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For MD-IQ on Family Practice News, but a regular topic for Rheumatology News
Will the headache field embrace rofecoxib?
In June, the Concord, Mass.–based company Tremeau Pharmaceuticals announced that the Food and Drug Administration was letting it proceed with a phase 3 clinical trial to test rofecoxib, the once-bestselling painkiller known as Vioxx, in patients with migraine.
The anti-inflammatory drug, a cyclooxygenase-2 (COX-2) inhibitor, received its first FDA approval in 1999 and became widely prescribed for arthritis and acute pain. In 2004 it was withdrawn by its manufacturer, Merck, after being shown to raise the risk of cardiovascular events.
In clinical trials and in real-world epidemiological studies, rofecoxib was associated with elevated heart attack, stroke, and related deaths; one 2005 study estimated that it had been responsible for some 38,000 excess deaths in the United States before being withdrawn. In 2007 Merck, beset with allegations that it had suppressed and mischaracterized rofecoxib’s safety data, paid out nearly $5 billion to settle thousands of lawsuits filed by patients and their families.
, an indication for which it received an orphan drug designation in 2017 and the agency’s green light for trials in 2020.
Brad Sippy, Tremeau’s chief executive officer, said that his company chose the two indications in part because both patient populations have low cardiovascular risk. Migraine patients are generally younger than the arthritis populations formerly treated with rofecoxib and are unlikely to take the drug for more than a day or 2 at time, avoiding the risks associated with extended exposure.
A crowded market
The past several years have seen the emergence of a cornucopia of new migraine treatments, including monoclonal antibodies such as erenumab (Aimovig, Amgen), which help prevent attacks by blocking the vasodilator calcitonin gene-related peptide, or CGRP. In addition to the standard arsenal of triptans and nonsteroidal anti-inflammatory drugs for acute pain relief, migraine patients can now choose among serotonin-blocking agents such as lasmiditan (Reyvow, Eli Lilly), known as “ditans,” and small-molecule CGRP antagonists such as ubrogepant (Ubrelvy, Abbie), known as “gepants.” Some NSAIDs, including one COX inhibitor, have been formulated into rapidly absorbed powders or liquids for migraine.
Mr. Sippy said he sees a role for rofecoxib even in this crowded space. “Migraine as you know is a multimodal situation – few people say that only one drug works for them,” he said. “We think this is an option that would basically be like a high dose of ibuprofen,” but with less frequent dosing and lower gastrointestinal and platelet effects compared with ibuprofen and other NSAIDs.
An improved formulation
Rofecoxib “crosses the blood brain barrier very readily – better than other COX inhibitors on the market,” Mr. Sippy added. “It was well absorbed in its original formulation, and our product is even better absorbed than the original – we estimate it’s probably an hour quicker to [peak concentration].” In addition, he said, “our formulation is more efficient at delivering the drug so we don’t need as much active ingredient – our 17.5 milligrams gets you the same systemic exposure as 25 milligrams of the old product.”
A different mechanism of action
Neurologist Alan M. Rapoport, MD, editor-in-chief of Neurology Reviews and professor of neurology at the University of California, Los Angeles, said that he was “cautiously optimistic” that “if used correctly and not too frequently, [rofecoxib] will find its niche in migraine treatment.”
“Patients liked Vioxx,” said Dr. Rapoport, past president of the International Headache Society. Even people currently on prevention “need to have an acute care drug handy.” While some patients on monoclonal antibodies have had success with gepants for acute care, “these both target the same pathway. It’s always nice to have options with a different mechanism of action.”
One of the arguments Tremeau has cited for reintroducing rofecoxib has been an urgent need for alternatives to opioid painkillers. Indeed some analysts have linked the demise of Vioxx with a subsequent increase in opioid prescribing.
Dr. Rapoport noted that he never prescribes opioids or butalbital, a barbiturate, for migraine, and that most headache specialists avoid them in clinical practice. But in the emergency setting, he said, patients receive them all too frequently.
Mr. Sippy said that opioid prescribing, while not unknown in migraine, was a bigger problem in hemophilic arthropathy, the first indication his company has pursued for rofecoxib. People with hemophilia “have a kind of arthritis that would respond well to an anti-inflammatory drug but they can’t take NSAIDs due to bleeding risk. This is why so many end up on opioids. Rofecoxib, as a COX-2 inhibitor, doesn’t have any effect on platelet aggregation, which would make it another option.”
No unique risks at prescribed doses
The migraine indication originally started out narrower: Patients with both migraine and bleeding disorders. “But in talking with the FDA, they encouraged us to develop it for migraine,” Mr. Sippy said. The company is considering pursuing a third indication: menstrual pain co-occurring with migraine. Tremeau has not ruled out seeking an indication in patients with arthritis who cannot take other painkillers, whether opioids or NSAIDs.
Five years ago, when Tremeau first announced its plans to bring rofecoxib back – indeed the company was set up for that purpose and has only this and another COX-2 inhibitor in development – some experts warned that there is little to prevent the drug from being used off-label, whether in higher doses or for other diseases.
“That’s something else we’re seeking to solve in addition to going for younger populations,” said Mr. Sippy, who worked at Merck during the Vioxx crisis and later headed neurology at Sunovion before starting his own company.
“We’re going for the former middle dose as our high dose and now we know that you don’t want to take more than the prescribed amount. If it doesn’t work you get off it; you don’t want to dose-creep on it. That’s been a key insight: At the appropriate dose, this product has no unique risk relative to the drug class and potentially some unique benefits,” he said.
Risk versus benefit
Joseph Ross, MD, a health policy researcher at Yale University in New Haven, Conn., who in a 2018 editorial expressed concerns about rofecoxib’s revival, said in an email that he felt its use in migraine could be justified, with caveats.
During Vioxx’s original approval and time on the market, “there was a cardiovascular risk associated with use that was not being transparently and clearly reported to patients and clinicians,” Dr. Ross said.
“In terms of testing the product for use in patients with migraine – a population of generally younger patients at lower risk of cardiovascular disease – my only concern is that the risk is clearly communicated and that there is adequate postmarket safety surveillance,” he said. “If patients are making fully informed decisions, the potential benefit of the drug with respect to pain control may be worth the risks.”
Dr. Rapoport serves as an adviser for AbbVie, Amgen, Biohaven, Cala Health, Collegium Pharmaceutical, Satsuma, Teva, Theranica and Xoc; he is on the speakers bureau of AbbVie, Amgen, Biohaven, Impel, Lundbeck, and Teva. Dr. Ross disclosed research support from Johnson and Johnson, the Medical Device Innovation Consortium, and the Laura and John Arnold Foundation, along with government grants; he is also an expert witness in a lawsuit against Biogen.
In June, the Concord, Mass.–based company Tremeau Pharmaceuticals announced that the Food and Drug Administration was letting it proceed with a phase 3 clinical trial to test rofecoxib, the once-bestselling painkiller known as Vioxx, in patients with migraine.
The anti-inflammatory drug, a cyclooxygenase-2 (COX-2) inhibitor, received its first FDA approval in 1999 and became widely prescribed for arthritis and acute pain. In 2004 it was withdrawn by its manufacturer, Merck, after being shown to raise the risk of cardiovascular events.
In clinical trials and in real-world epidemiological studies, rofecoxib was associated with elevated heart attack, stroke, and related deaths; one 2005 study estimated that it had been responsible for some 38,000 excess deaths in the United States before being withdrawn. In 2007 Merck, beset with allegations that it had suppressed and mischaracterized rofecoxib’s safety data, paid out nearly $5 billion to settle thousands of lawsuits filed by patients and their families.
, an indication for which it received an orphan drug designation in 2017 and the agency’s green light for trials in 2020.
Brad Sippy, Tremeau’s chief executive officer, said that his company chose the two indications in part because both patient populations have low cardiovascular risk. Migraine patients are generally younger than the arthritis populations formerly treated with rofecoxib and are unlikely to take the drug for more than a day or 2 at time, avoiding the risks associated with extended exposure.
A crowded market
The past several years have seen the emergence of a cornucopia of new migraine treatments, including monoclonal antibodies such as erenumab (Aimovig, Amgen), which help prevent attacks by blocking the vasodilator calcitonin gene-related peptide, or CGRP. In addition to the standard arsenal of triptans and nonsteroidal anti-inflammatory drugs for acute pain relief, migraine patients can now choose among serotonin-blocking agents such as lasmiditan (Reyvow, Eli Lilly), known as “ditans,” and small-molecule CGRP antagonists such as ubrogepant (Ubrelvy, Abbie), known as “gepants.” Some NSAIDs, including one COX inhibitor, have been formulated into rapidly absorbed powders or liquids for migraine.
Mr. Sippy said he sees a role for rofecoxib even in this crowded space. “Migraine as you know is a multimodal situation – few people say that only one drug works for them,” he said. “We think this is an option that would basically be like a high dose of ibuprofen,” but with less frequent dosing and lower gastrointestinal and platelet effects compared with ibuprofen and other NSAIDs.
An improved formulation
Rofecoxib “crosses the blood brain barrier very readily – better than other COX inhibitors on the market,” Mr. Sippy added. “It was well absorbed in its original formulation, and our product is even better absorbed than the original – we estimate it’s probably an hour quicker to [peak concentration].” In addition, he said, “our formulation is more efficient at delivering the drug so we don’t need as much active ingredient – our 17.5 milligrams gets you the same systemic exposure as 25 milligrams of the old product.”
A different mechanism of action
Neurologist Alan M. Rapoport, MD, editor-in-chief of Neurology Reviews and professor of neurology at the University of California, Los Angeles, said that he was “cautiously optimistic” that “if used correctly and not too frequently, [rofecoxib] will find its niche in migraine treatment.”
“Patients liked Vioxx,” said Dr. Rapoport, past president of the International Headache Society. Even people currently on prevention “need to have an acute care drug handy.” While some patients on monoclonal antibodies have had success with gepants for acute care, “these both target the same pathway. It’s always nice to have options with a different mechanism of action.”
One of the arguments Tremeau has cited for reintroducing rofecoxib has been an urgent need for alternatives to opioid painkillers. Indeed some analysts have linked the demise of Vioxx with a subsequent increase in opioid prescribing.
Dr. Rapoport noted that he never prescribes opioids or butalbital, a barbiturate, for migraine, and that most headache specialists avoid them in clinical practice. But in the emergency setting, he said, patients receive them all too frequently.
Mr. Sippy said that opioid prescribing, while not unknown in migraine, was a bigger problem in hemophilic arthropathy, the first indication his company has pursued for rofecoxib. People with hemophilia “have a kind of arthritis that would respond well to an anti-inflammatory drug but they can’t take NSAIDs due to bleeding risk. This is why so many end up on opioids. Rofecoxib, as a COX-2 inhibitor, doesn’t have any effect on platelet aggregation, which would make it another option.”
No unique risks at prescribed doses
The migraine indication originally started out narrower: Patients with both migraine and bleeding disorders. “But in talking with the FDA, they encouraged us to develop it for migraine,” Mr. Sippy said. The company is considering pursuing a third indication: menstrual pain co-occurring with migraine. Tremeau has not ruled out seeking an indication in patients with arthritis who cannot take other painkillers, whether opioids or NSAIDs.
Five years ago, when Tremeau first announced its plans to bring rofecoxib back – indeed the company was set up for that purpose and has only this and another COX-2 inhibitor in development – some experts warned that there is little to prevent the drug from being used off-label, whether in higher doses or for other diseases.
“That’s something else we’re seeking to solve in addition to going for younger populations,” said Mr. Sippy, who worked at Merck during the Vioxx crisis and later headed neurology at Sunovion before starting his own company.
“We’re going for the former middle dose as our high dose and now we know that you don’t want to take more than the prescribed amount. If it doesn’t work you get off it; you don’t want to dose-creep on it. That’s been a key insight: At the appropriate dose, this product has no unique risk relative to the drug class and potentially some unique benefits,” he said.
Risk versus benefit
Joseph Ross, MD, a health policy researcher at Yale University in New Haven, Conn., who in a 2018 editorial expressed concerns about rofecoxib’s revival, said in an email that he felt its use in migraine could be justified, with caveats.
During Vioxx’s original approval and time on the market, “there was a cardiovascular risk associated with use that was not being transparently and clearly reported to patients and clinicians,” Dr. Ross said.
“In terms of testing the product for use in patients with migraine – a population of generally younger patients at lower risk of cardiovascular disease – my only concern is that the risk is clearly communicated and that there is adequate postmarket safety surveillance,” he said. “If patients are making fully informed decisions, the potential benefit of the drug with respect to pain control may be worth the risks.”
Dr. Rapoport serves as an adviser for AbbVie, Amgen, Biohaven, Cala Health, Collegium Pharmaceutical, Satsuma, Teva, Theranica and Xoc; he is on the speakers bureau of AbbVie, Amgen, Biohaven, Impel, Lundbeck, and Teva. Dr. Ross disclosed research support from Johnson and Johnson, the Medical Device Innovation Consortium, and the Laura and John Arnold Foundation, along with government grants; he is also an expert witness in a lawsuit against Biogen.
In June, the Concord, Mass.–based company Tremeau Pharmaceuticals announced that the Food and Drug Administration was letting it proceed with a phase 3 clinical trial to test rofecoxib, the once-bestselling painkiller known as Vioxx, in patients with migraine.
The anti-inflammatory drug, a cyclooxygenase-2 (COX-2) inhibitor, received its first FDA approval in 1999 and became widely prescribed for arthritis and acute pain. In 2004 it was withdrawn by its manufacturer, Merck, after being shown to raise the risk of cardiovascular events.
In clinical trials and in real-world epidemiological studies, rofecoxib was associated with elevated heart attack, stroke, and related deaths; one 2005 study estimated that it had been responsible for some 38,000 excess deaths in the United States before being withdrawn. In 2007 Merck, beset with allegations that it had suppressed and mischaracterized rofecoxib’s safety data, paid out nearly $5 billion to settle thousands of lawsuits filed by patients and their families.
, an indication for which it received an orphan drug designation in 2017 and the agency’s green light for trials in 2020.
Brad Sippy, Tremeau’s chief executive officer, said that his company chose the two indications in part because both patient populations have low cardiovascular risk. Migraine patients are generally younger than the arthritis populations formerly treated with rofecoxib and are unlikely to take the drug for more than a day or 2 at time, avoiding the risks associated with extended exposure.
A crowded market
The past several years have seen the emergence of a cornucopia of new migraine treatments, including monoclonal antibodies such as erenumab (Aimovig, Amgen), which help prevent attacks by blocking the vasodilator calcitonin gene-related peptide, or CGRP. In addition to the standard arsenal of triptans and nonsteroidal anti-inflammatory drugs for acute pain relief, migraine patients can now choose among serotonin-blocking agents such as lasmiditan (Reyvow, Eli Lilly), known as “ditans,” and small-molecule CGRP antagonists such as ubrogepant (Ubrelvy, Abbie), known as “gepants.” Some NSAIDs, including one COX inhibitor, have been formulated into rapidly absorbed powders or liquids for migraine.
Mr. Sippy said he sees a role for rofecoxib even in this crowded space. “Migraine as you know is a multimodal situation – few people say that only one drug works for them,” he said. “We think this is an option that would basically be like a high dose of ibuprofen,” but with less frequent dosing and lower gastrointestinal and platelet effects compared with ibuprofen and other NSAIDs.
An improved formulation
Rofecoxib “crosses the blood brain barrier very readily – better than other COX inhibitors on the market,” Mr. Sippy added. “It was well absorbed in its original formulation, and our product is even better absorbed than the original – we estimate it’s probably an hour quicker to [peak concentration].” In addition, he said, “our formulation is more efficient at delivering the drug so we don’t need as much active ingredient – our 17.5 milligrams gets you the same systemic exposure as 25 milligrams of the old product.”
A different mechanism of action
Neurologist Alan M. Rapoport, MD, editor-in-chief of Neurology Reviews and professor of neurology at the University of California, Los Angeles, said that he was “cautiously optimistic” that “if used correctly and not too frequently, [rofecoxib] will find its niche in migraine treatment.”
“Patients liked Vioxx,” said Dr. Rapoport, past president of the International Headache Society. Even people currently on prevention “need to have an acute care drug handy.” While some patients on monoclonal antibodies have had success with gepants for acute care, “these both target the same pathway. It’s always nice to have options with a different mechanism of action.”
One of the arguments Tremeau has cited for reintroducing rofecoxib has been an urgent need for alternatives to opioid painkillers. Indeed some analysts have linked the demise of Vioxx with a subsequent increase in opioid prescribing.
Dr. Rapoport noted that he never prescribes opioids or butalbital, a barbiturate, for migraine, and that most headache specialists avoid them in clinical practice. But in the emergency setting, he said, patients receive them all too frequently.
Mr. Sippy said that opioid prescribing, while not unknown in migraine, was a bigger problem in hemophilic arthropathy, the first indication his company has pursued for rofecoxib. People with hemophilia “have a kind of arthritis that would respond well to an anti-inflammatory drug but they can’t take NSAIDs due to bleeding risk. This is why so many end up on opioids. Rofecoxib, as a COX-2 inhibitor, doesn’t have any effect on platelet aggregation, which would make it another option.”
No unique risks at prescribed doses
The migraine indication originally started out narrower: Patients with both migraine and bleeding disorders. “But in talking with the FDA, they encouraged us to develop it for migraine,” Mr. Sippy said. The company is considering pursuing a third indication: menstrual pain co-occurring with migraine. Tremeau has not ruled out seeking an indication in patients with arthritis who cannot take other painkillers, whether opioids or NSAIDs.
Five years ago, when Tremeau first announced its plans to bring rofecoxib back – indeed the company was set up for that purpose and has only this and another COX-2 inhibitor in development – some experts warned that there is little to prevent the drug from being used off-label, whether in higher doses or for other diseases.
“That’s something else we’re seeking to solve in addition to going for younger populations,” said Mr. Sippy, who worked at Merck during the Vioxx crisis and later headed neurology at Sunovion before starting his own company.
“We’re going for the former middle dose as our high dose and now we know that you don’t want to take more than the prescribed amount. If it doesn’t work you get off it; you don’t want to dose-creep on it. That’s been a key insight: At the appropriate dose, this product has no unique risk relative to the drug class and potentially some unique benefits,” he said.
Risk versus benefit
Joseph Ross, MD, a health policy researcher at Yale University in New Haven, Conn., who in a 2018 editorial expressed concerns about rofecoxib’s revival, said in an email that he felt its use in migraine could be justified, with caveats.
During Vioxx’s original approval and time on the market, “there was a cardiovascular risk associated with use that was not being transparently and clearly reported to patients and clinicians,” Dr. Ross said.
“In terms of testing the product for use in patients with migraine – a population of generally younger patients at lower risk of cardiovascular disease – my only concern is that the risk is clearly communicated and that there is adequate postmarket safety surveillance,” he said. “If patients are making fully informed decisions, the potential benefit of the drug with respect to pain control may be worth the risks.”
Dr. Rapoport serves as an adviser for AbbVie, Amgen, Biohaven, Cala Health, Collegium Pharmaceutical, Satsuma, Teva, Theranica and Xoc; he is on the speakers bureau of AbbVie, Amgen, Biohaven, Impel, Lundbeck, and Teva. Dr. Ross disclosed research support from Johnson and Johnson, the Medical Device Innovation Consortium, and the Laura and John Arnold Foundation, along with government grants; he is also an expert witness in a lawsuit against Biogen.
Bone density loss in lean male runners parallels similar issue in women
Similar to a phenomenon already well documented in women, inadequate nutrition appears to be linked to hormonal abnormalities and potentially preventable tibial cortical bone density loss in athletic men, according to results of a small, prospective study.
Based on these findings, “we suspect that a subset of male runners might not be fueling their bodies with enough nutrition and calories for their physical activity,” reported Melanie S. Haines, MD, at the annual meeting of the Endocrine Society.
