Osteoarthritis

SAN DIEGO – Hand osteoarthritis causes patients a wide range of daily problems, but popular functional assessment questionnaires may miss many of them, Norwegian researchers have found.

In response to a survey question, 211 Norwegians with hand osteoarthritis (OA) listed 311 tasks their OA made more challenging. Wringing out cloths and opening jars was a struggle for more than half. A third or more said buttoning and unbuttoning clothes were hard, as was carrying suitcases and other heavy objects. More than 20% reported having a hard time peeling raw vegetables.

Those items are among the nine tasks asked about on the widely used hand OA questionnaire, the Australian/Canadian (AUSCAN) Hand Osteoarthritis Index, said lead investigator Linda Fernandes, Ph.D., a physiotherapist at Diakonhjemmet Hospital in Oslo.

However, more than half of the Norwegian sample had a hard time opening bottles, too. About a third said writing by hand and slicing bread were tough. About 20% or more said knitting, putting on socks, vacuuming, carrying shopping bags, zipping pants, and wiping down floors, among other chores, were problems, and some patients listed those items as priorities. None are on the AUSCAN, she said at the World Congress on Osteoarthritis, sponsored by the Osteoarthritis Research Society International.

Patients also did not mention problems putting on jewelry; opening doors and turning on faucets weren’t problems either, likely because doors in Scandinavia have turning handles, not doorknobs, and most sinks have a single lever to control hot and cold water. All three items are on the AUSCAN, Dr. Fernandes said.

"The outcome measures we have today," which also include Dreiser’s Functional Index, "are all expert opinion–based questionnaires. They haven’t really asked the patients themselves" about their daily struggles, she said.

She and her colleagues are using their findings to develop what they hope will be a more comprehensive questionnaire, but they declined to give details pending publication.

In the meantime, physicians might learn more about the challenges their OA patients face by going beyond current questionnaires; the study suggests additional things about which to ask. For many chores, there are tools to help, such as lid handles to open jars. Grip-strength exercises and range of motion exercises, especially for the thumb, may also help, Dr. Fernandes said.

In general, patients said they were still able to perform the tasks they listed, just not as well as before. Pain or fear of it might have had something to do with the problems, she said.

The study included 201 women and 10 men recruited consecutively as they presented to rheumatology clinics in Oslo and Trondheim. They were 63 years old on average, with a mean disease duration of 12.5 years and 8.6 affected joints; 64% had a comorbidity, 49% were employed.

The Norwegian Occupational Therapy Association and the Oslo Rheumatism Association paid for the study. Dr. Fernandes said she has no disclosures.

SAN DIEGO – Hand osteoarthritis causes patients a wide range of daily problems, but popular functional assessment questionnaires may miss many of them, Norwegian researchers have found.

In response to a survey question, 211 Norwegians with hand osteoarthritis (OA) listed 311 tasks their OA made more challenging. Wringing out cloths and opening jars was a struggle for more than half. A third or more said buttoning and unbuttoning clothes were hard, as was carrying suitcases and other heavy objects. More than 20% reported having a hard time peeling raw vegetables.

Those items are among the nine tasks asked about on the widely used hand OA questionnaire, the Australian/Canadian (AUSCAN) Hand Osteoarthritis Index, said lead investigator Linda Fernandes, Ph.D., a physiotherapist at Diakonhjemmet Hospital in Oslo.

However, more than half of the Norwegian sample had a hard time opening bottles, too. About a third said writing by hand and slicing bread were tough. About 20% or more said knitting, putting on socks, vacuuming, carrying shopping bags, zipping pants, and wiping down floors, among other chores, were problems, and some patients listed those items as priorities. None are on the AUSCAN, she said at the World Congress on Osteoarthritis, sponsored by the Osteoarthritis Research Society International.

Patients also did not mention problems putting on jewelry; opening doors and turning on faucets weren’t problems either, likely because doors in Scandinavia have turning handles, not doorknobs, and most sinks have a single lever to control hot and cold water. All three items are on the AUSCAN, Dr. Fernandes said.

"The outcome measures we have today," which also include Dreiser’s Functional Index, "are all expert opinion–based questionnaires. They haven’t really asked the patients themselves" about their daily struggles, she said.

She and her colleagues are using their findings to develop what they hope will be a more comprehensive questionnaire, but they declined to give details pending publication.

In the meantime, physicians might learn more about the challenges their OA patients face by going beyond current questionnaires; the study suggests additional things about which to ask. For many chores, there are tools to help, such as lid handles to open jars. Grip-strength exercises and range of motion exercises, especially for the thumb, may also help, Dr. Fernandes said.

In general, patients said they were still able to perform the tasks they listed, just not as well as before. Pain or fear of it might have had something to do with the problems, she said.

The study included 201 women and 10 men recruited consecutively as they presented to rheumatology clinics in Oslo and Trondheim. They were 63 years old on average, with a mean disease duration of 12.5 years and 8.6 affected joints; 64% had a comorbidity, 49% were employed.

The Norwegian Occupational Therapy Association and the Oslo Rheumatism Association paid for the study. Dr. Fernandes said she has no disclosures.

SAN DIEGO – Hand osteoarthritis causes patients a wide range of daily problems, but popular functional assessment questionnaires may miss many of them, Norwegian researchers have found.

In response to a survey question, 211 Norwegians with hand osteoarthritis (OA) listed 311 tasks their OA made more challenging. Wringing out cloths and opening jars was a struggle for more than half. A third or more said buttoning and unbuttoning clothes were hard, as was carrying suitcases and other heavy objects. More than 20% reported having a hard time peeling raw vegetables.

Those items are among the nine tasks asked about on the widely used hand OA questionnaire, the Australian/Canadian (AUSCAN) Hand Osteoarthritis Index, said lead investigator Linda Fernandes, Ph.D., a physiotherapist at Diakonhjemmet Hospital in Oslo.

However, more than half of the Norwegian sample had a hard time opening bottles, too. About a third said writing by hand and slicing bread were tough. About 20% or more said knitting, putting on socks, vacuuming, carrying shopping bags, zipping pants, and wiping down floors, among other chores, were problems, and some patients listed those items as priorities. None are on the AUSCAN, she said at the World Congress on Osteoarthritis, sponsored by the Osteoarthritis Research Society International.

Patients also did not mention problems putting on jewelry; opening doors and turning on faucets weren’t problems either, likely because doors in Scandinavia have turning handles, not doorknobs, and most sinks have a single lever to control hot and cold water. All three items are on the AUSCAN, Dr. Fernandes said.

"The outcome measures we have today," which also include Dreiser’s Functional Index, "are all expert opinion–based questionnaires. They haven’t really asked the patients themselves" about their daily struggles, she said.

She and her colleagues are using their findings to develop what they hope will be a more comprehensive questionnaire, but they declined to give details pending publication.

In the meantime, physicians might learn more about the challenges their OA patients face by going beyond current questionnaires; the study suggests additional things about which to ask. For many chores, there are tools to help, such as lid handles to open jars. Grip-strength exercises and range of motion exercises, especially for the thumb, may also help, Dr. Fernandes said.

In general, patients said they were still able to perform the tasks they listed, just not as well as before. Pain or fear of it might have had something to do with the problems, she said.

The study included 201 women and 10 men recruited consecutively as they presented to rheumatology clinics in Oslo and Trondheim. They were 63 years old on average, with a mean disease duration of 12.5 years and 8.6 affected joints; 64% had a comorbidity, 49% were employed.

The Norwegian Occupational Therapy Association and the Oslo Rheumatism Association paid for the study. Dr. Fernandes said she has no disclosures.

SAN DIEGO – Oral salmon calcitonin significantly reduced pain and stiffness, improved physical function, and slowed cartilage loss, especially in the medial tibial compartment in a 2-year, placebo-controlled, phase III clinical trial involving 1,169 patients with painful knee osteoarthritis.

But the trial did not meet one of its primary end points, improvement in joint space width.

Even so, "this pivotal phase III clinical trial suggests that oral salmon calcitonin," dosed at 0.8 mg twice daily for 24 months, "is safe, and has sustained symptom-modifying" benefits in osteoarthritis and "some structure-modifying effects," said Dr. Morten Karsdal, CEO of Nordic Bioscience in Herlev, Denmark, which sponsored the trial and is developing the drug in collaboration with Novartis Pharma.

Oral calcitonin (oCT) holds the promise of offering the benefits of calcitonin – widely used for osteoporosis, among other problems – without the immunogenicity of currently available nasal and injectable formulations.

At month 24, 17% of the 585 oCT subjects had circulating antibodies against the drug; historically, 40%-70% of users develop antibodies against nasal and injectable formulations, Dr. Karsdal said.

The mean age of trial subjects was 64 years, and mean body mass index about 29 kg/m²; 68% were women. Most patients had Kellgren-Lawrence grade II disease, the rest were grade III. Rescue medication was allowed in both the placebo and treatment arms.

By month 24, oCT subjects demonstrated about a 5% loss in cartilage volume on MRI in both the signal and non-signal knee; placebo subjects demonstrated slightly more than a 7% loss in both knees. The differences were statistically significant.

"We prevent a decrease; we do not gain cartilage," Dr. Karsdal said.

Also at month 24, oCT bested placebo in WOMAC (Western Ontario and McMaster Universities) Osteoarthritis Index pain scores (–115.7 vs. –94.9 mm; P = .002), function scores (–338.7 vs. –283.0 mm; P = .013), and stiffness scores (–44.1 vs. –32.6 mm; P less than .001).

It took about 6 months of treatment before oCT began to clearly separate from placebo on the WOMAC pain score.

Oral calcitonin also beat placebo on 24-hour visual analog scale (VAS) pain scores (P = .018), patient global assessment (P = .008), and physician global assessment (P = .014).

The most common adverse events in the oCT group, vs. placebo, were hot flashes (18% vs. 4%), nausea (14% vs. 3%), dyspepsia (10% vs. 5%), and diarrhea (10% vs. 4%).

Almost 20% of oCT subjects dropped out of the trial because of those and other side effects; the drug-related discontinuation rate in the placebo arm was 6%.

The side effects "are associated with the mode of action of salmon calcitonin, and mostly happened early," Dr. Karsdal said.

The trial was sponsored by Nordic Bioscience, which is developing the drug in collaboration with Novartis Pharma. Dr. Karsdal is the CEO of Nordic Bioscience.

SAN DIEGO – Oral salmon calcitonin significantly reduced pain and stiffness, improved physical function, and slowed cartilage loss, especially in the medial tibial compartment in a 2-year, placebo-controlled, phase III clinical trial involving 1,169 patients with painful knee osteoarthritis.

But the trial did not meet one of its primary end points, improvement in joint space width.

Even so, "this pivotal phase III clinical trial suggests that oral salmon calcitonin," dosed at 0.8 mg twice daily for 24 months, "is safe, and has sustained symptom-modifying" benefits in osteoarthritis and "some structure-modifying effects," said Dr. Morten Karsdal, CEO of Nordic Bioscience in Herlev, Denmark, which sponsored the trial and is developing the drug in collaboration with Novartis Pharma.

Oral calcitonin (oCT) holds the promise of offering the benefits of calcitonin – widely used for osteoporosis, among other problems – without the immunogenicity of currently available nasal and injectable formulations.

At month 24, 17% of the 585 oCT subjects had circulating antibodies against the drug; historically, 40%-70% of users develop antibodies against nasal and injectable formulations, Dr. Karsdal said.

The mean age of trial subjects was 64 years, and mean body mass index about 29 kg/m²; 68% were women. Most patients had Kellgren-Lawrence grade II disease, the rest were grade III. Rescue medication was allowed in both the placebo and treatment arms.

By month 24, oCT subjects demonstrated about a 5% loss in cartilage volume on MRI in both the signal and non-signal knee; placebo subjects demonstrated slightly more than a 7% loss in both knees. The differences were statistically significant.

"We prevent a decrease; we do not gain cartilage," Dr. Karsdal said.

Also at month 24, oCT bested placebo in WOMAC (Western Ontario and McMaster Universities) Osteoarthritis Index pain scores (–115.7 vs. –94.9 mm; P = .002), function scores (–338.7 vs. –283.0 mm; P = .013), and stiffness scores (–44.1 vs. –32.6 mm; P less than .001).

It took about 6 months of treatment before oCT began to clearly separate from placebo on the WOMAC pain score.

Oral calcitonin also beat placebo on 24-hour visual analog scale (VAS) pain scores (P = .018), patient global assessment (P = .008), and physician global assessment (P = .014).

The most common adverse events in the oCT group, vs. placebo, were hot flashes (18% vs. 4%), nausea (14% vs. 3%), dyspepsia (10% vs. 5%), and diarrhea (10% vs. 4%).

Almost 20% of oCT subjects dropped out of the trial because of those and other side effects; the drug-related discontinuation rate in the placebo arm was 6%.

The side effects "are associated with the mode of action of salmon calcitonin, and mostly happened early," Dr. Karsdal said.

The trial was sponsored by Nordic Bioscience, which is developing the drug in collaboration with Novartis Pharma. Dr. Karsdal is the CEO of Nordic Bioscience.

SAN DIEGO – Oral salmon calcitonin significantly reduced pain and stiffness, improved physical function, and slowed cartilage loss, especially in the medial tibial compartment in a 2-year, placebo-controlled, phase III clinical trial involving 1,169 patients with painful knee osteoarthritis.

But the trial did not meet one of its primary end points, improvement in joint space width.

