User login
For MD-IQ on Family Practice News, but a regular topic for Rheumatology News
Walking disability raises red flag in diabetics with OA
PARIS – Walking disability from hip or knee osteoarthritis puts patients with comorbid diabetes at increased risk for serious diabetes complications, according to a retrospective cohort study.
After a median follow-up of 6.6 years among 437 patients with moderately severe symptomatic osteoarthritis (OA) and type 1 or type 2 diabetes, 37% experienced the composite diabetes-specific primary outcome of hospitalization for hypo- or hyperglycemia, soft tissue infection, amputation, or initiation of chronic dialysis.
Specifically, there were 51 hospitalizations for hypoglycemia, 11 for hyperglycemia, 127 for soft tissue infections, 10 amputations, and 4 patients who went on chronic dialysis.
After adjusting for age, sex, and preexisting cardiovascular disease, baseline walking disability was a significant independent predictor of risk for a non-CVD, diabetes-specific complication (Hazard ratio per unit increase in Health Assessment Questionnaire [HAQ] walking score, 1.26; P = .02), Dr. Gillian Hawker reported at the World Congress on Osteoarthritis.
In sensitivity analyses, the results were unchanged after additional adjustment for post-baseline receipt of a primary, elective hip or knee joint replacement or when retinopathy was included as an outcome.
"In people with diabetes, OA functional limitations may impede their ability to carry out diabetes self-management activities, increasing their risk for diabetes complications," noted Dr. Hawker, professor of medicine at the University of Toronto and physician-in-chief of medicine at Women’s College Hospital, Toronto.
This is particularly worrisome since the coprevalence of diabetes with OA is high, with as many as 50%-60% of patients with longstanding diabetes also having clinically evident hand, hip, or knee OA.
In an oral presentation at the same meeting, Dr. Hawker stressed the need for early identification of walking disability after reporting that greater walking disability was an independent predictor of all-cause death and major cardiovascular events in the overall cohort of patients with symptomatic hip or knee OA alone.
The retrospective cohort study linked provincial health administrative databases with surveys from a population cohort of 2,156 patients with at least moderately severe symptomatic hip or knee OA who were recruited from 1996 to 1998 through a screening survey in Ontario.
At baseline, 457 patients self-reported diabetes or met criteria for inclusion in the Ontario Diabetes Database (sensitivity 86%, specificity 97%) and were without preexisting retinopathy or renal failure. After censoring patients who died, emigrated, or had insufficient data, 434 patients were included in the current analysis. The study could not differentiate type 1 from type 2 diabetes.
Their mean age was 71.6 years (all were 55 years or older), 41% were obese, and 53.2% had preexisting CVD. Their median HAQ walking disability score was 2 on a 3-point scale, median HAQ grip score was 1 on a 3-point scale, and mean Western Ontario and McMaster Osteoarthritis Index (WOMAC) summary score was 43.4. Overall, 55.5% used a walking aid, and 39% reported using NSAIDs. (A walking disability score of 2 corresponds with walking outdoors on flat ground with much difficulty, whereas a score of 3 means the person is unable to do it. A grip score of 1 corresponds with some difficulty in just one of the following tasks: opening car doors, opening previously open jars, or turning faucets on and off.)
In multivariable analyses, no effect was found for baseline grip strength (adjusted HR, 1.16; P = .07), Dr. Hawker reported at the meeting, sponsored by the Osteoarthritis Research Society International.
However, in sensitivity analyses that further adjusted for receipt of a diabetes drug prescription or NSAID in patients at least 66 years old at baseline and thus eligible for drug benefits, both HAQ walking and grip scores were significant predictors of risk for a diabetes complication, she reported. Specific data were not shown in the poster presentation, but the adjusted hazard ratios per unit increase in HAQ were 1.36 (P = .003) and 1.26 (P = .01), respectively, according to the abstract.