This is not the first study to suggest male athletes are at risk of a condition equivalent to what has been commonly referred to as the female athlete triad, but it enlarges the objective data that the phenomenon is real, and it makes insufficient availability of energy the likely cause.
In women, the triad is described as a lack of adequate stored energy, irregular menses, and bone density loss. In men, menstrual cycles are not relevant, of course, but this study like others suggests a link between the failure to maintain adequate stores of energy, disturbances in hormone function, and decreased bone density in both men and women, Dr. Haines explained.
RED-S vs. male or female athlete triad
“There is now a move away from the term female athlete triad or male athlete triad,” Dr. Haines reported. Rather the factors of failing to maintain adequate energy for metabolic demands, hormonal disturbances, and bone density loss appear to be relevant to both sexes, according to Dr. Haines, an endocrinologist at Massachusetts General Hospital and assistant professor of medicine at Harvard Medical School, both in Boston. She said several groups, including the International Olympic Committee (IOC), have transitioned to the term RED-S to apply to both sexes.
“RED-S is an acronym for relative energy deficiency in sport, and it appears to be gaining traction,” Dr. Haines said in an interview.
According to her study and others, excessive lean body mass from failure to supply sufficient energy for physiological needs “negatively affects hormones and bone,” Dr. Haines explained. In men and women, endocrine disturbances are triggered when insufficient calories lead to inadequate macro- and micronutrients.
In this study, 31 men aged 16-30 years were evaluated. Fifteen were in the athlete group, defined by running at least 30 miles per week for at least the previous 6 months. There were 16 control subjects; all exercised less than 2 hours per week and did not participate in team sports, but they were not permitted in the study if their body mass index exceeded 27.5 kg/m2.
Athletes vs. otherwise healthy controls
Conditions that affect bone health were exclusion criteria in both groups, and neither group was permitted to take medications affecting bone health other than dietary calcium or vitamin D supplements for 2 months prior to the study.
Tibial cortical porosity was significantly greater – signaling deterioration in microarchitecture – in athletes, compared with control subjects (P = .003), according to quantitative computed tomography measurements. There was also significantly lower tibial cortical bone mineral density (P = .008) among athletes relative to controls.
Conversely, tibial trabecular measures of bone density and architecture were better among athletes than controls, but this was expected and did not contradict the hypothesis of the study.
“Trabecular bone refers to the inner part of the bone, which increases with weight-bearing exercise, but cortical bone is the outer shell, and the source of stress fractures,” Dr. Haines explained.
The median age of both the athletes and the controls was 24 years. Baseline measurements were similar. Body mass index, fat mass, estradiol, and leptin were all numerically lower in the athletes than controls, but none were significant, although there was a trend for the difference in leptin (P = .085).
Hormones correlated with tibial failure load
When these characteristics were evaluated in the context of mean tibial failure load, a metric related to strength, there was a strongly significant positive association with lean body mass (R = 0.85; P < 0.001) and estradiol level (R = 0.66; P = .007). The relationship with leptin also reached significance (R = 0.59; P = .046).
Unexpectedly, there was no relationship between testosterone and tibial failure load. The reason is unclear, but Dr. Haines’s interpretation is that the relationship between specific hormonal disturbances and bone density loss “might not be as simple” as once hypothesized.
The next step is a longitudinal evaluation of the same group of athletes to follow changes in the relationship between these variables over time, according to Dr. Haines.
Eventually, with evidence that there is a causal relationship between nutrition, hormonal changes, and bone loss, the research in this area will focus on better detection of risk and prophylactic strategies.
“Intervention trials to show that we can prevent stress factors will be difficult to perform,” Dr. Haines acknowledged, but she said that preventing adverse changes in bone at relatively young ages could have implications for long-term bone health, including protection from osteoporosis later in life.
The research presented by Dr. Haines is consistent with an area of research that is several decades old, at least in females, according to Siobhan M. Statuta, MD, a sports medicine primary care specialist at the University of Virginia, Charlottesville. The evidence that the same phenomenon occurs in men is more recent, but she said that it is now well accepted the there is a parallel hormonal issue in men and women.
“It is not a question of not eating enough. Often, athletes continue to consume the same diet, but their activity increases,” Dr. Statuta explained. “The problem is that they are not supplying enough of the calories they need to sustain the energy they are expending. You might say they are not fueling their engines appropriately.”
In 2014, the International Olympic Committee published a consensus statement on RED-S. They described this as a condition in which a state of energy deficiency leads to numerous complications in athletes, not just osteoporosis. Rather, a host of physiological systems, ranging from gastrointestinal complaints to cardiovascular events, were described.
RED-S addresses health beyond bones
“The RED-S theory is better described as a spoke-and-wheel concept rather than a triad. While inadequate energy availability is important to both, RED-S places this at the center of the wheel with spokes leading to all the possible complications rather than as a first event in a limited triad,” Dr. Statuta said in an interview.
However, she noted that the term RED-S is not yet appropriate to replace that of the male and female athlete triad.
“More research is required to hash out the relationship of a body in a state of energy deficiency and how it affects the entire body, which is the principle of RED-S,” Dr. Statuta said. “There likely are scientific effects, and we are currently investigating these relationships more.”
“These are really quite similar entities but have different foci,” she added. Based on data collected over several decades, “the triad narrows in on two body systems affected by low energy – the reproductive system and bones. RED-S incorporates these same systems yet adds on many more organ systems.
The original group of researchers have remained loyal to the concept of the triad that involves inadequate availability of energy followed by hormonal irregularities and osteoporosis. This group, the Female and Male Athlete Triad Coalition, has issued publications on this topic several times. Consensus statements were updated last year.
“The premise is that the triad leading to bone loss is shared by both men and women, even if the clinical manifestations differ,” said Dr. Statuta. The most notable difference is that men do not experience menstrual irregularities, but Dr. Statuta suggested that the clinical consequences are not necessarily any less.
“Males do not have menstrual cycles as an outward marker of an endocrine disturbance, so it is harder to recognize clinically, but I think there is agreement that not having enough energy available is the trigger of endocrine changes and then bone loss is relevant to both sexes,” she said. She said this is supported by a growing body of evidence, including the data presented by Dr. Haines at the Endocrine Society meeting.
Dr. Haines and Dr. Statuta report no potential conflicts of interest.
Similar to a phenomenon already well documented in women, inadequate nutrition appears to be linked to hormonal abnormalities and potentially preventable tibial cortical bone density loss in athletic men, according to results of a small, prospective study.
Based on these findings, “we suspect that a subset of male runners might not be fueling their bodies with enough nutrition and calories for their physical activity,” reported Melanie S. Haines, MD, at the annual meeting of the Endocrine Society.
This is not the first study to suggest male athletes are at risk of a condition equivalent to what has been commonly referred to as the female athlete triad, but it enlarges the objective data that the phenomenon is real, and it makes insufficient availability of energy the likely cause.
In women, the triad is described as a lack of adequate stored energy, irregular menses, and bone density loss. In men, menstrual cycles are not relevant, of course, but this study like others suggests a link between the failure to maintain adequate stores of energy, disturbances in hormone function, and decreased bone density in both men and women, Dr. Haines explained.
RED-S vs. male or female athlete triad
“There is now a move away from the term female athlete triad or male athlete triad,” Dr. Haines reported. Rather the factors of failing to maintain adequate energy for metabolic demands, hormonal disturbances, and bone density loss appear to be relevant to both sexes, according to Dr. Haines, an endocrinologist at Massachusetts General Hospital and assistant professor of medicine at Harvard Medical School, both in Boston. She said several groups, including the International Olympic Committee (IOC), have transitioned to the term RED-S to apply to both sexes.
“RED-S is an acronym for relative energy deficiency in sport, and it appears to be gaining traction,” Dr. Haines said in an interview.
According to her study and others, excessive lean body mass from failure to supply sufficient energy for physiological needs “negatively affects hormones and bone,” Dr. Haines explained. In men and women, endocrine disturbances are triggered when insufficient calories lead to inadequate macro- and micronutrients.
In this study, 31 men aged 16-30 years were evaluated. Fifteen were in the athlete group, defined by running at least 30 miles per week for at least the previous 6 months. There were 16 control subjects; all exercised less than 2 hours per week and did not participate in team sports, but they were not permitted in the study if their body mass index exceeded 27.5 kg/m2.
Athletes vs. otherwise healthy controls
Conditions that affect bone health were exclusion criteria in both groups, and neither group was permitted to take medications affecting bone health other than dietary calcium or vitamin D supplements for 2 months prior to the study.
Tibial cortical porosity was significantly greater – signaling deterioration in microarchitecture – in athletes, compared with control subjects (P = .003), according to quantitative computed tomography measurements. There was also significantly lower tibial cortical bone mineral density (P = .008) among athletes relative to controls.
Conversely, tibial trabecular measures of bone density and architecture were better among athletes than controls, but this was expected and did not contradict the hypothesis of the study.
“Trabecular bone refers to the inner part of the bone, which increases with weight-bearing exercise, but cortical bone is the outer shell, and the source of stress fractures,” Dr. Haines explained.
The median age of both the athletes and the controls was 24 years. Baseline measurements were similar. Body mass index, fat mass, estradiol, and leptin were all numerically lower in the athletes than controls, but none were significant, although there was a trend for the difference in leptin (P = .085).
Hormones correlated with tibial failure load
When these characteristics were evaluated in the context of mean tibial failure load, a metric related to strength, there was a strongly significant positive association with lean body mass (R = 0.85; P < 0.001) and estradiol level (R = 0.66; P = .007). The relationship with leptin also reached significance (R = 0.59; P = .046).
Unexpectedly, there was no relationship between testosterone and tibial failure load. The reason is unclear, but Dr. Haines’s interpretation is that the relationship between specific hormonal disturbances and bone density loss “might not be as simple” as once hypothesized.
The next step is a longitudinal evaluation of the same group of athletes to follow changes in the relationship between these variables over time, according to Dr. Haines.
Eventually, with evidence that there is a causal relationship between nutrition, hormonal changes, and bone loss, the research in this area will focus on better detection of risk and prophylactic strategies.
“Intervention trials to show that we can prevent stress factors will be difficult to perform,” Dr. Haines acknowledged, but she said that preventing adverse changes in bone at relatively young ages could have implications for long-term bone health, including protection from osteoporosis later in life.
The research presented by Dr. Haines is consistent with an area of research that is several decades old, at least in females, according to Siobhan M. Statuta, MD, a sports medicine primary care specialist at the University of Virginia, Charlottesville. The evidence that the same phenomenon occurs in men is more recent, but she said that it is now well accepted the there is a parallel hormonal issue in men and women.
“It is not a question of not eating enough. Often, athletes continue to consume the same diet, but their activity increases,” Dr. Statuta explained. “The problem is that they are not supplying enough of the calories they need to sustain the energy they are expending. You might say they are not fueling their engines appropriately.”
In 2014, the International Olympic Committee published a consensus statement on RED-S. They described this as a condition in which a state of energy deficiency leads to numerous complications in athletes, not just osteoporosis. Rather, a host of physiological systems, ranging from gastrointestinal complaints to cardiovascular events, were described.
RED-S addresses health beyond bones
“The RED-S theory is better described as a spoke-and-wheel concept rather than a triad. While inadequate energy availability is important to both, RED-S places this at the center of the wheel with spokes leading to all the possible complications rather than as a first event in a limited triad,” Dr. Statuta said in an interview.
However, she noted that the term RED-S is not yet appropriate to replace that of the male and female athlete triad.
“More research is required to hash out the relationship of a body in a state of energy deficiency and how it affects the entire body, which is the principle of RED-S,” Dr. Statuta said. “There likely are scientific effects, and we are currently investigating these relationships more.”
“These are really quite similar entities but have different foci,” she added. Based on data collected over several decades, “the triad narrows in on two body systems affected by low energy – the reproductive system and bones. RED-S incorporates these same systems yet adds on many more organ systems.
The original group of researchers have remained loyal to the concept of the triad that involves inadequate availability of energy followed by hormonal irregularities and osteoporosis. This group, the Female and Male Athlete Triad Coalition, has issued publications on this topic several times. Consensus statements were updated last year.
“The premise is that the triad leading to bone loss is shared by both men and women, even if the clinical manifestations differ,” said Dr. Statuta. The most notable difference is that men do not experience menstrual irregularities, but Dr. Statuta suggested that the clinical consequences are not necessarily any less.
“Males do not have menstrual cycles as an outward marker of an endocrine disturbance, so it is harder to recognize clinically, but I think there is agreement that not having enough energy available is the trigger of endocrine changes and then bone loss is relevant to both sexes,” she said. She said this is supported by a growing body of evidence, including the data presented by Dr. Haines at the Endocrine Society meeting.
Dr. Haines and Dr. Statuta report no potential conflicts of interest.
Similar to a phenomenon already well documented in women, inadequate nutrition appears to be linked to hormonal abnormalities and potentially preventable tibial cortical bone density loss in athletic men, according to results of a small, prospective study.
Based on these findings, “we suspect that a subset of male runners might not be fueling their bodies with enough nutrition and calories for their physical activity,” reported Melanie S. Haines, MD, at the annual meeting of the Endocrine Society.
This is not the first study to suggest male athletes are at risk of a condition equivalent to what has been commonly referred to as the female athlete triad, but it enlarges the objective data that the phenomenon is real, and it makes insufficient availability of energy the likely cause.
In women, the triad is described as a lack of adequate stored energy, irregular menses, and bone density loss. In men, menstrual cycles are not relevant, of course, but this study like others suggests a link between the failure to maintain adequate stores of energy, disturbances in hormone function, and decreased bone density in both men and women, Dr. Haines explained.
RED-S vs. male or female athlete triad
“There is now a move away from the term female athlete triad or male athlete triad,” Dr. Haines reported. Rather the factors of failing to maintain adequate energy for metabolic demands, hormonal disturbances, and bone density loss appear to be relevant to both sexes, according to Dr. Haines, an endocrinologist at Massachusetts General Hospital and assistant professor of medicine at Harvard Medical School, both in Boston. She said several groups, including the International Olympic Committee (IOC), have transitioned to the term RED-S to apply to both sexes.
“RED-S is an acronym for relative energy deficiency in sport, and it appears to be gaining traction,” Dr. Haines said in an interview.
According to her study and others, excessive lean body mass from failure to supply sufficient energy for physiological needs “negatively affects hormones and bone,” Dr. Haines explained. In men and women, endocrine disturbances are triggered when insufficient calories lead to inadequate macro- and micronutrients.
In this study, 31 men aged 16-30 years were evaluated. Fifteen were in the athlete group, defined by running at least 30 miles per week for at least the previous 6 months. There were 16 control subjects; all exercised less than 2 hours per week and did not participate in team sports, but they were not permitted in the study if their body mass index exceeded 27.5 kg/m2.
Athletes vs. otherwise healthy controls
Conditions that affect bone health were exclusion criteria in both groups, and neither group was permitted to take medications affecting bone health other than dietary calcium or vitamin D supplements for 2 months prior to the study.
Tibial cortical porosity was significantly greater – signaling deterioration in microarchitecture – in athletes, compared with control subjects (P = .003), according to quantitative computed tomography measurements. There was also significantly lower tibial cortical bone mineral density (P = .008) among athletes relative to controls.
Conversely, tibial trabecular measures of bone density and architecture were better among athletes than controls, but this was expected and did not contradict the hypothesis of the study.
“Trabecular bone refers to the inner part of the bone, which increases with weight-bearing exercise, but cortical bone is the outer shell, and the source of stress fractures,” Dr. Haines explained.
The median age of both the athletes and the controls was 24 years. Baseline measurements were similar. Body mass index, fat mass, estradiol, and leptin were all numerically lower in the athletes than controls, but none were significant, although there was a trend for the difference in leptin (P = .085).
Hormones correlated with tibial failure load
When these characteristics were evaluated in the context of mean tibial failure load, a metric related to strength, there was a strongly significant positive association with lean body mass (R = 0.85; P < 0.001) and estradiol level (R = 0.66; P = .007). The relationship with leptin also reached significance (R = 0.59; P = .046).
Unexpectedly, there was no relationship between testosterone and tibial failure load. The reason is unclear, but Dr. Haines’s interpretation is that the relationship between specific hormonal disturbances and bone density loss “might not be as simple” as once hypothesized.
The next step is a longitudinal evaluation of the same group of athletes to follow changes in the relationship between these variables over time, according to Dr. Haines.
Eventually, with evidence that there is a causal relationship between nutrition, hormonal changes, and bone loss, the research in this area will focus on better detection of risk and prophylactic strategies.
“Intervention trials to show that we can prevent stress factors will be difficult to perform,” Dr. Haines acknowledged, but she said that preventing adverse changes in bone at relatively young ages could have implications for long-term bone health, including protection from osteoporosis later in life.
The research presented by Dr. Haines is consistent with an area of research that is several decades old, at least in females, according to Siobhan M. Statuta, MD, a sports medicine primary care specialist at the University of Virginia, Charlottesville. The evidence that the same phenomenon occurs in men is more recent, but she said that it is now well accepted the there is a parallel hormonal issue in men and women.
“It is not a question of not eating enough. Often, athletes continue to consume the same diet, but their activity increases,” Dr. Statuta explained. “The problem is that they are not supplying enough of the calories they need to sustain the energy they are expending. You might say they are not fueling their engines appropriately.”
In 2014, the International Olympic Committee published a consensus statement on RED-S. They described this as a condition in which a state of energy deficiency leads to numerous complications in athletes, not just osteoporosis. Rather, a host of physiological systems, ranging from gastrointestinal complaints to cardiovascular events, were described.
RED-S addresses health beyond bones
“The RED-S theory is better described as a spoke-and-wheel concept rather than a triad. While inadequate energy availability is important to both, RED-S places this at the center of the wheel with spokes leading to all the possible complications rather than as a first event in a limited triad,” Dr. Statuta said in an interview.
However, she noted that the term RED-S is not yet appropriate to replace that of the male and female athlete triad.
“More research is required to hash out the relationship of a body in a state of energy deficiency and how it affects the entire body, which is the principle of RED-S,” Dr. Statuta said. “There likely are scientific effects, and we are currently investigating these relationships more.”
“These are really quite similar entities but have different foci,” she added. Based on data collected over several decades, “the triad narrows in on two body systems affected by low energy – the reproductive system and bones. RED-S incorporates these same systems yet adds on many more organ systems.
The original group of researchers have remained loyal to the concept of the triad that involves inadequate availability of energy followed by hormonal irregularities and osteoporosis. This group, the Female and Male Athlete Triad Coalition, has issued publications on this topic several times. Consensus statements were updated last year.
“The premise is that the triad leading to bone loss is shared by both men and women, even if the clinical manifestations differ,” said Dr. Statuta. The most notable difference is that men do not experience menstrual irregularities, but Dr. Statuta suggested that the clinical consequences are not necessarily any less.
“Males do not have menstrual cycles as an outward marker of an endocrine disturbance, so it is harder to recognize clinically, but I think there is agreement that not having enough energy available is the trigger of endocrine changes and then bone loss is relevant to both sexes,” she said. She said this is supported by a growing body of evidence, including the data presented by Dr. Haines at the Endocrine Society meeting.
Dr. Haines and Dr. Statuta report no potential conflicts of interest.
FROM ENDO 2022
‘Goodie bag’ pill mill doctor sentenced to 2 decades in prison
A Pennsylvania-based internist was sentenced to 20 years in prison by a federal judge on May 10 for running a prescription “pill mill” from his medical practice.
Since May 2005, Andrew Berkowitz, MD, 62, of Huntington Valley, Pa., was president and CEO of A+ Pain Management, a clinic in the Philadelphia area, according to his LinkedIn profile.