Even so, "this pivotal phase III clinical trial suggests that oral salmon calcitonin," dosed at 0.8 mg twice daily for 24 months, "is safe, and has sustained symptom-modifying" benefits in osteoarthritis and "some structure-modifying effects," said Dr. Morten Karsdal, CEO of Nordic Bioscience in Herlev, Denmark, which sponsored the trial and is developing the drug in collaboration with Novartis Pharma.

Oral calcitonin (oCT) holds the promise of offering the benefits of calcitonin – widely used for osteoporosis, among other problems – without the immunogenicity of currently available nasal and injectable formulations.

At month 24, 17% of the 585 oCT subjects had circulating antibodies against the drug; historically, 40%-70% of users develop antibodies against nasal and injectable formulations, Dr. Karsdal said.

The mean age of trial subjects was 64 years, and mean body mass index about 29 kg/m²; 68% were women. Most patients had Kellgren-Lawrence grade II disease, the rest were grade III. Rescue medication was allowed in both the placebo and treatment arms.

By month 24, oCT subjects demonstrated about a 5% loss in cartilage volume on MRI in both the signal and non-signal knee; placebo subjects demonstrated slightly more than a 7% loss in both knees. The differences were statistically significant.

"We prevent a decrease; we do not gain cartilage," Dr. Karsdal said.

Also at month 24, oCT bested placebo in WOMAC (Western Ontario and McMaster Universities) Osteoarthritis Index pain scores (–115.7 vs. –94.9 mm; P = .002), function scores (–338.7 vs. –283.0 mm; P = .013), and stiffness scores (–44.1 vs. –32.6 mm; P less than .001).

It took about 6 months of treatment before oCT began to clearly separate from placebo on the WOMAC pain score.

Oral calcitonin also beat placebo on 24-hour visual analog scale (VAS) pain scores (P = .018), patient global assessment (P = .008), and physician global assessment (P = .014).

The most common adverse events in the oCT group, vs. placebo, were hot flashes (18% vs. 4%), nausea (14% vs. 3%), dyspepsia (10% vs. 5%), and diarrhea (10% vs. 4%).

Almost 20% of oCT subjects dropped out of the trial because of those and other side effects; the drug-related discontinuation rate in the placebo arm was 6%.

The side effects "are associated with the mode of action of salmon calcitonin, and mostly happened early," Dr. Karsdal said.

The trial was sponsored by Nordic Bioscience, which is developing the drug in collaboration with Novartis Pharma. Dr. Karsdal is the CEO of Nordic Bioscience.

SAN DIEGO – People who are overweight or younger than 75 years when they have a total hip replacement face an increased risk for revision within 12 years; the risk is also increased if cement was used to hold the femoral stem of the implant in place.

"Patients and physicians may wish to weave some of these findings into their decisions about whether to undergo primary [total hip replacement] because they inform the subsequent risk of revision," said the study’s lead author, Dr. Jeffrey Katz, professor of medicine and orthopedic surgery at Harvard Medical School, Boston.

Using hospital records and Medicare claims data, Dr. Katz and his associates examined the presurgery characteristics of 836 people who had initial total hip replacements (THRs) from July 1995 to June 1996 and subsequent revisions sometime before 2009. The researchers then compared those patients to 836 matched controls who also had THRs in the mid-1990s but whose prosthetic hip had not been revised by the time their case had a revision.

Patients who had a prior contralateral hip replacement, a prior history of other orthopedic surgery, and those who lived with others, instead of alone, also had a higher revision risk. Odds ratios were modest but statistically significant, ranging from 1.3 to 1.7.

"Age and weight were not surprising. We thought we might see an effect of sex [since] there is a literature of males being at higher risk, but we did not. There is also literature on comorbidity being associated with revision, which we did not see," Dr. Katz said at the World Congress on Osteoarthritis.

The cement finding adds "to what is a rather conflicted literature on the durability of cemented versus uncemented designs," he said. The odds ratio for the finding was 1.4.

Cement techniques – including techniques for reaming out the femur and applying the pressure to the cement – have improved since the mid-1990s, so "you have to be careful interpreting the [cement] data. They may not apply to the way cement is used now," Dr. Katz said.

Based on the findings, "when you talk to somebody who is in their mid to late 70s about hip replacement, I think you can say revision is not particularly likely. For a younger person, they should recognize that we may have to go back again. At that point, they’ll be older and have greater surgical risk," he said.

The manufacturer of the implants, the initial surgeon’s level of experience with the procedure, and the reasons for the revisions were not captured by the study.

The researchers also found a higher risk of revision if, at the time of their initial surgery, patients had a body mass index (BMI) greater than 30 kg/m² (OR, 1.5) or were in the highest tertile for weight (OR, 1.7) or height (OR, 1.4).

Dr. Katz offered several interpretations. Height, weight, and BMI are likely related to the biomechanical load on the implant. Regarding the greater risk below age 75 years (OR, 1.5), younger, more active patients may be more likely to have a faulty THR fixed. Increased risk for prior contralateral hip replacements (OR, 1.4) or orthopedic surgery (OR, 1.5) may indicated a willingness and ability to undergo surgery.

The added risk from living with others (OR, 1.3) "may represent having the social support in place to deal with rehab and a temporary dependency," which facilitates elective surgery, he said.

There are about 280,000 primary THRs in the United States annually, and about 50,000 revisions. The revision rate is about 1% a year, "so 100 people who go out 20 years, you might expect 20 of them to be revised," Dr. Katz said at the congress, which was sponsored by the Osteoarthritis Research Society International.

The work was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Katz said he has no disclosures.

SAN DIEGO – People who are overweight or younger than 75 years when they have a total hip replacement face an increased risk for revision within 12 years; the risk is also increased if cement was used to hold the femoral stem of the implant in place.

"Patients and physicians may wish to weave some of these findings into their decisions about whether to undergo primary [total hip replacement] because they inform the subsequent risk of revision," said the study’s lead author, Dr. Jeffrey Katz, professor of medicine and orthopedic surgery at Harvard Medical School, Boston.

Using hospital records and Medicare claims data, Dr. Katz and his associates examined the presurgery characteristics of 836 people who had initial total hip replacements (THRs) from July 1995 to June 1996 and subsequent revisions sometime before 2009. The researchers then compared those patients to 836 matched controls who also had THRs in the mid-1990s but whose prosthetic hip had not been revised by the time their case had a revision.

Patients who had a prior contralateral hip replacement, a prior history of other orthopedic surgery, and those who lived with others, instead of alone, also had a higher revision risk. Odds ratios were modest but statistically significant, ranging from 1.3 to 1.7.

"Age and weight were not surprising. We thought we might see an effect of sex [since] there is a literature of males being at higher risk, but we did not. There is also literature on comorbidity being associated with revision, which we did not see," Dr. Katz said at the World Congress on Osteoarthritis.

The cement finding adds "to what is a rather conflicted literature on the durability of cemented versus uncemented designs," he said. The odds ratio for the finding was 1.4.

Cement techniques – including techniques for reaming out the femur and applying the pressure to the cement – have improved since the mid-1990s, so "you have to be careful interpreting the [cement] data. They may not apply to the way cement is used now," Dr. Katz said.

Based on the findings, "when you talk to somebody who is in their mid to late 70s about hip replacement, I think you can say revision is not particularly likely. For a younger person, they should recognize that we may have to go back again. At that point, they’ll be older and have greater surgical risk," he said.

The manufacturer of the implants, the initial surgeon’s level of experience with the procedure, and the reasons for the revisions were not captured by the study.

The researchers also found a higher risk of revision if, at the time of their initial surgery, patients had a body mass index (BMI) greater than 30 kg/m² (OR, 1.5) or were in the highest tertile for weight (OR, 1.7) or height (OR, 1.4).

Dr. Katz offered several interpretations. Height, weight, and BMI are likely related to the biomechanical load on the implant. Regarding the greater risk below age 75 years (OR, 1.5), younger, more active patients may be more likely to have a faulty THR fixed. Increased risk for prior contralateral hip replacements (OR, 1.4) or orthopedic surgery (OR, 1.5) may indicated a willingness and ability to undergo surgery.

The added risk from living with others (OR, 1.3) "may represent having the social support in place to deal with rehab and a temporary dependency," which facilitates elective surgery, he said.

There are about 280,000 primary THRs in the United States annually, and about 50,000 revisions. The revision rate is about 1% a year, "so 100 people who go out 20 years, you might expect 20 of them to be revised," Dr. Katz said at the congress, which was sponsored by the Osteoarthritis Research Society International.

The work was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Katz said he has no disclosures.

SAN DIEGO – People who are overweight or younger than 75 years when they have a total hip replacement face an increased risk for revision within 12 years; the risk is also increased if cement was used to hold the femoral stem of the implant in place.

"Patients and physicians may wish to weave some of these findings into their decisions about whether to undergo primary [total hip replacement] because they inform the subsequent risk of revision," said the study’s lead author, Dr. Jeffrey Katz, professor of medicine and orthopedic surgery at Harvard Medical School, Boston.

Using hospital records and Medicare claims data, Dr. Katz and his associates examined the presurgery characteristics of 836 people who had initial total hip replacements (THRs) from July 1995 to June 1996 and subsequent revisions sometime before 2009. The researchers then compared those patients to 836 matched controls who also had THRs in the mid-1990s but whose prosthetic hip had not been revised by the time their case had a revision.

Patients who had a prior contralateral hip replacement, a prior history of other orthopedic surgery, and those who lived with others, instead of alone, also had a higher revision risk. Odds ratios were modest but statistically significant, ranging from 1.3 to 1.7.

"Age and weight were not surprising. We thought we might see an effect of sex [since] there is a literature of males being at higher risk, but we did not. There is also literature on comorbidity being associated with revision, which we did not see," Dr. Katz said at the World Congress on Osteoarthritis.

The cement finding adds "to what is a rather conflicted literature on the durability of cemented versus uncemented designs," he said. The odds ratio for the finding was 1.4.

Cement techniques – including techniques for reaming out the femur and applying the pressure to the cement – have improved since the mid-1990s, so "you have to be careful interpreting the [cement] data. They may not apply to the way cement is used now," Dr. Katz said.

Based on the findings, "when you talk to somebody who is in their mid to late 70s about hip replacement, I think you can say revision is not particularly likely. For a younger person, they should recognize that we may have to go back again. At that point, they’ll be older and have greater surgical risk," he said.

The manufacturer of the implants, the initial surgeon’s level of experience with the procedure, and the reasons for the revisions were not captured by the study.

The researchers also found a higher risk of revision if, at the time of their initial surgery, patients had a body mass index (BMI) greater than 30 kg/m² (OR, 1.5) or were in the highest tertile for weight (OR, 1.7) or height (OR, 1.4).

Dr. Katz offered several interpretations. Height, weight, and BMI are likely related to the biomechanical load on the implant. Regarding the greater risk below age 75 years (OR, 1.5), younger, more active patients may be more likely to have a faulty THR fixed. Increased risk for prior contralateral hip replacements (OR, 1.4) or orthopedic surgery (OR, 1.5) may indicated a willingness and ability to undergo surgery.

The added risk from living with others (OR, 1.3) "may represent having the social support in place to deal with rehab and a temporary dependency," which facilitates elective surgery, he said.

There are about 280,000 primary THRs in the United States annually, and about 50,000 revisions. The revision rate is about 1% a year, "so 100 people who go out 20 years, you might expect 20 of them to be revised," Dr. Katz said at the congress, which was sponsored by the Osteoarthritis Research Society International.

The work was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Katz said he has no disclosures.

SAN DIEGO – In the majority of patients with knee osteoarthritis, the baseline volumes of associated bone marrow lesions change substantially within 6 to 12 weeks of diagnosis, judging from the findings of an ongoing drug study.

The findings suggest that volume changes – either decreases or increases as determined by magnetic resonance imaging – may help assess short-term fluctuations in joint damage.

"I think this may allow trials to be done with relatively smaller numbers of patients and briefer follow-ups," said the study’s lead author Dr. David Felson, professor of medicine and epidemiology at both Boston University and the University of Manchester (England).

A rapid marker for disease progress would be welcome; osteoarthritis (OA) is generally considered a slowly evolving disease "with glacial changes in cartilage morphology necessitating trials of potential treatments lasting 1-2 years," Dr. Felson said at the World Congress on Osteoarthritis.

"To the extent that they could be regarded as treatment targets, trials testing [bone marrow lesion] effects could avoid the usual prolonged structure modification trials," he said.

Bone marrow lesions (BMLs) are ill-defined, hyperintense lesions in subcortical bone detected during water-sensitive, fat-suppressed MRIs. Their presence indicates local bone damage and microfractures.

Recently, larger BMLs have been correlated with worse knee pain. Lesions have also been related to malalignment, risk of overlying cartilage loss, OA progression, and poor outcomes, Dr. Felson said.

He and his colleagues used axial and sagittal MRIs to assess BML volumes in patients with painful patellofemoral at baseline, 6, and 12 weeks. The patients were 40-70 years old, with a mean body mass index of about 30 kg/m². Baseline median BML volumes were a bit over 2,000 mm³.

During the study, 23 of 35 assessed knees had a greater than 50% change in volume. Eight had a greater than 50% change in volume at 6 weeks only, 4 at 12 weeks only, and 11 at both 6 and 12 weeks. BMLs increased or decreased in roughly equal numbers of knees during the study.

Volumes have been known to change at 1 year follow-up; the finding that they do so in as little as 6 weeks is new.

In short, "I think it’s a good marker," Dr. Felson said.

The patients were all participating in a larger treatment trial; the results are still blinded, so it’s not yet possible to correlate treatment outcomes with volume changes.

"Wait for next year," Dr. Felson said.

The congress was sponsored by Osteoarthritis Research Society International. Dr. Felson said he has no disclosures. The study was funded by Arthritis Research UK.

