionnaire walking/standing (MOXFQ-W/S) domain scores from baseline to 52 weeks after surgery. The MOXFQ-W/S uses a scale of 0-100, with lower scores representing better outcomes. Secondary outcomes included change in the MOXFQ-W/S scores at 26 weeks after surgery, as well as measures of patient quality of life.
No statistically significant difference
Overall, the mean MOXFQ-W/S scores improved significantly from baseline to 52 weeks for both groups, with average improvements of 49.9 in the TAR group and 44.4 points in the AF group. The average scores at 52 weeks were 31.4 in the TAR group and 36.8 in the AF group.
The adjusted difference in score change from baseline was –5.56, showing a slightly greater degree of improvement with TAR, but this difference was not clinically or statistically significant, the researchers noted.
Adverse event numbers were similar for both procedures, with 54% of TAR patients and 53% of AF patients experiencing at least 1 adverse event during the study period. Of those, 18% of TAR patients and 24% of AF patients experienced at least 1 serious adverse event.
However, the TAR patients experienced a higher rate of wound healing complications and nerve injuries, while thromboembolism was higher in the AF patients, the researchers noted.
A prespecified subgroup analysis of patients with osteoarthritis in adjacent joints suggested a greater improvement in TAR, compared with AF, a difference that increased when fixed-bearing TAR was compared with AF, the authors wrote.
“This reinforces previous reports that suggest that the presence of adjacent joint arthritis may be an indication for ankle replacement over AF,” the authors wrote in their discussion.
“Many of these patients did not have any symptoms in the adjacent joints,” they noted.
“The presence of adjacent joint arthritis, meaning the wear and tear of the joints around the ankle joint, seemed to favor ankle replacement,” Dr. Goldberg said. Approximately 30 joints in the foot continue to move after the ankle is fused, and if these adjacent joints are not healthy before surgery [as was the case in 42% of the study patients], the results of fusion were less successful, he explained.
A post hoc analysis between TAR subtypes showed that patients who had fixed-bearing TAR had significantly greater improvements, compared with AF patients, but this difference was not observed in patients who had mobile-bearing TAR, the researchers noted.
Dr. Goldberg said it was surprising “that, in a separate analysis, we found that the fixed-bearing ankle replacement patients [who accounted for half of the implants used] improved by a much greater difference when compared to ankle fusion.”
The study findings were limited by several factors including the short follow-up and study design that allowed surgeons to choose any implant and technique, the researchers noted.
Other limitations include a lack of data on cost-effectiveness and the impact of comorbidities on outcomes, they wrote. However, the study is the first completed multicenter randomized controlled trial to compare TAR and AF procedures for end-stage ankle osteoarthritis and shows that both yield similar clinical improvements, they concluded.
Data can inform treatment discussion
The take-home messages for clinicians are that both ankle replacement and ankle fusion are effective treatments that improve patients’ quality of life, and it is important to establish the health of adjacent joints before making treatment recommendations, Dr. Goldberg said.
“Careful counseling on the relative risks of each procedure should be part of the informed consent process,” he added. Ideally, all patients seeking surgical care for ankle arthritis should have a choice between ankle replacement and ankle fusion, but sometimes there is inequity of provision of the two treatments, he noted.
“We now encourage all surgeons to work in ankle arthritis networks so that every patient, no matter where they live, can have choice about the best treatment for them,” he said.
Researchers met the challenge of surgical RCT
Randomized trials of surgical interventions are challenging to conduct, and therefore limited, wrote Bruce Sangeorzan, MD, of the University of Washington, Seattle, and colleagues in an accompanying editorial. However, the new study was strengthened by the inclusion of 17 centers for heterogeneity of implant type and surgeon experience level, the editorialists said in the Annals of Internal Medicine.
The study is especially important, because ankle arthritis treatment is very understudied, compared with hip and knee arthritis, but it has a similar impact on activity, editorial coauthor Dr. Sangeorzan said in an interview.
“Randomized controlled trials are the gold standard for comparing medical therapies,” he said, “but they are very difficult to do in surgical treatments, particularly when the two treatments can be differentiated, in this case by movement of the ankle.”
In addition, there is a strong placebo effect attached to interventions, Dr. Sangeorzan noted. “Determining best-case treatment relies on prospective research, preferably randomized. Since both ankle fusion and ankle replacement are effective therapies, a prospective randomized trial is the best way to help make treatment decisions,” he said.
The current study findings are not surprising, but they are preliminary, and 1 year of follow-up is not enough to determine effectiveness, Dr. Sangeorzan emphasized. However, “the authors have done the hard work of randomizing the patients and collecting the data, and the patients can now be followed for a longer time,” he said.
“In addition, the trial was designed with multiple secondary outcome measures, so the data can be matched up with larger trials that were not randomized to identify key elements of success for each procedure,” he noted.
The key message for clinicians is that ankle arthritis has a significant impact on patients’ lives, but there are two effective treatments that can reduce the impact of the disease, said Dr. Sangeorzan. “The data suggest that there are differences in implant design and differences in comorbidities that should influence decision-making,” he added.
Additional research is needed in the form of a longer study duration with larger cohorts, said Dr. Sangeorzan. In particular, researchers need to determine what comorbidities might drive patients to one type of care vs. another, he said. “The suggestion that [patients receiving implants with two motion segments have better outcomes than those receiving implants with a one-motion segment] also deserves further study,” he added.
The research was supported by the UK National Institute for Health and Care Research Health Technology Assessment Programme. The trial was sponsored by University College London. Dr. Goldberg disclosed grant support from NIHR HTA, as well as financial relationships with companies including Stryker, Paragon 28, and stock options with Standing CT Company, Elstree Waterfront Outpatients, and X Bolt Orthopedics.
The editorialists had no financial conflicts to disclose.
Ankle osteoarthritis remains a cause of severe pain and disability. Patients are treated nonoperatively if possible, but surgery is often needed for individuals with end-stage disease, wrote Andrew Goldberg, MBBS, of University College London and colleagues in the Annals of Internal Medicine.
“Most patients with ankle arthritis respond to nonoperative treatments, such as weight loss, activity modification, support braces, and analgesia, [but] once the disease has progressed to end-stage osteoarthritis, the main surgical treatments are total ankle re-placement or ankle arthrodesis,” Dr. Goldberg said, in an interview.
In the new study, patients were randomized to receive either a total ankle replacement (TAR) or ankle fusion (AF).
“We showed that, in both treatment groups the clinical scores improved hugely, by more than three times the minimal clinically important difference,” Dr. Goldberg said in an interview.
“Although the ankle replacement arm improved, on average, by more than an extra 4 points over ankle fusion, this was not considered clinically or statistically significant,” he said.
The study is the first randomized trial to show high-quality and robust results, he noted, and findings support data from previous studies.
“Although both TAR and ankle fusion have been shown to be effective, they are very different treatments, with one fusing the bones so that there is no ankle joint movement, and the other replacing the joint with the aim of retaining ankle joint movement. It is difficult for a patient to know which treatment is more suitable for them, with most seeking guidance from their surgeon,” he said.
Generating high-quality evidence
The study, a randomized, multicenter, open-label trial known as TARVA (Total Ankle Replacement Versus Ankle Arthrodesis), aimed to compare the clinical effectiveness of the two existing publicly funded U.K. treatment options, the authors wrote.
Patients were recruited at 17 U.K. centers between March 6, 2015, and Jan. 10, 2019. The study enrolled 303 adults aged 50-85 years with end-stage ankle osteoarthritis. The mean age of the participants was 68 years; 71% were men. A total of 137 TAR patients and 144 ankle fusion patients completed their surgeries with clinical scores available for analysis. Baseline characteristics were mainly similar between the groups.
Blinding was not possible because of the nature of the procedures, but the surgeons who screened the patients were not aware of the randomization allocations, the researchers noted. A total of 33 surgeons participated in the trial, with a median number of seven patients per surgeon during the study period.
For TAR, U.K. surgeons use both two-component, fixed-bearing and three-component, mobile-bearing implants, the authors write. Ankle fusion was done using the surgeon’s usual technique of either arthroscopic-assisted or open ankle fusion.
The primary outcome was the change in the Manchester–Oxford Foot Questionnaire walking/standing (MOXFQ-W/S) domain scores from baseline to 52 weeks after surgery. The MOXFQ-W/S uses a scale of 0-100, with lower scores representing better outcomes. Secondary outcomes included change in the MOXFQ-W/S scores at 26 weeks after surgery, as well as measures of patient quality of life.
No statistically significant difference
Overall, the mean MOXFQ-W/S scores improved significantly from baseline to 52 weeks for both groups, with average improvements of 49.9 in the TAR group and 44.4 points in the AF group. The average scores at 52 weeks were 31.4 in the TAR group and 36.8 in the AF group.
The adjusted difference in score change from baseline was –5.56, showing a slightly greater degree of improvement with TAR, but this difference was not clinically or statistically significant, the researchers noted.
Adverse event numbers were similar for both procedures, with 54% of TAR patients and 53% of AF patients experiencing at least 1 adverse event during the study period. Of those, 18% of TAR patients and 24% of AF patients experienced at least 1 serious adverse event.
However, the TAR patients experienced a higher rate of wound healing complications and nerve injuries, while thromboembolism was higher in the AF patients, the researchers noted.
A prespecified subgroup analysis of patients with osteoarthritis in adjacent joints suggested a greater improvement in TAR, compared with AF, a difference that increased when fixed-bearing TAR was compared with AF, the authors wrote.
“This reinforces previous reports that suggest that the presence of adjacent joint arthritis may be an indication for ankle replacement over AF,” the authors wrote in their discussion.
“Many of these patients did not have any symptoms in the adjacent joints,” they noted.
“The presence of adjacent joint arthritis, meaning the wear and tear of the joints around the ankle joint, seemed to favor ankle replacement,” Dr. Goldberg said. Approximately 30 joints in the foot continue to move after the ankle is fused, and if these adjacent joints are not healthy before surgery [as was the case in 42% of the study patients], the results of fusion were less successful, he explained.
A post hoc analysis between TAR subtypes showed that patients who had fixed-bearing TAR had significantly greater improvements, compared with AF patients, but this difference was not observed in patients who had mobile-bearing TAR, the researchers noted.
Dr. Goldberg said it was surprising “that, in a separate analysis, we found that the fixed-bearing ankle replacement patients [who accounted for half of the implants used] improved by a much greater difference when compared to ankle fusion.”
The study findings were limited by several factors including the short follow-up and study design that allowed surgeons to choose any implant and technique, the researchers noted.
Other limitations include a lack of data on cost-effectiveness and the impact of comorbidities on outcomes, they wrote. However, the study is the first completed multicenter randomized controlled trial to compare TAR and AF procedures for end-stage ankle osteoarthritis and shows that both yield similar clinical improvements, they concluded.
Data can inform treatment discussion
The take-home messages for clinicians are that both ankle replacement and ankle fusion are effective treatments that improve patients’ quality of life, and it is important to establish the health of adjacent joints before making treatment recommendations, Dr. Goldberg said.
“Careful counseling on the relative risks of each procedure should be part of the informed consent process,” he added. Ideally, all patients seeking surgical care for ankle arthritis should have a choice between ankle replacement and ankle fusion, but sometimes there is inequity of provision of the two treatments, he noted.
“We now encourage all surgeons to work in ankle arthritis networks so that every patient, no matter where they live, can have choice about the best treatment for them,” he said.
Researchers met the challenge of surgical RCT
Randomized trials of surgical interventions are challenging to conduct, and therefore limited, wrote Bruce Sangeorzan, MD, of the University of Washington, Seattle, and colleagues in an accompanying editorial. However, the new study was strengthened by the inclusion of 17 centers for heterogeneity of implant type and surgeon experience level, the editorialists said in the Annals of Internal Medicine.
The study is especially important, because ankle arthritis treatment is very understudied, compared with hip and knee arthritis, but it has a similar impact on activity, editorial coauthor Dr. Sangeorzan said in an interview.
“Randomized controlled trials are the gold standard for comparing medical therapies,” he said, “but they are very difficult to do in surgical treatments, particularly when the two treatments can be differentiated, in this case by movement of the ankle.”
In addition, there is a strong placebo effect attached to interventions, Dr. Sangeorzan noted. “Determining best-case treatment relies on prospective research, preferably randomized. Since both ankle fusion and ankle replacement are effective therapies, a prospective randomized trial is the best way to help make treatment decisions,” he said.
The current study findings are not surprising, but they are preliminary, and 1 year of follow-up is not enough to determine effectiveness, Dr. Sangeorzan emphasized. However, “the authors have done the hard work of randomizing the patients and collecting the data, and the patients can now be followed for a longer time,” he said.
“In addition, the trial was designed with multiple secondary outcome measures, so the data can be matched up with larger trials that were not randomized to identify key elements of success for each procedure,” he noted.
The key message for clinicians is that ankle arthritis has a significant impact on patients’ lives, but there are two effective treatments that can reduce the impact of the disease, said Dr. Sangeorzan. “The data suggest that there are differences in implant design and differences in comorbidities that should influence decision-making,” he added.
Additional research is needed in the form of a longer study duration with larger cohorts, said Dr. Sangeorzan. In particular, researchers need to determine what comorbidities might drive patients to one type of care vs. another, he said. “The suggestion that [patients receiving implants with two motion segments have better outcomes than those receiving implants with a one-motion segment] also deserves further study,” he added.
The research was supported by the UK National Institute for Health and Care Research Health Technology Assessment Programme. The trial was sponsored by University College London. Dr. Goldberg disclosed grant support from NIHR HTA, as well as financial relationships with companies including Stryker, Paragon 28, and stock options with Standing CT Company, Elstree Waterfront Outpatients, and X Bolt Orthopedics.
The editorialists had no financial conflicts to disclose.
Ankle osteoarthritis remains a cause of severe pain and disability. Patients are treated nonoperatively if possible, but surgery is often needed for individuals with end-stage disease, wrote Andrew Goldberg, MBBS, of University College London and colleagues in the Annals of Internal Medicine.
“Most patients with ankle arthritis respond to nonoperative treatments, such as weight loss, activity modification, support braces, and analgesia, [but] once the disease has progressed to end-stage osteoarthritis, the main surgical treatments are total ankle re-placement or ankle arthrodesis,” Dr. Goldberg said, in an interview.
In the new study, patients were randomized to receive either a total ankle replacement (TAR) or ankle fusion (AF).
“We showed that, in both treatment groups the clinical scores improved hugely, by more than three times the minimal clinically important difference,” Dr. Goldberg said in an interview.
“Although the ankle replacement arm improved, on average, by more than an extra 4 points over ankle fusion, this was not considered clinically or statistically significant,” he said.
The study is the first randomized trial to show high-quality and robust results, he noted, and findings support data from previous studies.
“Although both TAR and ankle fusion have been shown to be effective, they are very different treatments, with one fusing the bones so that there is no ankle joint movement, and the other replacing the joint with the aim of retaining ankle joint movement. It is difficult for a patient to know which treatment is more suitable for them, with most seeking guidance from their surgeon,” he said.
Generating high-quality evidence
The study, a randomized, multicenter, open-label trial known as TARVA (Total Ankle Replacement Versus Ankle Arthrodesis), aimed to compare the clinical effectiveness of the two existing publicly funded U.K. treatment options, the authors wrote.
Patients were recruited at 17 U.K. centers between March 6, 2015, and Jan. 10, 2019. The study enrolled 303 adults aged 50-85 years with end-stage ankle osteoarthritis. The mean age of the participants was 68 years; 71% were men. A total of 137 TAR patients and 144 ankle fusion patients completed their surgeries with clinical scores available for analysis. Baseline characteristics were mainly similar between the groups.
Blinding was not possible because of the nature of the procedures, but the surgeons who screened the patients were not aware of the randomization allocations, the researchers noted. A total of 33 surgeons participated in the trial, with a median number of seven patients per surgeon during the study period.
For TAR, U.K. surgeons use both two-component, fixed-bearing and three-component, mobile-bearing implants, the authors write. Ankle fusion was done using the surgeon’s usual technique of either arthroscopic-assisted or open ankle fusion.
The primary outcome was the change in the Manchester–Oxford Foot Questionnaire walking/standing (MOXFQ-W/S) domain scores from baseline to 52 weeks after surgery. The MOXFQ-W/S uses a scale of 0-100, with lower scores representing better outcomes. Secondary outcomes included change in the MOXFQ-W/S scores at 26 weeks after surgery, as well as measures of patient quality of life.
No statistically significant difference
Overall, the mean MOXFQ-W/S scores improved significantly from baseline to 52 weeks for both groups, with average improvements of 49.9 in the TAR group and 44.4 points in the AF group. The average scores at 52 weeks were 31.4 in the TAR group and 36.8 in the AF group.
The adjusted difference in score change from baseline was –5.56, showing a slightly greater degree of improvement with TAR, but this difference was not clinically or statistically significant, the researchers noted.
Adverse event numbers were similar for both procedures, with 54% of TAR patients and 53% of AF patients experiencing at least 1 adverse event during the study period. Of those, 18% of TAR patients and 24% of AF patients experienced at least 1 serious adverse event.
However, the TAR patients experienced a higher rate of wound healing complications and nerve injuries, while thromboembolism was higher in the AF patients, the researchers noted.
A prespecified subgroup analysis of patients with osteoarthritis in adjacent joints suggested a greater improvement in TAR, compared with AF, a difference that increased when fixed-bearing TAR was compared with AF, the authors wrote.
“This reinforces previous reports that suggest that the presence of adjacent joint arthritis may be an indication for ankle replacement over AF,” the authors wrote in their discussion.
“Many of these patients did not have any symptoms in the adjacent joints,” they noted.
“The presence of adjacent joint arthritis, meaning the wear and tear of the joints around the ankle joint, seemed to favor ankle replacement,” Dr. Goldberg said. Approximately 30 joints in the foot continue to move after the ankle is fused, and if these adjacent joints are not healthy before surgery [as was the case in 42% of the study patients], the results of fusion were less successful, he explained.
A post hoc analysis between TAR subtypes showed that patients who had fixed-bearing TAR had significantly greater improvements, compared with AF patients, but this difference was not observed in patients who had mobile-bearing TAR, the researchers noted.
Dr. Goldberg said it was surprising “that, in a separate analysis, we found that the fixed-bearing ankle replacement patients [who accounted for half of the implants used] improved by a much greater difference when compared to ankle fusion.”
The study findings were limited by several factors including the short follow-up and study design that allowed surgeons to choose any implant and technique, the researchers noted.
Other limitations include a lack of data on cost-effectiveness and the impact of comorbidities on outcomes, they wrote. However, the study is the first completed multicenter randomized controlled trial to compare TAR and AF procedures for end-stage ankle osteoarthritis and shows that both yield similar clinical improvements, they concluded.
Data can inform treatment discussion
The take-home messages for clinicians are that both ankle replacement and ankle fusion are effective treatments that improve patients’ quality of life, and it is important to establish the health of adjacent joints before making treatment recommendations, Dr. Goldberg said.
“Careful counseling on the relative risks of each procedure should be part of the informed consent process,” he added. Ideally, all patients seeking surgical care for ankle arthritis should have a choice between ankle replacement and ankle fusion, but sometimes there is inequity of provision of the two treatments, he noted.
“We now encourage all surgeons to work in ankle arthritis networks so that every patient, no matter where they live, can have choice about the best treatment for them,” he said.