Prosecutors said patients, no matter their complaint, would leave Dr. Berkowitz’s offices with “goodie bags” filled with a selection of drugs. A typical haul included topical analgesics, such as Relyyt and/or lidocaine; muscle relaxants, including chlorzoxazone and/or cyclobenzaprine; anti-inflammatories, such as celecoxib and/or fenoprofen; and schedule IV substances, including tramadol, eszopiclone, and quazepam.
The practice was registered in Pennsylvania as a nonpharmacy dispensing site, allowing Dr. Berkowitz to bill insurers for the drugs, according to The Pennsylvania Record, a journal covering Pennsylvania’s legal system. Dr. Berkowitz also prescribed oxycodone for “pill seeking” patients, who gave him their tacit approval of submitting claims to their insurance providers, which included Medicare, Aetna, and others, for the items in the goodie bag.
In addition, Dr. Berkowitz fraudulently billed insurers for medically unnecessary physical therapy, acupuncture, and chiropractic adjustments, as well as for treatments that were never provided, according to federal officials.
According to the Department of Justice, Dr. Berkowitz collected more than $4,000 per bag from insurers. From 2015 to 2018, prosecutors estimate that Dr. Berkowitz took in more than $4 million in fraudulent proceeds from his scheme.
The pill mill came to the attention of federal authorities after Blue Cross investigators forwarded to the FBI several complaints it had received about Dr. Berkowitz. In 2017, the FBI sent a cooperating witness to Dr. Berkowitz’s clinic. The undercover patient received a prescription for oxycodone, Motrin, and Flexeril and paid $185, according to The Record.
After being indicted in 2019, Dr. Berkowitz pleaded guilty in January 2020 to 19 counts of health care fraud and to 23 counts of distributing oxycodone outside the course of professional practice and without a legitimate medical purpose.
On May 10, he was sentenced to 20 years in prison, followed by 5 years of supervised release. In addition, he was ordered to pay a $40,000 fine and almost $4 million in restitution. As a result of civil False Claims Act liability for false claims submitted to Medicare, he is also obligated to pay approximately $1.8 million and is subject to a permanent prohibition on prescribing, distributing, or dispensing controlled substances.
Dr. Berkowitz’s actions were deemed especially egregious in light of the opioid epidemic.
“Doctors are supposed to treat illness, not feed it,” said Jacqueline Maguire, special agent in charge of the FBI’s Philadelphia division. “Andrew Berkowitz prescribed patients unnecessary pills and handed out opioids to addicts.” Jennifer Arbittier Williams, acting U.S. Attorney, added upon announcing the sentence, “Doctors who dare engage in health care fraud and drug diversion, two drivers of the opioid epidemic ravaging our communities, should heed this sentence as a warning that they will be held responsible, criminally and financially.”
A version of this article first appeared on Medscape.com.
A Pennsylvania-based internist was sentenced to 20 years in prison by a federal judge on May 10 for running a prescription “pill mill” from his medical practice.
Since May 2005, Andrew Berkowitz, MD, 62, of Huntington Valley, Pa., was president and CEO of A+ Pain Management, a clinic in the Philadelphia area, according to his LinkedIn profile.
Prosecutors said patients, no matter their complaint, would leave Dr. Berkowitz’s offices with “goodie bags” filled with a selection of drugs. A typical haul included topical analgesics, such as Relyyt and/or lidocaine; muscle relaxants, including chlorzoxazone and/or cyclobenzaprine; anti-inflammatories, such as celecoxib and/or fenoprofen; and schedule IV substances, including tramadol, eszopiclone, and quazepam.
The practice was registered in Pennsylvania as a nonpharmacy dispensing site, allowing Dr. Berkowitz to bill insurers for the drugs, according to The Pennsylvania Record, a journal covering Pennsylvania’s legal system. Dr. Berkowitz also prescribed oxycodone for “pill seeking” patients, who gave him their tacit approval of submitting claims to their insurance providers, which included Medicare, Aetna, and others, for the items in the goodie bag.
In addition, Dr. Berkowitz fraudulently billed insurers for medically unnecessary physical therapy, acupuncture, and chiropractic adjustments, as well as for treatments that were never provided, according to federal officials.
According to the Department of Justice, Dr. Berkowitz collected more than $4,000 per bag from insurers. From 2015 to 2018, prosecutors estimate that Dr. Berkowitz took in more than $4 million in fraudulent proceeds from his scheme.
The pill mill came to the attention of federal authorities after Blue Cross investigators forwarded to the FBI several complaints it had received about Dr. Berkowitz. In 2017, the FBI sent a cooperating witness to Dr. Berkowitz’s clinic. The undercover patient received a prescription for oxycodone, Motrin, and Flexeril and paid $185, according to The Record.
After being indicted in 2019, Dr. Berkowitz pleaded guilty in January 2020 to 19 counts of health care fraud and to 23 counts of distributing oxycodone outside the course of professional practice and without a legitimate medical purpose.
On May 10, he was sentenced to 20 years in prison, followed by 5 years of supervised release. In addition, he was ordered to pay a $40,000 fine and almost $4 million in restitution. As a result of civil False Claims Act liability for false claims submitted to Medicare, he is also obligated to pay approximately $1.8 million and is subject to a permanent prohibition on prescribing, distributing, or dispensing controlled substances.
Dr. Berkowitz’s actions were deemed especially egregious in light of the opioid epidemic.
“Doctors are supposed to treat illness, not feed it,” said Jacqueline Maguire, special agent in charge of the FBI’s Philadelphia division. “Andrew Berkowitz prescribed patients unnecessary pills and handed out opioids to addicts.” Jennifer Arbittier Williams, acting U.S. Attorney, added upon announcing the sentence, “Doctors who dare engage in health care fraud and drug diversion, two drivers of the opioid epidemic ravaging our communities, should heed this sentence as a warning that they will be held responsible, criminally and financially.”
A version of this article first appeared on Medscape.com.
A Pennsylvania-based internist was sentenced to 20 years in prison by a federal judge on May 10 for running a prescription “pill mill” from his medical practice.
Since May 2005, Andrew Berkowitz, MD, 62, of Huntington Valley, Pa., was president and CEO of A+ Pain Management, a clinic in the Philadelphia area, according to his LinkedIn profile.
Prosecutors said patients, no matter their complaint, would leave Dr. Berkowitz’s offices with “goodie bags” filled with a selection of drugs. A typical haul included topical analgesics, such as Relyyt and/or lidocaine; muscle relaxants, including chlorzoxazone and/or cyclobenzaprine; anti-inflammatories, such as celecoxib and/or fenoprofen; and schedule IV substances, including tramadol, eszopiclone, and quazepam.
The practice was registered in Pennsylvania as a nonpharmacy dispensing site, allowing Dr. Berkowitz to bill insurers for the drugs, according to The Pennsylvania Record, a journal covering Pennsylvania’s legal system. Dr. Berkowitz also prescribed oxycodone for “pill seeking” patients, who gave him their tacit approval of submitting claims to their insurance providers, which included Medicare, Aetna, and others, for the items in the goodie bag.
In addition, Dr. Berkowitz fraudulently billed insurers for medically unnecessary physical therapy, acupuncture, and chiropractic adjustments, as well as for treatments that were never provided, according to federal officials.
According to the Department of Justice, Dr. Berkowitz collected more than $4,000 per bag from insurers. From 2015 to 2018, prosecutors estimate that Dr. Berkowitz took in more than $4 million in fraudulent proceeds from his scheme.
The pill mill came to the attention of federal authorities after Blue Cross investigators forwarded to the FBI several complaints it had received about Dr. Berkowitz. In 2017, the FBI sent a cooperating witness to Dr. Berkowitz’s clinic. The undercover patient received a prescription for oxycodone, Motrin, and Flexeril and paid $185, according to The Record.
After being indicted in 2019, Dr. Berkowitz pleaded guilty in January 2020 to 19 counts of health care fraud and to 23 counts of distributing oxycodone outside the course of professional practice and without a legitimate medical purpose.
On May 10, he was sentenced to 20 years in prison, followed by 5 years of supervised release. In addition, he was ordered to pay a $40,000 fine and almost $4 million in restitution. As a result of civil False Claims Act liability for false claims submitted to Medicare, he is also obligated to pay approximately $1.8 million and is subject to a permanent prohibition on prescribing, distributing, or dispensing controlled substances.
Dr. Berkowitz’s actions were deemed especially egregious in light of the opioid epidemic.
“Doctors are supposed to treat illness, not feed it,” said Jacqueline Maguire, special agent in charge of the FBI’s Philadelphia division. “Andrew Berkowitz prescribed patients unnecessary pills and handed out opioids to addicts.” Jennifer Arbittier Williams, acting U.S. Attorney, added upon announcing the sentence, “Doctors who dare engage in health care fraud and drug diversion, two drivers of the opioid epidemic ravaging our communities, should heed this sentence as a warning that they will be held responsible, criminally and financially.”
A version of this article first appeared on Medscape.com.
Bone, breath, heart, guts: Eight essential papers in primary care
1. Adding a New Medication Versus Maximizing Dose to Intensify Hypertension Treatment in Older Adults: A Retrospective Observational Study
Roughly one in three adults with hypertension have inadequate blood pressure control, and clinicians have two options for intensifying treatment: “The dose of the current drug regimen can be maximized, or a new drug can be added,” said deputy editor Christina C. Wee, MD, MPH, at the annual meeting of the American College of Physicians.
Data from randomized controlled trials suggest treatment with lower doses of combination therapy may be more effective, with fewer side effects – although the best strategy in older adults remains unclear.
To answer that question, researchers conducted a large-scale, population-based, retrospective cohort study, and observational data were used to emulate a target trial with two groups: new medication and maximizing dose.
The cohort comprised people aged 65 years or older with hypertension and was limited to those with a systolic blood pressure of 130 mm Hg or higher. Two intensification approaches were used: adding a new medication, defined as a total dose increase with a new medication; and maximizing dose, defined as a total dose increase without new medication.
A total of 178,562 patients were included in the study, and 45,575 (25.5%) had intensification by adding a new medication and 132,987 (74.5%) by maximizing dose.
“Both produced systolic blood pressure reduction with a slight advantage in the ‘add a new medication’ group,” Dr. Wee said. “That group reduced their systolic blood pressure by over 4.5 points as compared to 3.8 points in the maximized [dose] group.”
At 12 months the results were similar, but only 50% of patients in the new medication group were able to sustain that strategy, compared with two-thirds of patients who had their dose increased.
“This suggests that, in older adults, adding a new antihypertensive medication versus maximizing dosing of existing regimen is less common, only minimally more effective, and less sustainable,” Dr. Wee said. “Maximizing dose of antihypertensive medication is a reasonable approach [and] may be easier to sustain.”
2. Cost-Effectiveness of Screening Mammography Beyond Age 75 Years: A Cost-Effectiveness Analysis
The U.S. Preventive Services Task Force recommends biennial screening mammograms through the age of 74 years, and a meta-analysis of randomized controlled trials suggests mortality is reduced among women with at least a 10-year life expectancy, Dr. Wee said.
However, whether screening beyond age 75 years is cost effective, especially among women with comorbidities, is unclear.
To address that question, researchers estimated benefits, harms, and cost-effectiveness of extending mammography to age 80, 85, or 90 years according to comorbidity burden, using data from the Surveillance, Epidemiology, and End Results program and the Breast Cancer Surveillance Consortium.
The results showed that extending annual mammography beyond age 75 years was not cost effective, but biennial mammography was. “It was cost effective to age 80 regardless of baseline comorbidity score, but it averted only small, absolute numbers of breast cancer deaths – especially for women with comorbidities,” Dr. Wee said. “It was not cost effective beyond age 80.”
3. Prediction of End-Stage Kidney Disease Using Estimated Glomerular Filtration Rate With and Without Race: A Prospective Cohort Study
Estimated glomerular filtration rate (eGFR) is associated with end-stage kidney disease (ESKD) and is used to make dialysis and transplant decisions. “However, the accuracy of using eGFR alone has been questioned and, previously, some eGFR equations included a correction for race and this has been quite controversial,” Dr. Wee said. “And just last year, the Chronic Kidney Disease Epidemiology Collaboration released their new equations, removing the adjustment for race.”
The study authors posed two questions:
- How well does eGFR alone predict risk of ESKD, compared with Kidney Function Risk Equation (KFRE)?
- Does using different eGFR equations affect performance of either eGFR alone or KFRE in predicting the risk of ESKD?
During a maximum 16 years of follow-up, 856 participants (n = 3,873) developed ESKD. Across all eGFR equations, the KFRE score was superior for predicting 2-year incidence of end-stage kidney disease, compared with eGFR alone.
“KFRE score better predicted 2-year risk of ESKD than eGFR alone regardless of eGFR equations used,” Dr. Wee said. “Correcting eGFR equations for race did not improve performance and validates recent guidelines.”
4. Comparative Fracture Risk During Osteoporosis Drug Holidays After Long-Term Risedronate Versus Alendronate Therapy: A Propensity Score-Matched Cohort Study
The study looked at the comparative risks of drug holidays after long-term (≥ 3 years) risedronate versus alendronate therapy in a cohort of individuals aged 66 years or older. The primary outcome was hip fracture within 3 years after a 120-day ascertainment period.
The cohort included 25,077 propensity score–matched pairs (81% female) with a mean age of 81 years. Hip fracture rates were higher among risedronate than alendronate drug holidays, although this association was attenuated when any fracture was included as the outcome.
Overall, risedronate treatment before a drug holiday was associated with an 18% greater risk of hip fractures than alendronate, and this relative increase translated to a small absolute increase of 0.6%.
“These differences primarily manifested after 24 months, but given these small differences, I’m not sure if we need to change our current management strategy,” Dr. Wee said. “But further study is warranted.”
5. The Effects of Four Doses of Vitamin D Supplements on Falls in Older Adults: A Response-Adaptive, Randomized Clinical Trial
This study assessed the effects of four doses of vitamin D3 supplements on the risk of falls.
The cohort included 688 participants, aged 70 years and older, with an elevated fall risk and a serum 25-hydroxyvitamin D level of 25-72.5 nmol/L. The intervention was 200 (control), 1,000, 2,000, or 4,000 IU of vitamin D3 per day.
“Their results showed that supplementation at doses of 1,000 IU/day or higher did not prevent falls compared with 200 IU/day,” said deputy editor Stephanie Chang, MD, MPH. “Several analyses raised safety concerns about vitamin D3 doses of 1,000 IU/day or higher.”
6. Postdiagnosis Smoking Cessation and Reduced Risk for Lung Cancer Progression and Mortality: A Prospective Cohort Study
This study sought to determine if quitting smoking after a diagnosis of lung cancer reduced the risk for disease progression and mortality. Researchers prospectively analyzed patients with non–small cell lung cancer (NSCLC) who were recruited between 2007 and 2016 and followed annually through 2020. The cohort comprised 517 current smokers who were diagnosed with early-stage (IA-IIIA) NSCLC.
The adjusted median overall survival time was 21.6 months higher among patients who quit smoking versus those who continued smoking, and a higher 5-year overall and progression-free survival were observed among patients who quit than those who continued smoking. After adjusting for confounders, smoking cessation remained associated with a lower risk for all-cause mortality, cancer-specific mortality, and disease progression.
7. Acute Consumption of Alcohol and Discrete Atrial Fibrillation Events
This study sought to determine if alcohol consumption heightened the risk for an episode of atrial fibrillation (AFib). The cohort included 100 individuals with paroxysmal AFib who were fitted with a continuous electrocardiogram monitor and an ankle-worn transdermal ethanol sensor for 4 weeks. Real-time documentation of each alcoholic drink consumed was self-recorded and finger-stick blood tests for phosphatidylethanol were used to corroborate ascertainments of drinking events.
Phosphatidylethanol testing correlated with the number of real-time recorded drinks and with the transdermal alcohol sensor. Consuming one alcoholic drink was associated with a twofold increased risk of AFib over the next 4 hours. The risk rose threefold with the consumption of two drinks.
“There is evidence of dose-response relationship with higher risk with more drinks,” Dr. Chang said. “Even one drink may predispose to an acute episode of AF[ib] in those so predisposed.”
8. Evaluation and Management After Acute Left-Sided Colonic Diverticulitis: A Systematic Review
Management of uncomplicated diverticulitis is usually conservative and includes bowel rest and fluids. However, uncertainty remains about the role of hospitalization and antibiotics, Dr. Chang said. The new review included 51 studies looking at colonoscopy, nonsurgical treatments, and elective surgery for patients with diverticulitis.
It was unclear if patients with recent acute diverticulitis are at increased risk for colorectal cancer, although those with complicated diverticulitis do appear to be at a higher risk of the disease. Treatment with mesalamine was shown to be ineffective in preventing recurrence, and other nonsurgical treatments lacked adequate evidence.
As for surgery, elective procedures reduce recurrence in patients with prior complicated or smoldering or frequently recurrent diverticulitis, but it is unclear which of these patients may benefit most.
“The ACP recommends initial management without antibiotics,” said Dr. Chang, adding that other questions need to be addressed, such as inpatient versus outpatient management and elective surgery after an acute episode.
Dr. Wee and Dr. Chang disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
1. Adding a New Medication Versus Maximizing Dose to Intensify Hypertension Treatment in Older Adults: A Retrospective Observational Study
Roughly one in three adults with hypertension have inadequate blood pressure control, and clinicians have two options for intensifying treatment: “The dose of the current drug regimen can be maximized, or a new drug can be added,” said deputy editor Christina C. Wee, MD, MPH, at the annual meeting of the American College of Physicians.
Data from randomized controlled trials suggest treatment with lower doses of combination therapy may be more effective, with fewer side effects – although the best strategy in older adults remains unclear.
To answer that question, researchers conducted a large-scale, population-based, retrospective cohort study, and observational data were used to emulate a target trial with two groups: new medication and maximizing dose.
The cohort comprised people aged 65 years or older with hypertension and was limited to those with a systolic blood pressure of 130 mm Hg or higher. Two intensification approaches were used: adding a new medication, defined as a total dose increase with a new medication; and maximizing dose, defined as a total dose increase without new medication.
A total of 178,562 patients were included in the study, and 45,575 (25.5%) had intensification by adding a new medication and 132,987 (74.5%) by maximizing dose.
“Both produced systolic blood pressure reduction with a slight advantage in the ‘add a new medication’ group,” Dr. Wee said. “That group reduced their systolic blood pressure by over 4.5 points as compared to 3.8 points in the maximized [dose] group.”
At 12 months the results were similar, but only 50% of patients in the new medication group were able to sustain that strategy, compared with two-thirds of patients who had their dose increased.
“This suggests that, in older adults, adding a new antihypertensive medication versus maximizing dosing of existing regimen is less common, only minimally more effective, and less sustainable,” Dr. Wee said. “Maximizing dose of antihypertensive medication is a reasonable approach [and] may be easier to sustain.”
2. Cost-Effectiveness of Screening Mammography Beyond Age 75 Years: A Cost-Effectiveness Analysis
The U.S. Preventive Services Task Force recommends biennial screening mammograms through the age of 74 years, and a meta-analysis of randomized controlled trials suggests mortality is reduced among women with at least a 10-year life expectancy, Dr. Wee said.
However, whether screening beyond age 75 years is cost effective, especially among women with comorbidities, is unclear.
To address that question, researchers estimated benefits, harms, and cost-effectiveness of extending mammography to age 80, 85, or 90 years according to comorbidity burden, using data from the Surveillance, Epidemiology, and End Results program and the Breast Cancer Surveillance Consortium.
The results showed that extending annual mammography beyond age 75 years was not cost effective, but biennial mammography was. “It was cost effective to age 80 regardless of baseline comorbidity score, but it averted only small, absolute numbers of breast cancer deaths – especially for women with comorbidities,” Dr. Wee said. “It was not cost effective beyond age 80.”