SAN DIEGO – In the majority of patients with knee osteoarthritis, the baseline volumes of associated bone marrow lesions change substantially within 6 to 12 weeks of diagnosis, judging from the findings of an ongoing drug study.

The findings suggest that volume changes – either decreases or increases as determined by magnetic resonance imaging – may help assess short-term fluctuations in joint damage.

"I think this may allow trials to be done with relatively smaller numbers of patients and briefer follow-ups," said the study’s lead author Dr. David Felson, professor of medicine and epidemiology at both Boston University and the University of Manchester (England).

A rapid marker for disease progress would be welcome; osteoarthritis (OA) is generally considered a slowly evolving disease "with glacial changes in cartilage morphology necessitating trials of potential treatments lasting 1-2 years," Dr. Felson said at the World Congress on Osteoarthritis.

"To the extent that they could be regarded as treatment targets, trials testing [bone marrow lesion] effects could avoid the usual prolonged structure modification trials," he said.

Bone marrow lesions (BMLs) are ill-defined, hyperintense lesions in subcortical bone detected during water-sensitive, fat-suppressed MRIs. Their presence indicates local bone damage and microfractures.

Recently, larger BMLs have been correlated with worse knee pain. Lesions have also been related to malalignment, risk of overlying cartilage loss, OA progression, and poor outcomes, Dr. Felson said.

He and his colleagues used axial and sagittal MRIs to assess BML volumes in patients with painful patellofemoral at baseline, 6, and 12 weeks. The patients were 40-70 years old, with a mean body mass index of about 30 kg/m². Baseline median BML volumes were a bit over 2,000 mm³.

During the study, 23 of 35 assessed knees had a greater than 50% change in volume. Eight had a greater than 50% change in volume at 6 weeks only, 4 at 12 weeks only, and 11 at both 6 and 12 weeks. BMLs increased or decreased in roughly equal numbers of knees during the study.

Volumes have been known to change at 1 year follow-up; the finding that they do so in as little as 6 weeks is new.

In short, "I think it’s a good marker," Dr. Felson said.

The patients were all participating in a larger treatment trial; the results are still blinded, so it’s not yet possible to correlate treatment outcomes with volume changes.

"Wait for next year," Dr. Felson said.

The congress was sponsored by Osteoarthritis Research Society International. Dr. Felson said he has no disclosures. The study was funded by Arthritis Research UK.

SAN DIEGO – In the majority of patients with knee osteoarthritis, the baseline volumes of associated bone marrow lesions change substantially within 6 to 12 weeks of diagnosis, judging from the findings of an ongoing drug study.

The findings suggest that volume changes – either decreases or increases as determined by magnetic resonance imaging – may help assess short-term fluctuations in joint damage.

"I think this may allow trials to be done with relatively smaller numbers of patients and briefer follow-ups," said the study’s lead author Dr. David Felson, professor of medicine and epidemiology at both Boston University and the University of Manchester (England).

A rapid marker for disease progress would be welcome; osteoarthritis (OA) is generally considered a slowly evolving disease "with glacial changes in cartilage morphology necessitating trials of potential treatments lasting 1-2 years," Dr. Felson said at the World Congress on Osteoarthritis.

"To the extent that they could be regarded as treatment targets, trials testing [bone marrow lesion] effects could avoid the usual prolonged structure modification trials," he said.

Bone marrow lesions (BMLs) are ill-defined, hyperintense lesions in subcortical bone detected during water-sensitive, fat-suppressed MRIs. Their presence indicates local bone damage and microfractures.

Recently, larger BMLs have been correlated with worse knee pain. Lesions have also been related to malalignment, risk of overlying cartilage loss, OA progression, and poor outcomes, Dr. Felson said.

He and his colleagues used axial and sagittal MRIs to assess BML volumes in patients with painful patellofemoral at baseline, 6, and 12 weeks. The patients were 40-70 years old, with a mean body mass index of about 30 kg/m². Baseline median BML volumes were a bit over 2,000 mm³.

During the study, 23 of 35 assessed knees had a greater than 50% change in volume. Eight had a greater than 50% change in volume at 6 weeks only, 4 at 12 weeks only, and 11 at both 6 and 12 weeks. BMLs increased or decreased in roughly equal numbers of knees during the study.

Volumes have been known to change at 1 year follow-up; the finding that they do so in as little as 6 weeks is new.

In short, "I think it’s a good marker," Dr. Felson said.

The patients were all participating in a larger treatment trial; the results are still blinded, so it’s not yet possible to correlate treatment outcomes with volume changes.

"Wait for next year," Dr. Felson said.

The congress was sponsored by Osteoarthritis Research Society International. Dr. Felson said he has no disclosures. The study was funded by Arthritis Research UK.

Unilateral hip arthritis may cause alterations in the joint loading of the contralateral knee before the onset of symptomatic osteoarthritis in that knee.

This finding could open up the possibility of interventions that could prevent or slow the progression of knee osteoarthritis (OA) in those with unilateral hip arthritis.

The results come from a small study of 55 participants, who underwent gait analysis of dynamic joint loading and dual-energy x-ray absorptiometry (DXA) to determine bone mineral density (BMD) of the tibial plateau (Arthritis & Rheumatism 2011 [doi:10.1002/art.30626]).

"This study demonstrates that in unilateral hip OA, the contralateral knee is subjected to significantly higher dynamic joint loading, as assessed by PAddM [peak external knee adduction moment] and by total medial compartment loads, relative to the ipsilateral knee. Importantly, this asymmetry of knee loading is observed even though the knees are asymptomatic and do not have clinical evidence of OA," wrote Dr. Najia Shakoor and her coinvestigators at Rush Medical College, Chicago.

Asked to comment on the findings, Dr. Nancy E. Lane noted that it is "not a surprise that changes in gait are present before the disease becomes clinically symptomatic.

"The more we can study gait to provide early detection of OA, we might be able to provide an intervention that might slow the progression of the disease," noted Dr. Lane, who is professor of medicine and rheumatology at the University of California, Davis, and director of the Center for Healthy Aging at UC Davis.

Individuals were included if they had symptomatic OA of the hip, as defined by the American College of Rheumatology’s Clinical Criteria for Classification. They also had to have at least 30 mm of pain (on a 100-mm scale) while walking – which corresponds to question 1 of the visual analog format of the hip-directed WOMAC (Western Ontario and McMaster Universities Arthritis) Index. OA was confirmed radiographically.

Exclusion criteria included symptomatic OA of the contralateral hip or either knee with the presence of pain defined as 30 mm (on a 100-mm scale) while walking. They were also excluded if they had radiographic evidence of OA of the contralateral hip or either of the knees, in excess of grade 3 according to the modified Kellgren-Lawrence (KL) scale.

A total of 62 individuals met the study criteria and completed the study. The mean age was 62 years and more women (60%) were included than men. A total of 55 individuals had both appropriate gait data and evaluation of bone density at bilateral knees.

All individuals had anterior-posterior radiographs of the pelvis, which were evaluated for KL grade at the hips. They also underwent anterior-posterior standing knee radiographs that were evaluated for KL grade at the knees. All participants completed the WOMAC visual analog scale for pain at both knees and both hips. The WOMAC scores were normalized to a 100-mm scale.

Participants also underwent gait analysis to collect three-dimensional kinematics and ground reaction forces using optoelectronic cameras with passive markers and a multicomponent force plate. Passive markers were placed at the lateral-most aspect of the superior iliac crest, the superior aspect of the greater trochanter, the lateral knee joint line, lateral malleolus, lateral calcaneus, and the head of the fifth metatarsal.

DXA was used to scan the bilateral proximal tibia and determine BMD. Software was used to determine the subperiostial surface of the tibia. Cortical bone of the subchondral plate was excluded from the measurements, as sclerosis in this region can alter BMD. Therefore, the medial and lateral regions of interest include subchondral trabecular bone.

The primary end point was the PAddM, which is a validated gait parameter that reflects the load at the medial compartment of the knee. This measure has been associated with pain, radiographic severity, and progression of knee OA. The PAddM was defined as the external adduction moment of greatest magnitude during the stance phase of the gait cycle in this study. The co-primary end points were total loading of the medial compartment and medial compartment BMD.

Both primary gait outcomes at the knees – the PAddM and the total medial knee load – were significantly greater for the contralateral knee relative to the ipsilateral knee. Lateral compartment load was also greater for the contralateral knee. In addition, the medial tibial plateau BMD was significantly greater at the contralateral knee relative to the ipsilateral knee, though there were no significant differences at the lateral tibial plateau.

Interestingly, the ratio of the contralateral-to-ipsilateral medial compartment knee BMD was directly correlated with contralateral-to-ipsilateral knee PAddM and contralateral-to-ipsilateral knee medial compartment load, the investigators noted.

In addition, the significant asymmetries observed in the proximal tibial BMD of the contralateral vs. ipsilateral knees provide evidence of substantially altered load history in the knees as well.

"The current study demonstrates that loading asymmetries at the knees begin early in the disease course of hip OA to end-stage disease. These results may have implications for interventional strategies targeted in those with unilateral hip OA in order to prevent or minimized these asymmetries early in the disease course," the researchers concluded

The authors and Dr. Lane reported that they have no conflicts of interest. The study was sponsored by the National Institutes of Health and the Schweppe Foundation.

Unilateral hip arthritis may cause alterations in the joint loading of the contralateral knee before the onset of symptomatic osteoarthritis in that knee.

This finding could open up the possibility of interventions that could prevent or slow the progression of knee osteoarthritis (OA) in those with unilateral hip arthritis.

The results come from a small study of 55 participants, who underwent gait analysis of dynamic joint loading and dual-energy x-ray absorptiometry (DXA) to determine bone mineral density (BMD) of the tibial plateau (Arthritis & Rheumatism 2011 [doi:10.1002/art.30626]).

"This study demonstrates that in unilateral hip OA, the contralateral knee is subjected to significantly higher dynamic joint loading, as assessed by PAddM [peak external knee adduction moment] and by total medial compartment loads, relative to the ipsilateral knee. Importantly, this asymmetry of knee loading is observed even though the knees are asymptomatic and do not have clinical evidence of OA," wrote Dr. Najia Shakoor and her coinvestigators at Rush Medical College, Chicago.

Asked to comment on the findings, Dr. Nancy E. Lane noted that it is "not a surprise that changes in gait are present before the disease becomes clinically symptomatic.

"The more we can study gait to provide early detection of OA, we might be able to provide an intervention that might slow the progression of the disease," noted Dr. Lane, who is professor of medicine and rheumatology at the University of California, Davis, and director of the Center for Healthy Aging at UC Davis.

Individuals were included if they had symptomatic OA of the hip, as defined by the American College of Rheumatology’s Clinical Criteria for Classification. They also had to have at least 30 mm of pain (on a 100-mm scale) while walking – which corresponds to question 1 of the visual analog format of the hip-directed WOMAC (Western Ontario and McMaster Universities Arthritis) Index. OA was confirmed radiographically.

Exclusion criteria included symptomatic OA of the contralateral hip or either knee with the presence of pain defined as 30 mm (on a 100-mm scale) while walking. They were also excluded if they had radiographic evidence of OA of the contralateral hip or either of the knees, in excess of grade 3 according to the modified Kellgren-Lawrence (KL) scale.

A total of 62 individuals met the study criteria and completed the study. The mean age was 62 years and more women (60%) were included than men. A total of 55 individuals had both appropriate gait data and evaluation of bone density at bilateral knees.

All individuals had anterior-posterior radiographs of the pelvis, which were evaluated for KL grade at the hips. They also underwent anterior-posterior standing knee radiographs that were evaluated for KL grade at the knees. All participants completed the WOMAC visual analog scale for pain at both knees and both hips. The WOMAC scores were normalized to a 100-mm scale.

Participants also underwent gait analysis to collect three-dimensional kinematics and ground reaction forces using optoelectronic cameras with passive markers and a multicomponent force plate. Passive markers were placed at the lateral-most aspect of the superior iliac crest, the superior aspect of the greater trochanter, the lateral knee joint line, lateral malleolus, lateral calcaneus, and the head of the fifth metatarsal.

DXA was used to scan the bilateral proximal tibia and determine BMD. Software was used to determine the subperiostial surface of the tibia. Cortical bone of the subchondral plate was excluded from the measurements, as sclerosis in this region can alter BMD. Therefore, the medial and lateral regions of interest include subchondral trabecular bone.

The primary end point was the PAddM, which is a validated gait parameter that reflects the load at the medial compartment of the knee. This measure has been associated with pain, radiographic severity, and progression of knee OA. The PAddM was defined as the external adduction moment of greatest magnitude during the stance phase of the gait cycle in this study. The co-primary end points were total loading of the medial compartment and medial compartment BMD.

Both primary gait outcomes at the knees – the PAddM and the total medial knee load – were significantly greater for the contralateral knee relative to the ipsilateral knee. Lateral compartment load was also greater for the contralateral knee. In addition, the medial tibial plateau BMD was significantly greater at the contralateral knee relative to the ipsilateral knee, though there were no significant differences at the lateral tibial plateau.

Interestingly, the ratio of the contralateral-to-ipsilateral medial compartment knee BMD was directly correlated with contralateral-to-ipsilateral knee PAddM and contralateral-to-ipsilateral knee medial compartment load, the investigators noted.

In addition, the significant asymmetries observed in the proximal tibial BMD of the contralateral vs. ipsilateral knees provide evidence of substantially altered load history in the knees as well.