Researchers met the challenge of surgical RCT
Randomized trials of surgical interventions are challenging to conduct, and therefore limited, wrote Bruce Sangeorzan, MD, of the University of Washington, Seattle, and colleagues in an accompanying editorial. However, the new study was strengthened by the inclusion of 17 centers for heterogeneity of implant type and surgeon experience level, the editorialists said in the Annals of Internal Medicine.
The study is especially important, because ankle arthritis treatment is very understudied, compared with hip and knee arthritis, but it has a similar impact on activity, editorial coauthor Dr. Sangeorzan said in an interview.
“Randomized controlled trials are the gold standard for comparing medical therapies,” he said, “but they are very difficult to do in surgical treatments, particularly when the two treatments can be differentiated, in this case by movement of the ankle.”
In addition, there is a strong placebo effect attached to interventions, Dr. Sangeorzan noted. “Determining best-case treatment relies on prospective research, preferably randomized. Since both ankle fusion and ankle replacement are effective therapies, a prospective randomized trial is the best way to help make treatment decisions,” he said.
The current study findings are not surprising, but they are preliminary, and 1 year of follow-up is not enough to determine effectiveness, Dr. Sangeorzan emphasized. However, “the authors have done the hard work of randomizing the patients and collecting the data, and the patients can now be followed for a longer time,” he said.
“In addition, the trial was designed with multiple secondary outcome measures, so the data can be matched up with larger trials that were not randomized to identify key elements of success for each procedure,” he noted.
The key message for clinicians is that ankle arthritis has a significant impact on patients’ lives, but there are two effective treatments that can reduce the impact of the disease, said Dr. Sangeorzan. “The data suggest that there are differences in implant design and differences in comorbidities that should influence decision-making,” he added.
Additional research is needed in the form of a longer study duration with larger cohorts, said Dr. Sangeorzan. In particular, researchers need to determine what comorbidities might drive patients to one type of care vs. another, he said. “The suggestion that [patients receiving implants with two motion segments have better outcomes than those receiving implants with a one-motion segment] also deserves further study,” he added.
The research was supported by the UK National Institute for Health and Care Research Health Technology Assessment Programme. The trial was sponsored by University College London. Dr. Goldberg disclosed grant support from NIHR HTA, as well as financial relationships with companies including Stryker, Paragon 28, and stock options with Standing CT Company, Elstree Waterfront Outpatients, and X Bolt Orthopedics.
The editorialists had no financial conflicts to disclose.
How to prevent a feared complication after joint replacement
Knee and hip replacements can improve how well patients get around and can significantly increase their quality of life. But if a bone near the new joint breaks, the injury can be a major setback for the patient’s mobility, and the consequences can be life-threatening.
The proportion of patients who experience a periprosthetic fracture within 5 years of total hip arthroplasty is 0.9%. After total knee arthroplasty (TKA), the proportion is 0.6%, research shows.
Those rates might seem low. But given that more than a million of these joint replacement surgeries are performed each year in the United States – they are the most common inpatient surgical procedures among people aged 65 and older – thousands of revision surgeries due to periprosthetic fractures occur each year.
Primary care clinicians who make their patients’ bone health a priority early on – years before surgery, ideally – may help patients enjoy the benefits of new joints long term.
At the 2022 annual Santa Fe Bone Symposium this summer, Susan V. Bukata, MD, professor and chair of orthopedics at the University of California, San Diego, showed an image of “what we’re trying to avoid” – a patient with a broken bone and infection. Unfortunately, Dr. Bukata said, the patient’s clinicians had not adequately addressed her skeletal health before the injury.
“This is a complete disaster for this person who went in having a total hip to improve their function and now will probably never walk normally on that leg,” Dr. Bukata said at the meeting.
The patient eventually underwent total femur replacement. Five surgeries were required to clear the infection.
Medical and surgical advances have allowed more people – including older patients and those with other medical conditions – to undergo joint replacement surgery, including replacement of knees, hips, and shoulders.
The surgeries often are performed for adults whose bones are thinning. Sometimes surgeons don’t realize just how thin a patient’s bone is until they are operating.
Prioritizing bone health
In patients with osteoporosis, the bone surrounding the new joint is weaker than the metal of the prosthesis, and the metal can rip out of the bone, Dr. Bukata told this news organization. A periprosthetic fracture should be recognized as an osteoporotic fracture, too, although these fractures have not typically been categorized that way, she said.
People live with total joints in place for as long as 40 years, and fractures around the implants are “one of the fastest growing injuries that we are seeing in older patients,” Dr. Bukata said. “People don’t think of those as osteoporotic fractures. But a 90-year-old who falls and breaks next to their total knee, if they didn’t have that total knee in place, everybody would be, like, ‘Oh, that’s an osteoporotic fracture.’ ”
Periprosthetic fractures tend not to occur right after surgery but rather after the bone continues to lose density as the patient ages, Dr. Bukata said.
Missed chances
One approach to preventing periprosthetic fractures could involve prioritizing bone health earlier in life and diagnosing and treating osteoporosis well before a patient is scheduled for surgery.
A patient’s initial visit to their primary care doctor because of joint pain is an opportunity to check on and promote their bone health, given that they might be a candidate for surgery in the future, Dr. Bukata said.
Ahead of a scheduled surgery, patients can see endocrinologists or rheumatologists to receive medication to try to strengthen bones. Doctors may be limited in how much of a difference they can make in a matter of several weeks or months with these drugs, however. These patients still likely will need to be treated as if they have osteoporosis, Dr. Bukata said.
When surgeons realize that a patient has weaker bones while they are in the middle of an operation, they should emphasize the importance of bone health after the procedure, Dr. Bukata said.
Strengthening, maintaining, and protecting bone should be seen as a long-term investment in the patient’s success after a joint replacement. That said, “There is no clear evidence or protocol for us to follow,” she said. “The mantra at UCSD now is, let’s keep it simple. Get the patient on track. And then we can always refine things as we continue to treat the patient.”
Health systems should establish routines in which bone health is discussed before surgery in the way patient education programs address smoking cessation, nutrition, and weight management, Dr. Bukata said. Another step in the right direction could involve setting electronic medical records to automatically order assessments of bone health when a surgeon books a case.
Linda A. Russell, MD, rheumatologist and director of perioperative medicine at the Hospital for Special Surgery in New York, said periprosthetic fractures are a “complication we fear.”
“It’s a big deal to try to repair it,” Dr. Russell said. “Sometimes you need to revise the joint, or sometimes you need to put lots more hardware in.” Surgeons increasingly appreciate the need to pay attention to the quality of the bone before they operate, she said.
Nevertheless, Dr. Russell does not necessarily say that such cases call for alarm or particularly aggressive treatment regimens – just regular bone health evaluations before and after surgery to see whether patients have osteoporosis and are candidates for treatment.
Lifelong effort
In some ways, to address bone health at the time of surgery may be too late.
Bone health “is not something that you can have as an afterthought when you’re 75 years old,” said Elizabeth Matzkin, MD, chief of women’s sports medicine at Brigham and Women’s Hospital, in Boston.
The chance of being able to rebuild bone mass at that age is slim. If patients maximize bone density when they are young, they can afford to lose some bone mass each year as they age.
To that end, a healthy diet, exercise, not smoking, and cutting back on alcohol can help, she said.
For Dr. Matzkin, a fragility fracture is a red flag that the patient’s bone density is probably not optimal. In such cases, she prepares for various scenarios during surgery, such as a screw not holding in a low-density bone.
Recently published research reflects that prior fragility fractures are a significant risk factor for complications after surgery, including periprosthetic fractures.
Edward J. Testa, MD, of Brown University, Providence, R.I., and colleagues analyzed insurance claims to compare outcomes for 24,398 patients who had experienced a fragility fracture – that is, a break caused by low-velocity trauma such as a fall – during the 3 years before their TKA procedure and a matched group of patients who were similar in many respects but who had not had a fragility fracture in the 3 years before surgery.
Dr. Testa’s group found that a history of fragility fracture was associated with higher rates of complications in the year after surgery, including hospital readmissions (hazard ratio = 1.30; 95% CI, 1.22-1.38), periprosthetic fractures (odds ratio = 2.72; 95% CI, 1.89-3.99), and secondary fragility fractures (OR = 4.62; 95% CI, 4.19-5.12). Patients who had previously experienced fragility fractures also experienced dislocated prostheses (OR = 1.76; 95% CI, 1.22-2.56) and periprosthetic infections (OR = 1.49; 95% CI, 1.29-1.71) at higher rates.
The rates of complications were similar regardless of whether patients had filled a prescription for medications used to treat osteoporosis, including bisphosphonates, vitamin D replacement, raloxifene, and denosumab, the researchers reported.
The lack of a clear association between these treatments and patient outcomes could be related to an insufficient duration of pharmacotherapy before or after TKA, poor medication adherence, or small sample sizes, Dr. Testa said.
Given the findings, which were published online in the Journal of Arthroplasty, “patients with a history of fragility fracture should be identified and counseled appropriately for a possible increased risk of the aforementioned complications, and optimized when possible, prior to undergoing TKA,” Dr. Testa told this news organization. “Ultimately, the decision to move forward with surgery is far more complex than the identification of this sole, yet important, risk factor for certain postoperative, implant-related complications.”
Treatment gaps
Prior research has shown that women aged 70 years and older are at higher risk for periprosthetic fractures. Many women in this age group who could receive treatment for osteoporosis do not, and major treatment gaps exist worldwide, noted Neil Binkley, MD, with the University of Wisconsin–Madison, in a separate talk at the Santa Fe Bone Symposium.
Ensuring adequate protein intake and addressing the risk of falling are other measures that clinicians can take to promote healthy bones, apart from prescribing drugs, he said.
Unpublished data from one group show that nearly 90% of periprosthetic fractures may result from falls, while about 8% may be spontaneous. “We need to be thinking about falls,” Dr. Binkley said.
Dr. Bukata has consulted for Amgen, Radius, and Solarea Bio and has served on a speakers bureau for Radius. She also is a board member for the Orthopaedic Research Society and the American Academy of Orthopaedic Surgeons Board of Specialty Societies. Dr. Binkley has received research support from Radius and has consulted for Amgen.
A version of this article first appeared on Medscape.com.
Knee and hip replacements can improve how well patients get around and can significantly increase their quality of life. But if a bone near the new joint breaks, the injury can be a major setback for the patient’s mobility, and the consequences can be life-threatening.
The proportion of patients who experience a periprosthetic fracture within 5 years of total hip arthroplasty is 0.9%. After total knee arthroplasty (TKA), the proportion is 0.6%, research shows.
Those rates might seem low. But given that more than a million of these joint replacement surgeries are performed each year in the United States – they are the most common inpatient surgical procedures among people aged 65 and older – thousands of revision surgeries due to periprosthetic fractures occur each year.
Primary care clinicians who make their patients’ bone health a priority early on – years before surgery, ideally – may help patients enjoy the benefits of new joints long term.
At the 2022 annual Santa Fe Bone Symposium this summer, Susan V. Bukata, MD, professor and chair of orthopedics at the University of California, San Diego, showed an image of “what we’re trying to avoid” – a patient with a broken bone and infection. Unfortunately, Dr. Bukata said, the patient’s clinicians had not adequately addressed her skeletal health before the injury.
“This is a complete disaster for this person who went in having a total hip to improve their function and now will probably never walk normally on that leg,” Dr. Bukata said at the meeting.
The patient eventually underwent total femur replacement. Five surgeries were required to clear the infection.
Medical and surgical advances have allowed more people – including older patients and those with other medical conditions – to undergo joint replacement surgery, including replacement of knees, hips, and shoulders.
The surgeries often are performed for adults whose bones are thinning. Sometimes surgeons don’t realize just how thin a patient’s bone is until they are operating.
Prioritizing bone health
In patients with osteoporosis, the bone surrounding the new joint is weaker than the metal of the prosthesis, and the metal can rip out of the bone, Dr. Bukata told this news organization. A periprosthetic fracture should be recognized as an osteoporotic fracture, too, although these fractures have not typically been categorized that way, she said.
People live with total joints in place for as long as 40 years, and fractures around the implants are “one of the fastest growing injuries that we are seeing in older patients,” Dr. Bukata said. “People don’t think of those as osteoporotic fractures. But a 90-year-old who falls and breaks next to their total knee, if they didn’t have that total knee in place, everybody would be, like, ‘Oh, that’s an osteoporotic fracture.’ ”
Periprosthetic fractures tend not to occur right after surgery but rather after the bone continues to lose density as the patient ages, Dr. Bukata said.
Missed chances
One approach to preventing periprosthetic fractures could involve prioritizing bone health earlier in life and diagnosing and treating osteoporosis well before a patient is scheduled for surgery.
A patient’s initial visit to their primary care doctor because of joint pain is an opportunity to check on and promote their bone health, given that they might be a candidate for surgery in the future, Dr. Bukata said.
Ahead of a scheduled surgery, patients can see endocrinologists or rheumatologists to receive medication to try to strengthen bones. Doctors may be limited in how much of a difference they can make in a matter of several weeks or months with these drugs, however. These patients still likely will need to be treated as if they have osteoporosis, Dr. Bukata said.
When surgeons realize that a patient has weaker bones while they are in the middle of an operation, they should emphasize the importance of bone health after the procedure, Dr. Bukata said.
Strengthening, maintaining, and protecting bone should be seen as a long-term investment in the patient’s success after a joint replacement. That said, “There is no clear evidence or protocol for us to follow,” she said. “The mantra at UCSD now is, let’s keep it simple. Get the patient on track. And then we can always refine things as we continue to treat the patient.”
Health systems should establish routines in which bone health is discussed before surgery in the way patient education programs address smoking cessation, nutrition, and weight management, Dr. Bukata said. Another step in the right direction could involve setting electronic medical records to automatically order assessments of bone health when a surgeon books a case.
Linda A. Russell, MD, rheumatologist and director of perioperative medicine at the Hospital for Special Surgery in New York, said periprosthetic fractures are a “complication we fear.”
“It’s a big deal to try to repair it,” Dr. Russell said. “Sometimes you need to revise the joint, or sometimes you need to put lots more hardware in.” Surgeons increasingly appreciate the need to pay attention to the quality of the bone before they operate, she said.
Nevertheless, Dr. Russell does not necessarily say that such cases call for alarm or particularly aggressive treatment regimens – just regular bone health evaluations before and after surgery to see whether patients have osteoporosis and are candidates for treatment.
Lifelong effort
In some ways, to address bone health at the time of surgery may be too late.
Bone health “is not something that you can have as an afterthought when you’re 75 years old,” said Elizabeth Matzkin, MD, chief of women’s sports medicine at Brigham and Women’s Hospital, in Boston.
The chance of being able to rebuild bone mass at that age is slim. If patients maximize bone density when they are young, they can afford to lose some bone mass each year as they age.
To that end, a healthy diet, exercise, not smoking, and cutting back on alcohol can help, she said.
For Dr. Matzkin, a fragility fracture is a red flag that the patient’s bone density is probably not optimal. In such cases, she prepares for various scenarios during surgery, such as a screw not holding in a low-density bone.
Recently published research reflects that prior fragility fractures are a significant risk factor for complications after surgery, including periprosthetic fractures.
Edward J. Testa, MD, of Brown University, Providence, R.I., and colleagues analyzed insurance claims to compare outcomes for 24,398 patients who had experienced a fragility fracture – that is, a break caused by low-velocity trauma such as a fall – during the 3 years before their TKA procedure and a matched group of patients who were similar in many respects but who had not had a fragility fracture in the 3 years before surgery.
Dr. Testa’s group found that a history of fragility fracture was associated with higher rates of complications in the year after surgery, including hospital readmissions (hazard ratio = 1.30; 95% CI, 1.22-1.38), periprosthetic fractures (odds ratio = 2.72; 95% CI, 1.89-3.99), and secondary fragility fractures (OR = 4.62; 95% CI, 4.19-5.12). Patients who had previously experienced fragility fractures also experienced dislocated prostheses (OR = 1.76; 95% CI, 1.22-2.56) and periprosthetic infections (OR = 1.49; 95% CI, 1.29-1.71) at higher rates.
The rates of complications were similar regardless of whether patients had filled a prescription for medications used to treat osteoporosis, including bisphosphonates, vitamin D replacement, raloxifene, and denosumab, the researchers reported.
The lack of a clear association between these treatments and patient outcomes could be related to an insufficient duration of pharmacotherapy before or after TKA, poor medication adherence, or small sample sizes, Dr. Testa said.
Given the findings, which were published online in the Journal of Arthroplasty, “patients with a history of fragility fracture should be identified and counseled appropriately for a possible increased risk of the aforementioned complications, and optimized when possible, prior to undergoing TKA,” Dr. Testa told this news organization. “Ultimately, the decision to move forward with surgery is far more complex than the identification of this sole, yet important, risk factor for certain postoperative, implant-related complications.”
Treatment gaps
Prior research has shown that women aged 70 years and older are at higher risk for periprosthetic fractures. Many women in this age group who could receive treatment for osteoporosis do not, and major treatment gaps exist worldwide, noted Neil Binkley, MD, with the University of Wisconsin–Madison, in a separate talk at the Santa Fe Bone Symposium.
Ensuring adequate protein intake and addressing the risk of falling are other measures that clinicians can take to promote healthy bones, apart from prescribing drugs, he said.
Unpublished data from one group show that nearly 90% of periprosthetic fractures may result from falls, while about 8% may be spontaneous. “We need to be thinking about falls,” Dr. Binkley said.
Dr. Bukata has consulted for Amgen, Radius, and Solarea Bio and has served on a speakers bureau for Radius. She also is a board member for the Orthopaedic Research Society and the American Academy of Orthopaedic Surgeons Board of Specialty Societies. Dr. Binkley has received research support from Radius and has consulted for Amgen.
A version of this article first appeared on Medscape.com.
Knee and hip replacements can improve how well patients get around and can significantly increase their quality of life. But if a bone near the new joint breaks, the injury can be a major setback for the patient’s mobility, and the consequences can be life-threatening.
The proportion of patients who experience a periprosthetic fracture within 5 years of total hip arthroplasty is 0.9%. After total knee arthroplasty (TKA), the proportion is 0.6%, research shows.
Those rates might seem low. But given that more than a million of these joint replacement surgeries are performed each year in the United States – they are the most common inpatient surgical procedures among people aged 65 and older – thousands of revision surgeries due to periprosthetic fractures occur each year.
Primary care clinicians who make their patients’ bone health a priority early on – years before surgery, ideally – may help patients enjoy the benefits of new joints long term.
At the 2022 annual Santa Fe Bone Symposium this summer, Susan V. Bukata, MD, professor and chair of orthopedics at the University of California, San Diego, showed an image of “what we’re trying to avoid” – a patient with a broken bone and infection. Unfortunately, Dr. Bukata said, the patient’s clinicians had not adequately addressed her skeletal health before the injury.
“This is a complete disaster for this person who went in having a total hip to improve their function and now will probably never walk normally on that leg,” Dr. Bukata said at the meeting.
The patient eventually underwent total femur replacement. Five surgeries were required to clear the infection.
Medical and surgical advances have allowed more people – including older patients and those with other medical conditions – to undergo joint replacement surgery, including replacement of knees, hips, and shoulders.
The surgeries often are performed for adults whose bones are thinning. Sometimes surgeons don’t realize just how thin a patient’s bone is until they are operating.
Prioritizing bone health
In patients with osteoporosis, the bone surrounding the new joint is weaker than the metal of the prosthesis, and the metal can rip out of the bone, Dr. Bukata told this news organization. A periprosthetic fracture should be recognized as an osteoporotic fracture, too, although these fractures have not typically been categorized that way, she said.