3. Prediction of End-Stage Kidney Disease Using Estimated Glomerular Filtration Rate With and Without Race: A Prospective Cohort Study
Estimated glomerular filtration rate (eGFR) is associated with end-stage kidney disease (ESKD) and is used to make dialysis and transplant decisions. “However, the accuracy of using eGFR alone has been questioned and, previously, some eGFR equations included a correction for race and this has been quite controversial,” Dr. Wee said. “And just last year, the Chronic Kidney Disease Epidemiology Collaboration released their new equations, removing the adjustment for race.”
The study authors posed two questions:
- How well does eGFR alone predict risk of ESKD, compared with Kidney Function Risk Equation (KFRE)?
- Does using different eGFR equations affect performance of either eGFR alone or KFRE in predicting the risk of ESKD?
During a maximum 16 years of follow-up, 856 participants (n = 3,873) developed ESKD. Across all eGFR equations, the KFRE score was superior for predicting 2-year incidence of end-stage kidney disease, compared with eGFR alone.
“KFRE score better predicted 2-year risk of ESKD than eGFR alone regardless of eGFR equations used,” Dr. Wee said. “Correcting eGFR equations for race did not improve performance and validates recent guidelines.”
4. Comparative Fracture Risk During Osteoporosis Drug Holidays After Long-Term Risedronate Versus Alendronate Therapy: A Propensity Score-Matched Cohort Study
The study looked at the comparative risks of drug holidays after long-term (≥ 3 years) risedronate versus alendronate therapy in a cohort of individuals aged 66 years or older. The primary outcome was hip fracture within 3 years after a 120-day ascertainment period.
The cohort included 25,077 propensity score–matched pairs (81% female) with a mean age of 81 years. Hip fracture rates were higher among risedronate than alendronate drug holidays, although this association was attenuated when any fracture was included as the outcome.
Overall, risedronate treatment before a drug holiday was associated with an 18% greater risk of hip fractures than alendronate, and this relative increase translated to a small absolute increase of 0.6%.
“These differences primarily manifested after 24 months, but given these small differences, I’m not sure if we need to change our current management strategy,” Dr. Wee said. “But further study is warranted.”
5. The Effects of Four Doses of Vitamin D Supplements on Falls in Older Adults: A Response-Adaptive, Randomized Clinical Trial
This study assessed the effects of four doses of vitamin D3 supplements on the risk of falls.
The cohort included 688 participants, aged 70 years and older, with an elevated fall risk and a serum 25-hydroxyvitamin D level of 25-72.5 nmol/L. The intervention was 200 (control), 1,000, 2,000, or 4,000 IU of vitamin D3 per day.
“Their results showed that supplementation at doses of 1,000 IU/day or higher did not prevent falls compared with 200 IU/day,” said deputy editor Stephanie Chang, MD, MPH. “Several analyses raised safety concerns about vitamin D3 doses of 1,000 IU/day or higher.”
6. Postdiagnosis Smoking Cessation and Reduced Risk for Lung Cancer Progression and Mortality: A Prospective Cohort Study
This study sought to determine if quitting smoking after a diagnosis of lung cancer reduced the risk for disease progression and mortality. Researchers prospectively analyzed patients with non–small cell lung cancer (NSCLC) who were recruited between 2007 and 2016 and followed annually through 2020. The cohort comprised 517 current smokers who were diagnosed with early-stage (IA-IIIA) NSCLC.
The adjusted median overall survival time was 21.6 months higher among patients who quit smoking versus those who continued smoking, and a higher 5-year overall and progression-free survival were observed among patients who quit than those who continued smoking. After adjusting for confounders, smoking cessation remained associated with a lower risk for all-cause mortality, cancer-specific mortality, and disease progression.
7. Acute Consumption of Alcohol and Discrete Atrial Fibrillation Events
This study sought to determine if alcohol consumption heightened the risk for an episode of atrial fibrillation (AFib). The cohort included 100 individuals with paroxysmal AFib who were fitted with a continuous electrocardiogram monitor and an ankle-worn transdermal ethanol sensor for 4 weeks. Real-time documentation of each alcoholic drink consumed was self-recorded and finger-stick blood tests for phosphatidylethanol were used to corroborate ascertainments of drinking events.
Phosphatidylethanol testing correlated with the number of real-time recorded drinks and with the transdermal alcohol sensor. Consuming one alcoholic drink was associated with a twofold increased risk of AFib over the next 4 hours. The risk rose threefold with the consumption of two drinks.
“There is evidence of dose-response relationship with higher risk with more drinks,” Dr. Chang said. “Even one drink may predispose to an acute episode of AF[ib] in those so predisposed.”
8. Evaluation and Management After Acute Left-Sided Colonic Diverticulitis: A Systematic Review
Management of uncomplicated diverticulitis is usually conservative and includes bowel rest and fluids. However, uncertainty remains about the role of hospitalization and antibiotics, Dr. Chang said. The new review included 51 studies looking at colonoscopy, nonsurgical treatments, and elective surgery for patients with diverticulitis.
It was unclear if patients with recent acute diverticulitis are at increased risk for colorectal cancer, although those with complicated diverticulitis do appear to be at a higher risk of the disease. Treatment with mesalamine was shown to be ineffective in preventing recurrence, and other nonsurgical treatments lacked adequate evidence.
As for surgery, elective procedures reduce recurrence in patients with prior complicated or smoldering or frequently recurrent diverticulitis, but it is unclear which of these patients may benefit most.
“The ACP recommends initial management without antibiotics,” said Dr. Chang, adding that other questions need to be addressed, such as inpatient versus outpatient management and elective surgery after an acute episode.
Dr. Wee and Dr. Chang disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
1. Adding a New Medication Versus Maximizing Dose to Intensify Hypertension Treatment in Older Adults: A Retrospective Observational Study
Roughly one in three adults with hypertension have inadequate blood pressure control, and clinicians have two options for intensifying treatment: “The dose of the current drug regimen can be maximized, or a new drug can be added,” said deputy editor Christina C. Wee, MD, MPH, at the annual meeting of the American College of Physicians.
Data from randomized controlled trials suggest treatment with lower doses of combination therapy may be more effective, with fewer side effects – although the best strategy in older adults remains unclear.
To answer that question, researchers conducted a large-scale, population-based, retrospective cohort study, and observational data were used to emulate a target trial with two groups: new medication and maximizing dose.
The cohort comprised people aged 65 years or older with hypertension and was limited to those with a systolic blood pressure of 130 mm Hg or higher. Two intensification approaches were used: adding a new medication, defined as a total dose increase with a new medication; and maximizing dose, defined as a total dose increase without new medication.
A total of 178,562 patients were included in the study, and 45,575 (25.5%) had intensification by adding a new medication and 132,987 (74.5%) by maximizing dose.
“Both produced systolic blood pressure reduction with a slight advantage in the ‘add a new medication’ group,” Dr. Wee said. “That group reduced their systolic blood pressure by over 4.5 points as compared to 3.8 points in the maximized [dose] group.”
At 12 months the results were similar, but only 50% of patients in the new medication group were able to sustain that strategy, compared with two-thirds of patients who had their dose increased.
“This suggests that, in older adults, adding a new antihypertensive medication versus maximizing dosing of existing regimen is less common, only minimally more effective, and less sustainable,” Dr. Wee said. “Maximizing dose of antihypertensive medication is a reasonable approach [and] may be easier to sustain.”
2. Cost-Effectiveness of Screening Mammography Beyond Age 75 Years: A Cost-Effectiveness Analysis
The U.S. Preventive Services Task Force recommends biennial screening mammograms through the age of 74 years, and a meta-analysis of randomized controlled trials suggests mortality is reduced among women with at least a 10-year life expectancy, Dr. Wee said.
However, whether screening beyond age 75 years is cost effective, especially among women with comorbidities, is unclear.
To address that question, researchers estimated benefits, harms, and cost-effectiveness of extending mammography to age 80, 85, or 90 years according to comorbidity burden, using data from the Surveillance, Epidemiology, and End Results program and the Breast Cancer Surveillance Consortium.
The results showed that extending annual mammography beyond age 75 years was not cost effective, but biennial mammography was. “It was cost effective to age 80 regardless of baseline comorbidity score, but it averted only small, absolute numbers of breast cancer deaths – especially for women with comorbidities,” Dr. Wee said. “It was not cost effective beyond age 80.”
3. Prediction of End-Stage Kidney Disease Using Estimated Glomerular Filtration Rate With and Without Race: A Prospective Cohort Study
Estimated glomerular filtration rate (eGFR) is associated with end-stage kidney disease (ESKD) and is used to make dialysis and transplant decisions. “However, the accuracy of using eGFR alone has been questioned and, previously, some eGFR equations included a correction for race and this has been quite controversial,” Dr. Wee said. “And just last year, the Chronic Kidney Disease Epidemiology Collaboration released their new equations, removing the adjustment for race.”
The study authors posed two questions:
- How well does eGFR alone predict risk of ESKD, compared with Kidney Function Risk Equation (KFRE)?
- Does using different eGFR equations affect performance of either eGFR alone or KFRE in predicting the risk of ESKD?
During a maximum 16 years of follow-up, 856 participants (n = 3,873) developed ESKD. Across all eGFR equations, the KFRE score was superior for predicting 2-year incidence of end-stage kidney disease, compared with eGFR alone.
“KFRE score better predicted 2-year risk of ESKD than eGFR alone regardless of eGFR equations used,” Dr. Wee said. “Correcting eGFR equations for race did not improve performance and validates recent guidelines.”
4. Comparative Fracture Risk During Osteoporosis Drug Holidays After Long-Term Risedronate Versus Alendronate Therapy: A Propensity Score-Matched Cohort Study
The study looked at the comparative risks of drug holidays after long-term (≥ 3 years) risedronate versus alendronate therapy in a cohort of individuals aged 66 years or older. The primary outcome was hip fracture within 3 years after a 120-day ascertainment period.
The cohort included 25,077 propensity score–matched pairs (81% female) with a mean age of 81 years. Hip fracture rates were higher among risedronate than alendronate drug holidays, although this association was attenuated when any fracture was included as the outcome.
Overall, risedronate treatment before a drug holiday was associated with an 18% greater risk of hip fractures than alendronate, and this relative increase translated to a small absolute increase of 0.6%.
“These differences primarily manifested after 24 months, but given these small differences, I’m not sure if we need to change our current management strategy,” Dr. Wee said. “But further study is warranted.”
5. The Effects of Four Doses of Vitamin D Supplements on Falls in Older Adults: A Response-Adaptive, Randomized Clinical Trial
This study assessed the effects of four doses of vitamin D3 supplements on the risk of falls.
The cohort included 688 participants, aged 70 years and older, with an elevated fall risk and a serum 25-hydroxyvitamin D level of 25-72.5 nmol/L. The intervention was 200 (control), 1,000, 2,000, or 4,000 IU of vitamin D3 per day.
“Their results showed that supplementation at doses of 1,000 IU/day or higher did not prevent falls compared with 200 IU/day,” said deputy editor Stephanie Chang, MD, MPH. “Several analyses raised safety concerns about vitamin D3 doses of 1,000 IU/day or higher.”
6. Postdiagnosis Smoking Cessation and Reduced Risk for Lung Cancer Progression and Mortality: A Prospective Cohort Study
This study sought to determine if quitting smoking after a diagnosis of lung cancer reduced the risk for disease progression and mortality. Researchers prospectively analyzed patients with non–small cell lung cancer (NSCLC) who were recruited between 2007 and 2016 and followed annually through 2020. The cohort comprised 517 current smokers who were diagnosed with early-stage (IA-IIIA) NSCLC.
The adjusted median overall survival time was 21.6 months higher among patients who quit smoking versus those who continued smoking, and a higher 5-year overall and progression-free survival were observed among patients who quit than those who continued smoking. After adjusting for confounders, smoking cessation remained associated with a lower risk for all-cause mortality, cancer-specific mortality, and disease progression.
7. Acute Consumption of Alcohol and Discrete Atrial Fibrillation Events
This study sought to determine if alcohol consumption heightened the risk for an episode of atrial fibrillation (AFib). The cohort included 100 individuals with paroxysmal AFib who were fitted with a continuous electrocardiogram monitor and an ankle-worn transdermal ethanol sensor for 4 weeks. Real-time documentation of each alcoholic drink consumed was self-recorded and finger-stick blood tests for phosphatidylethanol were used to corroborate ascertainments of drinking events.
Phosphatidylethanol testing correlated with the number of real-time recorded drinks and with the transdermal alcohol sensor. Consuming one alcoholic drink was associated with a twofold increased risk of AFib over the next 4 hours. The risk rose threefold with the consumption of two drinks.
“There is evidence of dose-response relationship with higher risk with more drinks,” Dr. Chang said. “Even one drink may predispose to an acute episode of AF[ib] in those so predisposed.”
8. Evaluation and Management After Acute Left-Sided Colonic Diverticulitis: A Systematic Review
Management of uncomplicated diverticulitis is usually conservative and includes bowel rest and fluids. However, uncertainty remains about the role of hospitalization and antibiotics, Dr. Chang said. The new review included 51 studies looking at colonoscopy, nonsurgical treatments, and elective surgery for patients with diverticulitis.
It was unclear if patients with recent acute diverticulitis are at increased risk for colorectal cancer, although those with complicated diverticulitis do appear to be at a higher risk of the disease. Treatment with mesalamine was shown to be ineffective in preventing recurrence, and other nonsurgical treatments lacked adequate evidence.
As for surgery, elective procedures reduce recurrence in patients with prior complicated or smoldering or frequently recurrent diverticulitis, but it is unclear which of these patients may benefit most.
“The ACP recommends initial management without antibiotics,” said Dr. Chang, adding that other questions need to be addressed, such as inpatient versus outpatient management and elective surgery after an acute episode.
Dr. Wee and Dr. Chang disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM INTERNAL MEDICINE 2022
‘Where does it hurt?’: Primary care tips for common ortho problems
Knee and shoulder pain are common complaints for patients in the primary care office.
But identifying the source of the pain can be complicated,
and an accurate diagnosis of the underlying cause of discomfort is key to appropriate management – whether that involves simple home care options of ice and rest or a recommendation for a follow-up with a specialist.
Speaking at the annual meeting of the American College of Physicians, Greg Nakamoto, MD, department of orthopedics, Virginia Mason Medical Center, Seattle, discussed common knee and shoulder problems that patients often present with in the primary care setting, and offered tips on diagnosis and appropriate management.
The most common conditions causing knee pain are osteoarthritis and meniscal tears. “The differential for knee pain is broad,” Dr. Nakamoto said. “You have to have a way to divide it down, such as if it’s acute or chronic.”
The initial workup has several key components. The first steps: Determine the location of the pain – anterior, medial, lateral, posterior – and then whether it stems from an injury or is atraumatic.
“If you have to ask one question – ask where it hurts,” he said. “And is it from an injury or just wear and tear? That helps me when deciding if surgery is needed.”
Pain in the knee generally localizes well to the site of pathology, and knee pain of acute traumatic onset requires more scrutiny for problems best treated with early surgery. “This also helps establish whether radiographic findings are due to injury or degeneration,” Dr. Nakamoto said. “The presence of swelling guides the need for anti-inflammatories or cortisone.”
Palpating for tenderness along the joint line is important, as is palpating above and below the joint line, Dr. Nakamoto said.
“Tenderness limited to the joint line, combined with a meniscal exam maneuver that reproduces joint-line pain, is suggestive of pain from meniscal pathology,” he said.
Imaging is an important component of evaluating knee symptoms, and the question often arises as to when to order an MRI.
Dr. Nakamoto offered the following scenario: If significant osteoarthritis is evident on weight-bearing x-ray, treat the patient for the condition. However, if little or no osteoarthritis appears on x-ray, and if the onset of symptoms was traumatic and both patient history and physical examination suggest a meniscal tear, order an MRI.
An early MRI also is needed if the patient has had either atraumatic or traumatic onset of symptoms and their history and physical exams are suspicious for a mechanically locked or locking meniscus. For suspicion of a ruptured quadriceps or patellar tendon or a stress fracture, an MRI is needed urgently.
An MRI would be ordered later if the patient’s symptoms have not improved significantly after 3 months of conservative management.
Dr. Nakamoto stressed how common undiagnosed meniscus tears are in the general population. A third of men aged 50-59 years and nearly 20% of women in that age group have a tear, he said. “That number goes up to 56% and 51% in men and women aged 70-90 years, and 61% of these tears were in patients who were asymptomatic in the last month.”
In the setting of osteoarthritis, 76% of asymptomatic patients had a meniscus tear, and 91% of patients with symptomatic osteoarthritis had a meniscus tear, he added.
Treating knee pain
Treatment will vary depending on the underlying etiology of pain. For a possible meniscus tear, the recommendation is for a conservative intervention with ice, ibuprofen, knee immobilizer, and crutches, with a follow-up appointment in a week.
Three types of injections also can help:
- Cortisone for osteoarthritis or meniscus tears, swelling, and inflammation, and prophylaxis against inflammation.
- Viscosupplementation (intra‐articular hyaluronic acid) for chronic, baseline osteoarthritis symptoms.
- Regenerative therapies (platelet-rich plasma, stem cells, etc.) are used primarily for osteoarthritis (these do not regrow cartilage, but some patients report decreased pain).
The data on injections are mixed, Dr. Nakamoto said. For example, the results of a 2015 Cochrane review on cortisone injections for osteoarthritis reported that the benefits were small to moderate at 4‐6 weeks, and small to none at 13 weeks.
“There is a lot of controversy for viscosupplementation despite all of the data on it,” he said. “But the recommendations from professional organizations are mixed.”
He noted that he has been using viscosupplementation since the 1990s, and some patients do benefit from it.
Shoulder pain
The most common causes of shoulder pain are adhesive capsulitis, rotator cuff tears and tendinopathy, and impingement.
As with knee pain, the same assessment routine largely applies.
First, pinpoint the location: Is the trouble spot the lateral shoulder and upper arm, the trapezial ridge, or the shoulder blade?
Next, assess pain on movement: Does the patient experience discomfort reaching overhead or behind the back, or moving at the glenohumeral joint/capsule and engaging the rotator cuff? Check for stiffness, weakness, and decreased range of motion in the rotator cuff.
Determine if the cause of the pain is traumatic or atraumatic and stems from an acute injury versus degeneration or overuse.
As with the knee, imaging is a major component of the assessment and typically involves the use of x-ray. An MRI may be required for evaluating full- and partial-thickness tears and when contemplating surgery.
MRI also is necessary for evaluating cases of acute, traumatic shoulder injury, and patients exhibiting disability suggestive of a rotator cuff tear in an otherwise healthy tendon.
Some pain can be treated with cortisone injections or regenerative therapies, which generally are given at the acromioclavicular or glenohumeral joints or in the subacromial space. A 2005 meta-analysis found that subacromial injections of corticosteroids are effective for improvement for rotator cuff tendinitis up to a 9‐month period.
Surgery may be warranted in some cases, Dr. Nakamoto said. These include adhesive capsulitis, rotator cuff tear, acute traumatic injury in an otherwise healthy tendon, and chronic (or acute-on-chronic) tears in a degenerative tendon following a trial of conservative therapy.
A version of this article first appeared on Medscape.com.
Knee and shoulder pain are common complaints for patients in the primary care office.
But identifying the source of the pain can be complicated,
and an accurate diagnosis of the underlying cause of discomfort is key to appropriate management – whether that involves simple home care options of ice and rest or a recommendation for a follow-up with a specialist.
Speaking at the annual meeting of the American College of Physicians, Greg Nakamoto, MD, department of orthopedics, Virginia Mason Medical Center, Seattle, discussed common knee and shoulder problems that patients often present with in the primary care setting, and offered tips on diagnosis and appropriate management.
The most common conditions causing knee pain are osteoarthritis and meniscal tears. “The differential for knee pain is broad,” Dr. Nakamoto said. “You have to have a way to divide it down, such as if it’s acute or chronic.”