"The current study demonstrates that loading asymmetries at the knees begin early in the disease course of hip OA to end-stage disease. These results may have implications for interventional strategies targeted in those with unilateral hip OA in order to prevent or minimized these asymmetries early in the disease course," the researchers concluded

The authors and Dr. Lane reported that they have no conflicts of interest. The study was sponsored by the National Institutes of Health and the Schweppe Foundation.

Unilateral hip arthritis may cause alterations in the joint loading of the contralateral knee before the onset of symptomatic osteoarthritis in that knee.

This finding could open up the possibility of interventions that could prevent or slow the progression of knee osteoarthritis (OA) in those with unilateral hip arthritis.

The results come from a small study of 55 participants, who underwent gait analysis of dynamic joint loading and dual-energy x-ray absorptiometry (DXA) to determine bone mineral density (BMD) of the tibial plateau (Arthritis & Rheumatism 2011 [doi:10.1002/art.30626]).

"This study demonstrates that in unilateral hip OA, the contralateral knee is subjected to significantly higher dynamic joint loading, as assessed by PAddM [peak external knee adduction moment] and by total medial compartment loads, relative to the ipsilateral knee. Importantly, this asymmetry of knee loading is observed even though the knees are asymptomatic and do not have clinical evidence of OA," wrote Dr. Najia Shakoor and her coinvestigators at Rush Medical College, Chicago.

Asked to comment on the findings, Dr. Nancy E. Lane noted that it is "not a surprise that changes in gait are present before the disease becomes clinically symptomatic.

"The more we can study gait to provide early detection of OA, we might be able to provide an intervention that might slow the progression of the disease," noted Dr. Lane, who is professor of medicine and rheumatology at the University of California, Davis, and director of the Center for Healthy Aging at UC Davis.

Individuals were included if they had symptomatic OA of the hip, as defined by the American College of Rheumatology’s Clinical Criteria for Classification. They also had to have at least 30 mm of pain (on a 100-mm scale) while walking – which corresponds to question 1 of the visual analog format of the hip-directed WOMAC (Western Ontario and McMaster Universities Arthritis) Index. OA was confirmed radiographically.

Exclusion criteria included symptomatic OA of the contralateral hip or either knee with the presence of pain defined as 30 mm (on a 100-mm scale) while walking. They were also excluded if they had radiographic evidence of OA of the contralateral hip or either of the knees, in excess of grade 3 according to the modified Kellgren-Lawrence (KL) scale.

A total of 62 individuals met the study criteria and completed the study. The mean age was 62 years and more women (60%) were included than men. A total of 55 individuals had both appropriate gait data and evaluation of bone density at bilateral knees.

All individuals had anterior-posterior radiographs of the pelvis, which were evaluated for KL grade at the hips. They also underwent anterior-posterior standing knee radiographs that were evaluated for KL grade at the knees. All participants completed the WOMAC visual analog scale for pain at both knees and both hips. The WOMAC scores were normalized to a 100-mm scale.

Participants also underwent gait analysis to collect three-dimensional kinematics and ground reaction forces using optoelectronic cameras with passive markers and a multicomponent force plate. Passive markers were placed at the lateral-most aspect of the superior iliac crest, the superior aspect of the greater trochanter, the lateral knee joint line, lateral malleolus, lateral calcaneus, and the head of the fifth metatarsal.

DXA was used to scan the bilateral proximal tibia and determine BMD. Software was used to determine the subperiostial surface of the tibia. Cortical bone of the subchondral plate was excluded from the measurements, as sclerosis in this region can alter BMD. Therefore, the medial and lateral regions of interest include subchondral trabecular bone.

The primary end point was the PAddM, which is a validated gait parameter that reflects the load at the medial compartment of the knee. This measure has been associated with pain, radiographic severity, and progression of knee OA. The PAddM was defined as the external adduction moment of greatest magnitude during the stance phase of the gait cycle in this study. The co-primary end points were total loading of the medial compartment and medial compartment BMD.

Both primary gait outcomes at the knees – the PAddM and the total medial knee load – were significantly greater for the contralateral knee relative to the ipsilateral knee. Lateral compartment load was also greater for the contralateral knee. In addition, the medial tibial plateau BMD was significantly greater at the contralateral knee relative to the ipsilateral knee, though there were no significant differences at the lateral tibial plateau.

Interestingly, the ratio of the contralateral-to-ipsilateral medial compartment knee BMD was directly correlated with contralateral-to-ipsilateral knee PAddM and contralateral-to-ipsilateral knee medial compartment load, the investigators noted.

In addition, the significant asymmetries observed in the proximal tibial BMD of the contralateral vs. ipsilateral knees provide evidence of substantially altered load history in the knees as well.

"The current study demonstrates that loading asymmetries at the knees begin early in the disease course of hip OA to end-stage disease. These results may have implications for interventional strategies targeted in those with unilateral hip OA in order to prevent or minimized these asymmetries early in the disease course," the researchers concluded

The authors and Dr. Lane reported that they have no conflicts of interest. The study was sponsored by the National Institutes of Health and the Schweppe Foundation.

Repeated intra-articular injections of hyaluronic acid appear to lessen pain and improve function in knee osteoarthritis between treatment cycles, and for up to a year later.

The 40-month AMELIA (Osteoarthritis Modifying Effects of Long-Term Intra-Articular Adant) project found that, compared to those getting saline as a placebo injection, patients who got the treatment were 22% more likely to experience a clinical response – a 50% or greater improvement in pain or function (80% vs. 66%; risk ratio 1.22).

However, wrote Dr. Federico Navarro-Sarabia and his colleagues, the study could not determine why the improvement persisted as long as it did after treatments stopped. "In this regard, it is not possible to establish whether this carry-over effect reflects a true disease remission or just a modification of the natural course of the disease," the investigators wrote. The report was published online Aug. 17 in Annals of the Rheumatic Diseases.

AMELIA comprised 306 patients with knee osteoarthritis. They were randomized to four cycles of five weekly injections. The treatment groups received 2.5 mL 1% sodium hyaluronate derived from Streptococcus zooepidemicus. The placebo group received saline injections. Patients and evaluators were both blinded to the treatments by using a blinded evaluator and an unblended investigator to administer the injections.

Follow-up occurred during the 6 months after cycles 1 and 2; and 1 year after cycles 3 and 4. Patients were allowed to use aspirin or paracetamol, and short durations of nonsteroidal anti-inflammatories. "However, for 24 h and 1 week before efficacy evaluation, patients were required to abstain from any paracetamol or NSAID, respectively," the researchers wrote (Ann. Rheum. Dis. 2011 Aug. 17 [doi: 10.1136/ard.2011.152017). No corticosteroid injections were allowed in the treated knee throughout the entire study.

The patients were mostly women (87%), with a mean age of 63 years. The mean body mass index was 28 kg/m². The mean duration of knee osteoarthritis was 7.5 years. End-stage disease was not included and the mean joint space width of the medial tibiofemoral compartment was 3.5 mm.

Of the 306 randomized, 109 in the treatment group and 94 in the placebo group completed the entire study. In the treatment group, discontinuation was due to lack of efficacy (8), patient decision (12), adverse events (12), and investigator decision (1). The rest were lost to follow-up or left for other reasons. In the placebo group, reasons were lack of efficacy (19), patient decision (13), adverse events (16), and investigator decision (1). The rest were lost to follow-up or left for other reasons. Outcomes were assessed in an intent-to-treat analysis.

At the end of the 40-month study period, 22% more treated patients than placebo patients were judged responders according to the Osteoarthritis Research Society International 2004 criteria – a significant difference.

However, the number of responders in the treatment group progressively increased after each cycle, from 71% after the first cycle to 80% after the last cycle. Response rates in the placebo group remained stable throughout the study (68% after the first cycle and 66% after the last cycle).

The chances of response seemed to increase as the study progressed, the authors noted. Among the nonresponders in the treatment group, 54% became responders later on. Similarly, 38% of the nonresponders in the placebo group eventually became responders.

The high placebo response is not an unusual finding in osteoarthritis trials, said Dr. Navarro-Sarabi of Hospital Universitario Virgen Macarena, Seville, Spain, and coauthors.

"In AMELIA, however, the success of the study was in fact accentuated by the high placebo efficacy detected, making the results found [80% vs. 68%] even more clinically meaningful and remarkable."

Most of the patients (71% of each group) used either an NSAID or paracetamol as a rescue medication during the study. Among the 48% who took paracetamol over the study’s course, the mean daily dose declined by 27% in the treatment group and 4% in the placebo group.

Twenty-nine adverse events occurred (15 in the treatment group and 14 in the placebo group), among 22 patients (11 in each group). These included allergic reaction (three in each treatment group), bleeding and pain at the injection site, arthralgia, and other events.

The study was supported by Tedec Meiji Farma SA. Dr. Navarro-Sarabia and coauthors received research funds from the company as study investigators. Two coauthors are Tedec Meiji Farma SA employees.

Repeated intra-articular injections of hyaluronic acid appear to lessen pain and improve function in knee osteoarthritis between treatment cycles, and for up to a year later.

The 40-month AMELIA (Osteoarthritis Modifying Effects of Long-Term Intra-Articular Adant) project found that, compared to those getting saline as a placebo injection, patients who got the treatment were 22% more likely to experience a clinical response – a 50% or greater improvement in pain or function (80% vs. 66%; risk ratio 1.22).

However, wrote Dr. Federico Navarro-Sarabia and his colleagues, the study could not determine why the improvement persisted as long as it did after treatments stopped. "In this regard, it is not possible to establish whether this carry-over effect reflects a true disease remission or just a modification of the natural course of the disease," the investigators wrote. The report was published online Aug. 17 in Annals of the Rheumatic Diseases.

AMELIA comprised 306 patients with knee osteoarthritis. They were randomized to four cycles of five weekly injections. The treatment groups received 2.5 mL 1% sodium hyaluronate derived from Streptococcus zooepidemicus. The placebo group received saline injections. Patients and evaluators were both blinded to the treatments by using a blinded evaluator and an unblended investigator to administer the injections.

Follow-up occurred during the 6 months after cycles 1 and 2; and 1 year after cycles 3 and 4. Patients were allowed to use aspirin or paracetamol, and short durations of nonsteroidal anti-inflammatories. "However, for 24 h and 1 week before efficacy evaluation, patients were required to abstain from any paracetamol or NSAID, respectively," the researchers wrote (Ann. Rheum. Dis. 2011 Aug. 17 [doi: 10.1136/ard.2011.152017). No corticosteroid injections were allowed in the treated knee throughout the entire study.

The patients were mostly women (87%), with a mean age of 63 years. The mean body mass index was 28 kg/m². The mean duration of knee osteoarthritis was 7.5 years. End-stage disease was not included and the mean joint space width of the medial tibiofemoral compartment was 3.5 mm.

Of the 306 randomized, 109 in the treatment group and 94 in the placebo group completed the entire study. In the treatment group, discontinuation was due to lack of efficacy (8), patient decision (12), adverse events (12), and investigator decision (1). The rest were lost to follow-up or left for other reasons. In the placebo group, reasons were lack of efficacy (19), patient decision (13), adverse events (16), and investigator decision (1). The rest were lost to follow-up or left for other reasons. Outcomes were assessed in an intent-to-treat analysis.

At the end of the 40-month study period, 22% more treated patients than placebo patients were judged responders according to the Osteoarthritis Research Society International 2004 criteria – a significant difference.

However, the number of responders in the treatment group progressively increased after each cycle, from 71% after the first cycle to 80% after the last cycle. Response rates in the placebo group remained stable throughout the study (68% after the first cycle and 66% after the last cycle).

The chances of response seemed to increase as the study progressed, the authors noted. Among the nonresponders in the treatment group, 54% became responders later on. Similarly, 38% of the nonresponders in the placebo group eventually became responders.

The high placebo response is not an unusual finding in osteoarthritis trials, said Dr. Navarro-Sarabi of Hospital Universitario Virgen Macarena, Seville, Spain, and coauthors.

"In AMELIA, however, the success of the study was in fact accentuated by the high placebo efficacy detected, making the results found [80% vs. 68%] even more clinically meaningful and remarkable."

Most of the patients (71% of each group) used either an NSAID or paracetamol as a rescue medication during the study. Among the 48% who took paracetamol over the study’s course, the mean daily dose declined by 27% in the treatment group and 4% in the placebo group.

Twenty-nine adverse events occurred (15 in the treatment group and 14 in the placebo group), among 22 patients (11 in each group). These included allergic reaction (three in each treatment group), bleeding and pain at the injection site, arthralgia, and other events.

The study was supported by Tedec Meiji Farma SA. Dr. Navarro-Sarabia and coauthors received research funds from the company as study investigators. Two coauthors are Tedec Meiji Farma SA employees.

Repeated intra-articular injections of hyaluronic acid appear to lessen pain and improve function in knee osteoarthritis between treatment cycles, and for up to a year later.

The 40-month AMELIA (Osteoarthritis Modifying Effects of Long-Term Intra-Articular Adant) project found that, compared to those getting saline as a placebo injection, patients who got the treatment were 22% more likely to experience a clinical response – a 50% or greater improvement in pain or function (80% vs. 66%; risk ratio 1.22).

However, wrote Dr. Federico Navarro-Sarabia and his colleagues, the study could not determine why the improvement persisted as long as it did after treatments stopped. "In this regard, it is not possible to establish whether this carry-over effect reflects a true disease remission or just a modification of the natural course of the disease," the investigators wrote. The report was published online Aug. 17 in Annals of the Rheumatic Diseases.