"Controlling for confounders, reduced grip strength and increased walking disability were identified as potentially modifiable risk factors for serious diabetes complications in people with both OA and diabetes," the authors concluded. "Additional studies are warranted to confirm or refute our findings, and if confirmed, to elucidate potential mechanisms."
Dr. Hawker reported having no financial disclosures.
PARIS – Walking disability from hip or knee osteoarthritis puts patients with comorbid diabetes at increased risk for serious diabetes complications, according to a retrospective cohort study.
After a median follow-up of 6.6 years among 437 patients with moderately severe symptomatic osteoarthritis (OA) and type 1 or type 2 diabetes, 37% experienced the composite diabetes-specific primary outcome of hospitalization for hypo- or hyperglycemia, soft tissue infection, amputation, or initiation of chronic dialysis.
Specifically, there were 51 hospitalizations for hypoglycemia, 11 for hyperglycemia, 127 for soft tissue infections, 10 amputations, and 4 patients who went on chronic dialysis.
After adjusting for age, sex, and preexisting cardiovascular disease, baseline walking disability was a significant independent predictor of risk for a non-CVD, diabetes-specific complication (Hazard ratio per unit increase in Health Assessment Questionnaire [HAQ] walking score, 1.26; P = .02), Dr. Gillian Hawker reported at the World Congress on Osteoarthritis.
In sensitivity analyses, the results were unchanged after additional adjustment for post-baseline receipt of a primary, elective hip or knee joint replacement or when retinopathy was included as an outcome.
"In people with diabetes, OA functional limitations may impede their ability to carry out diabetes self-management activities, increasing their risk for diabetes complications," noted Dr. Hawker, professor of medicine at the University of Toronto and physician-in-chief of medicine at Women’s College Hospital, Toronto.
This is particularly worrisome since the coprevalence of diabetes with OA is high, with as many as 50%-60% of patients with longstanding diabetes also having clinically evident hand, hip, or knee OA.
In an oral presentation at the same meeting, Dr. Hawker stressed the need for early identification of walking disability after reporting that greater walking disability was an independent predictor of all-cause death and major cardiovascular events in the overall cohort of patients with symptomatic hip or knee OA alone.
The retrospective cohort study linked provincial health administrative databases with surveys from a population cohort of 2,156 patients with at least moderately severe symptomatic hip or knee OA who were recruited from 1996 to 1998 through a screening survey in Ontario.
At baseline, 457 patients self-reported diabetes or met criteria for inclusion in the Ontario Diabetes Database (sensitivity 86%, specificity 97%) and were without preexisting retinopathy or renal failure. After censoring patients who died, emigrated, or had insufficient data, 434 patients were included in the current analysis. The study could not differentiate type 1 from type 2 diabetes.
Their mean age was 71.6 years (all were 55 years or older), 41% were obese, and 53.2% had preexisting CVD. Their median HAQ walking disability score was 2 on a 3-point scale, median HAQ grip score was 1 on a 3-point scale, and mean Western Ontario and McMaster Osteoarthritis Index (WOMAC) summary score was 43.4. Overall, 55.5% used a walking aid, and 39% reported using NSAIDs. (A walking disability score of 2 corresponds with walking outdoors on flat ground with much difficulty, whereas a score of 3 means the person is unable to do it. A grip score of 1 corresponds with some difficulty in just one of the following tasks: opening car doors, opening previously open jars, or turning faucets on and off.)
In multivariable analyses, no effect was found for baseline grip strength (adjusted HR, 1.16; P = .07), Dr. Hawker reported at the meeting, sponsored by the Osteoarthritis Research Society International.
However, in sensitivity analyses that further adjusted for receipt of a diabetes drug prescription or NSAID in patients at least 66 years old at baseline and thus eligible for drug benefits, both HAQ walking and grip scores were significant predictors of risk for a diabetes complication, she reported. Specific data were not shown in the poster presentation, but the adjusted hazard ratios per unit increase in HAQ were 1.36 (P = .003) and 1.26 (P = .01), respectively, according to the abstract.