The initial workup has several key components. The first steps: Determine the location of the pain – anterior, medial, lateral, posterior – and then whether it stems from an injury or is atraumatic.
“If you have to ask one question – ask where it hurts,” he said. “And is it from an injury or just wear and tear? That helps me when deciding if surgery is needed.”
Pain in the knee generally localizes well to the site of pathology, and knee pain of acute traumatic onset requires more scrutiny for problems best treated with early surgery. “This also helps establish whether radiographic findings are due to injury or degeneration,” Dr. Nakamoto said. “The presence of swelling guides the need for anti-inflammatories or cortisone.”
Palpating for tenderness along the joint line is important, as is palpating above and below the joint line, Dr. Nakamoto said.
“Tenderness limited to the joint line, combined with a meniscal exam maneuver that reproduces joint-line pain, is suggestive of pain from meniscal pathology,” he said.
Imaging is an important component of evaluating knee symptoms, and the question often arises as to when to order an MRI.
Dr. Nakamoto offered the following scenario: If significant osteoarthritis is evident on weight-bearing x-ray, treat the patient for the condition. However, if little or no osteoarthritis appears on x-ray, and if the onset of symptoms was traumatic and both patient history and physical examination suggest a meniscal tear, order an MRI.
An early MRI also is needed if the patient has had either atraumatic or traumatic onset of symptoms and their history and physical exams are suspicious for a mechanically locked or locking meniscus. For suspicion of a ruptured quadriceps or patellar tendon or a stress fracture, an MRI is needed urgently.
An MRI would be ordered later if the patient’s symptoms have not improved significantly after 3 months of conservative management.
Dr. Nakamoto stressed how common undiagnosed meniscus tears are in the general population. A third of men aged 50-59 years and nearly 20% of women in that age group have a tear, he said. “That number goes up to 56% and 51% in men and women aged 70-90 years, and 61% of these tears were in patients who were asymptomatic in the last month.”
In the setting of osteoarthritis, 76% of asymptomatic patients had a meniscus tear, and 91% of patients with symptomatic osteoarthritis had a meniscus tear, he added.
Treating knee pain
Treatment will vary depending on the underlying etiology of pain. For a possible meniscus tear, the recommendation is for a conservative intervention with ice, ibuprofen, knee immobilizer, and crutches, with a follow-up appointment in a week.
Three types of injections also can help:
- Cortisone for osteoarthritis or meniscus tears, swelling, and inflammation, and prophylaxis against inflammation.
- Viscosupplementation (intra‐articular hyaluronic acid) for chronic, baseline osteoarthritis symptoms.
- Regenerative therapies (platelet-rich plasma, stem cells, etc.) are used primarily for osteoarthritis (these do not regrow cartilage, but some patients report decreased pain).
The data on injections are mixed, Dr. Nakamoto said. For example, the results of a 2015 Cochrane review on cortisone injections for osteoarthritis reported that the benefits were small to moderate at 4‐6 weeks, and small to none at 13 weeks.
“There is a lot of controversy for viscosupplementation despite all of the data on it,” he said. “But the recommendations from professional organizations are mixed.”
He noted that he has been using viscosupplementation since the 1990s, and some patients do benefit from it.
Shoulder pain
The most common causes of shoulder pain are adhesive capsulitis, rotator cuff tears and tendinopathy, and impingement.
As with knee pain, the same assessment routine largely applies.
First, pinpoint the location: Is the trouble spot the lateral shoulder and upper arm, the trapezial ridge, or the shoulder blade?
Next, assess pain on movement: Does the patient experience discomfort reaching overhead or behind the back, or moving at the glenohumeral joint/capsule and engaging the rotator cuff? Check for stiffness, weakness, and decreased range of motion in the rotator cuff.
Determine if the cause of the pain is traumatic or atraumatic and stems from an acute injury versus degeneration or overuse.
As with the knee, imaging is a major component of the assessment and typically involves the use of x-ray. An MRI may be required for evaluating full- and partial-thickness tears and when contemplating surgery.
MRI also is necessary for evaluating cases of acute, traumatic shoulder injury, and patients exhibiting disability suggestive of a rotator cuff tear in an otherwise healthy tendon.
Some pain can be treated with cortisone injections or regenerative therapies, which generally are given at the acromioclavicular or glenohumeral joints or in the subacromial space. A 2005 meta-analysis found that subacromial injections of corticosteroids are effective for improvement for rotator cuff tendinitis up to a 9‐month period.
Surgery may be warranted in some cases, Dr. Nakamoto said. These include adhesive capsulitis, rotator cuff tear, acute traumatic injury in an otherwise healthy tendon, and chronic (or acute-on-chronic) tears in a degenerative tendon following a trial of conservative therapy.
A version of this article first appeared on Medscape.com.
Knee and shoulder pain are common complaints for patients in the primary care office.
But identifying the source of the pain can be complicated,
and an accurate diagnosis of the underlying cause of discomfort is key to appropriate management – whether that involves simple home care options of ice and rest or a recommendation for a follow-up with a specialist.
Speaking at the annual meeting of the American College of Physicians, Greg Nakamoto, MD, department of orthopedics, Virginia Mason Medical Center, Seattle, discussed common knee and shoulder problems that patients often present with in the primary care setting, and offered tips on diagnosis and appropriate management.
The most common conditions causing knee pain are osteoarthritis and meniscal tears. “The differential for knee pain is broad,” Dr. Nakamoto said. “You have to have a way to divide it down, such as if it’s acute or chronic.”
The initial workup has several key components. The first steps: Determine the location of the pain – anterior, medial, lateral, posterior – and then whether it stems from an injury or is atraumatic.
“If you have to ask one question – ask where it hurts,” he said. “And is it from an injury or just wear and tear? That helps me when deciding if surgery is needed.”
Pain in the knee generally localizes well to the site of pathology, and knee pain of acute traumatic onset requires more scrutiny for problems best treated with early surgery. “This also helps establish whether radiographic findings are due to injury or degeneration,” Dr. Nakamoto said. “The presence of swelling guides the need for anti-inflammatories or cortisone.”
Palpating for tenderness along the joint line is important, as is palpating above and below the joint line, Dr. Nakamoto said.
“Tenderness limited to the joint line, combined with a meniscal exam maneuver that reproduces joint-line pain, is suggestive of pain from meniscal pathology,” he said.
Imaging is an important component of evaluating knee symptoms, and the question often arises as to when to order an MRI.
Dr. Nakamoto offered the following scenario: If significant osteoarthritis is evident on weight-bearing x-ray, treat the patient for the condition. However, if little or no osteoarthritis appears on x-ray, and if the onset of symptoms was traumatic and both patient history and physical examination suggest a meniscal tear, order an MRI.
An early MRI also is needed if the patient has had either atraumatic or traumatic onset of symptoms and their history and physical exams are suspicious for a mechanically locked or locking meniscus. For suspicion of a ruptured quadriceps or patellar tendon or a stress fracture, an MRI is needed urgently.
An MRI would be ordered later if the patient’s symptoms have not improved significantly after 3 months of conservative management.
Dr. Nakamoto stressed how common undiagnosed meniscus tears are in the general population. A third of men aged 50-59 years and nearly 20% of women in that age group have a tear, he said. “That number goes up to 56% and 51% in men and women aged 70-90 years, and 61% of these tears were in patients who were asymptomatic in the last month.”
In the setting of osteoarthritis, 76% of asymptomatic patients had a meniscus tear, and 91% of patients with symptomatic osteoarthritis had a meniscus tear, he added.
Treating knee pain
Treatment will vary depending on the underlying etiology of pain. For a possible meniscus tear, the recommendation is for a conservative intervention with ice, ibuprofen, knee immobilizer, and crutches, with a follow-up appointment in a week.
Three types of injections also can help:
- Cortisone for osteoarthritis or meniscus tears, swelling, and inflammation, and prophylaxis against inflammation.
- Viscosupplementation (intra‐articular hyaluronic acid) for chronic, baseline osteoarthritis symptoms.
- Regenerative therapies (platelet-rich plasma, stem cells, etc.) are used primarily for osteoarthritis (these do not regrow cartilage, but some patients report decreased pain).
The data on injections are mixed, Dr. Nakamoto said. For example, the results of a 2015 Cochrane review on cortisone injections for osteoarthritis reported that the benefits were small to moderate at 4‐6 weeks, and small to none at 13 weeks.
“There is a lot of controversy for viscosupplementation despite all of the data on it,” he said. “But the recommendations from professional organizations are mixed.”
He noted that he has been using viscosupplementation since the 1990s, and some patients do benefit from it.
Shoulder pain
The most common causes of shoulder pain are adhesive capsulitis, rotator cuff tears and tendinopathy, and impingement.
As with knee pain, the same assessment routine largely applies.
First, pinpoint the location: Is the trouble spot the lateral shoulder and upper arm, the trapezial ridge, or the shoulder blade?
Next, assess pain on movement: Does the patient experience discomfort reaching overhead or behind the back, or moving at the glenohumeral joint/capsule and engaging the rotator cuff? Check for stiffness, weakness, and decreased range of motion in the rotator cuff.
Determine if the cause of the pain is traumatic or atraumatic and stems from an acute injury versus degeneration or overuse.
As with the knee, imaging is a major component of the assessment and typically involves the use of x-ray. An MRI may be required for evaluating full- and partial-thickness tears and when contemplating surgery.
MRI also is necessary for evaluating cases of acute, traumatic shoulder injury, and patients exhibiting disability suggestive of a rotator cuff tear in an otherwise healthy tendon.
Some pain can be treated with cortisone injections or regenerative therapies, which generally are given at the acromioclavicular or glenohumeral joints or in the subacromial space. A 2005 meta-analysis found that subacromial injections of corticosteroids are effective for improvement for rotator cuff tendinitis up to a 9‐month period.
Surgery may be warranted in some cases, Dr. Nakamoto said. These include adhesive capsulitis, rotator cuff tear, acute traumatic injury in an otherwise healthy tendon, and chronic (or acute-on-chronic) tears in a degenerative tendon following a trial of conservative therapy.
A version of this article first appeared on Medscape.com.
FROM INTERNAL MEDICINE 2022
Use of bone densitometry to grade hip OA could be boon to diagnosis, prognosis
Bone densitometry scans provide useful information that can be used to classify radiographic hip osteoarthritis more objectively than does currently used methods, UK researchers believe.
Based on detecting osteophytes using high-resolution dual energy x-ray absorptiometry (DEXA), the novel grading system they have developed showed an exponential relationship with worsening clinical outcomes such as hip pain, hospital-diagnosed OA, and total hip replacement (THR).
“Given the low radiation doses involved in DEXA, this could open up opportunities for ascertaining OA in larger population-based cohorts than those available for x-rays,” Ben G. Faber, MBBS, BSc, reported at the annual meeting of the British Society for Rheumatology during the best oral abstracts session.
This not only supports further research into OA but also means that it might be possible to use DEXA scans to help screen for hip OA and assess the risk for hip replacement in the future, added Dr. Faber, a Medical Research Council Clinical Research Fellow at the University of Bristol and rheumatology registrar for the North Bristol NHS Trust in England.
Session chair Tonia Vincent, MBBS, PhD, FRCP, a consultant rheumatologist and director of the Centre for Osteoarthritis Pathogenesis at the Kennedy Institute of Rheumatology at the University of Oxford (England), found the relationship between the DEXA findings and Kellgren and Lawrence (KL) grade and clinical outcomes to be “really striking.”
It highlights “a very important structure-symptom relationship, which people in the textbooks say doesn’t exist for osteoarthritis,” Dr. Vincent observed.
New scanners, new score
DEXA scans are a mainstay of assessing fracture risk in osteoporosis. Although originally developed for assessing bone mineral density, the newer scanners have such high resolution that they can now show radiographic features such as joint space narrowing (JSN) and the presence of osteophytes.
Both are given equal weighting in existing x-ray grading or scoring systems, which are fairly subjective, Dr. Faber said, but recent research conducted by him and his collaborators has suggested that the presence of osteophytes may be a better indicator of hip pain than JSN.
Using more than 40,000 DEXA scans obtained from the UK Biobank, Dr. Faber and associates developed a semi-automated tool that measured both JSN and osteophytes, giving greater weight to the latter. These patients with DEXA scans in the Biobank had a mean age of 63.7 years. Hip pain was present in 8.1%, hospital-diagnosed OA in 1.3%, and total hip replacement occurred in 0.6%.
The tool the researchers developed automatically calculated the minimum joint space width using a machine-learning-based approach, whereas they manually identified osteophytes at three key locations – the lateral acetabulum, the superior lateral femoral head, and the inferior medial femoral head. However, Dr. Faber said, “we’re now very close to fully automating that part of the process.”
Minimum JSN and osteophyte presence at each location was quantified using a scale of 0 (none) to 3 (greatest) to give a total score out of a possible 12; they then used this score to create five ‘grades’ from 0 (least) to 4 (most).
Applying these new radiographic hip OA grades to the Biobank DEXA scans revealed a strong and increasing association between the presences of osteophytes and the clinical outcomes considered.
For instance, when any osteophytes were detected, the odds ratios (ORs) for having hip pain for more than 3 months, a hospital diagnosis of OA, or THR were a respective 2.05, 4.98, and 6.17.
The presence of inferior or superior femoral osteophytes carried higher ORs for the three outcomes than did acetabular osteophytes, with the greatest ORs seen in patients with osteophytes at all three locations (6.95, 20.53, and 21.79, respectively). By comparison, ORs for JSN were 1.37, 3.48, and 3.91.
There were “strong progressive relationships between each grade of OA and the clinical outcomes,” Dr. Faber said, noting that “the headline figure” was that comparing people with grade 4 with grade 0, the risk for needing THR was 58 times higher. This tallies with what would be expected, Dr. Faber said, since “one would expect to see OA on imaging findings before someone had a total hip replacement.”
What might the future hold?
“One of the strengths of this study is that by using a semi-automated approach, we feel that this is a more objective measure of radiographic hip OA, which hopefully will mean that it’s more reproducible in the future when repeating in other cohorts,” Dr. Faber said.
Asked what he thought the future held, Dr. Faber responded: “A grand vision might be that you’re already doing DEXA scans to look at bone health in individuals, and from those same DEXAs you could get information on radiographic hip OA,” he hypothesized.
“We do this with BMD and we feed that into FRAX [Fracture Risk Assessment Tool] to give someone a fracture risk. Could we do the same for total hip replacement to really identify people are high risk of OA in the future?” he wondered. “Then could we intervene to potentially prevent that ... or increase the duration that they’re healthy before they require the operation? There’s still plenty of work needed to get there.”
Dr. Faber and colleagues work was recently published in Rheumatology.
Dr. Faber had no conflicts of interest to disclose. Dr. Vincent had nothing to declare; her research is funded by Versus Arthritis, the Medical Research Council, the European Research Council, FOREUM (Foundation for Research in Rheumatology), the Dunhill Trust, and the Kennedy Trust for Rheumatology Research.
Bone densitometry scans provide useful information that can be used to classify radiographic hip osteoarthritis more objectively than does currently used methods, UK researchers believe.
Based on detecting osteophytes using high-resolution dual energy x-ray absorptiometry (DEXA), the novel grading system they have developed showed an exponential relationship with worsening clinical outcomes such as hip pain, hospital-diagnosed OA, and total hip replacement (THR).
“Given the low radiation doses involved in DEXA, this could open up opportunities for ascertaining OA in larger population-based cohorts than those available for x-rays,” Ben G. Faber, MBBS, BSc, reported at the annual meeting of the British Society for Rheumatology during the best oral abstracts session.
This not only supports further research into OA but also means that it might be possible to use DEXA scans to help screen for hip OA and assess the risk for hip replacement in the future, added Dr. Faber, a Medical Research Council Clinical Research Fellow at the University of Bristol and rheumatology registrar for the North Bristol NHS Trust in England.
Session chair Tonia Vincent, MBBS, PhD, FRCP, a consultant rheumatologist and director of the Centre for Osteoarthritis Pathogenesis at the Kennedy Institute of Rheumatology at the University of Oxford (England), found the relationship between the DEXA findings and Kellgren and Lawrence (KL) grade and clinical outcomes to be “really striking.”
It highlights “a very important structure-symptom relationship, which people in the textbooks say doesn’t exist for osteoarthritis,” Dr. Vincent observed.
New scanners, new score
DEXA scans are a mainstay of assessing fracture risk in osteoporosis. Although originally developed for assessing bone mineral density, the newer scanners have such high resolution that they can now show radiographic features such as joint space narrowing (JSN) and the presence of osteophytes.
Both are given equal weighting in existing x-ray grading or scoring systems, which are fairly subjective, Dr. Faber said, but recent research conducted by him and his collaborators has suggested that the presence of osteophytes may be a better indicator of hip pain than JSN.
Using more than 40,000 DEXA scans obtained from the UK Biobank, Dr. Faber and associates developed a semi-automated tool that measured both JSN and osteophytes, giving greater weight to the latter. These patients with DEXA scans in the Biobank had a mean age of 63.7 years. Hip pain was present in 8.1%, hospital-diagnosed OA in 1.3%, and total hip replacement occurred in 0.6%.
The tool the researchers developed automatically calculated the minimum joint space width using a machine-learning-based approach, whereas they manually identified osteophytes at three key locations – the lateral acetabulum, the superior lateral femoral head, and the inferior medial femoral head. However, Dr. Faber said, “we’re now very close to fully automating that part of the process.”
Minimum JSN and osteophyte presence at each location was quantified using a scale of 0 (none) to 3 (greatest) to give a total score out of a possible 12; they then used this score to create five ‘grades’ from 0 (least) to 4 (most).
Applying these new radiographic hip OA grades to the Biobank DEXA scans revealed a strong and increasing association between the presences of osteophytes and the clinical outcomes considered.
For instance, when any osteophytes were detected, the odds ratios (ORs) for having hip pain for more than 3 months, a hospital diagnosis of OA, or THR were a respective 2.05, 4.98, and 6.17.
The presence of inferior or superior femoral osteophytes carried higher ORs for the three outcomes than did acetabular osteophytes, with the greatest ORs seen in patients with osteophytes at all three locations (6.95, 20.53, and 21.79, respectively). By comparison, ORs for JSN were 1.37, 3.48, and 3.91.
There were “strong progressive relationships between each grade of OA and the clinical outcomes,” Dr. Faber said, noting that “the headline figure” was that comparing people with grade 4 with grade 0, the risk for needing THR was 58 times higher. This tallies with what would be expected, Dr. Faber said, since “one would expect to see OA on imaging findings before someone had a total hip replacement.”
What might the future hold?
“One of the strengths of this study is that by using a semi-automated approach, we feel that this is a more objective measure of radiographic hip OA, which hopefully will mean that it’s more reproducible in the future when repeating in other cohorts,” Dr. Faber said.
Asked what he thought the future held, Dr. Faber responded: “A grand vision might be that you’re already doing DEXA scans to look at bone health in individuals, and from those same DEXAs you could get information on radiographic hip OA,” he hypothesized.
“We do this with BMD and we feed that into FRAX [Fracture Risk Assessment Tool] to give someone a fracture risk. Could we do the same for total hip replacement to really identify people are high risk of OA in the future?” he wondered. “Then could we intervene to potentially prevent that ... or increase the duration that they’re healthy before they require the operation? There’s still plenty of work needed to get there.”
Dr. Faber and colleagues work was recently published in Rheumatology.
Dr. Faber had no conflicts of interest to disclose. Dr. Vincent had nothing to declare; her research is funded by Versus Arthritis, the Medical Research Council, the European Research Council, FOREUM (Foundation for Research in Rheumatology), the Dunhill Trust, and the Kennedy Trust for Rheumatology Research.
Bone densitometry scans provide useful information that can be used to classify radiographic hip osteoarthritis more objectively than does currently used methods, UK researchers believe.