AMELIA comprised 306 patients with knee osteoarthritis. They were randomized to four cycles of five weekly injections. The treatment groups received 2.5 mL 1% sodium hyaluronate derived from Streptococcus zooepidemicus. The placebo group received saline injections. Patients and evaluators were both blinded to the treatments by using a blinded evaluator and an unblended investigator to administer the injections.

Follow-up occurred during the 6 months after cycles 1 and 2; and 1 year after cycles 3 and 4. Patients were allowed to use aspirin or paracetamol, and short durations of nonsteroidal anti-inflammatories. "However, for 24 h and 1 week before efficacy evaluation, patients were required to abstain from any paracetamol or NSAID, respectively," the researchers wrote (Ann. Rheum. Dis. 2011 Aug. 17 [doi: 10.1136/ard.2011.152017). No corticosteroid injections were allowed in the treated knee throughout the entire study.

The patients were mostly women (87%), with a mean age of 63 years. The mean body mass index was 28 kg/m². The mean duration of knee osteoarthritis was 7.5 years. End-stage disease was not included and the mean joint space width of the medial tibiofemoral compartment was 3.5 mm.

Of the 306 randomized, 109 in the treatment group and 94 in the placebo group completed the entire study. In the treatment group, discontinuation was due to lack of efficacy (8), patient decision (12), adverse events (12), and investigator decision (1). The rest were lost to follow-up or left for other reasons. In the placebo group, reasons were lack of efficacy (19), patient decision (13), adverse events (16), and investigator decision (1). The rest were lost to follow-up or left for other reasons. Outcomes were assessed in an intent-to-treat analysis.

At the end of the 40-month study period, 22% more treated patients than placebo patients were judged responders according to the Osteoarthritis Research Society International 2004 criteria – a significant difference.

However, the number of responders in the treatment group progressively increased after each cycle, from 71% after the first cycle to 80% after the last cycle. Response rates in the placebo group remained stable throughout the study (68% after the first cycle and 66% after the last cycle).

The chances of response seemed to increase as the study progressed, the authors noted. Among the nonresponders in the treatment group, 54% became responders later on. Similarly, 38% of the nonresponders in the placebo group eventually became responders.

The high placebo response is not an unusual finding in osteoarthritis trials, said Dr. Navarro-Sarabi of Hospital Universitario Virgen Macarena, Seville, Spain, and coauthors.

"In AMELIA, however, the success of the study was in fact accentuated by the high placebo efficacy detected, making the results found [80% vs. 68%] even more clinically meaningful and remarkable."

Most of the patients (71% of each group) used either an NSAID or paracetamol as a rescue medication during the study. Among the 48% who took paracetamol over the study’s course, the mean daily dose declined by 27% in the treatment group and 4% in the placebo group.

Twenty-nine adverse events occurred (15 in the treatment group and 14 in the placebo group), among 22 patients (11 in each group). These included allergic reaction (three in each treatment group), bleeding and pain at the injection site, arthralgia, and other events.

The study was supported by Tedec Meiji Farma SA. Dr. Navarro-Sarabia and coauthors received research funds from the company as study investigators. Two coauthors are Tedec Meiji Farma SA employees.

SAN FRANCISCO – Before initiating osteoporosis therapy on the basis of a T score, investigate any correctable cases of secondary osteoporosis, urged Dr. Steven T. Harris of the University of California, San Francisco.

Screening for secondary causes of low bone mineral density (BMD) that starts with a careful history and examination, plus laboratory tests, identifies roughly 90% of new diagnoses of secondary osteoporosis at modest cost, he said at the meeting.

The differential diagnosis of low BMD includes a “hopelessly bewildering” list of problems that can cause secondary osteoporosis in adults, but these can be narrowed down to relatively common causes, including vitamin D deficiency, hypercalciuria, hypogonadism, malabsorption, chronic obstructive pulmonary disease, rheumatoid arthritis, and myeloma. Drug-induced causes – including secondary osteoporosis related to taking steroid therapy, antiepileptics, GnRH agonists, Depo-Provera, aromatase inhibitors, and excess thyroxine – also make the short list.

Neither age nor disease identifies patients who are most likely to have an occult disorder that's causing osteoporosis. “All patients deserve at least a limited laboratory evaluation prior to [initiating] treatment,” he said. Persistent, additional testing is warranted if BMD decreases significantly in patients who are on therapy for primary osteoporosis.

Patients with low z scores (indicating that they have BMD that is lower than expected for their age) require extra scrutiny because they're more likely to have an occult disease as the cause, and thus deserve closer attention and laboratory testing for secondary causes. “There is no research evidence to support that, but it's my clinical bias,” Dr. Harris added.

For lab tests, he orders a complete blood count to look for myeloma or malabsorption of iron, vitamin B

In a serum chemistry panel, the albumin level may point to malabsorption or malnutrition. Globulin results screen for myeloma. Alkaline phosphatase results help identify malignancy, cirrhosis, or vitamin D deficiency. Calcium levels may suggest hyperparathyroidism or malabsorption. Phosphate results can suggest malnutrition or osteomalacia. Creatinine or BUN results may point to renal disease.

He orders thyroid function testing if the patient is on thyroid replacement therapy or if symptoms warrant it.

Other tests to consider (based on symptoms and results of the laboratory tests) include parathyroid hormone levels if the urine or serum calcium level is abnormally high or low. He orders serum protein electrophoresis if the CBC is abnormal, and he tests for celiac disease if the patient has low 24-hour urine calcium or anemia.

Getting a 24-hour urine calcium level is particularly important because it effectively identifies hypercalciuria or malabsorption, two disorders that are associated with higher rates of bone loss. Without a 24-hour urine calcium test, 38% of new diagnoses of hypercalciuria or malabsorption would be missed, data suggest. “Spot urine calcium does not detect malabsorption,” he said.

Secondary causes of low BMD are common, multiple studies show. In one study of 664 consecutive postmenopausal women with a T score of −2.5 or below, 54% had known secondary causes of osteoporosis. Laboratory evaluations in 173 women without known secondary causes or prior laboratory abnormalities showed that 32% (55) had a previously unknown secondary cause of low BMD (J. Clin. Endocrinol. Metab. 2002;87:4431–7). A reanalysis of the data suggested that 44% of the 173 had secondary causes of low BMD, most commonly low vitamin D levels, Dr. Harris said.

The prevalence of occult secondary osteoporosis has been estimated at 37%–63% in women and men at various ages, at 60%–80% in patients after hip fracture, and at 50% or more in patients on pharmacologic therapy. The estimates are based on studies with varying criteria for inclusion, the extent of testing, and the definition of vitamin D deficiency. There have been no large, population-based studies of the prevalence of occult disorders causing osteoporosis, he said.

Dr. Harris disclosed financial ties with Amgen, Eli Lilly, Genentech, Gilead Sciences, Merck, Novartis, Roche, Sanofi-Aventis, and Warner Chilcott.

Screening identifies roughly 90% of new diagnoses of secondary osteoporosis at a modest cost.

Source DR. HARRIS

SAN FRANCISCO – Before initiating osteoporosis therapy on the basis of a T score, investigate any correctable cases of secondary osteoporosis, urged Dr. Steven T. Harris of the University of California, San Francisco.

Screening for secondary causes of low bone mineral density (BMD) that starts with a careful history and examination, plus laboratory tests, identifies roughly 90% of new diagnoses of secondary osteoporosis at modest cost, he said at the meeting.

The differential diagnosis of low BMD includes a “hopelessly bewildering” list of problems that can cause secondary osteoporosis in adults, but these can be narrowed down to relatively common causes, including vitamin D deficiency, hypercalciuria, hypogonadism, malabsorption, chronic obstructive pulmonary disease, rheumatoid arthritis, and myeloma. Drug-induced causes – including secondary osteoporosis related to taking steroid therapy, antiepileptics, GnRH agonists, Depo-Provera, aromatase inhibitors, and excess thyroxine – also make the short list.

Neither age nor disease identifies patients who are most likely to have an occult disorder that's causing osteoporosis. “All patients deserve at least a limited laboratory evaluation prior to [initiating] treatment,” he said. Persistent, additional testing is warranted if BMD decreases significantly in patients who are on therapy for primary osteoporosis.

Patients with low z scores (indicating that they have BMD that is lower than expected for their age) require extra scrutiny because they're more likely to have an occult disease as the cause, and thus deserve closer attention and laboratory testing for secondary causes. “There is no research evidence to support that, but it's my clinical bias,” Dr. Harris added.

For lab tests, he orders a complete blood count to look for myeloma or malabsorption of iron, vitamin B

In a serum chemistry panel, the albumin level may point to malabsorption or malnutrition. Globulin results screen for myeloma. Alkaline phosphatase results help identify malignancy, cirrhosis, or vitamin D deficiency. Calcium levels may suggest hyperparathyroidism or malabsorption. Phosphate results can suggest malnutrition or osteomalacia. Creatinine or BUN results may point to renal disease.

He orders thyroid function testing if the patient is on thyroid replacement therapy or if symptoms warrant it.

Other tests to consider (based on symptoms and results of the laboratory tests) include parathyroid hormone levels if the urine or serum calcium level is abnormally high or low. He orders serum protein electrophoresis if the CBC is abnormal, and he tests for celiac disease if the patient has low 24-hour urine calcium or anemia.

Getting a 24-hour urine calcium level is particularly important because it effectively identifies hypercalciuria or malabsorption, two disorders that are associated with higher rates of bone loss. Without a 24-hour urine calcium test, 38% of new diagnoses of hypercalciuria or malabsorption would be missed, data suggest. “Spot urine calcium does not detect malabsorption,” he said.

Secondary causes of low BMD are common, multiple studies show. In one study of 664 consecutive postmenopausal women with a T score of −2.5 or below, 54% had known secondary causes of osteoporosis. Laboratory evaluations in 173 women without known secondary causes or prior laboratory abnormalities showed that 32% (55) had a previously unknown secondary cause of low BMD (J. Clin. Endocrinol. Metab. 2002;87:4431–7). A reanalysis of the data suggested that 44% of the 173 had secondary causes of low BMD, most commonly low vitamin D levels, Dr. Harris said.

The prevalence of occult secondary osteoporosis has been estimated at 37%–63% in women and men at various ages, at 60%–80% in patients after hip fracture, and at 50% or more in patients on pharmacologic therapy. The estimates are based on studies with varying criteria for inclusion, the extent of testing, and the definition of vitamin D deficiency. There have been no large, population-based studies of the prevalence of occult disorders causing osteoporosis, he said.

Dr. Harris disclosed financial ties with Amgen, Eli Lilly, Genentech, Gilead Sciences, Merck, Novartis, Roche, Sanofi-Aventis, and Warner Chilcott.

Screening identifies roughly 90% of new diagnoses of secondary osteoporosis at a modest cost.

Source DR. HARRIS

SAN FRANCISCO – Before initiating osteoporosis therapy on the basis of a T score, investigate any correctable cases of secondary osteoporosis, urged Dr. Steven T. Harris of the University of California, San Francisco.

Screening for secondary causes of low bone mineral density (BMD) that starts with a careful history and examination, plus laboratory tests, identifies roughly 90% of new diagnoses of secondary osteoporosis at modest cost, he said at the meeting.

The differential diagnosis of low BMD includes a “hopelessly bewildering” list of problems that can cause secondary osteoporosis in adults, but these can be narrowed down to relatively common causes, including vitamin D deficiency, hypercalciuria, hypogonadism, malabsorption, chronic obstructive pulmonary disease, rheumatoid arthritis, and myeloma. Drug-induced causes – including secondary osteoporosis related to taking steroid therapy, antiepileptics, GnRH agonists, Depo-Provera, aromatase inhibitors, and excess thyroxine – also make the short list.

Neither age nor disease identifies patients who are most likely to have an occult disorder that's causing osteoporosis. “All patients deserve at least a limited laboratory evaluation prior to [initiating] treatment,” he said. Persistent, additional testing is warranted if BMD decreases significantly in patients who are on therapy for primary osteoporosis.

Patients with low z scores (indicating that they have BMD that is lower than expected for their age) require extra scrutiny because they're more likely to have an occult disease as the cause, and thus deserve closer attention and laboratory testing for secondary causes. “There is no research evidence to support that, but it's my clinical bias,” Dr. Harris added.

For lab tests, he orders a complete blood count to look for myeloma or malabsorption of iron, vitamin B

In a serum chemistry panel, the albumin level may point to malabsorption or malnutrition. Globulin results screen for myeloma. Alkaline phosphatase results help identify malignancy, cirrhosis, or vitamin D deficiency. Calcium levels may suggest hyperparathyroidism or malabsorption. Phosphate results can suggest malnutrition or osteomalacia. Creatinine or BUN results may point to renal disease.

He orders thyroid function testing if the patient is on thyroid replacement therapy or if symptoms warrant it.

Other tests to consider (based on symptoms and results of the laboratory tests) include parathyroid hormone levels if the urine or serum calcium level is abnormally high or low. He orders serum protein electrophoresis if the CBC is abnormal, and he tests for celiac disease if the patient has low 24-hour urine calcium or anemia.

Getting a 24-hour urine calcium level is particularly important because it effectively identifies hypercalciuria or malabsorption, two disorders that are associated with higher rates of bone loss. Without a 24-hour urine calcium test, 38% of new diagnoses of hypercalciuria or malabsorption would be missed, data suggest. “Spot urine calcium does not detect malabsorption,” he said.

Secondary causes of low BMD are common, multiple studies show. In one study of 664 consecutive postmenopausal women with a T score of −2.5 or below, 54% had known secondary causes of osteoporosis. Laboratory evaluations in 173 women without known secondary causes or prior laboratory abnormalities showed that 32% (55) had a previously unknown secondary cause of low BMD (J. Clin. Endocrinol. Metab. 2002;87:4431–7). A reanalysis of the data suggested that 44% of the 173 had secondary causes of low BMD, most commonly low vitamin D levels, Dr. Harris said.