People live with total joints in place for as long as 40 years, and fractures around the implants are “one of the fastest growing injuries that we are seeing in older patients,” Dr. Bukata said. “People don’t think of those as osteoporotic fractures. But a 90-year-old who falls and breaks next to their total knee, if they didn’t have that total knee in place, everybody would be, like, ‘Oh, that’s an osteoporotic fracture.’ ”
Periprosthetic fractures tend not to occur right after surgery but rather after the bone continues to lose density as the patient ages, Dr. Bukata said.
Missed chances
One approach to preventing periprosthetic fractures could involve prioritizing bone health earlier in life and diagnosing and treating osteoporosis well before a patient is scheduled for surgery.
A patient’s initial visit to their primary care doctor because of joint pain is an opportunity to check on and promote their bone health, given that they might be a candidate for surgery in the future, Dr. Bukata said.
Ahead of a scheduled surgery, patients can see endocrinologists or rheumatologists to receive medication to try to strengthen bones. Doctors may be limited in how much of a difference they can make in a matter of several weeks or months with these drugs, however. These patients still likely will need to be treated as if they have osteoporosis, Dr. Bukata said.
When surgeons realize that a patient has weaker bones while they are in the middle of an operation, they should emphasize the importance of bone health after the procedure, Dr. Bukata said.
Strengthening, maintaining, and protecting bone should be seen as a long-term investment in the patient’s success after a joint replacement. That said, “There is no clear evidence or protocol for us to follow,” she said. “The mantra at UCSD now is, let’s keep it simple. Get the patient on track. And then we can always refine things as we continue to treat the patient.”
Health systems should establish routines in which bone health is discussed before surgery in the way patient education programs address smoking cessation, nutrition, and weight management, Dr. Bukata said. Another step in the right direction could involve setting electronic medical records to automatically order assessments of bone health when a surgeon books a case.
Linda A. Russell, MD, rheumatologist and director of perioperative medicine at the Hospital for Special Surgery in New York, said periprosthetic fractures are a “complication we fear.”
“It’s a big deal to try to repair it,” Dr. Russell said. “Sometimes you need to revise the joint, or sometimes you need to put lots more hardware in.” Surgeons increasingly appreciate the need to pay attention to the quality of the bone before they operate, she said.
Nevertheless, Dr. Russell does not necessarily say that such cases call for alarm or particularly aggressive treatment regimens – just regular bone health evaluations before and after surgery to see whether patients have osteoporosis and are candidates for treatment.
Lifelong effort
In some ways, to address bone health at the time of surgery may be too late.
Bone health “is not something that you can have as an afterthought when you’re 75 years old,” said Elizabeth Matzkin, MD, chief of women’s sports medicine at Brigham and Women’s Hospital, in Boston.
The chance of being able to rebuild bone mass at that age is slim. If patients maximize bone density when they are young, they can afford to lose some bone mass each year as they age.
To that end, a healthy diet, exercise, not smoking, and cutting back on alcohol can help, she said.
For Dr. Matzkin, a fragility fracture is a red flag that the patient’s bone density is probably not optimal. In such cases, she prepares for various scenarios during surgery, such as a screw not holding in a low-density bone.
Recently published research reflects that prior fragility fractures are a significant risk factor for complications after surgery, including periprosthetic fractures.
Edward J. Testa, MD, of Brown University, Providence, R.I., and colleagues analyzed insurance claims to compare outcomes for 24,398 patients who had experienced a fragility fracture – that is, a break caused by low-velocity trauma such as a fall – during the 3 years before their TKA procedure and a matched group of patients who were similar in many respects but who had not had a fragility fracture in the 3 years before surgery.
Dr. Testa’s group found that a history of fragility fracture was associated with higher rates of complications in the year after surgery, including hospital readmissions (hazard ratio = 1.30; 95% CI, 1.22-1.38), periprosthetic fractures (odds ratio = 2.72; 95% CI, 1.89-3.99), and secondary fragility fractures (OR = 4.62; 95% CI, 4.19-5.12). Patients who had previously experienced fragility fractures also experienced dislocated prostheses (OR = 1.76; 95% CI, 1.22-2.56) and periprosthetic infections (OR = 1.49; 95% CI, 1.29-1.71) at higher rates.
The rates of complications were similar regardless of whether patients had filled a prescription for medications used to treat osteoporosis, including bisphosphonates, vitamin D replacement, raloxifene, and denosumab, the researchers reported.
The lack of a clear association between these treatments and patient outcomes could be related to an insufficient duration of pharmacotherapy before or after TKA, poor medication adherence, or small sample sizes, Dr. Testa said.
Given the findings, which were published online in the Journal of Arthroplasty, “patients with a history of fragility fracture should be identified and counseled appropriately for a possible increased risk of the aforementioned complications, and optimized when possible, prior to undergoing TKA,” Dr. Testa told this news organization. “Ultimately, the decision to move forward with surgery is far more complex than the identification of this sole, yet important, risk factor for certain postoperative, implant-related complications.”
Treatment gaps
Prior research has shown that women aged 70 years and older are at higher risk for periprosthetic fractures. Many women in this age group who could receive treatment for osteoporosis do not, and major treatment gaps exist worldwide, noted Neil Binkley, MD, with the University of Wisconsin–Madison, in a separate talk at the Santa Fe Bone Symposium.
Ensuring adequate protein intake and addressing the risk of falling are other measures that clinicians can take to promote healthy bones, apart from prescribing drugs, he said.
Unpublished data from one group show that nearly 90% of periprosthetic fractures may result from falls, while about 8% may be spontaneous. “We need to be thinking about falls,” Dr. Binkley said.
Dr. Bukata has consulted for Amgen, Radius, and Solarea Bio and has served on a speakers bureau for Radius. She also is a board member for the Orthopaedic Research Society and the American Academy of Orthopaedic Surgeons Board of Specialty Societies. Dr. Binkley has received research support from Radius and has consulted for Amgen.
A version of this article first appeared on Medscape.com.
Guide eases prayer for Muslims with knee osteoarthritis
For devout Muslims, praying multiple times a day is a lifelong observance and a core aspect of their faith. But osteoarthritis of the knee (KOA) can make kneeling and prostration challenging. To address this problem in an aging U.S. Muslim population, a multicenter team developed literature-based guidelines published online in Arthritis & Rheumatology.
In an interview, corresponding author Mahfujul Z. Haque, a medical student at Michigan State University, Grand Rapids, discussed the guide, which he assembled with Marina N. Magrey, MD, the Ronald Moskowitz Professor of Rheumatology at Case Western Reserve University, Cleveland, and orthopedic surgeon Karl C. Roberts, MD, president of West Michigan Orthopaedics in Grand Rapids, among others.
Could you detail the clinical and cultural context for these recommendations?
Mr. Haque: Muslims currently make up 1.1% of the U.S. population, or 3.45 million people. This guidance provides advice to Muslim patients with KOA in a culturally sensitive manner that can supplement standard care. Prayer, or Salah, is a religious obligation typically performed in 17-48 daily repetitions of squatting, floor sitting, full-knee flexion, and kneeling. For patients with KOA, prayer can be painful, and a few studies have found a link between these repeated movements and KOA progression.
Yet recommending stopping or limiting prayer is insensitive, so our group did a thorough literature search to identify easily implemented and culturally appropriate ways to ease praying.
Is there a traditional preference for praying on a hard surface?
Mr. Haque: Prayer can be performed on any surface that is clean and free from impurities. Cushioned and carpeted surfaces are permissible if the surface is somewhat firm and supportive for when worshippers prostrate themselves and put their faces on the ground. For example, compacted snow that wouldn’t allow the face to sink into it is permissible, but snow that is soft and would allow the face to sink in is not.
Have an increasing number of older patients raised the issue of knee pain during prayers?
Mr. Haque: We found no research on this in the literature. Anecdotally, however, two of our authors lead prayer in large Muslim communities in Detroit, and people often share with them that they feel discomfort during prayer and ask if there is anything they can do to limit this.
It is important to dispel the common myth that after total knee replacement one cannot kneel. About 20% of patients have some anterior knee discomfort after total knee arthroplasty, which can be exacerbated by kneeling, but kneeling causes no harm and can be done safely.
Could you outline the main recommendations?
Mr. Haque: These fall under three main categories: prayer surface, mechanics, and lifestyle modifications. The surface recommendations essentially advise using prayer rugs that provide cushioning or using cushioned kneepads.
The mechanics recommendations involve bracing with the palms down, standing up using the hands and knees, and guiding prayer motions with the hands. Chairs may be used as well.
Lifestyle recommendations outline home-exercise programs tailored to KOA and suggest the use of ice and compression during acute exacerbations.
Could these recommendations benefit other arthritic joints such as the wrists?
Mr. Haque: Anecdotally, our authors do not hear about pain in joints except for the knee and spine. To a limited extent, some of these recommendations may help patients with spinal arthritis as well.
What do you see as the greatest obstacle to implementation?
Mr. Haque: These recommendations, although permissible in the Muslim faith, are not part of traditional ritual and thus patients may simply forget to implement them. We advise physicians to ask patients which recommendations they are most likely to follow and to monitor how these have worked for them.
What is your best overall advice for broaching this issue with patients?
Mr. Haque: Holistic, functional, and culturally sensitive recommendations will be highly appreciated. Physicians are therefore encouraged to share this guidance with Muslim patients while using terms such as Salah, pronounced saa-laah, and Sajdah, pronounced sajduh and meaning prostration, and engage in a healthy dialogue.
These guidelines received no funding. The authors disclosed no competing interests relevant to their recommendations, but Dr. Magrey reported consulting and research relationships with private-sector companies outside of this work.
For devout Muslims, praying multiple times a day is a lifelong observance and a core aspect of their faith. But osteoarthritis of the knee (KOA) can make kneeling and prostration challenging. To address this problem in an aging U.S. Muslim population, a multicenter team developed literature-based guidelines published online in Arthritis & Rheumatology.
In an interview, corresponding author Mahfujul Z. Haque, a medical student at Michigan State University, Grand Rapids, discussed the guide, which he assembled with Marina N. Magrey, MD, the Ronald Moskowitz Professor of Rheumatology at Case Western Reserve University, Cleveland, and orthopedic surgeon Karl C. Roberts, MD, president of West Michigan Orthopaedics in Grand Rapids, among others.
Could you detail the clinical and cultural context for these recommendations?
Mr. Haque: Muslims currently make up 1.1% of the U.S. population, or 3.45 million people. This guidance provides advice to Muslim patients with KOA in a culturally sensitive manner that can supplement standard care. Prayer, or Salah, is a religious obligation typically performed in 17-48 daily repetitions of squatting, floor sitting, full-knee flexion, and kneeling. For patients with KOA, prayer can be painful, and a few studies have found a link between these repeated movements and KOA progression.
Yet recommending stopping or limiting prayer is insensitive, so our group did a thorough literature search to identify easily implemented and culturally appropriate ways to ease praying.
Is there a traditional preference for praying on a hard surface?
Mr. Haque: Prayer can be performed on any surface that is clean and free from impurities. Cushioned and carpeted surfaces are permissible if the surface is somewhat firm and supportive for when worshippers prostrate themselves and put their faces on the ground. For example, compacted snow that wouldn’t allow the face to sink into it is permissible, but snow that is soft and would allow the face to sink in is not.
Have an increasing number of older patients raised the issue of knee pain during prayers?
Mr. Haque: We found no research on this in the literature. Anecdotally, however, two of our authors lead prayer in large Muslim communities in Detroit, and people often share with them that they feel discomfort during prayer and ask if there is anything they can do to limit this.
It is important to dispel the common myth that after total knee replacement one cannot kneel. About 20% of patients have some anterior knee discomfort after total knee arthroplasty, which can be exacerbated by kneeling, but kneeling causes no harm and can be done safely.
Could you outline the main recommendations?
Mr. Haque: These fall under three main categories: prayer surface, mechanics, and lifestyle modifications. The surface recommendations essentially advise using prayer rugs that provide cushioning or using cushioned kneepads.
The mechanics recommendations involve bracing with the palms down, standing up using the hands and knees, and guiding prayer motions with the hands. Chairs may be used as well.
Lifestyle recommendations outline home-exercise programs tailored to KOA and suggest the use of ice and compression during acute exacerbations.
Could these recommendations benefit other arthritic joints such as the wrists?
Mr. Haque: Anecdotally, our authors do not hear about pain in joints except for the knee and spine. To a limited extent, some of these recommendations may help patients with spinal arthritis as well.
What do you see as the greatest obstacle to implementation?
Mr. Haque: These recommendations, although permissible in the Muslim faith, are not part of traditional ritual and thus patients may simply forget to implement them. We advise physicians to ask patients which recommendations they are most likely to follow and to monitor how these have worked for them.
What is your best overall advice for broaching this issue with patients?
Mr. Haque: Holistic, functional, and culturally sensitive recommendations will be highly appreciated. Physicians are therefore encouraged to share this guidance with Muslim patients while using terms such as Salah, pronounced saa-laah, and Sajdah, pronounced sajduh and meaning prostration, and engage in a healthy dialogue.
These guidelines received no funding. The authors disclosed no competing interests relevant to their recommendations, but Dr. Magrey reported consulting and research relationships with private-sector companies outside of this work.
For devout Muslims, praying multiple times a day is a lifelong observance and a core aspect of their faith. But osteoarthritis of the knee (KOA) can make kneeling and prostration challenging. To address this problem in an aging U.S. Muslim population, a multicenter team developed literature-based guidelines published online in Arthritis & Rheumatology.
In an interview, corresponding author Mahfujul Z. Haque, a medical student at Michigan State University, Grand Rapids, discussed the guide, which he assembled with Marina N. Magrey, MD, the Ronald Moskowitz Professor of Rheumatology at Case Western Reserve University, Cleveland, and orthopedic surgeon Karl C. Roberts, MD, president of West Michigan Orthopaedics in Grand Rapids, among others.
Could you detail the clinical and cultural context for these recommendations?
Mr. Haque: Muslims currently make up 1.1% of the U.S. population, or 3.45 million people. This guidance provides advice to Muslim patients with KOA in a culturally sensitive manner that can supplement standard care. Prayer, or Salah, is a religious obligation typically performed in 17-48 daily repetitions of squatting, floor sitting, full-knee flexion, and kneeling. For patients with KOA, prayer can be painful, and a few studies have found a link between these repeated movements and KOA progression.
Yet recommending stopping or limiting prayer is insensitive, so our group did a thorough literature search to identify easily implemented and culturally appropriate ways to ease praying.
Is there a traditional preference for praying on a hard surface?
Mr. Haque: Prayer can be performed on any surface that is clean and free from impurities. Cushioned and carpeted surfaces are permissible if the surface is somewhat firm and supportive for when worshippers prostrate themselves and put their faces on the ground. For example, compacted snow that wouldn’t allow the face to sink into it is permissible, but snow that is soft and would allow the face to sink in is not.
Have an increasing number of older patients raised the issue of knee pain during prayers?
Mr. Haque: We found no research on this in the literature. Anecdotally, however, two of our authors lead prayer in large Muslim communities in Detroit, and people often share with them that they feel discomfort during prayer and ask if there is anything they can do to limit this.
It is important to dispel the common myth that after total knee replacement one cannot kneel. About 20% of patients have some anterior knee discomfort after total knee arthroplasty, which can be exacerbated by kneeling, but kneeling causes no harm and can be done safely.
Could you outline the main recommendations?
Mr. Haque: These fall under three main categories: prayer surface, mechanics, and lifestyle modifications. The surface recommendations essentially advise using prayer rugs that provide cushioning or using cushioned kneepads.
The mechanics recommendations involve bracing with the palms down, standing up using the hands and knees, and guiding prayer motions with the hands. Chairs may be used as well.
Lifestyle recommendations outline home-exercise programs tailored to KOA and suggest the use of ice and compression during acute exacerbations.
Could these recommendations benefit other arthritic joints such as the wrists?
Mr. Haque: Anecdotally, our authors do not hear about pain in joints except for the knee and spine. To a limited extent, some of these recommendations may help patients with spinal arthritis as well.
What do you see as the greatest obstacle to implementation?
Mr. Haque: These recommendations, although permissible in the Muslim faith, are not part of traditional ritual and thus patients may simply forget to implement them. We advise physicians to ask patients which recommendations they are most likely to follow and to monitor how these have worked for them.
What is your best overall advice for broaching this issue with patients?
Mr. Haque: Holistic, functional, and culturally sensitive recommendations will be highly appreciated. Physicians are therefore encouraged to share this guidance with Muslim patients while using terms such as Salah, pronounced saa-laah, and Sajdah, pronounced sajduh and meaning prostration, and engage in a healthy dialogue.
These guidelines received no funding. The authors disclosed no competing interests relevant to their recommendations, but Dr. Magrey reported consulting and research relationships with private-sector companies outside of this work.
FROM ARTHRITIS & RHEUMATOLOGY
Lower BMI linked with better knee osteoarthritis outcomes
Losing weight and lowering body mass index may help people slow, delay, or even prevent the structural defects of knee osteoarthritis, especially on the medial side of the knee, results of a prospective multicohort study from Australia suggest.
“We showed that the more weight that is lost, the greater the apparent benefit for delaying or preventing knee joint degradation in osteoarthritis,” senior study author Amanda Sainsbury, PhD, professor of obesity research at the University of Western Australia, Perth, said in an interview. “For example, a person weighing 100 kilograms [220 pounds] who loses 10 kilograms [22 pounds] is likely to have double the benefit compared to losing 5 kilograms [11 pounds].”
“We showed evidence of association, not causality,” she and her colleagues wrote in Arthritis & Rheumatology. “Future randomized, controlled trials are required to demonstrate causality.”
Dr. Sainsbury and colleagues analyzed radiographs of knees from three independent cohort studies from the United States and the Netherlands – the Osteoarthritis Initiative (OAI), the Multicenter Osteoarthritis Study (MOST), and the Cohort Hip and Cohort Knee (CHECK) study – at baseline and again 4-5 years later.
The authors created two groups of knees at baseline: the “incidence cohort” of 9,683 knees from 5,774 participants without OA structural defects (Kellgren-Lawrence grade 0 or 1) and the “progression cohort” of 6,075 knees from 3,988 participants with OA structural defects (KL grade 2 or higher). After 4-5 years, they determined OA incidence (KL grade 2 or higher in participants without baseline knee OA) and progression (increase of one or more KL grades in those with baseline knee OA).At baseline, the mean patient age in both groups was around 60, and around 60% of participants were female. In the incidence and progression groups, respectively, White patients comprised 87.5% and 80.4% of participants; mean body mass index was 28.2 and 30.4 kg/m2; and 32.6% and 48.4% of participants were obese (BMI, 30 or higher). The authors combined data from the three studies and used logistic regression and generalized estimating equations, with clustering of both knees within individuals. On multivariable analysis, they found that change in BMI 4-5 years post baseline was positively linked with both incidence and progression of knee OA structural defects.
In the incidence group, BMI decreased 1 or more units in 1,101 patients and increased 1 or more units in 1,611. In the progression group, BMI decreased 1 or more units in 798 patients and increased in 1,008.
The adjusted odds ratio for overall structural defects in the incidence group was 1.05 (95% confidence interval, 1.02-1.09) and 1.05 (95% CI, 1.01-1.09) in the progression group was. A 1-unit decrease in BMI was linked with a nearly 5% drop in odds of incidence and progression of knee OA, and a 5-unit decrease was linked with a more than 21% drop in odds of incidence and progression.