Based on detecting osteophytes using high-resolution dual energy x-ray absorptiometry (DEXA), the novel grading system they have developed showed an exponential relationship with worsening clinical outcomes such as hip pain, hospital-diagnosed OA, and total hip replacement (THR).
“Given the low radiation doses involved in DEXA, this could open up opportunities for ascertaining OA in larger population-based cohorts than those available for x-rays,” Ben G. Faber, MBBS, BSc, reported at the annual meeting of the British Society for Rheumatology during the best oral abstracts session.
This not only supports further research into OA but also means that it might be possible to use DEXA scans to help screen for hip OA and assess the risk for hip replacement in the future, added Dr. Faber, a Medical Research Council Clinical Research Fellow at the University of Bristol and rheumatology registrar for the North Bristol NHS Trust in England.
Session chair Tonia Vincent, MBBS, PhD, FRCP, a consultant rheumatologist and director of the Centre for Osteoarthritis Pathogenesis at the Kennedy Institute of Rheumatology at the University of Oxford (England), found the relationship between the DEXA findings and Kellgren and Lawrence (KL) grade and clinical outcomes to be “really striking.”
It highlights “a very important structure-symptom relationship, which people in the textbooks say doesn’t exist for osteoarthritis,” Dr. Vincent observed.
New scanners, new score
DEXA scans are a mainstay of assessing fracture risk in osteoporosis. Although originally developed for assessing bone mineral density, the newer scanners have such high resolution that they can now show radiographic features such as joint space narrowing (JSN) and the presence of osteophytes.
Both are given equal weighting in existing x-ray grading or scoring systems, which are fairly subjective, Dr. Faber said, but recent research conducted by him and his collaborators has suggested that the presence of osteophytes may be a better indicator of hip pain than JSN.
Using more than 40,000 DEXA scans obtained from the UK Biobank, Dr. Faber and associates developed a semi-automated tool that measured both JSN and osteophytes, giving greater weight to the latter. These patients with DEXA scans in the Biobank had a mean age of 63.7 years. Hip pain was present in 8.1%, hospital-diagnosed OA in 1.3%, and total hip replacement occurred in 0.6%.
The tool the researchers developed automatically calculated the minimum joint space width using a machine-learning-based approach, whereas they manually identified osteophytes at three key locations – the lateral acetabulum, the superior lateral femoral head, and the inferior medial femoral head. However, Dr. Faber said, “we’re now very close to fully automating that part of the process.”
Minimum JSN and osteophyte presence at each location was quantified using a scale of 0 (none) to 3 (greatest) to give a total score out of a possible 12; they then used this score to create five ‘grades’ from 0 (least) to 4 (most).
Applying these new radiographic hip OA grades to the Biobank DEXA scans revealed a strong and increasing association between the presences of osteophytes and the clinical outcomes considered.
For instance, when any osteophytes were detected, the odds ratios (ORs) for having hip pain for more than 3 months, a hospital diagnosis of OA, or THR were a respective 2.05, 4.98, and 6.17.
The presence of inferior or superior femoral osteophytes carried higher ORs for the three outcomes than did acetabular osteophytes, with the greatest ORs seen in patients with osteophytes at all three locations (6.95, 20.53, and 21.79, respectively). By comparison, ORs for JSN were 1.37, 3.48, and 3.91.
There were “strong progressive relationships between each grade of OA and the clinical outcomes,” Dr. Faber said, noting that “the headline figure” was that comparing people with grade 4 with grade 0, the risk for needing THR was 58 times higher. This tallies with what would be expected, Dr. Faber said, since “one would expect to see OA on imaging findings before someone had a total hip replacement.”
What might the future hold?
“One of the strengths of this study is that by using a semi-automated approach, we feel that this is a more objective measure of radiographic hip OA, which hopefully will mean that it’s more reproducible in the future when repeating in other cohorts,” Dr. Faber said.
Asked what he thought the future held, Dr. Faber responded: “A grand vision might be that you’re already doing DEXA scans to look at bone health in individuals, and from those same DEXAs you could get information on radiographic hip OA,” he hypothesized.
“We do this with BMD and we feed that into FRAX [Fracture Risk Assessment Tool] to give someone a fracture risk. Could we do the same for total hip replacement to really identify people are high risk of OA in the future?” he wondered. “Then could we intervene to potentially prevent that ... or increase the duration that they’re healthy before they require the operation? There’s still plenty of work needed to get there.”
Dr. Faber and colleagues work was recently published in Rheumatology.
Dr. Faber had no conflicts of interest to disclose. Dr. Vincent had nothing to declare; her research is funded by Versus Arthritis, the Medical Research Council, the European Research Council, FOREUM (Foundation for Research in Rheumatology), the Dunhill Trust, and the Kennedy Trust for Rheumatology Research.
FROM BSR 2022
Wearable sensors deemed reliable for home gait assessment in knee OA
Remote gait assessment in people with knee osteoarthritis using wearable sensors appears reliable but yields results slightly different from those achieved in the laboratory, researchers from Boston University have found.
As reported at the OARSI 2022 World Congress, there was “good to excellent reliability” in repeated measures collected by patients at home while being instructed via video teleconferencing.
Agreement was “moderate to excellent” when the findings were compared with those recorded in the lab, Michael J. Rose of Boston University reported at the congress, sponsored by the Osteoarthritis Research Society International.
“People walked faster and stood up faster in the lab,” Mr. Rose said. “Later we found that the difference in gait speed was statistically significant between the lab and home environment.”
This has been suggested previously and implies that data collected at home may have “greater ecological validity,” he observed.
Accelerated adoption of telehealth
Assessing how well someone walks or can stand from a seated position are well known and important assessments in knee OA, but these have but have traditionally only been done in large and expensive gait labs, Mr. Rose said.
Wearable technologies, such as the ones used in the study he presented, could help move these assessments out into the community. This is particularly timely considering the increased adoption of telehealth practices during the COVID-19 pandemic.
To look at the reliability measurements obtained via wearable sensors versus lab assessments, Mr. Rose and associates set up a substudy within a larger ongoing, single-arm trial looking at the use of digital assessments to measure the efficacy of an exercise intervention in reducing knee pain and improving knee function.
For inclusion in the main trial (n = 60), and hence the substudy (n = 20), participants had to have physician-diagnosed knee OA, be 50 years of age or older, have a body mass index of 40 kg/m2 or lower, be able to walk at for a least 20 minutes, and have a score of three or higher on the Knee Injury and Osteoarthritis Outcome Score pain subscale for weight-bearing items.
Acceptance of in-lab versus home testing
The substudy participants (mean age, 70.5 years) all underwent in-person lab visits in which a wearable sensor was placed on each foot and one around the lower back and the participant asked to perform walking and chair stand tests. The latter involved standing from a seated position as quickly as possible without using the arms five times, while the former involved walking 28 meters in two laps of a 7-meter path defined by two cones. These tests were repeated twice.
Participants were then given the equipment to repeat these tests at home; this included the three sensors, a tablet computer, and chair and cones. The home assessments were conducted via video conferencing, with the researchers reminding how to place the sensors correctly. The walking and chair stand tests were then each performed four times: Twice in a row and then a 15-minute rest period before being performed twice in a row again.
The researchers collected participants’ feedback about the process on questionnaires and Likert scales that showed an overall positive experience for the remote home visit, with the median rating being “very likely” to participate in another home visit and that the time commitment required was “very manageable.”
Good correlation found
To determine the correlation and the test-retest reliability of the data obtained during the repeated home tasks, Mr. Rose and collaborators used Pearson’s correlation R2 and the intra-class correlation coefficients (ICC).
ICCs for various gait and chair stand variables obtained with the sensors were between 0.85 and 0.96 for the test-retest reliability during the remote home visit, and R2 ranged between 0.81 and 0.95. Variables include stance, cadence (steps per minute), step duration and length, speed, and chair stand duration.
With regard to the agreement between the home versus lab results, ICCs ranged between 0.63 and 0.9.
“There were some logistical and technological challenges with the approach,” Mr. Rose conceded. “Despite written and verbal instructions, 2 of the 20 participants ended up having gait data that was unusable in the home visit.”
Another limitation is that the study population, while “representative,” contained a higher number of individuals than the general population who identified as being White (95%) and female (85%), and 90% had a college degree.
“Individuals typically representative of an OA population were generally accepting and willing to participate in remote visits showing the feasibility of our approach,” Mr. Rose said.
“We need to determine the responsiveness of gait and chair stand outcomes from wearable sensors at home to change over time.”
The study was sponsored by Boston University with funding from Pfizer and Eli Lilly. The researchers used the OPAL inertial sensor (APDM Wearable Technologies) in the study. Mr. Rose made no personal disclosures. Four of his collaborators were employees of Pfizer and one is an employee of Eli Lilly & Company, all with stock or stock options.
Remote gait assessment in people with knee osteoarthritis using wearable sensors appears reliable but yields results slightly different from those achieved in the laboratory, researchers from Boston University have found.
As reported at the OARSI 2022 World Congress, there was “good to excellent reliability” in repeated measures collected by patients at home while being instructed via video teleconferencing.
Agreement was “moderate to excellent” when the findings were compared with those recorded in the lab, Michael J. Rose of Boston University reported at the congress, sponsored by the Osteoarthritis Research Society International.
“People walked faster and stood up faster in the lab,” Mr. Rose said. “Later we found that the difference in gait speed was statistically significant between the lab and home environment.”
This has been suggested previously and implies that data collected at home may have “greater ecological validity,” he observed.
Accelerated adoption of telehealth
Assessing how well someone walks or can stand from a seated position are well known and important assessments in knee OA, but these have but have traditionally only been done in large and expensive gait labs, Mr. Rose said.
Wearable technologies, such as the ones used in the study he presented, could help move these assessments out into the community. This is particularly timely considering the increased adoption of telehealth practices during the COVID-19 pandemic.
To look at the reliability measurements obtained via wearable sensors versus lab assessments, Mr. Rose and associates set up a substudy within a larger ongoing, single-arm trial looking at the use of digital assessments to measure the efficacy of an exercise intervention in reducing knee pain and improving knee function.
For inclusion in the main trial (n = 60), and hence the substudy (n = 20), participants had to have physician-diagnosed knee OA, be 50 years of age or older, have a body mass index of 40 kg/m2 or lower, be able to walk at for a least 20 minutes, and have a score of three or higher on the Knee Injury and Osteoarthritis Outcome Score pain subscale for weight-bearing items.
Acceptance of in-lab versus home testing
The substudy participants (mean age, 70.5 years) all underwent in-person lab visits in which a wearable sensor was placed on each foot and one around the lower back and the participant asked to perform walking and chair stand tests. The latter involved standing from a seated position as quickly as possible without using the arms five times, while the former involved walking 28 meters in two laps of a 7-meter path defined by two cones. These tests were repeated twice.
Participants were then given the equipment to repeat these tests at home; this included the three sensors, a tablet computer, and chair and cones. The home assessments were conducted via video conferencing, with the researchers reminding how to place the sensors correctly. The walking and chair stand tests were then each performed four times: Twice in a row and then a 15-minute rest period before being performed twice in a row again.
The researchers collected participants’ feedback about the process on questionnaires and Likert scales that showed an overall positive experience for the remote home visit, with the median rating being “very likely” to participate in another home visit and that the time commitment required was “very manageable.”
Good correlation found
To determine the correlation and the test-retest reliability of the data obtained during the repeated home tasks, Mr. Rose and collaborators used Pearson’s correlation R2 and the intra-class correlation coefficients (ICC).
ICCs for various gait and chair stand variables obtained with the sensors were between 0.85 and 0.96 for the test-retest reliability during the remote home visit, and R2 ranged between 0.81 and 0.95. Variables include stance, cadence (steps per minute), step duration and length, speed, and chair stand duration.
With regard to the agreement between the home versus lab results, ICCs ranged between 0.63 and 0.9.
“There were some logistical and technological challenges with the approach,” Mr. Rose conceded. “Despite written and verbal instructions, 2 of the 20 participants ended up having gait data that was unusable in the home visit.”
Another limitation is that the study population, while “representative,” contained a higher number of individuals than the general population who identified as being White (95%) and female (85%), and 90% had a college degree.
“Individuals typically representative of an OA population were generally accepting and willing to participate in remote visits showing the feasibility of our approach,” Mr. Rose said.
“We need to determine the responsiveness of gait and chair stand outcomes from wearable sensors at home to change over time.”
The study was sponsored by Boston University with funding from Pfizer and Eli Lilly. The researchers used the OPAL inertial sensor (APDM Wearable Technologies) in the study. Mr. Rose made no personal disclosures. Four of his collaborators were employees of Pfizer and one is an employee of Eli Lilly & Company, all with stock or stock options.
Remote gait assessment in people with knee osteoarthritis using wearable sensors appears reliable but yields results slightly different from those achieved in the laboratory, researchers from Boston University have found.
As reported at the OARSI 2022 World Congress, there was “good to excellent reliability” in repeated measures collected by patients at home while being instructed via video teleconferencing.
Agreement was “moderate to excellent” when the findings were compared with those recorded in the lab, Michael J. Rose of Boston University reported at the congress, sponsored by the Osteoarthritis Research Society International.
“People walked faster and stood up faster in the lab,” Mr. Rose said. “Later we found that the difference in gait speed was statistically significant between the lab and home environment.”
This has been suggested previously and implies that data collected at home may have “greater ecological validity,” he observed.
Accelerated adoption of telehealth
Assessing how well someone walks or can stand from a seated position are well known and important assessments in knee OA, but these have but have traditionally only been done in large and expensive gait labs, Mr. Rose said.
Wearable technologies, such as the ones used in the study he presented, could help move these assessments out into the community. This is particularly timely considering the increased adoption of telehealth practices during the COVID-19 pandemic.
To look at the reliability measurements obtained via wearable sensors versus lab assessments, Mr. Rose and associates set up a substudy within a larger ongoing, single-arm trial looking at the use of digital assessments to measure the efficacy of an exercise intervention in reducing knee pain and improving knee function.
For inclusion in the main trial (n = 60), and hence the substudy (n = 20), participants had to have physician-diagnosed knee OA, be 50 years of age or older, have a body mass index of 40 kg/m2 or lower, be able to walk at for a least 20 minutes, and have a score of three or higher on the Knee Injury and Osteoarthritis Outcome Score pain subscale for weight-bearing items.
Acceptance of in-lab versus home testing
The substudy participants (mean age, 70.5 years) all underwent in-person lab visits in which a wearable sensor was placed on each foot and one around the lower back and the participant asked to perform walking and chair stand tests. The latter involved standing from a seated position as quickly as possible without using the arms five times, while the former involved walking 28 meters in two laps of a 7-meter path defined by two cones. These tests were repeated twice.
Participants were then given the equipment to repeat these tests at home; this included the three sensors, a tablet computer, and chair and cones. The home assessments were conducted via video conferencing, with the researchers reminding how to place the sensors correctly. The walking and chair stand tests were then each performed four times: Twice in a row and then a 15-minute rest period before being performed twice in a row again.
The researchers collected participants’ feedback about the process on questionnaires and Likert scales that showed an overall positive experience for the remote home visit, with the median rating being “very likely” to participate in another home visit and that the time commitment required was “very manageable.”
Good correlation found
To determine the correlation and the test-retest reliability of the data obtained during the repeated home tasks, Mr. Rose and collaborators used Pearson’s correlation R2 and the intra-class correlation coefficients (ICC).
ICCs for various gait and chair stand variables obtained with the sensors were between 0.85 and 0.96 for the test-retest reliability during the remote home visit, and R2 ranged between 0.81 and 0.95. Variables include stance, cadence (steps per minute), step duration and length, speed, and chair stand duration.
With regard to the agreement between the home versus lab results, ICCs ranged between 0.63 and 0.9.
“There were some logistical and technological challenges with the approach,” Mr. Rose conceded. “Despite written and verbal instructions, 2 of the 20 participants ended up having gait data that was unusable in the home visit.”
Another limitation is that the study population, while “representative,” contained a higher number of individuals than the general population who identified as being White (95%) and female (85%), and 90% had a college degree.
“Individuals typically representative of an OA population were generally accepting and willing to participate in remote visits showing the feasibility of our approach,” Mr. Rose said.
“We need to determine the responsiveness of gait and chair stand outcomes from wearable sensors at home to change over time.”
The study was sponsored by Boston University with funding from Pfizer and Eli Lilly. The researchers used the OPAL inertial sensor (APDM Wearable Technologies) in the study. Mr. Rose made no personal disclosures. Four of his collaborators were employees of Pfizer and one is an employee of Eli Lilly & Company, all with stock or stock options.
FROM OARSI 2022
OARSI sets sights on classifying early-stage knee OA
An expert task force convened by the Osteoarthritis Research Society International (OARSI) has started the process of consolidating classification criteria for early-stage knee osteoarthritis (OA).
“Early-stage knee OA classification criteria, we believe are critically required,” Gillian Hawker, MD, MSc, said at the OARSI 2022 World Congress.
Dr. Hawker, who is the chair of the Task Force Steering Committee, noted that classification criteria are needed for several reasons, such as “to advance OA therapeutics and [the] earlier identification of people with knee OA who can benefit from existing treatments.”
Moreover, they are needed so that people with knee OA can “be poised and ready to receive available therapies once we develop them,” said Dr. Hawker, professor of medicine at the University of Toronto and a senior clinician-scientist in the Women’s College Research Institute at Women’s College Hospital in Toronto.
Reasoning for looking at early OA
“Osteoarthritis is a very serious disease with a growing population burden,” Dr. Hawker reminded delegates at the congress. Yet despite “amazing advances” in the understanding of the pathophysiology of disease and several potential druggable targets being identified, “we still have no safe and effective interventions to prevent or slow the progression of the disease.”
“Why have all the DMOADs [disease-modifying osteoarthritis drugs] failed?” she questioned.
One hypothesis is that it’s down to the heterogeneity of OA. “We’ve been plugging people with different kinds or phenotypes of OA into the same clinical trials, and we need to better match OA phenotypes with appropriate treatment,” Dr. Hawker said.
Also, “structural changes on imaging, and the symptoms that characterize the disease of function, pain, stiffness, etc., are not super well correlated. It may be that any attempts at structure modification alone won’t adequately improve clinical symptoms.”
Perhaps most importantly, however, “we’re treating people way too late in the course of their disease,” Dr. Hawker said. “When we keep putting people with Kellgren and Lawrence [grade] 2 or 3 into clinical trials, it may be that we there’s nothing that we’re going to be able to do that’s really going to make a difference.”
Why just knee OA?
The reason for looking at early-stage OA specifically is that current knee OA classification criteria were developed nearly 40 years ago and were looking at a later stage of disease, mainly differentiating OA from other types of inflammatory arthritis, notably rheumatoid arthritis (RA).
The aim of the OARSI Early OA Task Force is thus to develop, refine, and validate classification criteria that will not only help identify people with early-stage OA who can then be entered into clinical trials of new therapies but also define a population that can be used in preclinical and prognostic work.
“The task force decided to start with early-stage knee OA due to the highest burden and the focus of most clinical trials,” steering committee member Martin Englund, MD, PhD, observed during the discussion.
“When we see how that goes, we may consider early hip OA,” said Dr. Englund, of Lund University and Skåne University Hospital in Sweden.
Dr. Hawker added that the task force felt that lumping hip and knee OA together would complicate matters because they thought that the classification criteria will likely look very different from each other.
“But the good news is we think that if we can identify early knee OA, we will likely also identify people with at least hand OA,” she said.
Building on previous work
The OARSI Task Force initiative will build on the early OA work by Stefan Lohmander, MD, PhD, and Frank Luyten, MD, PhD, who were part of a consensus panel that proposed draft classification criteria a few years ago. Those criteria, derived from a consensus workshop that had included basic scientists, physician-scientists, rheumatologists, orthopedic surgeons, and physiotherapists, identified three main areas of importance: Patient symptoms such as pain and function, the presence of crepitus or tender joints on clinical examination, and having a low Kellgren and Lawrence grade (0 or 1).