The prevalence of occult secondary osteoporosis has been estimated at 37%–63% in women and men at various ages, at 60%–80% in patients after hip fracture, and at 50% or more in patients on pharmacologic therapy. The estimates are based on studies with varying criteria for inclusion, the extent of testing, and the definition of vitamin D deficiency. There have been no large, population-based studies of the prevalence of occult disorders causing osteoporosis, he said.

Dr. Harris disclosed financial ties with Amgen, Eli Lilly, Genentech, Gilead Sciences, Merck, Novartis, Roche, Sanofi-Aventis, and Warner Chilcott.

Screening identifies roughly 90% of new diagnoses of secondary osteoporosis at a modest cost.

Source DR. HARRIS

SAN FRANCISCO – Falls are the main cause of hip fractures, and proven prevention strategies should be in every clinician's toolbox.

Physicians should ask patients aged 75 years or older if they've had any falls in the prior year or if they have balance or gait difficulties and observe them walking and getting into and out of a chair, said Dr. Edgar Pierluissi, medical director of the Acute Care for Elders Unit at San Francisco General Hospital.

A fall in the previous year increases the risk for a future fall three- to fourfold.

Studies suggest that approximately 30% of U.S. adults over 65 years of age who are living in the community and half of adults over age 80 years will fall in the next year. Falls in adults aged 65 years or older cause injury in approximately 31%. Among those injured, 56% go to an emergency department and 38% visit a medical clinic, he said at the meeting.

An exercise program with balance and strength training might be appropriate for older patients who've had only one or no falls and who don't have balance or gait difficulties, various guidelines suggest. If a patient reports two or more falls or has balance or gait difficulties, do a “falls evaluation,” an assessment of predisposing or precipitating factors that can point to appropriate preventive interventions, he said.

“We can perhaps make a difference” in many of the most common risk factors for falls that have been identified in 16 studies, Dr. Pierluissi said.

Muscle weakness quadruples the risk for a fall. A gait deficit, balance deficit, or use of an assistive device nearly triples the risk for falling. A visual deficit, arthritis, depression, or impaired activities of daily living more than double the risk for a fall. Cognitive impairment, use of some types of medications, or age older than 80 years each nearly doubles the risk for falling.

To conduct a falls evaluation, get a good history of the patient's falls and their circumstances. Do a cardiovascular examination, medication review, neurological examination, and assessment for cognitive impairment. Assess gait, balance and mobility, muscle weakness, visual impairment, home hazards that might precipitate a fall, and the patient's perceived functional ability and fear related to falling (because many people who fear falling restrict their activity, which can lead to deconditioning and increased risk of falling).

A Cochrane Review of 111 randomized, controlled trials with 55,303 participants identified effective interventions to reduce the risk of falling (Cochrane Database Syst. Rev. 2009 [doi:10.1002/14651858.CD007146.pub2]).

A number of forms of exercise reduced both the number of people who fell and the number of falls. Group tai chi exercise or individually prescribed exercise programs at home were effective. Multiple-component group exercise was effective if it targeted at least two of the following: strength, balance, flexibility, and endurance.

Conducting a multifactorial falls evaluation reduces the number of falls. In patients with visual impairment and a high risk of falling, assessing and modifying home hazards was effective.

Withdrawing psychotropic medications and educating primary care physicians about the risk of falls associated with drug therapy reduced the number of falls but not the number who fell. In patients with cardioinhibitory carotid sinus hypersensitivity, cardiac pacing reduced the number of falls.

Vitamin D supplementation may reduce falls in people with low vitamin D levels, but it's unclear whether this helps people with adequate vitamin D levels. Other preventive strategies of unknown effectiveness include correction of visual deficiency, hormone replacement therapy, or modifying home hazards for people who have not fallen.

The Cochrane Review suggested that wearing hip protectors may provide some marginally significant benefit to frail, older adults in institutional care but not for older people who remain ambulant in the community, Dr. Pierluissi said.

One randomized, controlled trial of 1,042 residents in 37 nursing homes found a high rate of adherence to wearing hip protectors (74%) but these did not reduce the risk for hip fracture during the 20-month study.

Residents served as their own controls by wearing hip protectors with padding on one hip but not the other. Investigators stopped the study early due to lack of efficacy, with hip fractures on 3.1% of the protected hips and 2.5% of unprotected hips, a statistically nonsignificant difference (JAMA 2007;298:413–22).

Dr. Pierluissi said he has no relevant disclosures.

SAN FRANCISCO – Falls are the main cause of hip fractures, and proven prevention strategies should be in every clinician's toolbox.

Physicians should ask patients aged 75 years or older if they've had any falls in the prior year or if they have balance or gait difficulties and observe them walking and getting into and out of a chair, said Dr. Edgar Pierluissi, medical director of the Acute Care for Elders Unit at San Francisco General Hospital.

A fall in the previous year increases the risk for a future fall three- to fourfold.

Studies suggest that approximately 30% of U.S. adults over 65 years of age who are living in the community and half of adults over age 80 years will fall in the next year. Falls in adults aged 65 years or older cause injury in approximately 31%. Among those injured, 56% go to an emergency department and 38% visit a medical clinic, he said at the meeting.

An exercise program with balance and strength training might be appropriate for older patients who've had only one or no falls and who don't have balance or gait difficulties, various guidelines suggest. If a patient reports two or more falls or has balance or gait difficulties, do a “falls evaluation,” an assessment of predisposing or precipitating factors that can point to appropriate preventive interventions, he said.

“We can perhaps make a difference” in many of the most common risk factors for falls that have been identified in 16 studies, Dr. Pierluissi said.

Muscle weakness quadruples the risk for a fall. A gait deficit, balance deficit, or use of an assistive device nearly triples the risk for falling. A visual deficit, arthritis, depression, or impaired activities of daily living more than double the risk for a fall. Cognitive impairment, use of some types of medications, or age older than 80 years each nearly doubles the risk for falling.

To conduct a falls evaluation, get a good history of the patient's falls and their circumstances. Do a cardiovascular examination, medication review, neurological examination, and assessment for cognitive impairment. Assess gait, balance and mobility, muscle weakness, visual impairment, home hazards that might precipitate a fall, and the patient's perceived functional ability and fear related to falling (because many people who fear falling restrict their activity, which can lead to deconditioning and increased risk of falling).

A Cochrane Review of 111 randomized, controlled trials with 55,303 participants identified effective interventions to reduce the risk of falling (Cochrane Database Syst. Rev. 2009 [doi:10.1002/14651858.CD007146.pub2]).

A number of forms of exercise reduced both the number of people who fell and the number of falls. Group tai chi exercise or individually prescribed exercise programs at home were effective. Multiple-component group exercise was effective if it targeted at least two of the following: strength, balance, flexibility, and endurance.

Conducting a multifactorial falls evaluation reduces the number of falls. In patients with visual impairment and a high risk of falling, assessing and modifying home hazards was effective.

Withdrawing psychotropic medications and educating primary care physicians about the risk of falls associated with drug therapy reduced the number of falls but not the number who fell. In patients with cardioinhibitory carotid sinus hypersensitivity, cardiac pacing reduced the number of falls.

Vitamin D supplementation may reduce falls in people with low vitamin D levels, but it's unclear whether this helps people with adequate vitamin D levels. Other preventive strategies of unknown effectiveness include correction of visual deficiency, hormone replacement therapy, or modifying home hazards for people who have not fallen.

The Cochrane Review suggested that wearing hip protectors may provide some marginally significant benefit to frail, older adults in institutional care but not for older people who remain ambulant in the community, Dr. Pierluissi said.

One randomized, controlled trial of 1,042 residents in 37 nursing homes found a high rate of adherence to wearing hip protectors (74%) but these did not reduce the risk for hip fracture during the 20-month study.

Residents served as their own controls by wearing hip protectors with padding on one hip but not the other. Investigators stopped the study early due to lack of efficacy, with hip fractures on 3.1% of the protected hips and 2.5% of unprotected hips, a statistically nonsignificant difference (JAMA 2007;298:413–22).

Dr. Pierluissi said he has no relevant disclosures.

SAN FRANCISCO – Falls are the main cause of hip fractures, and proven prevention strategies should be in every clinician's toolbox.

Physicians should ask patients aged 75 years or older if they've had any falls in the prior year or if they have balance or gait difficulties and observe them walking and getting into and out of a chair, said Dr. Edgar Pierluissi, medical director of the Acute Care for Elders Unit at San Francisco General Hospital.

A fall in the previous year increases the risk for a future fall three- to fourfold.

Studies suggest that approximately 30% of U.S. adults over 65 years of age who are living in the community and half of adults over age 80 years will fall in the next year. Falls in adults aged 65 years or older cause injury in approximately 31%. Among those injured, 56% go to an emergency department and 38% visit a medical clinic, he said at the meeting.

An exercise program with balance and strength training might be appropriate for older patients who've had only one or no falls and who don't have balance or gait difficulties, various guidelines suggest. If a patient reports two or more falls or has balance or gait difficulties, do a “falls evaluation,” an assessment of predisposing or precipitating factors that can point to appropriate preventive interventions, he said.

“We can perhaps make a difference” in many of the most common risk factors for falls that have been identified in 16 studies, Dr. Pierluissi said.

Muscle weakness quadruples the risk for a fall. A gait deficit, balance deficit, or use of an assistive device nearly triples the risk for falling. A visual deficit, arthritis, depression, or impaired activities of daily living more than double the risk for a fall. Cognitive impairment, use of some types of medications, or age older than 80 years each nearly doubles the risk for falling.

To conduct a falls evaluation, get a good history of the patient's falls and their circumstances. Do a cardiovascular examination, medication review, neurological examination, and assessment for cognitive impairment. Assess gait, balance and mobility, muscle weakness, visual impairment, home hazards that might precipitate a fall, and the patient's perceived functional ability and fear related to falling (because many people who fear falling restrict their activity, which can lead to deconditioning and increased risk of falling).

A Cochrane Review of 111 randomized, controlled trials with 55,303 participants identified effective interventions to reduce the risk of falling (Cochrane Database Syst. Rev. 2009 [doi:10.1002/14651858.CD007146.pub2]).

A number of forms of exercise reduced both the number of people who fell and the number of falls. Group tai chi exercise or individually prescribed exercise programs at home were effective. Multiple-component group exercise was effective if it targeted at least two of the following: strength, balance, flexibility, and endurance.

Conducting a multifactorial falls evaluation reduces the number of falls. In patients with visual impairment and a high risk of falling, assessing and modifying home hazards was effective.

Withdrawing psychotropic medications and educating primary care physicians about the risk of falls associated with drug therapy reduced the number of falls but not the number who fell. In patients with cardioinhibitory carotid sinus hypersensitivity, cardiac pacing reduced the number of falls.

Vitamin D supplementation may reduce falls in people with low vitamin D levels, but it's unclear whether this helps people with adequate vitamin D levels. Other preventive strategies of unknown effectiveness include correction of visual deficiency, hormone replacement therapy, or modifying home hazards for people who have not fallen.

The Cochrane Review suggested that wearing hip protectors may provide some marginally significant benefit to frail, older adults in institutional care but not for older people who remain ambulant in the community, Dr. Pierluissi said.

One randomized, controlled trial of 1,042 residents in 37 nursing homes found a high rate of adherence to wearing hip protectors (74%) but these did not reduce the risk for hip fracture during the 20-month study.

Residents served as their own controls by wearing hip protectors with padding on one hip but not the other. Investigators stopped the study early due to lack of efficacy, with hip fractures on 3.1% of the protected hips and 2.5% of unprotected hips, a statistically nonsignificant difference (JAMA 2007;298:413–22).

Dr. Pierluissi said he has no relevant disclosures.

SAN FRANCISCO – Talking to patients after they start an antiresorptive drug for osteoporosis is better than laboratory testing to convince them to stay on therapy, according to Dr. Douglas C. Bauer.

Bone mineral density testing determines the need for antiresorptive medication, but it's less helpful in monitoring the effects of treatment or adherence to therapy than is talking to patients. A test showing bone loss in the first year of treatment can confuse patients and doesn't necessarily mean they are not responding to treatment, said Dr. Bauer, professor of medicine and of epidemiology and biostatistics at the university.

Besides, most of the patients who stop osteoporosis therapy within 3 years do so within the first few months of treatment, so annual bone density testing is unlikely to improve adherence, he added.

Biochemical markers of bone turnover eventually may become the standard for monitoring treatment, “but we're not there yet,” he said at the meeting.

Studies have shown that follow-up discussions after a patient starts antiresorptive medication is the factor that improves adherence, not measuring bone density or bone turnover markers.

Dr. Bauer said he tells patients not to expect routine follow-up bone density testing and asks about and encourages adherence at every patient visit. If a patient develops a fracture while on therapy or is considering a drug holiday after 5 years on alendronate, he then considers ordering follow-up bone mineral density testing.

“There's a caveat: This may not be the right algorithm for tertiary care centers with severe or complex patients,” said Dr. Bauer.

Although bone mineral density measurements are very precise, small differences in position or “noise” in the measures can produce apparent changes that are not clinically meaningful. To assess whether a change in bone density is “real,” he recommended a useful equation called the “least significant change” equation: Multiply the coefficient of variations by three; if the sum is less than 4.5%, then the change may be due to chance.

For example, if the coefficient of variations in hip bone density is 1.5%, the least significant change is 4.5%. If a patient lost 3% in bone density, there is approximately a 10% chance that there was no change in bone density, he said.