"Controlling for confounders, reduced grip strength and increased walking disability were identified as potentially modifiable risk factors for serious diabetes complications in people with both OA and diabetes," the authors concluded. "Additional studies are warranted to confirm or refute our findings, and if confirmed, to elucidate potential mechanisms."
Dr. Hawker reported having no financial disclosures.
PARIS – Walking disability from hip or knee osteoarthritis puts patients with comorbid diabetes at increased risk for serious diabetes complications, according to a retrospective cohort study.
After a median follow-up of 6.6 years among 437 patients with moderately severe symptomatic osteoarthritis (OA) and type 1 or type 2 diabetes, 37% experienced the composite diabetes-specific primary outcome of hospitalization for hypo- or hyperglycemia, soft tissue infection, amputation, or initiation of chronic dialysis.
Specifically, there were 51 hospitalizations for hypoglycemia, 11 for hyperglycemia, 127 for soft tissue infections, 10 amputations, and 4 patients who went on chronic dialysis.
After adjusting for age, sex, and preexisting cardiovascular disease, baseline walking disability was a significant independent predictor of risk for a non-CVD, diabetes-specific complication (Hazard ratio per unit increase in Health Assessment Questionnaire [HAQ] walking score, 1.26; P = .02), Dr. Gillian Hawker reported at the World Congress on Osteoarthritis.
In sensitivity analyses, the results were unchanged after additional adjustment for post-baseline receipt of a primary, elective hip or knee joint replacement or when retinopathy was included as an outcome.
"In people with diabetes, OA functional limitations may impede their ability to carry out diabetes self-management activities, increasing their risk for diabetes complications," noted Dr. Hawker, professor of medicine at the University of Toronto and physician-in-chief of medicine at Women’s College Hospital, Toronto.
This is particularly worrisome since the coprevalence of diabetes with OA is high, with as many as 50%-60% of patients with longstanding diabetes also having clinically evident hand, hip, or knee OA.
In an oral presentation at the same meeting, Dr. Hawker stressed the need for early identification of walking disability after reporting that greater walking disability was an independent predictor of all-cause death and major cardiovascular events in the overall cohort of patients with symptomatic hip or knee OA alone.
The retrospective cohort study linked provincial health administrative databases with surveys from a population cohort of 2,156 patients with at least moderately severe symptomatic hip or knee OA who were recruited from 1996 to 1998 through a screening survey in Ontario.
At baseline, 457 patients self-reported diabetes or met criteria for inclusion in the Ontario Diabetes Database (sensitivity 86%, specificity 97%) and were without preexisting retinopathy or renal failure. After censoring patients who died, emigrated, or had insufficient data, 434 patients were included in the current analysis. The study could not differentiate type 1 from type 2 diabetes.
Their mean age was 71.6 years (all were 55 years or older), 41% were obese, and 53.2% had preexisting CVD. Their median HAQ walking disability score was 2 on a 3-point scale, median HAQ grip score was 1 on a 3-point scale, and mean Western Ontario and McMaster Osteoarthritis Index (WOMAC) summary score was 43.4. Overall, 55.5% used a walking aid, and 39% reported using NSAIDs. (A walking disability score of 2 corresponds with walking outdoors on flat ground with much difficulty, whereas a score of 3 means the person is unable to do it. A grip score of 1 corresponds with some difficulty in just one of the following tasks: opening car doors, opening previously open jars, or turning faucets on and off.)
In multivariable analyses, no effect was found for baseline grip strength (adjusted HR, 1.16; P = .07), Dr. Hawker reported at the meeting, sponsored by the Osteoarthritis Research Society International.
However, in sensitivity analyses that further adjusted for receipt of a diabetes drug prescription or NSAID in patients at least 66 years old at baseline and thus eligible for drug benefits, both HAQ walking and grip scores were significant predictors of risk for a diabetes complication, she reported. Specific data were not shown in the poster presentation, but the adjusted hazard ratios per unit increase in HAQ were 1.36 (P = .003) and 1.26 (P = .01), respectively, according to the abstract.