Dr. Lohmander remains heavily involved, heading up the advisory committee, with many other ad hoc committees likely to be set up during the project.
“We had over 70 people in the OARSI community volunteering to participate in some way, shape, or form,” Dr. Hawker said. All will be needed, she said, as there will be a lot of work to do. The starting point is people with undifferentiated knee symptoms, identifying the factors that increase or decrease the likelihood of having early-stage OA. Once a population has been found, the outcomes for prevention need to be defined.
A systematic search of the available literature has started and full-text review of more than 200 papers is in progress. The challenge ahead is to define what the ‘anchor question’ will be. That is, what question should be asked in order to determine whether a patient fulfills the criteria?
Dr. Hawker noted that when the American College of Rheumatology developed the RA classification criteria, the anchor question had been around whether methotrexate should be prescribed.
“We don’t have a ‘methotrexate’ in osteoarthritis, and it’s pretty low risk to start weight management or physical activity or even prescribe a topical anti-inflammatory,” she said. “So, we’re still trying to work out exactly how we create our anchor.”
It’s likely that the anchor question will be based on expert opinion rather than hard data. Perhaps it will focus on the chances that a patient’s symptoms will become persistent with loss of function or that they will develop established OA. It could perhaps be around the initiation of a novel DMOAD, if one proved effective enough to be used.
“We have many, many, many, questions!” Dr. Hawker said. One of the important ones is deciding what exactly should be prevented. Symptoms? Structural damage?
“I think a combination of symptoms and loss of function are probably what we want to prevent. But again, we’re going to have to define that very clearly. This is going to take us quite a bit of time.”
It’s likely to be a two-stage process: “First we define what is early stage OA, and then we identify those who are at the highest risk of rapid progression so that we can target those individuals for clinical trials.”
Dr. Hawker and Dr. Englund had no conflicts of interest to disclose.
An expert task force convened by the Osteoarthritis Research Society International (OARSI) has started the process of consolidating classification criteria for early-stage knee osteoarthritis (OA).
“Early-stage knee OA classification criteria, we believe are critically required,” Gillian Hawker, MD, MSc, said at the OARSI 2022 World Congress.
Dr. Hawker, who is the chair of the Task Force Steering Committee, noted that classification criteria are needed for several reasons, such as “to advance OA therapeutics and [the] earlier identification of people with knee OA who can benefit from existing treatments.”
Moreover, they are needed so that people with knee OA can “be poised and ready to receive available therapies once we develop them,” said Dr. Hawker, professor of medicine at the University of Toronto and a senior clinician-scientist in the Women’s College Research Institute at Women’s College Hospital in Toronto.
Reasoning for looking at early OA
“Osteoarthritis is a very serious disease with a growing population burden,” Dr. Hawker reminded delegates at the congress. Yet despite “amazing advances” in the understanding of the pathophysiology of disease and several potential druggable targets being identified, “we still have no safe and effective interventions to prevent or slow the progression of the disease.”
“Why have all the DMOADs [disease-modifying osteoarthritis drugs] failed?” she questioned.
One hypothesis is that it’s down to the heterogeneity of OA. “We’ve been plugging people with different kinds or phenotypes of OA into the same clinical trials, and we need to better match OA phenotypes with appropriate treatment,” Dr. Hawker said.
Also, “structural changes on imaging, and the symptoms that characterize the disease of function, pain, stiffness, etc., are not super well correlated. It may be that any attempts at structure modification alone won’t adequately improve clinical symptoms.”
Perhaps most importantly, however, “we’re treating people way too late in the course of their disease,” Dr. Hawker said. “When we keep putting people with Kellgren and Lawrence [grade] 2 or 3 into clinical trials, it may be that we there’s nothing that we’re going to be able to do that’s really going to make a difference.”
Why just knee OA?
The reason for looking at early-stage OA specifically is that current knee OA classification criteria were developed nearly 40 years ago and were looking at a later stage of disease, mainly differentiating OA from other types of inflammatory arthritis, notably rheumatoid arthritis (RA).
The aim of the OARSI Early OA Task Force is thus to develop, refine, and validate classification criteria that will not only help identify people with early-stage OA who can then be entered into clinical trials of new therapies but also define a population that can be used in preclinical and prognostic work.
“The task force decided to start with early-stage knee OA due to the highest burden and the focus of most clinical trials,” steering committee member Martin Englund, MD, PhD, observed during the discussion.
“When we see how that goes, we may consider early hip OA,” said Dr. Englund, of Lund University and Skåne University Hospital in Sweden.
Dr. Hawker added that the task force felt that lumping hip and knee OA together would complicate matters because they thought that the classification criteria will likely look very different from each other.
“But the good news is we think that if we can identify early knee OA, we will likely also identify people with at least hand OA,” she said.
Building on previous work
The OARSI Task Force initiative will build on the early OA work by Stefan Lohmander, MD, PhD, and Frank Luyten, MD, PhD, who were part of a consensus panel that proposed draft classification criteria a few years ago. Those criteria, derived from a consensus workshop that had included basic scientists, physician-scientists, rheumatologists, orthopedic surgeons, and physiotherapists, identified three main areas of importance: Patient symptoms such as pain and function, the presence of crepitus or tender joints on clinical examination, and having a low Kellgren and Lawrence grade (0 or 1).
Dr. Lohmander remains heavily involved, heading up the advisory committee, with many other ad hoc committees likely to be set up during the project.
“We had over 70 people in the OARSI community volunteering to participate in some way, shape, or form,” Dr. Hawker said. All will be needed, she said, as there will be a lot of work to do. The starting point is people with undifferentiated knee symptoms, identifying the factors that increase or decrease the likelihood of having early-stage OA. Once a population has been found, the outcomes for prevention need to be defined.
A systematic search of the available literature has started and full-text review of more than 200 papers is in progress. The challenge ahead is to define what the ‘anchor question’ will be. That is, what question should be asked in order to determine whether a patient fulfills the criteria?
Dr. Hawker noted that when the American College of Rheumatology developed the RA classification criteria, the anchor question had been around whether methotrexate should be prescribed.
“We don’t have a ‘methotrexate’ in osteoarthritis, and it’s pretty low risk to start weight management or physical activity or even prescribe a topical anti-inflammatory,” she said. “So, we’re still trying to work out exactly how we create our anchor.”
It’s likely that the anchor question will be based on expert opinion rather than hard data. Perhaps it will focus on the chances that a patient’s symptoms will become persistent with loss of function or that they will develop established OA. It could perhaps be around the initiation of a novel DMOAD, if one proved effective enough to be used.
“We have many, many, many, questions!” Dr. Hawker said. One of the important ones is deciding what exactly should be prevented. Symptoms? Structural damage?
“I think a combination of symptoms and loss of function are probably what we want to prevent. But again, we’re going to have to define that very clearly. This is going to take us quite a bit of time.”
It’s likely to be a two-stage process: “First we define what is early stage OA, and then we identify those who are at the highest risk of rapid progression so that we can target those individuals for clinical trials.”
Dr. Hawker and Dr. Englund had no conflicts of interest to disclose.
An expert task force convened by the Osteoarthritis Research Society International (OARSI) has started the process of consolidating classification criteria for early-stage knee osteoarthritis (OA).
“Early-stage knee OA classification criteria, we believe are critically required,” Gillian Hawker, MD, MSc, said at the OARSI 2022 World Congress.
Dr. Hawker, who is the chair of the Task Force Steering Committee, noted that classification criteria are needed for several reasons, such as “to advance OA therapeutics and [the] earlier identification of people with knee OA who can benefit from existing treatments.”
Moreover, they are needed so that people with knee OA can “be poised and ready to receive available therapies once we develop them,” said Dr. Hawker, professor of medicine at the University of Toronto and a senior clinician-scientist in the Women’s College Research Institute at Women’s College Hospital in Toronto.
Reasoning for looking at early OA
“Osteoarthritis is a very serious disease with a growing population burden,” Dr. Hawker reminded delegates at the congress. Yet despite “amazing advances” in the understanding of the pathophysiology of disease and several potential druggable targets being identified, “we still have no safe and effective interventions to prevent or slow the progression of the disease.”
“Why have all the DMOADs [disease-modifying osteoarthritis drugs] failed?” she questioned.
One hypothesis is that it’s down to the heterogeneity of OA. “We’ve been plugging people with different kinds or phenotypes of OA into the same clinical trials, and we need to better match OA phenotypes with appropriate treatment,” Dr. Hawker said.
Also, “structural changes on imaging, and the symptoms that characterize the disease of function, pain, stiffness, etc., are not super well correlated. It may be that any attempts at structure modification alone won’t adequately improve clinical symptoms.”
Perhaps most importantly, however, “we’re treating people way too late in the course of their disease,” Dr. Hawker said. “When we keep putting people with Kellgren and Lawrence [grade] 2 or 3 into clinical trials, it may be that we there’s nothing that we’re going to be able to do that’s really going to make a difference.”
Why just knee OA?
The reason for looking at early-stage OA specifically is that current knee OA classification criteria were developed nearly 40 years ago and were looking at a later stage of disease, mainly differentiating OA from other types of inflammatory arthritis, notably rheumatoid arthritis (RA).
The aim of the OARSI Early OA Task Force is thus to develop, refine, and validate classification criteria that will not only help identify people with early-stage OA who can then be entered into clinical trials of new therapies but also define a population that can be used in preclinical and prognostic work.
“The task force decided to start with early-stage knee OA due to the highest burden and the focus of most clinical trials,” steering committee member Martin Englund, MD, PhD, observed during the discussion.
“When we see how that goes, we may consider early hip OA,” said Dr. Englund, of Lund University and Skåne University Hospital in Sweden.
Dr. Hawker added that the task force felt that lumping hip and knee OA together would complicate matters because they thought that the classification criteria will likely look very different from each other.
“But the good news is we think that if we can identify early knee OA, we will likely also identify people with at least hand OA,” she said.
Building on previous work
The OARSI Task Force initiative will build on the early OA work by Stefan Lohmander, MD, PhD, and Frank Luyten, MD, PhD, who were part of a consensus panel that proposed draft classification criteria a few years ago. Those criteria, derived from a consensus workshop that had included basic scientists, physician-scientists, rheumatologists, orthopedic surgeons, and physiotherapists, identified three main areas of importance: Patient symptoms such as pain and function, the presence of crepitus or tender joints on clinical examination, and having a low Kellgren and Lawrence grade (0 or 1).
Dr. Lohmander remains heavily involved, heading up the advisory committee, with many other ad hoc committees likely to be set up during the project.
“We had over 70 people in the OARSI community volunteering to participate in some way, shape, or form,” Dr. Hawker said. All will be needed, she said, as there will be a lot of work to do. The starting point is people with undifferentiated knee symptoms, identifying the factors that increase or decrease the likelihood of having early-stage OA. Once a population has been found, the outcomes for prevention need to be defined.
A systematic search of the available literature has started and full-text review of more than 200 papers is in progress. The challenge ahead is to define what the ‘anchor question’ will be. That is, what question should be asked in order to determine whether a patient fulfills the criteria?
Dr. Hawker noted that when the American College of Rheumatology developed the RA classification criteria, the anchor question had been around whether methotrexate should be prescribed.
“We don’t have a ‘methotrexate’ in osteoarthritis, and it’s pretty low risk to start weight management or physical activity or even prescribe a topical anti-inflammatory,” she said. “So, we’re still trying to work out exactly how we create our anchor.”
It’s likely that the anchor question will be based on expert opinion rather than hard data. Perhaps it will focus on the chances that a patient’s symptoms will become persistent with loss of function or that they will develop established OA. It could perhaps be around the initiation of a novel DMOAD, if one proved effective enough to be used.
“We have many, many, many, questions!” Dr. Hawker said. One of the important ones is deciding what exactly should be prevented. Symptoms? Structural damage?
“I think a combination of symptoms and loss of function are probably what we want to prevent. But again, we’re going to have to define that very clearly. This is going to take us quite a bit of time.”
It’s likely to be a two-stage process: “First we define what is early stage OA, and then we identify those who are at the highest risk of rapid progression so that we can target those individuals for clinical trials.”
Dr. Hawker and Dr. Englund had no conflicts of interest to disclose.
FROM OARSI 2022
Inadequate pain relief in OA, high opioid use before TKA
Inadequate pain relief was recorded in 68.8% of a sample of people with hip or knee OA who participated in the population-based EpiReumaPt study, researchers reported at the OARSI 2022 World Congress.
“This can be explained by a lack of effectiveness of current management strategies, low uptake of recommended interventions by health care professionals, and also by low adherence by patients to medication and lifestyle interventions,” said Daniela Sofia Albino Costa, MSc, a PhD student at NOVA University Lisbon.
In addition to looking at the prevalence of inadequate pain relief – defined as a score of 5 or higher on the Numeric Pain Rating Scale (NPRS) – the study she presented at the congress, which was sponsored by the Osteoarthritis Research Society International, looked at the predictors for inadequate pain control.
It was found that being female, obesity, and having multimorbidity doubled the risk of inadequate versus adequate pain control, with respective odds ratios of 2.32 (P < .001), 2.26 (P = .006), and 2.07 (P = .001). Overweight was also associated with an increased odds ratio for poor pain control (OR, 1.84; P = .0035).
“We found that patients with inadequate pain relief also have a low performance on activities of daily living and a low quality of life,” Ms. Costa said.
Nearly one-third (29%) of patients in the inadequate pain relief group (n = 765) took medication, versus 15% of patients in the adequate pain relief group (n = 270). This was mostly NSAIDs, but also included analgesics and antipyretics, and in a few cases (4.8% vs. 1.3%), simple opioids.
“We know that current care is not concordant with recommendations,” said Ms. Costa, noting that medication being used as first-line treatment and core nonpharmacologic interventions are being offered to less than half of patients who are eligible.
In addition, the rate for total joint replacement has increased globally, and pain is an important predictor for this.
“So, we need to evaluate pain control and current management offered to people with hip or knee arthritis to identify to identify areas for improvement,” Ms. Costa said.
High rates of prescription opioid use before TKA
In a separate study also presented at the congress, Daniel Rhon, DPT, DSc, director of musculoskeletal research in primary care at Brooke Army Medical Center in San Antonio, gave a worrying glimpse of high rates of opioid use in the 4 years before total knee arthroplasty (TKA).
Using data from the U.S. Military Health System, the records of all individuals who had a knee replacement procedure between January 2017 and December 2018 were studied, to identify and characterize the use of prescription opioids.
Of the 46,362 individuals, 52.9% had prior opioid use, despite the fact that “opioids are not recommended for the management of knee OA,” said Dr. Rhon.
He also reported that as many as 40% of those who had at least one prescription for opioids had received a high-potency drug, such as fentanyl or oxycodone. The mean age of participants overall was 65 years, with a higher mean for those receiving opioids than those who did not (68 vs. 61.5 years). Data on sex and ethnicity were not available in time for presentation at the congress.
“Most of these individuals are getting these opioid prescriptions probably within 6 months, which maybe aligns with escalation of pain and maybe the decision to have that knee replacement,” Dr. Rhon said. Individuals that used opioids filled their most recent prescription a median of 146 days before TKA to surgery, with a mean of 317 days.
“You can’t always link the reason for the opioid prescription, that’s not really clear in the database,” he admitted; however, an analysis was performed to check if other surgeries had been performed that may have warranted the opioid treatment. The results revealed that very few of the opioid users (4%-7%) had undergone another type of surgical procedure.
“So, we feel a little bit better, that these findings weren’t for other surgical procedures,” said Dr. Rhon. He added that future qualitative research was needed to understand why health care professionals were prescribing opioids, and why patients felt like they needed them.
“That’s bad,” Haxby Abbott, PhD, DPT, a research professor at the University of Otago, Dunedin, New Zealand, commented on Twitter.
Dr. Abbott, who was not involved in the study, added: “We’ve done a similar study of the whole NZ population [currently under review] – similar to Australia and not nearly as bad as you found. That needs urgent attention.”
Sharp rise in opioid use 2 years before TKA
Lower rates of opioid use before TKA were seen in two European cohorts, at 43% in England and 33% in Sweden, as reported by Clara Hellberg, PhD, MD, of Lund (Sweden) University. However, rates had increased over a 10-year study period from a respective 23% and 16%, with a sharp increase in use in the 2 years before knee replacement.
The analysis was based on 49,043 patients from the English national database Clinical Practice Research Datalink, and 5,955 patients from the Swedish Skåne Healthcare register who had undergone total knee replacement between 2015 and 2019 and were matched by age, sex and general practice to individuals not undergoing knee replacement.
The prevalence ratio for using opioids over a 10-year period increased from 1.6 to 2.7 in England, and from 1.6 to 2.6 in Sweden.
“While the overall prevalence of opioid use was higher in England, the majority of both cases and controls were using weak opioids,” Dr. Hellberg said.
“Codeine was classified as a weak opioid, whereas morphine was classified as a strong opioid,” she added.
In contrast, the proportion of people using strong opioids in Sweden was greater than in England, she said.
The high opioid use found in the study highlights “the need for better opioid stewardship, and the availability of acceptable, effective alternatives,” Dr. Hellberg and associates concluded in their abstract.
The study presented by Ms. Costa was funded by the Portuguese national funding agency for science, research and technology and by an independent research grant from Pfizer. Dr. Rhon acknowledged grant funding from the National Institutes of Health and the U.S. Department of Defense. Dr. Hellberg had no conflicts of interest to disclose.
Inadequate pain relief was recorded in 68.8% of a sample of people with hip or knee OA who participated in the population-based EpiReumaPt study, researchers reported at the OARSI 2022 World Congress.
“This can be explained by a lack of effectiveness of current management strategies, low uptake of recommended interventions by health care professionals, and also by low adherence by patients to medication and lifestyle interventions,” said Daniela Sofia Albino Costa, MSc, a PhD student at NOVA University Lisbon.
In addition to looking at the prevalence of inadequate pain relief – defined as a score of 5 or higher on the Numeric Pain Rating Scale (NPRS) – the study she presented at the congress, which was sponsored by the Osteoarthritis Research Society International, looked at the predictors for inadequate pain control.
It was found that being female, obesity, and having multimorbidity doubled the risk of inadequate versus adequate pain control, with respective odds ratios of 2.32 (P < .001), 2.26 (P = .006), and 2.07 (P = .001). Overweight was also associated with an increased odds ratio for poor pain control (OR, 1.84; P = .0035).
“We found that patients with inadequate pain relief also have a low performance on activities of daily living and a low quality of life,” Ms. Costa said.
Nearly one-third (29%) of patients in the inadequate pain relief group (n = 765) took medication, versus 15% of patients in the adequate pain relief group (n = 270). This was mostly NSAIDs, but also included analgesics and antipyretics, and in a few cases (4.8% vs. 1.3%), simple opioids.
“We know that current care is not concordant with recommendations,” said Ms. Costa, noting that medication being used as first-line treatment and core nonpharmacologic interventions are being offered to less than half of patients who are eligible.
In addition, the rate for total joint replacement has increased globally, and pain is an important predictor for this.
“So, we need to evaluate pain control and current management offered to people with hip or knee arthritis to identify to identify areas for improvement,” Ms. Costa said.
High rates of prescription opioid use before TKA
In a separate study also presented at the congress, Daniel Rhon, DPT, DSc, director of musculoskeletal research in primary care at Brooke Army Medical Center in San Antonio, gave a worrying glimpse of high rates of opioid use in the 4 years before total knee arthroplasty (TKA).
Using data from the U.S. Military Health System, the records of all individuals who had a knee replacement procedure between January 2017 and December 2018 were studied, to identify and characterize the use of prescription opioids.
Of the 46,362 individuals, 52.9% had prior opioid use, despite the fact that “opioids are not recommended for the management of knee OA,” said Dr. Rhon.