In the incidence group, change in BMI was positively linked with medial, but not lateral, joint space degeneration (narrowing; OR, 1.08; 95% CI, 1.04-1.12) and with medial femoral surface degeneration indicated by osteophytes (OR, 1.07; 95% CI, 1.03-1.12).
In the progression group, change in BMI was positively linked with overall structural defects (OR, 1.05; 95% CI, 1.01-1.09) as well as medial, but not lateral, joint space degeneration (OR, 1.08; 95% CI, 1.03-1.12).
“Previous research showed that weight loss helps reduce symptoms of knee osteoarthritis, such as pain and impaired physical function,” said lead study author Zübeyir Salis, BEng, a PhD student in public health at the University of New South Wales, Kensington, Australia. “Weight loss is emerging as a suitable strategy for potentially delaying and preventing osteoarthritic knee joint degeneration.”
Two experts not involved in the study welcome its results
Kai Sun, MD, MS, assistant professor of medicine, rheumatology, and immunology at Duke University, Durham, N. C., said it makes mechanical sense that less weight bearing decreases knee damage over time, but she was somewhat surprised that even people who started with normal BMI improved their outcomes by decreasing BMI further.
“Knee osteoarthritis and obesity prevalence are both growing,” Dr. Sun said. “Knee osteoarthritis may one day be considered an obesity-related comorbidity like hypertension and diabetes and be used as additional justification for pharmacologic or nonpharmacologic interventions to treat obesity.”
She noted that the study’s major strengths include its large sample size, long follow-up, and separate inclusion of disease incidence and progression, but also noted some limitations.
“BMI data at only two time points does not consider BMI fluctuations between those times,” she added. “Limited data were presented on physical activity levels, and most participants being White and elderly limited the generalizability of the results.”
Eduardo Grunvald, MD, professor of medicine and medical director of the weight management program at the University of California, San Diego, agreed about the study’s strengths and pointed out its lack of information about the cause of BMI changes.
Dr. Grunvald would like to know whether the BMI changes contributed to the knee changes or vice versa. “An individual’s worsening knee pain could lead to less physical activity and possible increased BMI.
“Long-term weight-loss maintenance is extremely challenging, and for optimal outcomes, medical professionals who treat joint disease should partner with clinicians trained to treat obesity,” he advised.
The authors are planning further related research. “We’re looking forward to running a randomized, controlled clinical weight-loss trial,” Dr. Sainsbury said.The study was supported by scholarship and fellowship funds from the Australian government. Mr. Salis and Dr. Sainsbury each own 50% of shares in a company that provides educational resources and services in adult weight management. Dr. Sainsbury and one coauthor reported relevant financial relationships with various pharmaceutical companies. Dr. Sun and Dr. Grunvald reported no relevant financial relationships.
Losing weight and lowering body mass index may help people slow, delay, or even prevent the structural defects of knee osteoarthritis, especially on the medial side of the knee, results of a prospective multicohort study from Australia suggest.
“We showed that the more weight that is lost, the greater the apparent benefit for delaying or preventing knee joint degradation in osteoarthritis,” senior study author Amanda Sainsbury, PhD, professor of obesity research at the University of Western Australia, Perth, said in an interview. “For example, a person weighing 100 kilograms [220 pounds] who loses 10 kilograms [22 pounds] is likely to have double the benefit compared to losing 5 kilograms [11 pounds].”
“We showed evidence of association, not causality,” she and her colleagues wrote in Arthritis & Rheumatology. “Future randomized, controlled trials are required to demonstrate causality.”
Dr. Sainsbury and colleagues analyzed radiographs of knees from three independent cohort studies from the United States and the Netherlands – the Osteoarthritis Initiative (OAI), the Multicenter Osteoarthritis Study (MOST), and the Cohort Hip and Cohort Knee (CHECK) study – at baseline and again 4-5 years later.
The authors created two groups of knees at baseline: the “incidence cohort” of 9,683 knees from 5,774 participants without OA structural defects (Kellgren-Lawrence grade 0 or 1) and the “progression cohort” of 6,075 knees from 3,988 participants with OA structural defects (KL grade 2 or higher). After 4-5 years, they determined OA incidence (KL grade 2 or higher in participants without baseline knee OA) and progression (increase of one or more KL grades in those with baseline knee OA).At baseline, the mean patient age in both groups was around 60, and around 60% of participants were female. In the incidence and progression groups, respectively, White patients comprised 87.5% and 80.4% of participants; mean body mass index was 28.2 and 30.4 kg/m2; and 32.6% and 48.4% of participants were obese (BMI, 30 or higher). The authors combined data from the three studies and used logistic regression and generalized estimating equations, with clustering of both knees within individuals. On multivariable analysis, they found that change in BMI 4-5 years post baseline was positively linked with both incidence and progression of knee OA structural defects.
In the incidence group, BMI decreased 1 or more units in 1,101 patients and increased 1 or more units in 1,611. In the progression group, BMI decreased 1 or more units in 798 patients and increased in 1,008.
The adjusted odds ratio for overall structural defects in the incidence group was 1.05 (95% confidence interval, 1.02-1.09) and 1.05 (95% CI, 1.01-1.09) in the progression group was. A 1-unit decrease in BMI was linked with a nearly 5% drop in odds of incidence and progression of knee OA, and a 5-unit decrease was linked with a more than 21% drop in odds of incidence and progression.
In the incidence group, change in BMI was positively linked with medial, but not lateral, joint space degeneration (narrowing; OR, 1.08; 95% CI, 1.04-1.12) and with medial femoral surface degeneration indicated by osteophytes (OR, 1.07; 95% CI, 1.03-1.12).
In the progression group, change in BMI was positively linked with overall structural defects (OR, 1.05; 95% CI, 1.01-1.09) as well as medial, but not lateral, joint space degeneration (OR, 1.08; 95% CI, 1.03-1.12).
“Previous research showed that weight loss helps reduce symptoms of knee osteoarthritis, such as pain and impaired physical function,” said lead study author Zübeyir Salis, BEng, a PhD student in public health at the University of New South Wales, Kensington, Australia. “Weight loss is emerging as a suitable strategy for potentially delaying and preventing osteoarthritic knee joint degeneration.”
Two experts not involved in the study welcome its results
Kai Sun, MD, MS, assistant professor of medicine, rheumatology, and immunology at Duke University, Durham, N. C., said it makes mechanical sense that less weight bearing decreases knee damage over time, but she was somewhat surprised that even people who started with normal BMI improved their outcomes by decreasing BMI further.
“Knee osteoarthritis and obesity prevalence are both growing,” Dr. Sun said. “Knee osteoarthritis may one day be considered an obesity-related comorbidity like hypertension and diabetes and be used as additional justification for pharmacologic or nonpharmacologic interventions to treat obesity.”
She noted that the study’s major strengths include its large sample size, long follow-up, and separate inclusion of disease incidence and progression, but also noted some limitations.
“BMI data at only two time points does not consider BMI fluctuations between those times,” she added. “Limited data were presented on physical activity levels, and most participants being White and elderly limited the generalizability of the results.”
Eduardo Grunvald, MD, professor of medicine and medical director of the weight management program at the University of California, San Diego, agreed about the study’s strengths and pointed out its lack of information about the cause of BMI changes.
Dr. Grunvald would like to know whether the BMI changes contributed to the knee changes or vice versa. “An individual’s worsening knee pain could lead to less physical activity and possible increased BMI.
“Long-term weight-loss maintenance is extremely challenging, and for optimal outcomes, medical professionals who treat joint disease should partner with clinicians trained to treat obesity,” he advised.
The authors are planning further related research. “We’re looking forward to running a randomized, controlled clinical weight-loss trial,” Dr. Sainsbury said.The study was supported by scholarship and fellowship funds from the Australian government. Mr. Salis and Dr. Sainsbury each own 50% of shares in a company that provides educational resources and services in adult weight management. Dr. Sainsbury and one coauthor reported relevant financial relationships with various pharmaceutical companies. Dr. Sun and Dr. Grunvald reported no relevant financial relationships.
Losing weight and lowering body mass index may help people slow, delay, or even prevent the structural defects of knee osteoarthritis, especially on the medial side of the knee, results of a prospective multicohort study from Australia suggest.
“We showed that the more weight that is lost, the greater the apparent benefit for delaying or preventing knee joint degradation in osteoarthritis,” senior study author Amanda Sainsbury, PhD, professor of obesity research at the University of Western Australia, Perth, said in an interview. “For example, a person weighing 100 kilograms [220 pounds] who loses 10 kilograms [22 pounds] is likely to have double the benefit compared to losing 5 kilograms [11 pounds].”
“We showed evidence of association, not causality,” she and her colleagues wrote in Arthritis & Rheumatology. “Future randomized, controlled trials are required to demonstrate causality.”
Dr. Sainsbury and colleagues analyzed radiographs of knees from three independent cohort studies from the United States and the Netherlands – the Osteoarthritis Initiative (OAI), the Multicenter Osteoarthritis Study (MOST), and the Cohort Hip and Cohort Knee (CHECK) study – at baseline and again 4-5 years later.
The authors created two groups of knees at baseline: the “incidence cohort” of 9,683 knees from 5,774 participants without OA structural defects (Kellgren-Lawrence grade 0 or 1) and the “progression cohort” of 6,075 knees from 3,988 participants with OA structural defects (KL grade 2 or higher). After 4-5 years, they determined OA incidence (KL grade 2 or higher in participants without baseline knee OA) and progression (increase of one or more KL grades in those with baseline knee OA).At baseline, the mean patient age in both groups was around 60, and around 60% of participants were female. In the incidence and progression groups, respectively, White patients comprised 87.5% and 80.4% of participants; mean body mass index was 28.2 and 30.4 kg/m2; and 32.6% and 48.4% of participants were obese (BMI, 30 or higher). The authors combined data from the three studies and used logistic regression and generalized estimating equations, with clustering of both knees within individuals. On multivariable analysis, they found that change in BMI 4-5 years post baseline was positively linked with both incidence and progression of knee OA structural defects.
In the incidence group, BMI decreased 1 or more units in 1,101 patients and increased 1 or more units in 1,611. In the progression group, BMI decreased 1 or more units in 798 patients and increased in 1,008.
The adjusted odds ratio for overall structural defects in the incidence group was 1.05 (95% confidence interval, 1.02-1.09) and 1.05 (95% CI, 1.01-1.09) in the progression group was. A 1-unit decrease in BMI was linked with a nearly 5% drop in odds of incidence and progression of knee OA, and a 5-unit decrease was linked with a more than 21% drop in odds of incidence and progression.
In the incidence group, change in BMI was positively linked with medial, but not lateral, joint space degeneration (narrowing; OR, 1.08; 95% CI, 1.04-1.12) and with medial femoral surface degeneration indicated by osteophytes (OR, 1.07; 95% CI, 1.03-1.12).
In the progression group, change in BMI was positively linked with overall structural defects (OR, 1.05; 95% CI, 1.01-1.09) as well as medial, but not lateral, joint space degeneration (OR, 1.08; 95% CI, 1.03-1.12).
“Previous research showed that weight loss helps reduce symptoms of knee osteoarthritis, such as pain and impaired physical function,” said lead study author Zübeyir Salis, BEng, a PhD student in public health at the University of New South Wales, Kensington, Australia. “Weight loss is emerging as a suitable strategy for potentially delaying and preventing osteoarthritic knee joint degeneration.”
Two experts not involved in the study welcome its results
Kai Sun, MD, MS, assistant professor of medicine, rheumatology, and immunology at Duke University, Durham, N. C., said it makes mechanical sense that less weight bearing decreases knee damage over time, but she was somewhat surprised that even people who started with normal BMI improved their outcomes by decreasing BMI further.
“Knee osteoarthritis and obesity prevalence are both growing,” Dr. Sun said. “Knee osteoarthritis may one day be considered an obesity-related comorbidity like hypertension and diabetes and be used as additional justification for pharmacologic or nonpharmacologic interventions to treat obesity.”
She noted that the study’s major strengths include its large sample size, long follow-up, and separate inclusion of disease incidence and progression, but also noted some limitations.
“BMI data at only two time points does not consider BMI fluctuations between those times,” she added. “Limited data were presented on physical activity levels, and most participants being White and elderly limited the generalizability of the results.”
Eduardo Grunvald, MD, professor of medicine and medical director of the weight management program at the University of California, San Diego, agreed about the study’s strengths and pointed out its lack of information about the cause of BMI changes.
Dr. Grunvald would like to know whether the BMI changes contributed to the knee changes or vice versa. “An individual’s worsening knee pain could lead to less physical activity and possible increased BMI.
“Long-term weight-loss maintenance is extremely challenging, and for optimal outcomes, medical professionals who treat joint disease should partner with clinicians trained to treat obesity,” he advised.
The authors are planning further related research. “We’re looking forward to running a randomized, controlled clinical weight-loss trial,” Dr. Sainsbury said.The study was supported by scholarship and fellowship funds from the Australian government. Mr. Salis and Dr. Sainsbury each own 50% of shares in a company that provides educational resources and services in adult weight management. Dr. Sainsbury and one coauthor reported relevant financial relationships with various pharmaceutical companies. Dr. Sun and Dr. Grunvald reported no relevant financial relationships.
FROM ARTHRITIS & RHEUMATOLOGY
Online yoga program improves physical function in OA
Although pain did not significantly improve in the yoga group, participants only completed about two-thirds of the recommended sessions, suggesting that more benefit may be possible with greater adherence, wrote lead author Kim L. Bennell, PhD, of the University of Melbourne, and colleagues in the Annals of Internal Medicine.
“To date, an online yoga program specifically for people with knee osteoarthritis has not been investigated,” the investigators said. “The need for such evidence-based packaged online exercise programs is highlighted in the 2020 U.S. National Public Health Agenda for Osteoarthritis.”
Methods and results
The trial involved 212 adults aged 45 years or older with symptomatic knee osteoarthritis. All patients had access to online educational materials about managing osteoarthritis.
Half of the participants were randomized into the 12-week online yoga program. This self-directed, unsupervised course consisted of 12 prerecorded 30-minute instructional yoga sessions, each with a unique sequence of poses to be completed three times in one week before moving on to the next class the following week. After 12 weeks, these participants could choose to continue doing yoga via the online program for 12 additional weeks, if desired.
The primary outcomes were knee pain and physical function, gauged by a 10-point numerical rating scale and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), respectively. Adherence was defined as completion of at least 2 yoga sessions within the preceding week.
At the 12-week mark, the yoga group did not show any significant improvement in knee pain (–0.6; 95% confidence interval, –1.2 to 0.1), but they did achieve a mean 4-point reduction in WOMAC, suggesting significant improvement in knee function (–4.0; 95% CI, –6.8 to –1.3). Of note, however, this improvement was not enough to meet the threshold for minimal clinically important difference. At 24 weeks, the yoga group no longer showed significant improvement in knee function versus baseline.
“I don’t think a longer program would necessarily reduce knee pain, as benefits from a whole range of different types of exercise for knee osteoarthritis generally can show benefits within 8 weeks,” Dr. Bennell said in an interview.
Still, she noted that the average outcome in the trial may not represent what is possible if a patient commits to a regular yoga routine.
“I think it relates more to adherence [than duration], and I think benefits for knee pain would have been seen if a greater number of people had fully adhered to the program three times a week,” she said.
At 12 weeks, 68.8% of those in the yoga group were adherent, while just 28.4% were still adherent at week 24 after the optional extension period.
“As this was a self-directed program, adherence might be expected to be less than that of a supervised program,” Dr. Bennell noted.
Referring to unpublished data, Dr. Bennell said a sensitivity analysis showed that participants in the yoga group who completed yoga at least twice a week did show greater improvements in function and pain than those who did yoga less than twice per week.
“So it does suggest that adherence is important, as we might expect,” she said.
Another tool in the OA toolbox
Nick Trasolini, MD, of Wake Forest University School of Medicine, Winston-Salem, N.C., described the benefits in the trial as “modest” and noted that the improvement in function did not meet the threshold for minimal clinically important difference.
“Nevertheless,” he said in a written comment, “the [yoga] program was safe and associated with high participant satisfaction [mean satisfaction, 8 out of 10]. While this may not be the ‘silver bullet,’ it is another tool that we can offer to sufficiently motivated patients seeking non-operative solutions for knee osteoarthritis.”
Unfortunately, these tools remain “fraught with challenges,” Dr. Trasolini added.
“While multiple injection options are available (including corticosteroid, hyaluronic acid viscosupplementation, and biologic injections), the benefits of these injections can be short-lived,” he said. “This is frustrating to patients and physicians alike. Physical therapy is beneficial for knee osteoarthritis when deconditioning has led to decreased knee, hip, and core stability. However, physical therapy can be time consuming, painful, and cost prohibitive.”
In the present study, participants in the yoga group were somewhat willing (mean willingness, 5 out of 10) to pay for their 12-week yoga program. They reported that they would pay approximately $80 U.S. dollars for chance to do it all again.
The study was supported by grants from the National Health and Medical Research Council Program and the Centres of Research Excellence. The investigators disclosed additional relationships with Pfizer, Lilly, TLCBio, and others. Dr. Trasolini disclosed no relevant conflicts of interest.
Although pain did not significantly improve in the yoga group, participants only completed about two-thirds of the recommended sessions, suggesting that more benefit may be possible with greater adherence, wrote lead author Kim L. Bennell, PhD, of the University of Melbourne, and colleagues in the Annals of Internal Medicine.
“To date, an online yoga program specifically for people with knee osteoarthritis has not been investigated,” the investigators said. “The need for such evidence-based packaged online exercise programs is highlighted in the 2020 U.S. National Public Health Agenda for Osteoarthritis.”
Methods and results
The trial involved 212 adults aged 45 years or older with symptomatic knee osteoarthritis. All patients had access to online educational materials about managing osteoarthritis.
Half of the participants were randomized into the 12-week online yoga program. This self-directed, unsupervised course consisted of 12 prerecorded 30-minute instructional yoga sessions, each with a unique sequence of poses to be completed three times in one week before moving on to the next class the following week. After 12 weeks, these participants could choose to continue doing yoga via the online program for 12 additional weeks, if desired.
The primary outcomes were knee pain and physical function, gauged by a 10-point numerical rating scale and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), respectively. Adherence was defined as completion of at least 2 yoga sessions within the preceding week.
At the 12-week mark, the yoga group did not show any significant improvement in knee pain (–0.6; 95% confidence interval, –1.2 to 0.1), but they did achieve a mean 4-point reduction in WOMAC, suggesting significant improvement in knee function (–4.0; 95% CI, –6.8 to –1.3). Of note, however, this improvement was not enough to meet the threshold for minimal clinically important difference. At 24 weeks, the yoga group no longer showed significant improvement in knee function versus baseline.
“I don’t think a longer program would necessarily reduce knee pain, as benefits from a whole range of different types of exercise for knee osteoarthritis generally can show benefits within 8 weeks,” Dr. Bennell said in an interview.
Still, she noted that the average outcome in the trial may not represent what is possible if a patient commits to a regular yoga routine.
“I think it relates more to adherence [than duration], and I think benefits for knee pain would have been seen if a greater number of people had fully adhered to the program three times a week,” she said.
At 12 weeks, 68.8% of those in the yoga group were adherent, while just 28.4% were still adherent at week 24 after the optional extension period.