“A somewhat more fundamental question is not just whether the measurements [are] real, but are they meaningful?” Dr. Bauer said.

Analyses of data from the Fracture Intervention Trial (FIT) show that patients on alendronate who lost up to 4% in total hip bone density in the 1-2 years of treatment still had 53% fewer vertebral fractures compared with their counterparts on placebo who lost similar amounts of bone density. Patients who lost up to 4% in spine density had 60% fewer vertebral fractures compared with their counterparts on placebo (Osteoporos. Int. 2005;16:842–8).

Then there's the “regression to the mean” argument that patients who have an unusual response in the first year of antiresorptive therapy will develop a more typical response if treatment is continued, he said. A separate analysis of FIT data showed that 92% of patients who lost up to 4% of hip bone density in the first year of therapy gained an average of nearly 5% in bone density in the second year of treatment (JAMA 2000;283:1318–21).

A more recent analysis of annual bone mineral density data in FIT showed that variation in the change in bone density over a 3-year period was mainly measurement-related, within-person variation. Treatment-related, between-person variation played a much smaller role (BMJ 2009;338:b2266).

That helps explain how patients can “lose” bone density but still have fewer fractures, Dr. Bauer said at the meeting. “It's reassuring that 98% on alendronate gained more than 0.02 g/cm

Antiresorptive therapy decreases biochemical markers of bone turnover, but there is a lot of biologic variability and no clear threshold for efficacy. Biochemical marker measurements could be used to identify nonadherence to treatment, but “it's cheaper just to ask,” he said.

In a study of 2,382 osteoporotic women starting a year of risedronate therapy, the women were randomized to get bone turnover markers measured at weeks 13 and 25 or to routine visits without marker measurements.

The results showed no difference in adherence rates between the groups (J. Clin. Endocrinol. Metab. 2007;92:1296–304). In the marker measurement group, the adherence rate was 225% worse than in the control group if the marker results suggested a “bad” response to therapy (less than a 30% decrease in marker levels).

“That was unexpected,” Dr. Bauer said. “Bone turnover markers by themselves are not helpful for increasing adherence” to therapy.

A separate randomized study of 75 women starting raloxifene treatment for low bone density randomized them to no monitoring; nurse visits at months 3, 6, and 9; or nurse visits plus bone turnover marker measurements. The nurse visits improved adherence to therapy compared with no monitoring, but biomarker measurements did not add anything to the nurse visits (J. Clin. Endocrinol. Metab. 2004;89:1117–23).

In general, approximately 30%–40% of patients stop taking antiresorptive drugs within 1 year, he said.

Dr. Bauer said he has received research funding from Amgen, Novartis, and Procter & Gamble.

Biochemical marker measurements could identify nonadherence, but 'it's cheaper just to ask.'

Source DR. BAUER

SAN FRANCISCO – Talking to patients after they start an antiresorptive drug for osteoporosis is better than laboratory testing to convince them to stay on therapy, according to Dr. Douglas C. Bauer.

Bone mineral density testing determines the need for antiresorptive medication, but it's less helpful in monitoring the effects of treatment or adherence to therapy than is talking to patients. A test showing bone loss in the first year of treatment can confuse patients and doesn't necessarily mean they are not responding to treatment, said Dr. Bauer, professor of medicine and of epidemiology and biostatistics at the university.

Besides, most of the patients who stop osteoporosis therapy within 3 years do so within the first few months of treatment, so annual bone density testing is unlikely to improve adherence, he added.

Biochemical markers of bone turnover eventually may become the standard for monitoring treatment, “but we're not there yet,” he said at the meeting.

Studies have shown that follow-up discussions after a patient starts antiresorptive medication is the factor that improves adherence, not measuring bone density or bone turnover markers.

Dr. Bauer said he tells patients not to expect routine follow-up bone density testing and asks about and encourages adherence at every patient visit. If a patient develops a fracture while on therapy or is considering a drug holiday after 5 years on alendronate, he then considers ordering follow-up bone mineral density testing.

“There's a caveat: This may not be the right algorithm for tertiary care centers with severe or complex patients,” said Dr. Bauer.

Although bone mineral density measurements are very precise, small differences in position or “noise” in the measures can produce apparent changes that are not clinically meaningful. To assess whether a change in bone density is “real,” he recommended a useful equation called the “least significant change” equation: Multiply the coefficient of variations by three; if the sum is less than 4.5%, then the change may be due to chance.

For example, if the coefficient of variations in hip bone density is 1.5%, the least significant change is 4.5%. If a patient lost 3% in bone density, there is approximately a 10% chance that there was no change in bone density, he said.

“A somewhat more fundamental question is not just whether the measurements [are] real, but are they meaningful?” Dr. Bauer said.

Analyses of data from the Fracture Intervention Trial (FIT) show that patients on alendronate who lost up to 4% in total hip bone density in the 1-2 years of treatment still had 53% fewer vertebral fractures compared with their counterparts on placebo who lost similar amounts of bone density. Patients who lost up to 4% in spine density had 60% fewer vertebral fractures compared with their counterparts on placebo (Osteoporos. Int. 2005;16:842–8).

Then there's the “regression to the mean” argument that patients who have an unusual response in the first year of antiresorptive therapy will develop a more typical response if treatment is continued, he said. A separate analysis of FIT data showed that 92% of patients who lost up to 4% of hip bone density in the first year of therapy gained an average of nearly 5% in bone density in the second year of treatment (JAMA 2000;283:1318–21).

A more recent analysis of annual bone mineral density data in FIT showed that variation in the change in bone density over a 3-year period was mainly measurement-related, within-person variation. Treatment-related, between-person variation played a much smaller role (BMJ 2009;338:b2266).

That helps explain how patients can “lose” bone density but still have fewer fractures, Dr. Bauer said at the meeting. “It's reassuring that 98% on alendronate gained more than 0.02 g/cm

Antiresorptive therapy decreases biochemical markers of bone turnover, but there is a lot of biologic variability and no clear threshold for efficacy. Biochemical marker measurements could be used to identify nonadherence to treatment, but “it's cheaper just to ask,” he said.

In a study of 2,382 osteoporotic women starting a year of risedronate therapy, the women were randomized to get bone turnover markers measured at weeks 13 and 25 or to routine visits without marker measurements.

The results showed no difference in adherence rates between the groups (J. Clin. Endocrinol. Metab. 2007;92:1296–304). In the marker measurement group, the adherence rate was 225% worse than in the control group if the marker results suggested a “bad” response to therapy (less than a 30% decrease in marker levels).

“That was unexpected,” Dr. Bauer said. “Bone turnover markers by themselves are not helpful for increasing adherence” to therapy.

A separate randomized study of 75 women starting raloxifene treatment for low bone density randomized them to no monitoring; nurse visits at months 3, 6, and 9; or nurse visits plus bone turnover marker measurements. The nurse visits improved adherence to therapy compared with no monitoring, but biomarker measurements did not add anything to the nurse visits (J. Clin. Endocrinol. Metab. 2004;89:1117–23).

In general, approximately 30%–40% of patients stop taking antiresorptive drugs within 1 year, he said.

Dr. Bauer said he has received research funding from Amgen, Novartis, and Procter & Gamble.

Biochemical marker measurements could identify nonadherence, but 'it's cheaper just to ask.'

Source DR. BAUER

SAN FRANCISCO – Talking to patients after they start an antiresorptive drug for osteoporosis is better than laboratory testing to convince them to stay on therapy, according to Dr. Douglas C. Bauer.

Bone mineral density testing determines the need for antiresorptive medication, but it's less helpful in monitoring the effects of treatment or adherence to therapy than is talking to patients. A test showing bone loss in the first year of treatment can confuse patients and doesn't necessarily mean they are not responding to treatment, said Dr. Bauer, professor of medicine and of epidemiology and biostatistics at the university.

Besides, most of the patients who stop osteoporosis therapy within 3 years do so within the first few months of treatment, so annual bone density testing is unlikely to improve adherence, he added.

Biochemical markers of bone turnover eventually may become the standard for monitoring treatment, “but we're not there yet,” he said at the meeting.

Studies have shown that follow-up discussions after a patient starts antiresorptive medication is the factor that improves adherence, not measuring bone density or bone turnover markers.

Dr. Bauer said he tells patients not to expect routine follow-up bone density testing and asks about and encourages adherence at every patient visit. If a patient develops a fracture while on therapy or is considering a drug holiday after 5 years on alendronate, he then considers ordering follow-up bone mineral density testing.

“There's a caveat: This may not be the right algorithm for tertiary care centers with severe or complex patients,” said Dr. Bauer.

Although bone mineral density measurements are very precise, small differences in position or “noise” in the measures can produce apparent changes that are not clinically meaningful. To assess whether a change in bone density is “real,” he recommended a useful equation called the “least significant change” equation: Multiply the coefficient of variations by three; if the sum is less than 4.5%, then the change may be due to chance.

For example, if the coefficient of variations in hip bone density is 1.5%, the least significant change is 4.5%. If a patient lost 3% in bone density, there is approximately a 10% chance that there was no change in bone density, he said.

“A somewhat more fundamental question is not just whether the measurements [are] real, but are they meaningful?” Dr. Bauer said.

Analyses of data from the Fracture Intervention Trial (FIT) show that patients on alendronate who lost up to 4% in total hip bone density in the 1-2 years of treatment still had 53% fewer vertebral fractures compared with their counterparts on placebo who lost similar amounts of bone density. Patients who lost up to 4% in spine density had 60% fewer vertebral fractures compared with their counterparts on placebo (Osteoporos. Int. 2005;16:842–8).

Then there's the “regression to the mean” argument that patients who have an unusual response in the first year of antiresorptive therapy will develop a more typical response if treatment is continued, he said. A separate analysis of FIT data showed that 92% of patients who lost up to 4% of hip bone density in the first year of therapy gained an average of nearly 5% in bone density in the second year of treatment (JAMA 2000;283:1318–21).

A more recent analysis of annual bone mineral density data in FIT showed that variation in the change in bone density over a 3-year period was mainly measurement-related, within-person variation. Treatment-related, between-person variation played a much smaller role (BMJ 2009;338:b2266).

That helps explain how patients can “lose” bone density but still have fewer fractures, Dr. Bauer said at the meeting. “It's reassuring that 98% on alendronate gained more than 0.02 g/cm

Antiresorptive therapy decreases biochemical markers of bone turnover, but there is a lot of biologic variability and no clear threshold for efficacy. Biochemical marker measurements could be used to identify nonadherence to treatment, but “it's cheaper just to ask,” he said.

In a study of 2,382 osteoporotic women starting a year of risedronate therapy, the women were randomized to get bone turnover markers measured at weeks 13 and 25 or to routine visits without marker measurements.

The results showed no difference in adherence rates between the groups (J. Clin. Endocrinol. Metab. 2007;92:1296–304). In the marker measurement group, the adherence rate was 225% worse than in the control group if the marker results suggested a “bad” response to therapy (less than a 30% decrease in marker levels).

“That was unexpected,” Dr. Bauer said. “Bone turnover markers by themselves are not helpful for increasing adherence” to therapy.

A separate randomized study of 75 women starting raloxifene treatment for low bone density randomized them to no monitoring; nurse visits at months 3, 6, and 9; or nurse visits plus bone turnover marker measurements. The nurse visits improved adherence to therapy compared with no monitoring, but biomarker measurements did not add anything to the nurse visits (J. Clin. Endocrinol. Metab. 2004;89:1117–23).

In general, approximately 30%–40% of patients stop taking antiresorptive drugs within 1 year, he said.

Dr. Bauer said he has received research funding from Amgen, Novartis, and Procter & Gamble.

Biochemical marker measurements could identify nonadherence, but 'it's cheaper just to ask.'

Source DR. BAUER

SAN FRANCISCO – Vertebroplasty worked no better than sham surgery to reduce pain and disability from vertebral fracture, according to data from recent randomized, controlled trials that put nonsurgical therapies firmly in the first line of treatment.

Osteoporotic vertebral fractures should be treated aggressively with antiresorptive or anabolic therapy for at least 6-12 weeks before considering surgery, Dr. Douglas C. Bauer said at a meeting on osteoporosis sponsored by the University of California, San Francisco. Optimize medical therapy, physical therapy, and other options that might be appropriate such as adding calcitonin or referring the patient for a facet joint injection, he said.

Even after all that, clinicians should consider kyphoplasty before resorting to vertebroplasty, said Dr. Bauer, who is professor of medicine and of epidemiology and biostatistics at the university.

Findings from one unblinded, randomized trial suggest that kyphoplasty may reduce pain and disability, compared with conservative care initially, though the difference in results is less apparent 1 year after surgery.

Despite data from numerous uncontrolled studies suggesting that vertebroplasty also lessens pain and improves function, findings from two well-designed controlled trials “raised a brouhaha” and surprised investigators by showing vertebroplasty to have no benefit, “suggesting that a very commonly done procedure is not helpful,” he said. It's unclear whether the uncontrolled trial results were due to an extended placebo effect or some other factor.

In kyphoplasty, surgeons insert a balloon device to reduce the cervical fracture, remove the balloon, and replace it with cement. Vertebroplasty injects cement only, without the balloon, and does not attempt to increase vertebral height. Both are minimally invasive surgeries that usually are performed under general anesthesia but can be done using local anesthesia, often with conscious sedation.

The unblinded trial of kyphoplasty randomized 149 patients to kyphoplasty and 151 to usual nonsurgical care. “The patients were typical of who we see with vertebral fracture,” Dr. Bauer noted.