He also reported that as many as 40% of those who had at least one prescription for opioids had received a high-potency drug, such as fentanyl or oxycodone. The mean age of participants overall was 65 years, with a higher mean for those receiving opioids than those who did not (68 vs. 61.5 years). Data on sex and ethnicity were not available in time for presentation at the congress.
“Most of these individuals are getting these opioid prescriptions probably within 6 months, which maybe aligns with escalation of pain and maybe the decision to have that knee replacement,” Dr. Rhon said. Individuals that used opioids filled their most recent prescription a median of 146 days before TKA to surgery, with a mean of 317 days.
“You can’t always link the reason for the opioid prescription, that’s not really clear in the database,” he admitted; however, an analysis was performed to check if other surgeries had been performed that may have warranted the opioid treatment. The results revealed that very few of the opioid users (4%-7%) had undergone another type of surgical procedure.
“So, we feel a little bit better, that these findings weren’t for other surgical procedures,” said Dr. Rhon. He added that future qualitative research was needed to understand why health care professionals were prescribing opioids, and why patients felt like they needed them.
“That’s bad,” Haxby Abbott, PhD, DPT, a research professor at the University of Otago, Dunedin, New Zealand, commented on Twitter.
Dr. Abbott, who was not involved in the study, added: “We’ve done a similar study of the whole NZ population [currently under review] – similar to Australia and not nearly as bad as you found. That needs urgent attention.”
Sharp rise in opioid use 2 years before TKA
Lower rates of opioid use before TKA were seen in two European cohorts, at 43% in England and 33% in Sweden, as reported by Clara Hellberg, PhD, MD, of Lund (Sweden) University. However, rates had increased over a 10-year study period from a respective 23% and 16%, with a sharp increase in use in the 2 years before knee replacement.
The analysis was based on 49,043 patients from the English national database Clinical Practice Research Datalink, and 5,955 patients from the Swedish Skåne Healthcare register who had undergone total knee replacement between 2015 and 2019 and were matched by age, sex and general practice to individuals not undergoing knee replacement.
The prevalence ratio for using opioids over a 10-year period increased from 1.6 to 2.7 in England, and from 1.6 to 2.6 in Sweden.
“While the overall prevalence of opioid use was higher in England, the majority of both cases and controls were using weak opioids,” Dr. Hellberg said.
“Codeine was classified as a weak opioid, whereas morphine was classified as a strong opioid,” she added.
In contrast, the proportion of people using strong opioids in Sweden was greater than in England, she said.
The high opioid use found in the study highlights “the need for better opioid stewardship, and the availability of acceptable, effective alternatives,” Dr. Hellberg and associates concluded in their abstract.
The study presented by Ms. Costa was funded by the Portuguese national funding agency for science, research and technology and by an independent research grant from Pfizer. Dr. Rhon acknowledged grant funding from the National Institutes of Health and the U.S. Department of Defense. Dr. Hellberg had no conflicts of interest to disclose.
Inadequate pain relief was recorded in 68.8% of a sample of people with hip or knee OA who participated in the population-based EpiReumaPt study, researchers reported at the OARSI 2022 World Congress.
“This can be explained by a lack of effectiveness of current management strategies, low uptake of recommended interventions by health care professionals, and also by low adherence by patients to medication and lifestyle interventions,” said Daniela Sofia Albino Costa, MSc, a PhD student at NOVA University Lisbon.
In addition to looking at the prevalence of inadequate pain relief – defined as a score of 5 or higher on the Numeric Pain Rating Scale (NPRS) – the study she presented at the congress, which was sponsored by the Osteoarthritis Research Society International, looked at the predictors for inadequate pain control.
It was found that being female, obesity, and having multimorbidity doubled the risk of inadequate versus adequate pain control, with respective odds ratios of 2.32 (P < .001), 2.26 (P = .006), and 2.07 (P = .001). Overweight was also associated with an increased odds ratio for poor pain control (OR, 1.84; P = .0035).
“We found that patients with inadequate pain relief also have a low performance on activities of daily living and a low quality of life,” Ms. Costa said.
Nearly one-third (29%) of patients in the inadequate pain relief group (n = 765) took medication, versus 15% of patients in the adequate pain relief group (n = 270). This was mostly NSAIDs, but also included analgesics and antipyretics, and in a few cases (4.8% vs. 1.3%), simple opioids.
“We know that current care is not concordant with recommendations,” said Ms. Costa, noting that medication being used as first-line treatment and core nonpharmacologic interventions are being offered to less than half of patients who are eligible.
In addition, the rate for total joint replacement has increased globally, and pain is an important predictor for this.
“So, we need to evaluate pain control and current management offered to people with hip or knee arthritis to identify to identify areas for improvement,” Ms. Costa said.
High rates of prescription opioid use before TKA
In a separate study also presented at the congress, Daniel Rhon, DPT, DSc, director of musculoskeletal research in primary care at Brooke Army Medical Center in San Antonio, gave a worrying glimpse of high rates of opioid use in the 4 years before total knee arthroplasty (TKA).
Using data from the U.S. Military Health System, the records of all individuals who had a knee replacement procedure between January 2017 and December 2018 were studied, to identify and characterize the use of prescription opioids.
Of the 46,362 individuals, 52.9% had prior opioid use, despite the fact that “opioids are not recommended for the management of knee OA,” said Dr. Rhon.
He also reported that as many as 40% of those who had at least one prescription for opioids had received a high-potency drug, such as fentanyl or oxycodone. The mean age of participants overall was 65 years, with a higher mean for those receiving opioids than those who did not (68 vs. 61.5 years). Data on sex and ethnicity were not available in time for presentation at the congress.
“Most of these individuals are getting these opioid prescriptions probably within 6 months, which maybe aligns with escalation of pain and maybe the decision to have that knee replacement,” Dr. Rhon said. Individuals that used opioids filled their most recent prescription a median of 146 days before TKA to surgery, with a mean of 317 days.
“You can’t always link the reason for the opioid prescription, that’s not really clear in the database,” he admitted; however, an analysis was performed to check if other surgeries had been performed that may have warranted the opioid treatment. The results revealed that very few of the opioid users (4%-7%) had undergone another type of surgical procedure.
“So, we feel a little bit better, that these findings weren’t for other surgical procedures,” said Dr. Rhon. He added that future qualitative research was needed to understand why health care professionals were prescribing opioids, and why patients felt like they needed them.
“That’s bad,” Haxby Abbott, PhD, DPT, a research professor at the University of Otago, Dunedin, New Zealand, commented on Twitter.
Dr. Abbott, who was not involved in the study, added: “We’ve done a similar study of the whole NZ population [currently under review] – similar to Australia and not nearly as bad as you found. That needs urgent attention.”
Sharp rise in opioid use 2 years before TKA
Lower rates of opioid use before TKA were seen in two European cohorts, at 43% in England and 33% in Sweden, as reported by Clara Hellberg, PhD, MD, of Lund (Sweden) University. However, rates had increased over a 10-year study period from a respective 23% and 16%, with a sharp increase in use in the 2 years before knee replacement.
The analysis was based on 49,043 patients from the English national database Clinical Practice Research Datalink, and 5,955 patients from the Swedish Skåne Healthcare register who had undergone total knee replacement between 2015 and 2019 and were matched by age, sex and general practice to individuals not undergoing knee replacement.
The prevalence ratio for using opioids over a 10-year period increased from 1.6 to 2.7 in England, and from 1.6 to 2.6 in Sweden.
“While the overall prevalence of opioid use was higher in England, the majority of both cases and controls were using weak opioids,” Dr. Hellberg said.
“Codeine was classified as a weak opioid, whereas morphine was classified as a strong opioid,” she added.
In contrast, the proportion of people using strong opioids in Sweden was greater than in England, she said.
The high opioid use found in the study highlights “the need for better opioid stewardship, and the availability of acceptable, effective alternatives,” Dr. Hellberg and associates concluded in their abstract.
The study presented by Ms. Costa was funded by the Portuguese national funding agency for science, research and technology and by an independent research grant from Pfizer. Dr. Rhon acknowledged grant funding from the National Institutes of Health and the U.S. Department of Defense. Dr. Hellberg had no conflicts of interest to disclose.
FROM OARSI 2022
Weight gain may exacerbate structural damage in knee OA
researchers reported at the OARSI 2022 World Congress.
Using data from the Osteoarthritis Initiative (OAI), researchers from the University of California found that a greater than 5% increase in body weight over 4 years was associated with a 29% increased risk for medial joint space narrowing (JSN), compared with controls (P = .038). There was also a 34% increased risk for developing frequent knee pain (P = .009)
Conversely, weight loss appeared to offer some protection from structural damage in knee OA, Gabby B. Joseph, PhD, a specialist in radiology and biomedical imaging, said at the congress, sponsored by the Osteoarthritis Research Society International.
Indeed, individuals who had achieved a weight loss of more than 5% at 4-year follow up were less likely to have a worsened Kellgren and Lawrence (KL) grade than those whose body weight remained the same (odds ratio, 0.69, P = .009).
Weight loss was also associated with a higher change of experiencing resolution in knee pain over 12 months, with an OR of 1.40 (P = .019).
Importance of weight change in OA
“We know that weight loss has beneficial effects on knee OA symptoms, such as pain relief and improvement in physical function,” commented Xingzhong Jin, PhD, an NHMRC Early Career Fellow at the Centre for Big Data Research in Health at the University of New South Wales, Sydney.
“But what is unclear is whether weight loss could slow down structural degradation in the joint in the long run,” he said in an interview. “These findings mean that weight control is clearly very important for knee OA, in terms of improving symptoms as well as preventing structural progression.”
He added: “The evidence on hip OA is less clear. As most of the knowledge in this space was generated from people with knee OA, this work is an important contribution to knowledge around the care of people with hip OA.”
Why look at weight change effects in OA?
“Obesity is a modifiable risk factor for osteoarthritis,” Dr. Joseph said at the start of her virtual presentation. Indeed, patients with obesity are more than twice as likely to develop knee OA than their normal weight counterparts.
Although there have been various studies looking at weight loss and weight gain in OA, most have focused on weight loss rather than gain, and OA in the knee rather than the hip, she explained.
The aim of the present study, therefore, was to take a closer look at the possible effect of both weight gain and weight loss in people with hip or knee OA in terms of radiographic outcomes (KL grade change, medial JSN), symptomatic outcomes (knee pain and resolution at 12 months), and the need for joint replacement.
“The clinical implications are to develop targeted long-term strategies for site-specific informed recommendations to prevent joint degeneration,” Dr. Joseph said.
Using data on nearly 3,000 individuals from the OAI, Dr Joseph and collaborators classified people with OA into one of three groups: those with at least a 5% gain in weight, (n = 714), those with no (–3% to 3%) change in weight (n = 1,553), and those with at least a 5% loss in weight over a 4-year period.
The results, which were published in Arthritis Care & Research, also revealed no differences in the rate of total hip or knee arthroplasties between the groups, and no differences between the weight gain and weight loss groups and controls in term of hip radiographic or symptomatic changes.
“Why are there differing effects of weight change in the knee versus the hip? This could be multifactorial, but there could be a few things going on,” said Dr. Joseph. “First, the joint structure is clearly different between the knee and the hip. The knee is a hinge joint. The hip is a ball and socket joint malalignment could affect these in different ways.”
Additionally, “the knee also has thicker cartilage, the hip has thinner cartilage again, and the loading patterns may be different in these joints.”
There were also differences in the rate of progression between the knee and the hip, “this was especially noticeable for the radiographic progression,” Dr. Joseph said, with rates being higher in the knee.
Noting that the study is limited by its retrospective design, Dr. Joseph concluded: “We don’t know why these people lost or gained weight. So, this would be something that would be more apparent in a prospective study.
“Also, there were no MRI outcomes, as MRI imaging was not available in the hip in the OAI, but clearly morphology T1 and T2 would be useful to assess as outcomes here as well.”
The OAI is a public-private partnership funded by the National Institutes of Health and initial support from Merck, Novartis, GlaxoSmithKline and Pfizer. Dr. Joseph and Dr. Jin reported having no conflicts of interest to disclose.
researchers reported at the OARSI 2022 World Congress.
Using data from the Osteoarthritis Initiative (OAI), researchers from the University of California found that a greater than 5% increase in body weight over 4 years was associated with a 29% increased risk for medial joint space narrowing (JSN), compared with controls (P = .038). There was also a 34% increased risk for developing frequent knee pain (P = .009)
Conversely, weight loss appeared to offer some protection from structural damage in knee OA, Gabby B. Joseph, PhD, a specialist in radiology and biomedical imaging, said at the congress, sponsored by the Osteoarthritis Research Society International.
Indeed, individuals who had achieved a weight loss of more than 5% at 4-year follow up were less likely to have a worsened Kellgren and Lawrence (KL) grade than those whose body weight remained the same (odds ratio, 0.69, P = .009).
Weight loss was also associated with a higher change of experiencing resolution in knee pain over 12 months, with an OR of 1.40 (P = .019).
Importance of weight change in OA
“We know that weight loss has beneficial effects on knee OA symptoms, such as pain relief and improvement in physical function,” commented Xingzhong Jin, PhD, an NHMRC Early Career Fellow at the Centre for Big Data Research in Health at the University of New South Wales, Sydney.
“But what is unclear is whether weight loss could slow down structural degradation in the joint in the long run,” he said in an interview. “These findings mean that weight control is clearly very important for knee OA, in terms of improving symptoms as well as preventing structural progression.”
He added: “The evidence on hip OA is less clear. As most of the knowledge in this space was generated from people with knee OA, this work is an important contribution to knowledge around the care of people with hip OA.”
Why look at weight change effects in OA?
“Obesity is a modifiable risk factor for osteoarthritis,” Dr. Joseph said at the start of her virtual presentation. Indeed, patients with obesity are more than twice as likely to develop knee OA than their normal weight counterparts.
Although there have been various studies looking at weight loss and weight gain in OA, most have focused on weight loss rather than gain, and OA in the knee rather than the hip, she explained.
The aim of the present study, therefore, was to take a closer look at the possible effect of both weight gain and weight loss in people with hip or knee OA in terms of radiographic outcomes (KL grade change, medial JSN), symptomatic outcomes (knee pain and resolution at 12 months), and the need for joint replacement.
“The clinical implications are to develop targeted long-term strategies for site-specific informed recommendations to prevent joint degeneration,” Dr. Joseph said.
Using data on nearly 3,000 individuals from the OAI, Dr Joseph and collaborators classified people with OA into one of three groups: those with at least a 5% gain in weight, (n = 714), those with no (–3% to 3%) change in weight (n = 1,553), and those with at least a 5% loss in weight over a 4-year period.
The results, which were published in Arthritis Care & Research, also revealed no differences in the rate of total hip or knee arthroplasties between the groups, and no differences between the weight gain and weight loss groups and controls in term of hip radiographic or symptomatic changes.
“Why are there differing effects of weight change in the knee versus the hip? This could be multifactorial, but there could be a few things going on,” said Dr. Joseph. “First, the joint structure is clearly different between the knee and the hip. The knee is a hinge joint. The hip is a ball and socket joint malalignment could affect these in different ways.”
Additionally, “the knee also has thicker cartilage, the hip has thinner cartilage again, and the loading patterns may be different in these joints.”
There were also differences in the rate of progression between the knee and the hip, “this was especially noticeable for the radiographic progression,” Dr. Joseph said, with rates being higher in the knee.
Noting that the study is limited by its retrospective design, Dr. Joseph concluded: “We don’t know why these people lost or gained weight. So, this would be something that would be more apparent in a prospective study.
“Also, there were no MRI outcomes, as MRI imaging was not available in the hip in the OAI, but clearly morphology T1 and T2 would be useful to assess as outcomes here as well.”
The OAI is a public-private partnership funded by the National Institutes of Health and initial support from Merck, Novartis, GlaxoSmithKline and Pfizer. Dr. Joseph and Dr. Jin reported having no conflicts of interest to disclose.
researchers reported at the OARSI 2022 World Congress.
Using data from the Osteoarthritis Initiative (OAI), researchers from the University of California found that a greater than 5% increase in body weight over 4 years was associated with a 29% increased risk for medial joint space narrowing (JSN), compared with controls (P = .038). There was also a 34% increased risk for developing frequent knee pain (P = .009)
Conversely, weight loss appeared to offer some protection from structural damage in knee OA, Gabby B. Joseph, PhD, a specialist in radiology and biomedical imaging, said at the congress, sponsored by the Osteoarthritis Research Society International.
Indeed, individuals who had achieved a weight loss of more than 5% at 4-year follow up were less likely to have a worsened Kellgren and Lawrence (KL) grade than those whose body weight remained the same (odds ratio, 0.69, P = .009).
Weight loss was also associated with a higher change of experiencing resolution in knee pain over 12 months, with an OR of 1.40 (P = .019).
Importance of weight change in OA
“We know that weight loss has beneficial effects on knee OA symptoms, such as pain relief and improvement in physical function,” commented Xingzhong Jin, PhD, an NHMRC Early Career Fellow at the Centre for Big Data Research in Health at the University of New South Wales, Sydney.
“But what is unclear is whether weight loss could slow down structural degradation in the joint in the long run,” he said in an interview. “These findings mean that weight control is clearly very important for knee OA, in terms of improving symptoms as well as preventing structural progression.”
He added: “The evidence on hip OA is less clear. As most of the knowledge in this space was generated from people with knee OA, this work is an important contribution to knowledge around the care of people with hip OA.”
Why look at weight change effects in OA?
“Obesity is a modifiable risk factor for osteoarthritis,” Dr. Joseph said at the start of her virtual presentation. Indeed, patients with obesity are more than twice as likely to develop knee OA than their normal weight counterparts.
Although there have been various studies looking at weight loss and weight gain in OA, most have focused on weight loss rather than gain, and OA in the knee rather than the hip, she explained.
The aim of the present study, therefore, was to take a closer look at the possible effect of both weight gain and weight loss in people with hip or knee OA in terms of radiographic outcomes (KL grade change, medial JSN), symptomatic outcomes (knee pain and resolution at 12 months), and the need for joint replacement.
“The clinical implications are to develop targeted long-term strategies for site-specific informed recommendations to prevent joint degeneration,” Dr. Joseph said.
Using data on nearly 3,000 individuals from the OAI, Dr Joseph and collaborators classified people with OA into one of three groups: those with at least a 5% gain in weight, (n = 714), those with no (–3% to 3%) change in weight (n = 1,553), and those with at least a 5% loss in weight over a 4-year period.
The results, which were published in Arthritis Care & Research, also revealed no differences in the rate of total hip or knee arthroplasties between the groups, and no differences between the weight gain and weight loss groups and controls in term of hip radiographic or symptomatic changes.
“Why are there differing effects of weight change in the knee versus the hip? This could be multifactorial, but there could be a few things going on,” said Dr. Joseph. “First, the joint structure is clearly different between the knee and the hip. The knee is a hinge joint. The hip is a ball and socket joint malalignment could affect these in different ways.”
Additionally, “the knee also has thicker cartilage, the hip has thinner cartilage again, and the loading patterns may be different in these joints.”
There were also differences in the rate of progression between the knee and the hip, “this was especially noticeable for the radiographic progression,” Dr. Joseph said, with rates being higher in the knee.
Noting that the study is limited by its retrospective design, Dr. Joseph concluded: “We don’t know why these people lost or gained weight. So, this would be something that would be more apparent in a prospective study.
“Also, there were no MRI outcomes, as MRI imaging was not available in the hip in the OAI, but clearly morphology T1 and T2 would be useful to assess as outcomes here as well.”
The OAI is a public-private partnership funded by the National Institutes of Health and initial support from Merck, Novartis, GlaxoSmithKline and Pfizer. Dr. Joseph and Dr. Jin reported having no conflicts of interest to disclose.
FROM OARSI 2022