“As this was a self-directed program, adherence might be expected to be less than that of a supervised program,” Dr. Bennell noted.
Referring to unpublished data, Dr. Bennell said a sensitivity analysis showed that participants in the yoga group who completed yoga at least twice a week did show greater improvements in function and pain than those who did yoga less than twice per week.
“So it does suggest that adherence is important, as we might expect,” she said.
Another tool in the OA toolbox
Nick Trasolini, MD, of Wake Forest University School of Medicine, Winston-Salem, N.C., described the benefits in the trial as “modest” and noted that the improvement in function did not meet the threshold for minimal clinically important difference.
“Nevertheless,” he said in a written comment, “the [yoga] program was safe and associated with high participant satisfaction [mean satisfaction, 8 out of 10]. While this may not be the ‘silver bullet,’ it is another tool that we can offer to sufficiently motivated patients seeking non-operative solutions for knee osteoarthritis.”
Unfortunately, these tools remain “fraught with challenges,” Dr. Trasolini added.
“While multiple injection options are available (including corticosteroid, hyaluronic acid viscosupplementation, and biologic injections), the benefits of these injections can be short-lived,” he said. “This is frustrating to patients and physicians alike. Physical therapy is beneficial for knee osteoarthritis when deconditioning has led to decreased knee, hip, and core stability. However, physical therapy can be time consuming, painful, and cost prohibitive.”
In the present study, participants in the yoga group were somewhat willing (mean willingness, 5 out of 10) to pay for their 12-week yoga program. They reported that they would pay approximately $80 U.S. dollars for chance to do it all again.
The study was supported by grants from the National Health and Medical Research Council Program and the Centres of Research Excellence. The investigators disclosed additional relationships with Pfizer, Lilly, TLCBio, and others. Dr. Trasolini disclosed no relevant conflicts of interest.
Although pain did not significantly improve in the yoga group, participants only completed about two-thirds of the recommended sessions, suggesting that more benefit may be possible with greater adherence, wrote lead author Kim L. Bennell, PhD, of the University of Melbourne, and colleagues in the Annals of Internal Medicine.
“To date, an online yoga program specifically for people with knee osteoarthritis has not been investigated,” the investigators said. “The need for such evidence-based packaged online exercise programs is highlighted in the 2020 U.S. National Public Health Agenda for Osteoarthritis.”
Methods and results
The trial involved 212 adults aged 45 years or older with symptomatic knee osteoarthritis. All patients had access to online educational materials about managing osteoarthritis.
Half of the participants were randomized into the 12-week online yoga program. This self-directed, unsupervised course consisted of 12 prerecorded 30-minute instructional yoga sessions, each with a unique sequence of poses to be completed three times in one week before moving on to the next class the following week. After 12 weeks, these participants could choose to continue doing yoga via the online program for 12 additional weeks, if desired.
The primary outcomes were knee pain and physical function, gauged by a 10-point numerical rating scale and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), respectively. Adherence was defined as completion of at least 2 yoga sessions within the preceding week.
At the 12-week mark, the yoga group did not show any significant improvement in knee pain (–0.6; 95% confidence interval, –1.2 to 0.1), but they did achieve a mean 4-point reduction in WOMAC, suggesting significant improvement in knee function (–4.0; 95% CI, –6.8 to –1.3). Of note, however, this improvement was not enough to meet the threshold for minimal clinically important difference. At 24 weeks, the yoga group no longer showed significant improvement in knee function versus baseline.
“I don’t think a longer program would necessarily reduce knee pain, as benefits from a whole range of different types of exercise for knee osteoarthritis generally can show benefits within 8 weeks,” Dr. Bennell said in an interview.
Still, she noted that the average outcome in the trial may not represent what is possible if a patient commits to a regular yoga routine.
“I think it relates more to adherence [than duration], and I think benefits for knee pain would have been seen if a greater number of people had fully adhered to the program three times a week,” she said.
At 12 weeks, 68.8% of those in the yoga group were adherent, while just 28.4% were still adherent at week 24 after the optional extension period.
“As this was a self-directed program, adherence might be expected to be less than that of a supervised program,” Dr. Bennell noted.
Referring to unpublished data, Dr. Bennell said a sensitivity analysis showed that participants in the yoga group who completed yoga at least twice a week did show greater improvements in function and pain than those who did yoga less than twice per week.
“So it does suggest that adherence is important, as we might expect,” she said.
Another tool in the OA toolbox
Nick Trasolini, MD, of Wake Forest University School of Medicine, Winston-Salem, N.C., described the benefits in the trial as “modest” and noted that the improvement in function did not meet the threshold for minimal clinically important difference.
“Nevertheless,” he said in a written comment, “the [yoga] program was safe and associated with high participant satisfaction [mean satisfaction, 8 out of 10]. While this may not be the ‘silver bullet,’ it is another tool that we can offer to sufficiently motivated patients seeking non-operative solutions for knee osteoarthritis.”
Unfortunately, these tools remain “fraught with challenges,” Dr. Trasolini added.
“While multiple injection options are available (including corticosteroid, hyaluronic acid viscosupplementation, and biologic injections), the benefits of these injections can be short-lived,” he said. “This is frustrating to patients and physicians alike. Physical therapy is beneficial for knee osteoarthritis when deconditioning has led to decreased knee, hip, and core stability. However, physical therapy can be time consuming, painful, and cost prohibitive.”
In the present study, participants in the yoga group were somewhat willing (mean willingness, 5 out of 10) to pay for their 12-week yoga program. They reported that they would pay approximately $80 U.S. dollars for chance to do it all again.
The study was supported by grants from the National Health and Medical Research Council Program and the Centres of Research Excellence. The investigators disclosed additional relationships with Pfizer, Lilly, TLCBio, and others. Dr. Trasolini disclosed no relevant conflicts of interest.
FROM ANNALS OF INTERNAL MEDICINE
Fish oil pills do not reduce fractures in healthy seniors: VITAL
Omega-3 supplements did not reduce fractures during a median 5.3-year follow-up in the more than 25,000 generally healthy men and women (≥ age 50 and ≥ age 55, respectively) in the Vitamin D and Omega-3 Trial (VITAL).
The large randomized controlled trial tested whether omega-3 fatty acid or vitamin D supplements prevented cardiovascular disease or cancer in a representative sample of midlife and older adults from 50 U.S. states – which they did not. In a further analysis of VITAL, vitamin D supplements (cholecalciferol, 2,000 IU/day) did not lower the risk of incident total, nonvertebral, and hip fractures, compared with placebo.
Now this new analysis shows that omega-3 fatty acid supplements (1 g/day of fish oil) did not reduce the risk of such fractures in the VITAL population either. Meryl S. LeBoff, MD, presented the latest findings during an oral session at the annual meeting of the American Society for Bone and Mineral Research.
“In this, the largest randomized controlled trial in the world, we did not find an effect of omega-3 fatty acid supplements on fractures,” Dr. LeBoff, from Brigham and Women’s Hospital and Harvard Medical School, both in Boston, told this news organization.
The current analysis did “unexpectedly” show that among participants who received the omega-3 fatty acid supplements, there was an increase in fractures in men, and fracture risk was higher in people with a normal or low body mass index and lower in people with higher BMI.
However, these subgroup findings need to be interpreted with caution and may be caused by chance, Dr. LeBoff warned. The researchers will be investigating these findings in further analyses.
Should patients take omega-3 supplements or not?
Asked whether, in the meantime, patients should start or keep taking fish oil supplements for possible health benefits, she noted that certain individuals might benefit.
For example, in VITAL, participants who ate less than 1.5 servings of fish per week and received omega-3 fatty acid supplements had a decrease in the combined cardiovascular endpoint, and Black participants who took fish oil supplements had a substantially reduced risk of the outcome, regardless of fish intake.
“I think everybody needs to review [the study findings] with clinicians and make a decision in terms of what would be best for them,” she said.
Session comoderator Bente Langdahl, MD, PhD, commented that “many people take omega-3 because they think it will help” knee, hip, or other joint pain.
Perhaps men are more prone to joint pain because of osteoarthritis and the supplements lessen the pain, so these men became more physically active and more prone to fractures, she speculated.
The current study shows that, “so far, we haven’t been able to demonstrate a reduced rate of fractures with fish oil supplements in clinical randomized trials” conducted in relatively healthy and not the oldest patients, she summarized. “We’re not talking about 80-year-olds.”
In this “well-conducted study, they were not able to see any difference” with omega-3 fatty acid supplements versus placebo, but apparently, there are no harms associated with taking these supplements, she said.
To patients who ask her about such supplements, Dr. Langdahl advised: “Try it out for 3 months. If it really helps you, if it takes away your joint pain or whatever, then that might work for you. But then remember to stop again because it might just be a temporary effect.”
Could fish oil supplements protect against fractures?
An estimated 22% of U.S. adults aged 60 and older take omega-3 fatty acid supplements, Dr. LeBoff noted.
Preclinical studies have shown that omega-3 fatty acids reduce bone resorption and have anti-inflammatory effects, but observational studies have reported conflicting findings.
The researchers conducted this ancillary study of VITAL to fill these knowledge gaps.
VITAL enrolled a national sample of 25,871 U.S. men and women, including 5,106 Black participants, with a mean age of 67 and a mean BMI of 28 kg/m2.
Importantly, participants were not recruited by low bone density, fractures, or vitamin D deficiency. Prior to entry, participants were required to stop taking omega-3 supplements and limit nonstudy vitamin D and calcium supplements.
The omega-3 fatty acid supplements used in the study contained eicosapentaenoic acid and docosahexaenoic acid in a 1.2:1 ratio.
VITAL had a 2x2 factorial design whereby 6,463 participants were randomized to receive the omega-3 fatty acid supplement and 6,474 were randomized to placebo. (Remaining participants were randomized to receive vitamin D or placebo.)
Participants in the omega-3 fatty acid and placebo groups had similar baseline characteristics. For example, about half (50.5%) were women, and on average, they ate 1.1 servings of dark-meat fish (such as salmon) per week.
Participants completed detailed questionnaires at baseline and each year.
Plasma omega-3 levels were measured at baseline and, in 1,583 participants, at 1 year of follow-up. The mean omega-3 index rose 54.7% in the omega-3 fatty acid group and changed less than 2% in the placebo group at 1 year.
Study pill adherence was 87.0% at 2 years and 85.7% at 5 years.
Fractures were self-reported on annual questionnaires and centrally adjudicated in medical record review.
No clinically meaningful effect of omega-3 fatty acids on fractures
During a median 5.3-year follow-up, researchers adjudicated 2,133 total fractures and confirmed 1,991 fractures (93%) in 1551 participants.
Incidences of total, nonvertebral, and hip fractures were similar in both groups.
Compared with placebo, omega-3 fatty acid supplements had no significant effect on risk of total fractures (hazard ratio, 1.02; 95% confidence interval, 0.92-1.13), nonvertebral fractures (HR, 1.01; 95% CI, 0.91-1.12), or hip fractures (HR, 0.89; 95% CI, 0.61-1.30), all adjusted for age, sex, and race.
The “confidence intervals were narrow, likely excluding a clinically meaningful effect,” Dr. LeBoff noted.
Among men, those who received fish oil supplements had a greater risk of fracture than those who received placebo (HR, 1.27; 95% CI, 1.07-1.51), but this result “was not corrected for multiple hypothesis testing,” Dr. LeBoff cautioned.
In the overall population, participants with a BMI less than 25 who received fish oil versus placebo had an increased risk of fracture, and those with a BMI of at least 30 who received fish oil versus placebo had a decreased risk of fracture, but the limits of the confidence intervals crossed 1.00.
After excluding digit, skull, and pathologic fractures, there was no significant reduction in total fractures (HR, 1.02; 95% CI, 0.92-1.14), nonvertebral fractures (HR, 1.02; 95% CI, 0.92-1.14), or hip fractures (HR, 0.90; 95% CI, 0.61-1.33), with omega-3 supplements versus placebo.
Similarly, there was no significant reduction in risk of major osteoporotic fractures (hip, wrist, humerus, and clinical spine fractures) or wrist fractures with omega-3 supplements versus placebo.
VITAL only studied one dose of omega-3 fatty acid supplements, and results may not be generalizable to younger adults, or older adults living in residential communities, Dr. LeBoff noted.
The study was supported by grants from the National Institute of Arthritis Musculoskeletal and Skin Diseases. VITAL was funded by the National Cancer Institute and the National Heart, Lung, and Blood Institute. Dr. LeBoff and Dr. Langdahl have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Omega-3 supplements did not reduce fractures during a median 5.3-year follow-up in the more than 25,000 generally healthy men and women (≥ age 50 and ≥ age 55, respectively) in the Vitamin D and Omega-3 Trial (VITAL).
The large randomized controlled trial tested whether omega-3 fatty acid or vitamin D supplements prevented cardiovascular disease or cancer in a representative sample of midlife and older adults from 50 U.S. states – which they did not. In a further analysis of VITAL, vitamin D supplements (cholecalciferol, 2,000 IU/day) did not lower the risk of incident total, nonvertebral, and hip fractures, compared with placebo.
Now this new analysis shows that omega-3 fatty acid supplements (1 g/day of fish oil) did not reduce the risk of such fractures in the VITAL population either. Meryl S. LeBoff, MD, presented the latest findings during an oral session at the annual meeting of the American Society for Bone and Mineral Research.
“In this, the largest randomized controlled trial in the world, we did not find an effect of omega-3 fatty acid supplements on fractures,” Dr. LeBoff, from Brigham and Women’s Hospital and Harvard Medical School, both in Boston, told this news organization.
The current analysis did “unexpectedly” show that among participants who received the omega-3 fatty acid supplements, there was an increase in fractures in men, and fracture risk was higher in people with a normal or low body mass index and lower in people with higher BMI.
However, these subgroup findings need to be interpreted with caution and may be caused by chance, Dr. LeBoff warned. The researchers will be investigating these findings in further analyses.
Should patients take omega-3 supplements or not?
Asked whether, in the meantime, patients should start or keep taking fish oil supplements for possible health benefits, she noted that certain individuals might benefit.
For example, in VITAL, participants who ate less than 1.5 servings of fish per week and received omega-3 fatty acid supplements had a decrease in the combined cardiovascular endpoint, and Black participants who took fish oil supplements had a substantially reduced risk of the outcome, regardless of fish intake.
“I think everybody needs to review [the study findings] with clinicians and make a decision in terms of what would be best for them,” she said.
Session comoderator Bente Langdahl, MD, PhD, commented that “many people take omega-3 because they think it will help” knee, hip, or other joint pain.
Perhaps men are more prone to joint pain because of osteoarthritis and the supplements lessen the pain, so these men became more physically active and more prone to fractures, she speculated.
The current study shows that, “so far, we haven’t been able to demonstrate a reduced rate of fractures with fish oil supplements in clinical randomized trials” conducted in relatively healthy and not the oldest patients, she summarized. “We’re not talking about 80-year-olds.”
In this “well-conducted study, they were not able to see any difference” with omega-3 fatty acid supplements versus placebo, but apparently, there are no harms associated with taking these supplements, she said.
To patients who ask her about such supplements, Dr. Langdahl advised: “Try it out for 3 months. If it really helps you, if it takes away your joint pain or whatever, then that might work for you. But then remember to stop again because it might just be a temporary effect.”
Could fish oil supplements protect against fractures?
An estimated 22% of U.S. adults aged 60 and older take omega-3 fatty acid supplements, Dr. LeBoff noted.
Preclinical studies have shown that omega-3 fatty acids reduce bone resorption and have anti-inflammatory effects, but observational studies have reported conflicting findings.
The researchers conducted this ancillary study of VITAL to fill these knowledge gaps.
VITAL enrolled a national sample of 25,871 U.S. men and women, including 5,106 Black participants, with a mean age of 67 and a mean BMI of 28 kg/m2.
Importantly, participants were not recruited by low bone density, fractures, or vitamin D deficiency. Prior to entry, participants were required to stop taking omega-3 supplements and limit nonstudy vitamin D and calcium supplements.
The omega-3 fatty acid supplements used in the study contained eicosapentaenoic acid and docosahexaenoic acid in a 1.2:1 ratio.
VITAL had a 2x2 factorial design whereby 6,463 participants were randomized to receive the omega-3 fatty acid supplement and 6,474 were randomized to placebo. (Remaining participants were randomized to receive vitamin D or placebo.)
Participants in the omega-3 fatty acid and placebo groups had similar baseline characteristics. For example, about half (50.5%) were women, and on average, they ate 1.1 servings of dark-meat fish (such as salmon) per week.
Participants completed detailed questionnaires at baseline and each year.
Plasma omega-3 levels were measured at baseline and, in 1,583 participants, at 1 year of follow-up. The mean omega-3 index rose 54.7% in the omega-3 fatty acid group and changed less than 2% in the placebo group at 1 year.
Study pill adherence was 87.0% at 2 years and 85.7% at 5 years.
Fractures were self-reported on annual questionnaires and centrally adjudicated in medical record review.
No clinically meaningful effect of omega-3 fatty acids on fractures
During a median 5.3-year follow-up, researchers adjudicated 2,133 total fractures and confirmed 1,991 fractures (93%) in 1551 participants.
Incidences of total, nonvertebral, and hip fractures were similar in both groups.
Compared with placebo, omega-3 fatty acid supplements had no significant effect on risk of total fractures (hazard ratio, 1.02; 95% confidence interval, 0.92-1.13), nonvertebral fractures (HR, 1.01; 95% CI, 0.91-1.12), or hip fractures (HR, 0.89; 95% CI, 0.61-1.30), all adjusted for age, sex, and race.
The “confidence intervals were narrow, likely excluding a clinically meaningful effect,” Dr. LeBoff noted.
Among men, those who received fish oil supplements had a greater risk of fracture than those who received placebo (HR, 1.27; 95% CI, 1.07-1.51), but this result “was not corrected for multiple hypothesis testing,” Dr. LeBoff cautioned.
In the overall population, participants with a BMI less than 25 who received fish oil versus placebo had an increased risk of fracture, and those with a BMI of at least 30 who received fish oil versus placebo had a decreased risk of fracture, but the limits of the confidence intervals crossed 1.00.
After excluding digit, skull, and pathologic fractures, there was no significant reduction in total fractures (HR, 1.02; 95% CI, 0.92-1.14), nonvertebral fractures (HR, 1.02; 95% CI, 0.92-1.14), or hip fractures (HR, 0.90; 95% CI, 0.61-1.33), with omega-3 supplements versus placebo.
Similarly, there was no significant reduction in risk of major osteoporotic fractures (hip, wrist, humerus, and clinical spine fractures) or wrist fractures with omega-3 supplements versus placebo.
VITAL only studied one dose of omega-3 fatty acid supplements, and results may not be generalizable to younger adults, or older adults living in residential communities, Dr. LeBoff noted.
The study was supported by grants from the National Institute of Arthritis Musculoskeletal and Skin Diseases. VITAL was funded by the National Cancer Institute and the National Heart, Lung, and Blood Institute. Dr. LeBoff and Dr. Langdahl have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Omega-3 supplements did not reduce fractures during a median 5.3-year follow-up in the more than 25,000 generally healthy men and women (≥ age 50 and ≥ age 55, respectively) in the Vitamin D and Omega-3 Trial (VITAL).