The primary results showed that 1 month after surgery, scores on the Short Form-36 (SF-36) Physical Component Summary had increased from 26 at baseline in both groups to 27 in the kyphoplasty group and 33 in the control group, a significant difference between groups (Lancet 2009;373:1016–24).

Follow-up continued out to 3, 6, and 12 months after surgery, and results were significantly better in the kyphoplasty group at all time points for the SF-36 Physical Component, patient-reported Visual Analog Scale (VAS) scores for back pain, and the number of days of limited activity in the previous 2 weeks.

Although statistically significant, some of the differences between groups were more clinically significant than others. The self-reported VAS pain scores, for example, differed between groups by only 1 point on a 10-point scale at 12 months. The kyphoplasty group, however, enjoyed an average of 60 fewer days of limited activity during those 12 months, compared with the control group, which “patients may be most interested in,” Dr. Bauer said.

At 24 months, only the difference in pain scores remained statistically significant between groups (J. Bone Miner. Res. 2011;26:1627–37).

More trials of kyphoplasty are needed before the surgery becomes widespread, Dr. Bauer said.

A separate uncontrolled trial that randomized 202 patients to vertebroplasty or usual care similarly found statistically greater improvements in the vertebroplasty group in VAS pain scores at 1 month (a decrease of 5 points) and 1 year (a 6-point drop), compared with usual care (a 3- and 4-point drop, respectively). Patients in the surgery arm also reported less narcotic use (Lancet 2010;376:1085–92).

The two well-designed controlled trials of vertebroplasty contradict other findings, however. Patients were taken to the operating room before randomization. The members of the control group received sham surgery that included needle insertions in their backs and the breaking of a vial of chemicals to disperse a chemical smell. Outcomes assessors were blinded to randomization.

In one study of 71 patients, scores for back pain decreased significantly in both the real and sham surgery groups, but outcomes did not differ significantly between the groups at any time point out to 6 months (N. Engl. J. Med. 2009;361:557–68).

In the other study of 131 patients, both groups showed immediate improvements in disability and pain scores but no outcomes differed significantly between groups at 1 month (N. Engl. J. Med. 2009;361:569–79).

While it's conceivable that the benefits reported for vertebroplasty and kyphoplasty in uncontrolled studies are due to an extended placebo effect, the likelihood that the placebo effect would last for as much as 24 months of follow-up is unclear, Dr. Bauer said.

Some have suggested that the sham-surgery studies included a harder-to-treat population by accepting patients with vertebral fractures up to 1 year in duration, but a subsequent analysis of data limited to fractures of less than 6 weeks duration found no change in the overall results.

Case series have shown that anesthetic or steroid injections alone can reduce vertebral fracture pain, which may explain the improvement in pain scores in both the real and sham-surgery groups in the vertebroplasty trials, he suggested.

There also may be a difference between the two surgeries that produce different results from kyphoplasty or vertebroplasty. Randomized, controlled trials comparing the two are underway.

Further research is needed on optimal patient selection, on whether the surgeries prevent kyphosis, and on long-term outcomes, Dr. Bauer said.

The 700,000 vertebral compression fractures in the United States each year hospitalize more than 150,000 people.

Dr. Bauer has received research funding from Amgen and Novartis.

Clinicians should consider kyphoplasty before resorting to vertebroplasty for an osteoporotic fracture (above).

Source Courtesy Dr. Victor Jaramillo/Dr. Aravind Pothineni

SAN FRANCISCO – Vertebroplasty worked no better than sham surgery to reduce pain and disability from vertebral fracture, according to data from recent randomized, controlled trials that put nonsurgical therapies firmly in the first line of treatment.

Osteoporotic vertebral fractures should be treated aggressively with antiresorptive or anabolic therapy for at least 6-12 weeks before considering surgery, Dr. Douglas C. Bauer said at a meeting on osteoporosis sponsored by the University of California, San Francisco. Optimize medical therapy, physical therapy, and other options that might be appropriate such as adding calcitonin or referring the patient for a facet joint injection, he said.

Even after all that, clinicians should consider kyphoplasty before resorting to vertebroplasty, said Dr. Bauer, who is professor of medicine and of epidemiology and biostatistics at the university.

Findings from one unblinded, randomized trial suggest that kyphoplasty may reduce pain and disability, compared with conservative care initially, though the difference in results is less apparent 1 year after surgery.

Despite data from numerous uncontrolled studies suggesting that vertebroplasty also lessens pain and improves function, findings from two well-designed controlled trials “raised a brouhaha” and surprised investigators by showing vertebroplasty to have no benefit, “suggesting that a very commonly done procedure is not helpful,” he said. It's unclear whether the uncontrolled trial results were due to an extended placebo effect or some other factor.

In kyphoplasty, surgeons insert a balloon device to reduce the cervical fracture, remove the balloon, and replace it with cement. Vertebroplasty injects cement only, without the balloon, and does not attempt to increase vertebral height. Both are minimally invasive surgeries that usually are performed under general anesthesia but can be done using local anesthesia, often with conscious sedation.

The unblinded trial of kyphoplasty randomized 149 patients to kyphoplasty and 151 to usual nonsurgical care. “The patients were typical of who we see with vertebral fracture,” Dr. Bauer noted.

The primary results showed that 1 month after surgery, scores on the Short Form-36 (SF-36) Physical Component Summary had increased from 26 at baseline in both groups to 27 in the kyphoplasty group and 33 in the control group, a significant difference between groups (Lancet 2009;373:1016–24).

Follow-up continued out to 3, 6, and 12 months after surgery, and results were significantly better in the kyphoplasty group at all time points for the SF-36 Physical Component, patient-reported Visual Analog Scale (VAS) scores for back pain, and the number of days of limited activity in the previous 2 weeks.

Although statistically significant, some of the differences between groups were more clinically significant than others. The self-reported VAS pain scores, for example, differed between groups by only 1 point on a 10-point scale at 12 months. The kyphoplasty group, however, enjoyed an average of 60 fewer days of limited activity during those 12 months, compared with the control group, which “patients may be most interested in,” Dr. Bauer said.

At 24 months, only the difference in pain scores remained statistically significant between groups (J. Bone Miner. Res. 2011;26:1627–37).

More trials of kyphoplasty are needed before the surgery becomes widespread, Dr. Bauer said.

A separate uncontrolled trial that randomized 202 patients to vertebroplasty or usual care similarly found statistically greater improvements in the vertebroplasty group in VAS pain scores at 1 month (a decrease of 5 points) and 1 year (a 6-point drop), compared with usual care (a 3- and 4-point drop, respectively). Patients in the surgery arm also reported less narcotic use (Lancet 2010;376:1085–92).

The two well-designed controlled trials of vertebroplasty contradict other findings, however. Patients were taken to the operating room before randomization. The members of the control group received sham surgery that included needle insertions in their backs and the breaking of a vial of chemicals to disperse a chemical smell. Outcomes assessors were blinded to randomization.

In one study of 71 patients, scores for back pain decreased significantly in both the real and sham surgery groups, but outcomes did not differ significantly between the groups at any time point out to 6 months (N. Engl. J. Med. 2009;361:557–68).

In the other study of 131 patients, both groups showed immediate improvements in disability and pain scores but no outcomes differed significantly between groups at 1 month (N. Engl. J. Med. 2009;361:569–79).

While it's conceivable that the benefits reported for vertebroplasty and kyphoplasty in uncontrolled studies are due to an extended placebo effect, the likelihood that the placebo effect would last for as much as 24 months of follow-up is unclear, Dr. Bauer said.

Some have suggested that the sham-surgery studies included a harder-to-treat population by accepting patients with vertebral fractures up to 1 year in duration, but a subsequent analysis of data limited to fractures of less than 6 weeks duration found no change in the overall results.

Case series have shown that anesthetic or steroid injections alone can reduce vertebral fracture pain, which may explain the improvement in pain scores in both the real and sham-surgery groups in the vertebroplasty trials, he suggested.

There also may be a difference between the two surgeries that produce different results from kyphoplasty or vertebroplasty. Randomized, controlled trials comparing the two are underway.

Further research is needed on optimal patient selection, on whether the surgeries prevent kyphosis, and on long-term outcomes, Dr. Bauer said.

The 700,000 vertebral compression fractures in the United States each year hospitalize more than 150,000 people.

Dr. Bauer has received research funding from Amgen and Novartis.

Clinicians should consider kyphoplasty before resorting to vertebroplasty for an osteoporotic fracture (above).

Source Courtesy Dr. Victor Jaramillo/Dr. Aravind Pothineni

SAN FRANCISCO – Vertebroplasty worked no better than sham surgery to reduce pain and disability from vertebral fracture, according to data from recent randomized, controlled trials that put nonsurgical therapies firmly in the first line of treatment.

Osteoporotic vertebral fractures should be treated aggressively with antiresorptive or anabolic therapy for at least 6-12 weeks before considering surgery, Dr. Douglas C. Bauer said at a meeting on osteoporosis sponsored by the University of California, San Francisco. Optimize medical therapy, physical therapy, and other options that might be appropriate such as adding calcitonin or referring the patient for a facet joint injection, he said.

Even after all that, clinicians should consider kyphoplasty before resorting to vertebroplasty, said Dr. Bauer, who is professor of medicine and of epidemiology and biostatistics at the university.

Findings from one unblinded, randomized trial suggest that kyphoplasty may reduce pain and disability, compared with conservative care initially, though the difference in results is less apparent 1 year after surgery.

Despite data from numerous uncontrolled studies suggesting that vertebroplasty also lessens pain and improves function, findings from two well-designed controlled trials “raised a brouhaha” and surprised investigators by showing vertebroplasty to have no benefit, “suggesting that a very commonly done procedure is not helpful,” he said. It's unclear whether the uncontrolled trial results were due to an extended placebo effect or some other factor.

In kyphoplasty, surgeons insert a balloon device to reduce the cervical fracture, remove the balloon, and replace it with cement. Vertebroplasty injects cement only, without the balloon, and does not attempt to increase vertebral height. Both are minimally invasive surgeries that usually are performed under general anesthesia but can be done using local anesthesia, often with conscious sedation.

The unblinded trial of kyphoplasty randomized 149 patients to kyphoplasty and 151 to usual nonsurgical care. “The patients were typical of who we see with vertebral fracture,” Dr. Bauer noted.

The primary results showed that 1 month after surgery, scores on the Short Form-36 (SF-36) Physical Component Summary had increased from 26 at baseline in both groups to 27 in the kyphoplasty group and 33 in the control group, a significant difference between groups (Lancet 2009;373:1016–24).

Follow-up continued out to 3, 6, and 12 months after surgery, and results were significantly better in the kyphoplasty group at all time points for the SF-36 Physical Component, patient-reported Visual Analog Scale (VAS) scores for back pain, and the number of days of limited activity in the previous 2 weeks.

Although statistically significant, some of the differences between groups were more clinically significant than others. The self-reported VAS pain scores, for example, differed between groups by only 1 point on a 10-point scale at 12 months. The kyphoplasty group, however, enjoyed an average of 60 fewer days of limited activity during those 12 months, compared with the control group, which “patients may be most interested in,” Dr. Bauer said.

At 24 months, only the difference in pain scores remained statistically significant between groups (J. Bone Miner. Res. 2011;26:1627–37).

More trials of kyphoplasty are needed before the surgery becomes widespread, Dr. Bauer said.

A separate uncontrolled trial that randomized 202 patients to vertebroplasty or usual care similarly found statistically greater improvements in the vertebroplasty group in VAS pain scores at 1 month (a decrease of 5 points) and 1 year (a 6-point drop), compared with usual care (a 3- and 4-point drop, respectively). Patients in the surgery arm also reported less narcotic use (Lancet 2010;376:1085–92).

The two well-designed controlled trials of vertebroplasty contradict other findings, however. Patients were taken to the operating room before randomization. The members of the control group received sham surgery that included needle insertions in their backs and the breaking of a vial of chemicals to disperse a chemical smell. Outcomes assessors were blinded to randomization.

In one study of 71 patients, scores for back pain decreased significantly in both the real and sham surgery groups, but outcomes did not differ significantly between the groups at any time point out to 6 months (N. Engl. J. Med. 2009;361:557–68).

In the other study of 131 patients, both groups showed immediate improvements in disability and pain scores but no outcomes differed significantly between groups at 1 month (N. Engl. J. Med. 2009;361:569–79).

While it's conceivable that the benefits reported for vertebroplasty and kyphoplasty in uncontrolled studies are due to an extended placebo effect, the likelihood that the placebo effect would last for as much as 24 months of follow-up is unclear, Dr. Bauer said.

Some have suggested that the sham-surgery studies included a harder-to-treat population by accepting patients with vertebral fractures up to 1 year in duration, but a subsequent analysis of data limited to fractures of less than 6 weeks duration found no change in the overall results.

Case series have shown that anesthetic or steroid injections alone can reduce vertebral fracture pain, which may explain the improvement in pain scores in both the real and sham-surgery groups in the vertebroplasty trials, he suggested.

There also may be a difference between the two surgeries that produce different results from kyphoplasty or vertebroplasty. Randomized, controlled trials comparing the two are underway.

Further research is needed on optimal patient selection, on whether the surgeries prevent kyphosis, and on long-term outcomes, Dr. Bauer said.

The 700,000 vertebral compression fractures in the United States each year hospitalize more than 150,000 people.

Dr. Bauer has received research funding from Amgen and Novartis.

Clinicians should consider kyphoplasty before resorting to vertebroplasty for an osteoporotic fracture (above).

Source Courtesy Dr. Victor Jaramillo/Dr. Aravind Pothineni