The large randomized controlled trial tested whether omega-3 fatty acid or vitamin D supplements prevented cardiovascular disease or cancer in a representative sample of midlife and older adults from 50 U.S. states – which they did not. In a further analysis of VITAL, vitamin D supplements (cholecalciferol, 2,000 IU/day) did not lower the risk of incident total, nonvertebral, and hip fractures, compared with placebo.
Now this new analysis shows that omega-3 fatty acid supplements (1 g/day of fish oil) did not reduce the risk of such fractures in the VITAL population either. Meryl S. LeBoff, MD, presented the latest findings during an oral session at the annual meeting of the American Society for Bone and Mineral Research.
“In this, the largest randomized controlled trial in the world, we did not find an effect of omega-3 fatty acid supplements on fractures,” Dr. LeBoff, from Brigham and Women’s Hospital and Harvard Medical School, both in Boston, told this news organization.
The current analysis did “unexpectedly” show that among participants who received the omega-3 fatty acid supplements, there was an increase in fractures in men, and fracture risk was higher in people with a normal or low body mass index and lower in people with higher BMI.
However, these subgroup findings need to be interpreted with caution and may be caused by chance, Dr. LeBoff warned. The researchers will be investigating these findings in further analyses.
Should patients take omega-3 supplements or not?
Asked whether, in the meantime, patients should start or keep taking fish oil supplements for possible health benefits, she noted that certain individuals might benefit.
For example, in VITAL, participants who ate less than 1.5 servings of fish per week and received omega-3 fatty acid supplements had a decrease in the combined cardiovascular endpoint, and Black participants who took fish oil supplements had a substantially reduced risk of the outcome, regardless of fish intake.
“I think everybody needs to review [the study findings] with clinicians and make a decision in terms of what would be best for them,” she said.
Session comoderator Bente Langdahl, MD, PhD, commented that “many people take omega-3 because they think it will help” knee, hip, or other joint pain.
Perhaps men are more prone to joint pain because of osteoarthritis and the supplements lessen the pain, so these men became more physically active and more prone to fractures, she speculated.
The current study shows that, “so far, we haven’t been able to demonstrate a reduced rate of fractures with fish oil supplements in clinical randomized trials” conducted in relatively healthy and not the oldest patients, she summarized. “We’re not talking about 80-year-olds.”
In this “well-conducted study, they were not able to see any difference” with omega-3 fatty acid supplements versus placebo, but apparently, there are no harms associated with taking these supplements, she said.
To patients who ask her about such supplements, Dr. Langdahl advised: “Try it out for 3 months. If it really helps you, if it takes away your joint pain or whatever, then that might work for you. But then remember to stop again because it might just be a temporary effect.”
Could fish oil supplements protect against fractures?
An estimated 22% of U.S. adults aged 60 and older take omega-3 fatty acid supplements, Dr. LeBoff noted.
Preclinical studies have shown that omega-3 fatty acids reduce bone resorption and have anti-inflammatory effects, but observational studies have reported conflicting findings.
The researchers conducted this ancillary study of VITAL to fill these knowledge gaps.
VITAL enrolled a national sample of 25,871 U.S. men and women, including 5,106 Black participants, with a mean age of 67 and a mean BMI of 28 kg/m2.
Importantly, participants were not recruited by low bone density, fractures, or vitamin D deficiency. Prior to entry, participants were required to stop taking omega-3 supplements and limit nonstudy vitamin D and calcium supplements.
The omega-3 fatty acid supplements used in the study contained eicosapentaenoic acid and docosahexaenoic acid in a 1.2:1 ratio.
VITAL had a 2x2 factorial design whereby 6,463 participants were randomized to receive the omega-3 fatty acid supplement and 6,474 were randomized to placebo. (Remaining participants were randomized to receive vitamin D or placebo.)
Participants in the omega-3 fatty acid and placebo groups had similar baseline characteristics. For example, about half (50.5%) were women, and on average, they ate 1.1 servings of dark-meat fish (such as salmon) per week.
Participants completed detailed questionnaires at baseline and each year.
Plasma omega-3 levels were measured at baseline and, in 1,583 participants, at 1 year of follow-up. The mean omega-3 index rose 54.7% in the omega-3 fatty acid group and changed less than 2% in the placebo group at 1 year.
Study pill adherence was 87.0% at 2 years and 85.7% at 5 years.
Fractures were self-reported on annual questionnaires and centrally adjudicated in medical record review.
No clinically meaningful effect of omega-3 fatty acids on fractures
During a median 5.3-year follow-up, researchers adjudicated 2,133 total fractures and confirmed 1,991 fractures (93%) in 1551 participants.
Incidences of total, nonvertebral, and hip fractures were similar in both groups.
Compared with placebo, omega-3 fatty acid supplements had no significant effect on risk of total fractures (hazard ratio, 1.02; 95% confidence interval, 0.92-1.13), nonvertebral fractures (HR, 1.01; 95% CI, 0.91-1.12), or hip fractures (HR, 0.89; 95% CI, 0.61-1.30), all adjusted for age, sex, and race.
The “confidence intervals were narrow, likely excluding a clinically meaningful effect,” Dr. LeBoff noted.
Among men, those who received fish oil supplements had a greater risk of fracture than those who received placebo (HR, 1.27; 95% CI, 1.07-1.51), but this result “was not corrected for multiple hypothesis testing,” Dr. LeBoff cautioned.
In the overall population, participants with a BMI less than 25 who received fish oil versus placebo had an increased risk of fracture, and those with a BMI of at least 30 who received fish oil versus placebo had a decreased risk of fracture, but the limits of the confidence intervals crossed 1.00.
After excluding digit, skull, and pathologic fractures, there was no significant reduction in total fractures (HR, 1.02; 95% CI, 0.92-1.14), nonvertebral fractures (HR, 1.02; 95% CI, 0.92-1.14), or hip fractures (HR, 0.90; 95% CI, 0.61-1.33), with omega-3 supplements versus placebo.
Similarly, there was no significant reduction in risk of major osteoporotic fractures (hip, wrist, humerus, and clinical spine fractures) or wrist fractures with omega-3 supplements versus placebo.
VITAL only studied one dose of omega-3 fatty acid supplements, and results may not be generalizable to younger adults, or older adults living in residential communities, Dr. LeBoff noted.
The study was supported by grants from the National Institute of Arthritis Musculoskeletal and Skin Diseases. VITAL was funded by the National Cancer Institute and the National Heart, Lung, and Blood Institute. Dr. LeBoff and Dr. Langdahl have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ASMBR 2022
OMERACT continues to set standards on research outcomes, enhancing the patient voice
Clinical research in rheumatology was suffering from an identity crisis of sorts 40 years ago. A lack of consensus across continents resulted in differing views about clinical outcome measures and judgments about treatments.
Patients were not allowed to be the generating source of a clinical outcome, according to Peter Tugwell, MSc, MD. “The only outcomes that were acceptable were clinician assessments, blood tests, and imaging,” said Dr. Tugwell, professor of medicine, epidemiology, and public health at the University of Ottawa (Ont.) and a practicing rheumatologist at Ottawa Hospital.
Clinicians were coming to different conclusions about patient responses to treatment when managing rheumatoid arthritis in clinical practice.
OMERACT sought to address this lack of uniformity. This international group, formed in 1992, leverages stakeholder groups to improve outcome measurement in rheumatology endpoints through a consensus-building, data-driven format.
It was originally known as “Outcome Measures in Rheumatoid Arthritis Clinical Trials,” but its leaders have since broadened its scope to “Outcome Measures in Rheumatology.” Over the years, it has evolved into an international network that assesses measurement across a wide variety of intervention studies. Now 30 years old, the network spans 40 active working groups and has influenced work in patient outcomes across 500 peer-reviewed publications.
The network meets every 2 years to address what is always a challenging agenda, said Dr. Tugwell, one of its founding members and chair. “There’s lots of strong opinions.” Participating in the discussions are individuals from all stages of seniority in rheumatology and clinical epidemiology, patient research partners, industry, approval agencies, and many countries who are committed to the spirit of OMERACT.
“The secret to our success has been getting world leaders to come together and have those discussions, work them through, and identify common ground in such a way that the approval agencies accept these outcome measures in clinical trials,” he added.
“My impression was the founders perceived a problem in the early 1990s and devised a consensus method in an attempt to quantify clinical parameters to define disease activity in rheumatoid arthritis – an important first step to do clinical trials and allow comparisons between them,” said Patricia Woo, CBE, FMedSci, FRCP, emeritus professor of pediatric rheumatology and previous head of the Centre for Paediatric and Adolescent Rheumatology at UCL, London. At that time, even disease definitions varied between the United States and Europe and other parts of the world, said Dr. Woo, who is not a part of OMERACT. “This was especially true for pediatric rheumatology.”
Fusing the continental divide
OMERACT arose from a need to streamline clinical outcome measures in rheumatology. Research papers during the 1980s demonstrated a lack of coherence in managing patients with rheumatoid arthritis in routine practice. In addition, the measures used to define clinical endpoints in clinical trials operated in silos – they were either too specific to a certain trial, overlapped with other concepts, or didn’t reflect changes in treatment.
Approval agencies in Europe and North America were approving only outcomes measures developed by their respective researchers. This was also true of patients they tested on. “This seemed crazy,” Dr. Tugwell said.
Dr. Tugwell was involved in the Cochrane collaboration, which conducts systematic reviews of best evidence across the world that assesses the magnitude of benefits versus harms.
To achieve this goal, “you need to pull studies from around the world,” he said. Maarten Boers, MD, PhD, a rheumatologist (and later professor of clinical epidemiology at Amsterdam University Medical Center) from the Netherlands, spent a year in Ontario, Canada, to train as a clinical epidemiologist. Together, Dr. Tugwell and Dr. Boers began discussing options to develop more streamlined outcome measures.
They initiated the first OMERACT conference in Maastricht, the Netherlands, in 1992. The Food and Drug Administration and European Medicines Agency participated, along with leaders of outcomes measurement in Europe and in North America.
Discussions centered on methods to develop outcomes in a meaningful fashion. During the first meeting, North American and European approval agencies agreed to accept each other’s studies and endpoints and patient reported outcomes.
Agreement was achieved on a preliminary set of outcome domains and measures that later became known as the WHO-ILAR (World Health Organization–International League of Associations for Rheumatology) core set. The set included seven outcome domains: tender joints, swollen joints, pain, physician global assessment, patient global assessment, physical disability, and acute phase reactants, and one additional outcome domain for studies lasting 1 year or more: radiographs of the joints.
“A proactive program was planned to test not only the validity of these endpoints, but also the methods for their measurement. This was the start of a continuing process,” OMERACT members said in a joint statement for this article. Meetings have since taken place every 2 years.
OMERACT accomplishments
OMERACT now requires buy-in from four continents: Asia, Australia, Europe, and North America.
Its leaders have developed an explicit process for gaining endorsement of core outcome domains and instrument measurement sets. To fully capture the possibilities of “what to measure,” i.e., “measurable aspects of health conditions,” OMERACT has developed a framework of concepts, core areas, and outcome domains. The key concepts are pathophysiology (with a core area termed “manifestations/abnormalities”) and impact (with core areas of “death/lifespan,” and “life impact,” and the optional area of “societal/resource use”). An outcome domain defines an element of a core area to measure the effects of a treatment, such as blood markers, pain intensity, physical function, or emotional well-being.
A core outcome domain set is developed by agreeing to at least one outcome domain within one of the three core areas. Subsequently, a core outcome measurement set is developed by agreeing to at least one applicable measurement instrument for each core outcome domain. This requires documentation of validity, summarized under three metrics: truth, discrimination, and feasibility.
OMERACT’s handbook provides tutelage on establishing and implementing core outcomes, and several workbooks offer guidance on developing core outcome domain sets, selecting instruments for core outcome measurement sets, and OMERACT methodology.
All this work has led to widespread adoption.
Approval agencies have accepted OMERACT’s filter and methods advances, which have been adopted by many research groups in rheumatology and among nonrheumatology research groups. Organizations such as the U.S. National Institutes of Health’s National Institute of Neurological Disorders and Stroke have sought its advice.
Its core outcomes have been adopted and used for approval in the great majority of studies on rheumatoid arthritis, Dr. Tugwell said.
Several BMJ articles underscore the influence and uptake of OMERACT’s core outcome set. One 2017 paper, which analyzed 273 randomized trials of rheumatoid arthritis drug treatments on ClinicalTrials.gov, found that the WHO-ILAR arthritis core outcome set was reported in 81% of the studies. “The adoption of a core outcome set has the potential to increase consistency in outcomes measured across trials and ensure that trials are more likely to measure appropriate outcomes,” the authors concluded.
Since the initial 1992 meeting, OMERACT has broadened its focus from rheumatoid arthritis to 25 other musculoskeletal conditions.
For example, other OMERACT conferences have led to consensus on core sets of measures for osteoarthritis and osteoporosis, psoriasis/psoriatic arthritis, psychosocial measures, and a core set of data for cost-effectiveness evaluations.
‘Speed is a limitation’
OMERACT is a bottom-up volunteer organization. It doesn’t represent any official organization of any clinical society. “We’ve not asked to be adopted by the American College of Rheumatology, EULAR [European Alliance of Associations for Rheumatology], or other international organizations,” Dr. Tugwell said. It offers a chance for patients, users, and doers of research to work together to agree on rigorous criteria accepted by the approval agencies and take the necessary time to work things through.
This is not a fast process, usually taking 4-6 years to initiate and establish an outcome domain set, he emphasized. “It would be beneficial to do it faster if we had the resources to meet every year. The fact is we’re a volunteer organization that meets every 2 years.”
Speed is a limitation, he acknowledged, but it’s an acceptable trade-off for doing things correctly.
The group has faced other challenges during the COVID-19 pandemic, pivoting to a virtual format that had benefits and limitations.
In one respect, moving to a virtual meeting increased uptake in participation and voting, Dr. Tugwell said. Patient participants with severe rheumatoid arthritis no longer faced the challenges of travel. “On the other hand, we didn’t have the same opportunity to achieve common ground virtually,” he said. “Where there are strong disagreements, I’m a great believer that people need to know one another. There needs to be relationship building.”
OMERACT’s emerging leader program has been a cornerstone of its in-person meetings, engaging young rheumatologists to interact with some of the leaders of outcome measurement. The virtual format dampened this process somewhat, eliminating those important “café chats” between the stakeholders.
The hope is to bring people face-to-face once more at the next meeting in May 2023. The agenda will focus on relationship building, identifying controversial areas, and bringing younger people to develop relationships, Dr. Tugwell said. OMERACT will retain a virtual option for the worldwide voting, “which will allow for more buy-in from so many more people,” he added.
A consensus on pain
The onus of developing outcome measures that move with the times is sometimes too great for one group to manage. In 2018, OMERACT became a part of the Red Hat Group (RHG), an organization conceived at the COMET (Core Outcome Measures in Effectiveness Trials) VII meeting in Amsterdam.
RHG aims to improve the choice of outcomes in health research. It includes eight groups: COMET; OMERACT; the Cochrane Skin Core Outcome Set Initiative; Grading of Recommendations, Assessment, Development and Evaluations; Center for Medical Technology Policy; COnsensus-based Standards for the selection of health Measurement Instruments; Clinical Data Interchange Standards Consortium; and Standardized Outcomes in Nephrology.
The collaboration between groups offers a “very interesting interface between consensus building as well as hard evidence,” Dr. Tugwell said. The focus goes beyond rheumatology to other clinical areas of common interest, exploring how one classifies outcome domains in terms of symptoms, life impact, or death.
Pain is an important common denominator that the RHG has evaluated.
“We believe it’s too general. We’re trying to define pain across all Red Hat Groups because it’s clear that the research community has all these different scales for defining pain severity,” Dr. Tugwell said. “We have to find a way to make ruthless decisions and rules for doing it. And of course, it has to be transparent.”
Looking ahead
As part of its ongoing work, OMERACT is evaluating the robustness of instruments that rheumatologists use as outcome measures in clinical trials, which can be a laborious process. The OMERACT Filter 2.0, part of the latest iteration of the handbook, offers strong guidance for researchers but needs a long-term strategy and key methodological support. “To that end, we set up a technical advisory group to help people in the instrument selection work and that remains an ongoing process,” OMERACT leaders said in their joint statement.
OMERACT is looking at opportunities to create benchmark processes for developing core sets outside of rheumatology and a methodology around outcome measures such as contextual factors, composites, and surrogates.
It will also be taking a step back to solicit opinions from the approval agencies represented by the OMERACT membership on the OMERACT handbook.
The goal is to make sure the handbook aligns with everyone else’s approval and labeling requirements.
OMERACT’s patient participants bring important perspectives
OMERACT over the years has sought to become a more patient-centered group. Patients have been involved in OMERACT activities since its sixth meeting, forming an independent, yet integrated, group within the network. They have their own steering committee and produced and helped to update a glossary for OMERACT patients and professionals.
Catherine (McGowan) Hofstetter, who was diagnosed with rheumatoid arthritis 30 years ago, chairs OMERACT’s Patient Research Partners Support Team. In a Q&A, she discussed the importance of patient voices and OMERACT’s plans to further educate and include patients in the dialogue on outcomes.
Question: Have patients always been a part of OMERACT meetings?
Answer: Patients have been involved with OMERACT since 2002. The patient voice adds relevance to all the work that OMERACT does. You can’t begin to talk about outcomes unless there is a patient at the table with lived experience.
Q: Can you cite a few examples of how the patient voice enriches the conversation on outcomes research?
A: Outcomes and priorities that are important to patients are often completely different than those of the clinician. For instance, a work outcome is important to someone who doesn’t have any medical insurance or disability insurance, so that you can ensure that there is food on the table and a roof over your head. Or it may be important to someone because the employment provides medical and disability insurance to provide security for them and their family. These are two different perspectives on work and therefore work priorities and outcomes.
Q: What have been some of the challenges of getting patients to participate?
A: Training patients is one challenge. OMERACT’s work has a very steep learning curve, and while the basics are the same between the groups in terms of looking at what we measure and how we measure it, the nuances of different working groups require a lot of time and energy to be comfortable enough with the work, and then be confident enough to bring your perspective and lived experience to the table. It’s also a very accomplished group, which can be quite intimidating. Self-disclosure is a very personal and intimate undertaking that requires patience, compassion, and respect.
Q: Are there any plans to enhance patient engagement?
A: When we had OMERACT 2020 it was a virtual conference that took place over about 6 months. We had far more patient research partners [PRPs] participate than we have ever had at any OMERACT face-to-face meeting. There is a desire and passion on the part of patients to lend their voices to the work. The working groups meet virtually throughout the year to advance their agendas, and PRPs are a part of each of the working groups.
Hopefully, we can start working toward including more voices at the conferences by enabling a hybrid model. The PRP Support Team will begin engaging patients this fall with education, mentoring, and team-building exercises so by the time we meet in person in May 2023, they will have enough background knowledge and information to give them the confidence that will enhance their experience at the face-to-face meeting.
We also need to ensure that those patients who want to stay engaged can. This means that the education and training should continue long after the face-to-face meeting is over. We need to build capacity in the PRP group and look to succession planning and be a resource to working groups struggling to find PRPs to work with them on a longer-term basis.
Clinical research in rheumatology was suffering from an identity crisis of sorts 40 years ago. A lack of consensus across continents resulted in differing views about clinical outcome measures and judgments about treatments.
Patients were not allowed to be the generating source of a clinical outcome, according to Peter Tugwell, MSc, MD. “The only outcomes that were acceptable were clinician assessments, blood tests, and imaging,” said Dr. Tugwell, professor of medicine, epidemiology, and public health at the University of Ottawa (Ont.) and a practicing rheumatologist at Ottawa Hospital.
Clinicians were coming to different conclusions about patient responses to treatment when managing rheumatoid arthritis in clinical practice.
OMERACT sought to address this lack of uniformity. This international group, formed in 1992, leverages stakeholder groups to improve outcome measurement in rheumatology endpoints through a consensus-building, data-driven format.
It was originally known as “Outcome Measures in Rheumatoid Arthritis Clinical Trials,” but its leaders have since broadened its scope to “Outcome Measures in Rheumatology.” Over the years, it has evolved into an international network that assesses measurement across a wide variety of intervention studies. Now 30 years old, the network spans 40 active working groups and has influenced work in patient outcomes across 500 peer-reviewed publications.
The network meets every 2 years to address what is always a challenging agenda, said Dr. Tugwell, one of its founding members and chair. “There’s lots of strong opinions.” Participating in the discussions are individuals from all stages of seniority in rheumatology and clinical epidemiology, patient research partners, industry, approval agencies, and many countries who are committed to the spirit of OMERACT.
“The secret to our success has been getting world leaders to come together and have those discussions, work them through, and identify common ground in such a way that the approval agencies accept these outcome measures in clinical trials,” he added.
“My impression was the founders perceived a problem in the early 1990s and devised a consensus method in an attempt to quantify clinical parameters to define disease activity in rheumatoid arthritis – an important first step to do clinical trials and allow comparisons between them,” said Patricia Woo, CBE, FMedSci, FRCP, emeritus professor of pediatric rheumatology and previous head of the Centre for Paediatric and Adolescent Rheumatology at UCL, London. At that time, even disease definitions varied between the United States and Europe and other parts of the world, said Dr. Woo, who is not a part of OMERACT. “This was especially true for pediatric rheumatology.”
Fusing the continental divide
OMERACT arose from a need to streamline clinical outcome measures in rheumatology. Research papers during the 1980s demonstrated a lack of coherence in managing patients with rheumatoid arthritis in routine practice. In addition, the measures used to define clinical endpoints in clinical trials operated in silos – they were either too specific to a certain trial, overlapped with other concepts, or didn’t reflect changes in treatment.
Approval agencies in Europe and North America were approving only outcomes measures developed by their respective researchers. This was also true of patients they tested on. “This seemed crazy,” Dr. Tugwell said.
Dr. Tugwell was involved in the Cochrane collaboration, which conducts systematic reviews of best evidence across the world that assesses the magnitude of benefits versus harms.
To achieve this goal, “you need to pull studies from around the world,” he said. Maarten Boers, MD, PhD, a rheumatologist (and later professor of clinical epidemiology at Amsterdam University Medical Center) from the Netherlands, spent a year in Ontario, Canada, to train as a clinical epidemiologist. Together, Dr. Tugwell and Dr. Boers began discussing options to develop more streamlined outcome measures.
They initiated the first OMERACT conference in Maastricht, the Netherlands, in 1992. The Food and Drug Administration and European Medicines Agency participated, along with leaders of outcomes measurement in Europe and in North America.
Discussions centered on methods to develop outcomes in a meaningful fashion. During the first meeting, North American and European approval agencies agreed to accept each other’s studies and endpoints and patient reported outcomes.
Agreement was achieved on a preliminary set of outcome domains and measures that later became known as the WHO-ILAR (World Health Organization–International League of Associations for Rheumatology) core set. The set included seven outcome domains: tender joints, swollen joints, pain, physician global assessment, patient global assessment, physical disability, and acute phase reactants, and one additional outcome domain for studies lasting 1 year or more: radiographs of the joints.
“A proactive program was planned to test not only the validity of these endpoints, but also the methods for their measurement. This was the start of a continuing process,” OMERACT members said in a joint statement for this article. Meetings have since taken place every 2 years.
OMERACT accomplishments
OMERACT now requires buy-in from four continents: Asia, Australia, Europe, and North America.
Its leaders have developed an explicit process for gaining endorsement of core outcome domains and instrument measurement sets. To fully capture the possibilities of “what to measure,” i.e., “measurable aspects of health conditions,” OMERACT has developed a framework of concepts, core areas, and outcome domains. The key concepts are pathophysiology (with a core area termed “manifestations/abnormalities”) and impact (with core areas of “death/lifespan,” and “life impact,” and the optional area of “societal/resource use”). An outcome domain defines an element of a core area to measure the effects of a treatment, such as blood markers, pain intensity, physical function, or emotional well-being.
A core outcome domain set is developed by agreeing to at least one outcome domain within one of the three core areas. Subsequently, a core outcome measurement set is developed by agreeing to at least one applicable measurement instrument for each core outcome domain. This requires documentation of validity, summarized under three metrics: truth, discrimination, and feasibility.
OMERACT’s handbook provides tutelage on establishing and implementing core outcomes, and several workbooks offer guidance on developing core outcome domain sets, selecting instruments for core outcome measurement sets, and OMERACT methodology.
All this work has led to widespread adoption.
Approval agencies have accepted OMERACT’s filter and methods advances, which have been adopted by many research groups in rheumatology and among nonrheumatology research groups. Organizations such as the U.S. National Institutes of Health’s National Institute of Neurological Disorders and Stroke have sought its advice.
Its core outcomes have been adopted and used for approval in the great majority of studies on rheumatoid arthritis, Dr. Tugwell said.
Several BMJ articles underscore the influence and uptake of OMERACT’s core outcome set. One 2017 paper, which analyzed 273 randomized trials of rheumatoid arthritis drug treatments on ClinicalTrials.gov, found that the WHO-ILAR arthritis core outcome set was reported in 81% of the studies. “The adoption of a core outcome set has the potential to increase consistency in outcomes measured across trials and ensure that trials are more likely to measure appropriate outcomes,” the authors concluded.
Since the initial 1992 meeting, OMERACT has broadened its focus from rheumatoid arthritis to 25 other musculoskeletal conditions.
For example, other OMERACT conferences have led to consensus on core sets of measures for osteoarthritis and osteoporosis, psoriasis/psoriatic arthritis, psychosocial measures, and a core set of data for cost-effectiveness evaluations.
‘Speed is a limitation’
OMERACT is a bottom-up volunteer organization. It doesn’t represent any official organization of any clinical society. “We’ve not asked to be adopted by the American College of Rheumatology, EULAR [European Alliance of Associations for Rheumatology], or other international organizations,” Dr. Tugwell said. It offers a chance for patients, users, and doers of research to work together to agree on rigorous criteria accepted by the approval agencies and take the necessary time to work things through.
This is not a fast process, usually taking 4-6 years to initiate and establish an outcome domain set, he emphasized. “It would be beneficial to do it faster if we had the resources to meet every year. The fact is we’re a volunteer organization that meets every 2 years.”
Speed is a limitation, he acknowledged, but it’s an acceptable trade-off for doing things correctly.
The group has faced other challenges during the COVID-19 pandemic, pivoting to a virtual format that had benefits and limitations.
In one respect, moving to a virtual meeting increased uptake in participation and voting, Dr. Tugwell said. Patient participants with severe rheumatoid arthritis no longer faced the challenges of travel. “On the other hand, we didn’t have the same opportunity to achieve common ground virtually,” he said. “Where there are strong disagreements, I’m a great believer that people need to know one another. There needs to be relationship building.”
OMERACT’s emerging leader program has been a cornerstone of its in-person meetings, engaging young rheumatologists to interact with some of the leaders of outcome measurement. The virtual format dampened this process somewhat, eliminating those important “café chats” between the stakeholders.
The hope is to bring people face-to-face once more at the next meeting in May 2023. The agenda will focus on relationship building, identifying controversial areas, and bringing younger people to develop relationships, Dr. Tugwell said. OMERACT will retain a virtual option for the worldwide voting, “which will allow for more buy-in from so many more people,” he added.
A consensus on pain
The onus of developing outcome measures that move with the times is sometimes too great for one group to manage. In 2018, OMERACT became a part of the Red Hat Group (RHG), an organization conceived at the COMET (Core Outcome Measures in Effectiveness Trials) VII meeting in Amsterdam.
RHG aims to improve the choice of outcomes in health research. It includes eight groups: COMET; OMERACT; the Cochrane Skin Core Outcome Set Initiative; Grading of Recommendations, Assessment, Development and Evaluations; Center for Medical Technology Policy; COnsensus-based Standards for the selection of health Measurement Instruments; Clinical Data Interchange Standards Consortium; and Standardized Outcomes in Nephrology.
The collaboration between groups offers a “very interesting interface between consensus building as well as hard evidence,” Dr. Tugwell said. The focus goes beyond rheumatology to other clinical areas of common interest, exploring how one classifies outcome domains in terms of symptoms, life impact, or death.
Pain is an important common denominator that the RHG has evaluated.
“We believe it’s too general. We’re trying to define pain across all Red Hat Groups because it’s clear that the research community has all these different scales for defining pain severity,” Dr. Tugwell said. “We have to find a way to make ruthless decisions and rules for doing it. And of course, it has to be transparent.”
Looking ahead
As part of its ongoing work, OMERACT is evaluating the robustness of instruments that rheumatologists use as outcome measures in clinical trials, which can be a laborious process. The OMERACT Filter 2.0, part of the latest iteration of the handbook, offers strong guidance for researchers but needs a long-term strategy and key methodological support. “To that end, we set up a technical advisory group to help people in the instrument selection work and that remains an ongoing process,” OMERACT leaders said in their joint statement.
OMERACT is looking at opportunities to create benchmark processes for developing core sets outside of rheumatology and a methodology around outcome measures such as contextual factors, composites, and surrogates.
It will also be taking a step back to solicit opinions from the approval agencies represented by the OMERACT membership on the OMERACT handbook.
The goal is to make sure the handbook aligns with everyone else’s approval and labeling requirements.
OMERACT’s patient participants bring important perspectives
OMERACT over the years has sought to become a more patient-centered group. Patients have been involved in OMERACT activities since its sixth meeting, forming an independent, yet integrated, group within the network. They have their own steering committee and produced and helped to update a glossary for OMERACT patients and professionals.
Catherine (McGowan) Hofstetter, who was diagnosed with rheumatoid arthritis 30 years ago, chairs OMERACT’s Patient Research Partners Support Team. In a Q&A, she discussed the importance of patient voices and OMERACT’s plans to further educate and include patients in the dialogue on outcomes.
Question: Have patients always been a part of OMERACT meetings?
Answer: Patients have been involved with OMERACT since 2002. The patient voice adds relevance to all the work that OMERACT does. You can’t begin to talk about outcomes unless there is a patient at the table with lived experience.
Q: Can you cite a few examples of how the patient voice enriches the conversation on outcomes research?
A: Outcomes and priorities that are important to patients are often completely different than those of the clinician. For instance, a work outcome is important to someone who doesn’t have any medical insurance or disability insurance, so that you can ensure that there is food on the table and a roof over your head. Or it may be important to someone because the employment provides medical and disability insurance to provide security for them and their family. These are two different perspectives on work and therefore work priorities and outcomes.
Q: What have been some of the challenges of getting patients to participate?
A: Training patients is one challenge. OMERACT’s work has a very steep learning curve, and while the basics are the same between the groups in terms of looking at what we measure and how we measure it, the nuances of different working groups require a lot of time and energy to be comfortable enough with the work, and then be confident enough to bring your perspective and lived experience to the table. It’s also a very accomplished group, which can be quite intimidating. Self-disclosure is a very personal and intimate undertaking that requires patience, compassion, and respect.
Q: Are there any plans to enhance patient engagement?
A: When we had OMERACT 2020 it was a virtual conference that took place over about 6 months. We had far more patient research partners [PRPs] participate than we have ever had at any OMERACT face-to-face meeting. There is a desire and passion on the part of patients to lend their voices to the work. The working groups meet virtually throughout the year to advance their agendas, and PRPs are a part of each of the working groups.
Hopefully, we can start working toward including more voices at the conferences by enabling a hybrid model. The PRP Support Team will begin engaging patients this fall with education, mentoring, and team-building exercises so by the time we meet in person in May 2023, they will have enough background knowledge and information to give them the confidence that will enhance their experience at the face-to-face meeting.
We also need to ensure that those patients who want to stay engaged can. This means that the education and training should continue long after the face-to-face meeting is over. We need to build capacity in the PRP group and look to succession planning and be a resource to working groups struggling to find PRPs to work with them on a longer-term basis.
Clinical research in rheumatology was suffering from an identity crisis of sorts 40 years ago. A lack of consensus across continents resulted in differing views about clinical outcome measures and judgments about treatments.
Patients were not allowed to be the generating source of a clinical outcome, according to Peter Tugwell, MSc, MD. “The only outcomes that were acceptable were clinician assessments, blood tests, and imaging,” said Dr. Tugwell, professor of medicine, epidemiology, and public health at the University of Ottawa (Ont.) and a practicing rheumatologist at Ottawa Hospital.
Clinicians were coming to different conclusions about patient responses to treatment when managing rheumatoid arthritis in clinical practice.
OMERACT sought to address this lack of uniformity. This international group, formed in 1992, leverages stakeholder groups to improve outcome measurement in rheumatology endpoints through a consensus-building, data-driven format.
It was originally known as “Outcome Measures in Rheumatoid Arthritis Clinical Trials,” but its leaders have since broadened its scope to “Outcome Measures in Rheumatology.” Over the years, it has evolved into an international network that assesses measurement across a wide variety of intervention studies. Now 30 years old, the network spans 40 active working groups and has influenced work in patient outcomes across 500 peer-reviewed publications.
The network meets every 2 years to address what is always a challenging agenda, said Dr. Tugwell, one of its founding members and chair. “There’s lots of strong opinions.” Participating in the discussions are individuals from all stages of seniority in rheumatology and clinical epidemiology, patient research partners, industry, approval agencies, and many countries who are committed to the spirit of OMERACT.
“The secret to our success has been getting world leaders to come together and have those discussions, work them through, and identify common ground in such a way that the approval agencies accept these outcome measures in clinical trials,” he added.
“My impression was the founders perceived a problem in the early 1990s and devised a consensus method in an attempt to quantify clinical parameters to define disease activity in rheumatoid arthritis – an important first step to do clinical trials and allow comparisons between them,” said Patricia Woo, CBE, FMedSci, FRCP, emeritus professor of pediatric rheumatology and previous head of the Centre for Paediatric and Adolescent Rheumatology at UCL, London. At that time, even disease definitions varied between the United States and Europe and other parts of the world, said Dr. Woo, who is not a part of OMERACT. “This was especially true for pediatric rheumatology.”
Fusing the continental divide
OMERACT arose from a need to streamline clinical outcome measures in rheumatology. Research papers during the 1980s demonstrated a lack of coherence in managing patients with rheumatoid arthritis in routine practice. In addition, the measures used to define clinical endpoints in clinical trials operated in silos – they were either too specific to a certain trial, overlapped with other concepts, or didn’t reflect changes in treatment.
Approval agencies in Europe and North America were approving only outcomes measures developed by their respective researchers. This was also true of patients they tested on. “This seemed crazy,” Dr. Tugwell said.
Dr. Tugwell was involved in the Cochrane collaboration, which conducts systematic reviews of best evidence across the world that assesses the magnitude of benefits versus harms.
To achieve this goal, “you need to pull studies from around the world,” he said. Maarten Boers, MD, PhD, a rheumatologist (and later professor of clinical epidemiology at Amsterdam University Medical Center) from the Netherlands, spent a year in Ontario, Canada, to train as a clinical epidemiologist. Together, Dr. Tugwell and Dr. Boers began discussing options to develop more streamlined outcome measures.
They initiated the first OMERACT conference in Maastricht, the Netherlands, in 1992. The Food and Drug Administration and European Medicines Agency participated, along with leaders of outcomes measurement in Europe and in North America.
Discussions centered on methods to develop outcomes in a meaningful fashion. During the first meeting, North American and European approval agencies agreed to accept each other’s studies and endpoints and patient reported outcomes.
Agreement was achieved on a preliminary set of outcome domains and measures that later became known as the WHO-ILAR (World Health Organization–International League of Associations for Rheumatology) core set. The set included seven outcome domains: tender joints, swollen joints, pain, physician global assessment, patient global assessment, physical disability, and acute phase reactants, and one additional outcome domain for studies lasting 1 year or more: radiographs of the joints.
“A proactive program was planned to test not only the validity of these endpoints, but also the methods for their measurement. This was the start of a continuing process,” OMERACT members said in a joint statement for this article. Meetings have since taken place every 2 years.
OMERACT accomplishments
OMERACT now requires buy-in from four continents: Asia, Australia, Europe, and North America.
Its leaders have developed an explicit process for gaining endorsement of core outcome domains and instrument measurement sets. To fully capture the possibilities of “what to measure,” i.e., “measurable aspects of health conditions,” OMERACT has developed a framework of concepts, core areas, and outcome domains. The key concepts are pathophysiology (with a core area termed “manifestations/abnormalities”) and impact (with core areas of “death/lifespan,” and “life impact,” and the optional area of “societal/resource use”). An outcome domain defines an element of a core area to measure the effects of a treatment, such as blood markers, pain intensity, physical function, or emotional well-being.
A core outcome domain set is developed by agreeing to at least one outcome domain within one of the three core areas. Subsequently, a core outcome measurement set is developed by agreeing to at least one applicable measurement instrument for each core outcome domain. This requires documentation of validity, summarized under three metrics: truth, discrimination, and feasibility.
OMERACT’s handbook provides tutelage on establishing and implementing core outcomes, and several workbooks offer guidance on developing core outcome domain sets, selecting instruments for core outcome measurement sets, and OMERACT methodology.
All this work has led to widespread adoption.
Approval agencies have accepted OMERACT’s filter and methods advances, which have been adopted by many research groups in rheumatology and among nonrheumatology research groups. Organizations such as the U.S. National Institutes of Health’s National Institute of Neurological Disorders and Stroke have sought its advice.
Its core outcomes have been adopted and used for approval in the great majority of studies on rheumatoid arthritis, Dr. Tugwell said.
Several BMJ articles underscore the influence and uptake of OMERACT’s core outcome set. One 2017 paper, which analyzed 273 randomized trials of rheumatoid arthritis drug treatments on ClinicalTrials.gov, found that the WHO-ILAR arthritis core outcome set was reported in 81% of the studies. “The adoption of a core outcome set has the potential to increase consistency in outcomes measured across trials and ensure that trials are more likely to measure appropriate outcomes,” the authors concluded.
Since the initial 1992 meeting, OMERACT has broadened its focus from rheumatoid arthritis to 25 other musculoskeletal conditions.
For example, other OMERACT conferences have led to consensus on core sets of measures for osteoarthritis and osteoporosis, psoriasis/psoriatic arthritis, psychosocial measures, and a core set of data for cost-effectiveness evaluations.
‘Speed is a limitation’
OMERACT is a bottom-up volunteer organization. It doesn’t represent any official organization of any clinical society. “We’ve not asked to be adopted by the American College of Rheumatology, EULAR [European Alliance of Associations for Rheumatology], or other international organizations,” Dr. Tugwell said. It offers a chance for patients, users, and doers of research to work together to agree on rigorous criteria accepted by the approval agencies and take the necessary time to work things through.
This is not a fast process, usually taking 4-6 years to initiate and establish an outcome domain set, he emphasized. “It would be beneficial to do it faster if we had the resources to meet every year. The fact is we’re a volunteer organization that meets every 2 years.”
Speed is a limitation, he acknowledged, but it’s an acceptable trade-off for doing things correctly.
The group has faced other challenges during the COVID-19 pandemic, pivoting to a virtual format that had benefits and limitations.
In one respect, moving to a virtual meeting increased uptake in participation and voting, Dr. Tugwell said. Patient participants with severe rheumatoid arthritis no longer faced the challenges of travel. “On the other hand, we didn’t have the same opportunity to achieve common ground virtually,” he said. “Where there are strong disagreements, I’m a great believer that people need to know one another. There needs to be relationship building.”
OMERACT’s emerging leader program has been a cornerstone of its in-person meetings, engaging young rheumatologists to interact with some of the leaders of outcome measurement. The virtual format dampened this process somewhat, eliminating those important “café chats” between the stakeholders.
The hope is to bring people face-to-face once more at the next meeting in May 2023. The agenda will focus on relationship building, identifying controversial areas, and bringing younger people to develop relationships, Dr. Tugwell said. OMERACT will retain a virtual option for the worldwide voting, “which will allow for more buy-in from so many more people,” he added.
A consensus on pain
The onus of developing outcome measures that move with the times is sometimes too great for one group to manage. In 2018, OMERACT became a part of the Red Hat Group (RHG), an organization conceived at the COMET (Core Outcome Measures in Effectiveness Trials) VII meeting in Amsterdam.
RHG aims to improve the choice of outcomes in health research. It includes eight groups: COMET; OMERACT; the Cochrane Skin Core Outcome Set Initiative; Grading of Recommendations, Assessment, Development and Evaluations; Center for Medical Technology Policy; COnsensus-based Standards for the selection of health Measurement Instruments; Clinical Data Interchange Standards Consortium; and Standardized Outcomes in Nephrology.
The collaboration between groups offers a “very interesting interface between consensus building as well as hard evidence,” Dr. Tugwell said. The focus goes beyond rheumatology to other clinical areas of common interest, exploring how one classifies outcome domains in terms of symptoms, life impact, or death.
Pain is an important common denominator that the RHG has evaluated.
“We believe it’s too general. We’re trying to define pain across all Red Hat Groups because it’s clear that the research community has all these different scales for defining pain severity,” Dr. Tugwell said. “We have to find a way to make ruthless decisions and rules for doing it. And of course, it has to be transparent.”
Looking ahead
As part of its ongoing work, OMERACT is evaluating the robustness of instruments that rheumatologists use as outcome measures in clinical trials, which can be a laborious process. The OMERACT Filter 2.0, part of the latest iteration of the handbook, offers strong guidance for researchers but needs a long-term strategy and key methodological support. “To that end, we set up a technical advisory group to help people in the instrument selection work and that remains an ongoing process,” OMERACT leaders said in their joint statement.
OMERACT is looking at opportunities to create benchmark processes for developing core sets outside of rheumatology and a methodology around outcome measures such as contextual factors, composites, and surrogates.
It will also be taking a step back to solicit opinions from the approval agencies represented by the OMERACT membership on the OMERACT handbook.
The goal is to make sure the handbook aligns with everyone else’s approval and labeling requirements.
OMERACT’s patient participants bring important perspectives
OMERACT over the years has sought to become a more patient-centered group. Patients have been involved in OMERACT activities since its sixth meeting, forming an independent, yet integrated, group within the network. They have their own steering committee and produced and helped to update a glossary for OMERACT patients and professionals.
Catherine (McGowan) Hofstetter, who was diagnosed with rheumatoid arthritis 30 years ago, chairs OMERACT’s Patient Research Partners Support Team. In a Q&A, she discussed the importance of patient voices and OMERACT’s plans to further educate and include patients in the dialogue on outcomes.
Question: Have patients always been a part of OMERACT meetings?
Answer: Patients have been involved with OMERACT since 2002. The patient voice adds relevance to all the work that OMERACT does. You can’t begin to talk about outcomes unless there is a patient at the table with lived experience.
Q: Can you cite a few examples of how the patient voice enriches the conversation on outcomes research?
A: Outcomes and priorities that are important to patients are often completely different than those of the clinician. For instance, a work outcome is important to someone who doesn’t have any medical insurance or disability insurance, so that you can ensure that there is food on the table and a roof over your head. Or it may be important to someone because the employment provides medical and disability insurance to provide security for them and their family. These are two different perspectives on work and therefore work priorities and outcomes.
Q: What have been some of the challenges of getting patients to participate?
A: Training patients is one challenge. OMERACT’s work has a very steep learning curve, and while the basics are the same between the groups in terms of looking at what we measure and how we measure it, the nuances of different working groups require a lot of time and energy to be comfortable enough with the work, and then be confident enough to bring your perspective and lived experience to the table. It’s also a very accomplished group, which can be quite intimidating. Self-disclosure is a very personal and intimate undertaking that requires patience, compassion, and respect.
Q: Are there any plans to enhance patient engagement?
A: When we had OMERACT 2020 it was a virtual conference that took place over about 6 months. We had far more patient research partners [PRPs] participate than we have ever had at any OMERACT face-to-face meeting. There is a desire and passion on the part of patients to lend their voices to the work. The working groups meet virtually throughout the year to advance their agendas, and PRPs are a part of each of the working groups.
Hopefully, we can start working toward including more voices at the conferences by enabling a hybrid model. The PRP Support Team will begin engaging patients this fall with education, mentoring, and team-building exercises so by the time we meet in person in May 2023, they will have enough background knowledge and information to give them the confidence that will enhance their experience at the face-to-face meeting.
We also need to ensure that those patients who want to stay engaged can. This means that the education and training should continue long after the face-to-face meeting is over. We need to build capacity in the PRP group and look to succession planning and be a resource to working groups struggling to find PRPs to work with them on a longer-term basis.
NSAIDs linked to heart failure risk in diabetes
People with diabetes who take nonsteroidal anti-inflammatory drugs even on a short-term basis may have about a 50% greater risk of developing heart failure, according to results from a national registry study of more than 330,000 patients to be presented at the annual congress of the European Society of Cardiology.
“According to data from this study, even short-term NSAID use – within 28 days – in patients with type 2 diabetes mellitus are associated with an increased risk of first-time heart failure hospitalization,” lead author Anders Holt, MD, said in an interview.
“Further, it seems that patients above 79 years of age or with elevated hemoglobin A1c levels, along with new users of NSAIDs, are particularly susceptible.” He added that no such association was found in patients below age 65 years with normal A1c levels.
Dr. Holt has a dual appointment as a cardiologist at Copenhagen University and Herlev-Gentofte Hospital in Hellerup, Denmark, and the department of epidemiology and biostatistics at the University of Auckland (New Zealand). Jarl Emmanuel Strange, MD, PhD, a fellow at Copenhagen University, is to present the abstract on Aug. 26.
“This is quite an important observation given that, unfortunately, NSAIDs continue to be prescribed rather easily to people with diabetes and these agents do have risk,” said Rodica Busui, MD, PhD, codirector of the JDRF Center of Excellence at the University of Michigan, Ann Arbor, and president-elect for medicine and science of the American Diabetes Association. Dr. Busui is also lead author of an ADA/American College of Cardiology consensus report on heart failure in diabetes.
The study hypothesized that fluid retention “is a known but underappreciated side effect” of NSAID use and that short-term NSAID use could lead to heart failure in patients with type 2 diabetes, which has been linked to subclinical cardiomyopathy and kidney dysfunction.
“According to this study and particularly the subgroups analyses, it seems that incident heart failure associated with short-term NSAID use could be more than ‘just fluid overload,’ ” Dr. Holt said. “Further investigations into the specific mechanisms causing these associations are warranted.”
The study identified 331,189 patients with type 2 diabetes in nationwide Danish registries from 1998 to 2018. Median age was 62 years, and 23,308 (7%) were hospitalized with heart failure during follow-up, Dr. Holt said. Of them, 16% claimed at least one NSAID prescription within 2 years and 3% claimed they had at least three prescriptions.
Study follow-up started 120 days after the first-time type 2 diabetes diagnosis and focused on patients who had no previous diagnosis of heart failure or rheumatologic disease. The investigators reported on patients who had one, two, three or four prescriptions for NSAID within a year of starting follow-up.
The study used a case-crossover design, which, the abstract stated, “uses each individual as his or her own control making it suitable to study the effect of short-term exposure on immediate events while mitigating unmeasured confounding.”
Dr. Holt noted that short-term NSAID use was linked to increased risk of heart failure hospitalization (odds ratio, 1.43; 95% confidence interval, 1.27-1.63). The investigators identified even greater risks in three subgroups: age of at least 80 years (OR, 1.78; 95% CI, 1.39-2.28), elevated A1c levels treated with one or less antidiabetic medication (OR 1.68; 95% CI, 1-2.88), and patients without previous NSAID use (OR, 2.71; 95% CI, 1.78-4.23).
In the cohort, celecoxib and naproxen were rarely used (0.4 and 0.9%, respectively), while 3.3% of patients took diclofenac or 12.2% ibuprofen. The latter two NSAIDs had ORs of 1.48 and 1.46, respectively, for hospitalization for new-onset heart failure using 28-day exposure windows (95% CI for both, 1.1-2 and 1.26-1.69). No increased risk emerged for celecoxib or naproxen.
“High age and A1c levels and being a new user were tied to the strongest associations, along with known use of RASi [renin-angiotensin system inhibitors] and diuretics,” Dr. Holt said. “On the contrary, it seemed safe – from our data – to prescribe short-term NSAIDs for patients below 65 years of age and patients with normal A1c levels.
“Interestingly,” he added, “subclinical structural heart disease among patients with type 2 diabetes could play an important role.”
The findings are noteworthy, Dr. Busui said. “Although there are some limitations with the study design in general when one looks at data extracted from registers, the very large sample size and the fact that the Danish national register captures data in a standardized fashion does make the findings very relevant, especially now that we have confirmed that heart failure is the most prevalent cardiovascular complication in people with diabetes, as we have highlighted in the most recent ADA/ACC consensus on heart failure in diabetes.”
The study received funding from the Danish Heart Foundation and a number of private foundations. Dr. Holt and colleagues have no disclosures. Dr. Busui disclosed relationships with AstraZeneca, Boehringer Ingelheim–Lilly Alliance, Novo Nordisk, Averitas Pharma, Nevro, Regenacy Pharmaceuticals and Roche Diagnostics.
People with diabetes who take nonsteroidal anti-inflammatory drugs even on a short-term basis may have about a 50% greater risk of developing heart failure, according to results from a national registry study of more than 330,000 patients to be presented at the annual congress of the European Society of Cardiology.
“According to data from this study, even short-term NSAID use – within 28 days – in patients with type 2 diabetes mellitus are associated with an increased risk of first-time heart failure hospitalization,” lead author Anders Holt, MD, said in an interview.
“Further, it seems that patients above 79 years of age or with elevated hemoglobin A1c levels, along with new users of NSAIDs, are particularly susceptible.” He added that no such association was found in patients below age 65 years with normal A1c levels.
Dr. Holt has a dual appointment as a cardiologist at Copenhagen University and Herlev-Gentofte Hospital in Hellerup, Denmark, and the department of epidemiology and biostatistics at the University of Auckland (New Zealand). Jarl Emmanuel Strange, MD, PhD, a fellow at Copenhagen University, is to present the abstract on Aug. 26.
“This is quite an important observation given that, unfortunately, NSAIDs continue to be prescribed rather easily to people with diabetes and these agents do have risk,” said Rodica Busui, MD, PhD, codirector of the JDRF Center of Excellence at the University of Michigan, Ann Arbor, and president-elect for medicine and science of the American Diabetes Association. Dr. Busui is also lead author of an ADA/American College of Cardiology consensus report on heart failure in diabetes.
The study hypothesized that fluid retention “is a known but underappreciated side effect” of NSAID use and that short-term NSAID use could lead to heart failure in patients with type 2 diabetes, which has been linked to subclinical cardiomyopathy and kidney dysfunction.
“According to this study and particularly the subgroups analyses, it seems that incident heart failure associated with short-term NSAID use could be more than ‘just fluid overload,’ ” Dr. Holt said. “Further investigations into the specific mechanisms causing these associations are warranted.”
The study identified 331,189 patients with type 2 diabetes in nationwide Danish registries from 1998 to 2018. Median age was 62 years, and 23,308 (7%) were hospitalized with heart failure during follow-up, Dr. Holt said. Of them, 16% claimed at least one NSAID prescription within 2 years and 3% claimed they had at least three prescriptions.
Study follow-up started 120 days after the first-time type 2 diabetes diagnosis and focused on patients who had no previous diagnosis of heart failure or rheumatologic disease. The investigators reported on patients who had one, two, three or four prescriptions for NSAID within a year of starting follow-up.
The study used a case-crossover design, which, the abstract stated, “uses each individual as his or her own control making it suitable to study the effect of short-term exposure on immediate events while mitigating unmeasured confounding.”
Dr. Holt noted that short-term NSAID use was linked to increased risk of heart failure hospitalization (odds ratio, 1.43; 95% confidence interval, 1.27-1.63). The investigators identified even greater risks in three subgroups: age of at least 80 years (OR, 1.78; 95% CI, 1.39-2.28), elevated A1c levels treated with one or less antidiabetic medication (OR 1.68; 95% CI, 1-2.88), and patients without previous NSAID use (OR, 2.71; 95% CI, 1.78-4.23).
In the cohort, celecoxib and naproxen were rarely used (0.4 and 0.9%, respectively), while 3.3% of patients took diclofenac or 12.2% ibuprofen. The latter two NSAIDs had ORs of 1.48 and 1.46, respectively, for hospitalization for new-onset heart failure using 28-day exposure windows (95% CI for both, 1.1-2 and 1.26-1.69). No increased risk emerged for celecoxib or naproxen.
“High age and A1c levels and being a new user were tied to the strongest associations, along with known use of RASi [renin-angiotensin system inhibitors] and diuretics,” Dr. Holt said. “On the contrary, it seemed safe – from our data – to prescribe short-term NSAIDs for patients below 65 years of age and patients with normal A1c levels.
“Interestingly,” he added, “subclinical structural heart disease among patients with type 2 diabetes could play an important role.”
The findings are noteworthy, Dr. Busui said. “Although there are some limitations with the study design in general when one looks at data extracted from registers, the very large sample size and the fact that the Danish national register captures data in a standardized fashion does make the findings very relevant, especially now that we have confirmed that heart failure is the most prevalent cardiovascular complication in people with diabetes, as we have highlighted in the most recent ADA/ACC consensus on heart failure in diabetes.”
The study received funding from the Danish Heart Foundation and a number of private foundations. Dr. Holt and colleagues have no disclosures. Dr. Busui disclosed relationships with AstraZeneca, Boehringer Ingelheim–Lilly Alliance, Novo Nordisk, Averitas Pharma, Nevro, Regenacy Pharmaceuticals and Roche Diagnostics.
People with diabetes who take nonsteroidal anti-inflammatory drugs even on a short-term basis may have about a 50% greater risk of developing heart failure, according to results from a national registry study of more than 330,000 patients to be presented at the annual congress of the European Society of Cardiology.
“According to data from this study, even short-term NSAID use – within 28 days – in patients with type 2 diabetes mellitus are associated with an increased risk of first-time heart failure hospitalization,” lead author Anders Holt, MD, said in an interview.
“Further, it seems that patients above 79 years of age or with elevated hemoglobin A1c levels, along with new users of NSAIDs, are particularly susceptible.” He added that no such association was found in patients below age 65 years with normal A1c levels.
Dr. Holt has a dual appointment as a cardiologist at Copenhagen University and Herlev-Gentofte Hospital in Hellerup, Denmark, and the department of epidemiology and biostatistics at the University of Auckland (New Zealand). Jarl Emmanuel Strange, MD, PhD, a fellow at Copenhagen University, is to present the abstract on Aug. 26.
“This is quite an important observation given that, unfortunately, NSAIDs continue to be prescribed rather easily to people with diabetes and these agents do have risk,” said Rodica Busui, MD, PhD, codirector of the JDRF Center of Excellence at the University of Michigan, Ann Arbor, and president-elect for medicine and science of the American Diabetes Association. Dr. Busui is also lead author of an ADA/American College of Cardiology consensus report on heart failure in diabetes.
The study hypothesized that fluid retention “is a known but underappreciated side effect” of NSAID use and that short-term NSAID use could lead to heart failure in patients with type 2 diabetes, which has been linked to subclinical cardiomyopathy and kidney dysfunction.
“According to this study and particularly the subgroups analyses, it seems that incident heart failure associated with short-term NSAID use could be more than ‘just fluid overload,’ ” Dr. Holt said. “Further investigations into the specific mechanisms causing these associations are warranted.”
The study identified 331,189 patients with type 2 diabetes in nationwide Danish registries from 1998 to 2018. Median age was 62 years, and 23,308 (7%) were hospitalized with heart failure during follow-up, Dr. Holt said. Of them, 16% claimed at least one NSAID prescription within 2 years and 3% claimed they had at least three prescriptions.
Study follow-up started 120 days after the first-time type 2 diabetes diagnosis and focused on patients who had no previous diagnosis of heart failure or rheumatologic disease. The investigators reported on patients who had one, two, three or four prescriptions for NSAID within a year of starting follow-up.
The study used a case-crossover design, which, the abstract stated, “uses each individual as his or her own control making it suitable to study the effect of short-term exposure on immediate events while mitigating unmeasured confounding.”
Dr. Holt noted that short-term NSAID use was linked to increased risk of heart failure hospitalization (odds ratio, 1.43; 95% confidence interval, 1.27-1.63). The investigators identified even greater risks in three subgroups: age of at least 80 years (OR, 1.78; 95% CI, 1.39-2.28), elevated A1c levels treated with one or less antidiabetic medication (OR 1.68; 95% CI, 1-2.88), and patients without previous NSAID use (OR, 2.71; 95% CI, 1.78-4.23).
In the cohort, celecoxib and naproxen were rarely used (0.4 and 0.9%, respectively), while 3.3% of patients took diclofenac or 12.2% ibuprofen. The latter two NSAIDs had ORs of 1.48 and 1.46, respectively, for hospitalization for new-onset heart failure using 28-day exposure windows (95% CI for both, 1.1-2 and 1.26-1.69). No increased risk emerged for celecoxib or naproxen.
“High age and A1c levels and being a new user were tied to the strongest associations, along with known use of RASi [renin-angiotensin system inhibitors] and diuretics,” Dr. Holt said. “On the contrary, it seemed safe – from our data – to prescribe short-term NSAIDs for patients below 65 years of age and patients with normal A1c levels.
“Interestingly,” he added, “subclinical structural heart disease among patients with type 2 diabetes could play an important role.”
The findings are noteworthy, Dr. Busui said. “Although there are some limitations with the study design in general when one looks at data extracted from registers, the very large sample size and the fact that the Danish national register captures data in a standardized fashion does make the findings very relevant, especially now that we have confirmed that heart failure is the most prevalent cardiovascular complication in people with diabetes, as we have highlighted in the most recent ADA/ACC consensus on heart failure in diabetes.”
The study received funding from the Danish Heart Foundation and a number of private foundations. Dr. Holt and colleagues have no disclosures. Dr. Busui disclosed relationships with AstraZeneca, Boehringer Ingelheim–Lilly Alliance, Novo Nordisk, Averitas Pharma, Nevro, Regenacy Pharmaceuticals and Roche Diagnostics.
FROM ESC CONGRESS 2022