"Controlling for confounders, reduced grip strength and increased walking disability were identified as potentially modifiable risk factors for serious diabetes complications in people with both OA and diabetes," the authors concluded. "Additional studies are warranted to confirm or refute our findings, and if confirmed, to elucidate potential mechanisms."
Dr. Hawker reported having no financial disclosures.
AT OARSI 2014
Key clinical point: Early identification of walking disability is important in patients with OA and diabetes to help them to carry out diabetes self-management activities.
Major finding: Baseline walking disability was associated with an increased risk for a non-CVD, diabetes-specific complication (adjusted HR, 1.26; P = .02).
Data source: A retrospective cohort study in 437 patients with OA and diabetes.
Disclosures: Dr. Hawker reported having no financial disclosures.
OA-related walking disability on par with diabetes as CVD risk factor
PARIS – Greater walking disability is an independent predictor of all-cause death and major cardiovascular events in patients with symptomatic hip or knee osteoarthritis, according to a population-based study that confirms previous research.
For the composite cardiovascular disease (CVD) outcome of hospitalization for angina, acute myocardial infarction, coronary revascularization, congestive heart failure, stroke, or transient ischemic attack, the risk associated with a Health Assessment Questionnaire (HAQ) walking disability score of 2 was the same as that of diabetes and pre-existing CVD.
Total joint replacement reduced those risks by about 40%, Dr. Gillian A. Hawker said at the World Congress on Osteoarthritis (OA).
"I think the key piece here is that these data at least suggest that walking disability is a cardiovascular risk factor similar to diabetes," she said. "When we’re talking about risk assessment for cardiovascular outcomes, which everyone does pretty routinely in medicine, walking disability, which is really osteoarthritis, is one of the risk factors that they should be assessing ... If we can just start asking, hopefully it will get us thinking about, ‘Wow, this person has OA,’ and we need to start assessing it."
Session comoderator Ana M. Valdes, Ph.D., of the University of Nottingham (England) commented that the results are fascinating because this is not the first study to identify these associations. In 2011, British investigators reported that all-cause mortality, particularly due to CVD causes, was significantly related to baseline walking disability in patients with knee or hip OA (Br. Med. J. 2011;342:d1165).
"One of the things that happens often with OA is that it’s seen as just pain and if we can give them plenty of relief, they’ll be OK, but it’s actually life-threatening because if we do not address their disability, they are at risk of dying," Dr. Valdes said in an interview. "I think this should be put on the front pages of the weekly medical journals, so that people are aware of the dangers of not treating osteoarthritis properly."
Comorbidity is a barrier to OA care, and 90% of those aged 65 years and older with OA have at least one other chronic condition, such as diabetes and heart disease, observed Dr. Hawker, professor of medicine at the University of Toronto and physician-in-chief of medicine, Women’s College Hospital in Toronto.
Her group reported in a separate presentation at the meeting that walking disability also raises the risk for diabetes complications in those with both OA and diabetes.
For the current population-based study, the investigators linked provincial health administrative databases to baseline surveys from a population cohort of 2,156 patients with symptomatic moderate to severe OA who were recruited in 1996-1998 through a screening survey in Ontario.
Their mean age was 71 years (all were 55 years or older), 72% were female, 34% obese, 20% had diabetes, and 40% had prebaseline CVD. Their average HAQ walking disability score was 2 on a 3-point scale, and they had a mean WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) summary score of 41. Overall, 44% used a walking aid. (A walking disability score of 2 corresponds with walking outdoors on flat ground with much difficulty, whereas a score of 3 means the person is unable to do it.)
After a median follow-up period of 13.2 years, 57% of patients had died, and 38% experienced the composite CVD outcome with a median of 9.2 years follow-up.
In multivariable analysis, there was a very clear dose-response, where increased walking disability was associated with increasing risk of all-cause death, Dr. Hawker said. The adjusted hazard ratio per unit increase in HAQ walking score was 1.30 (P less than .001), after controlling for confounders including age, sex, preexisting CVD, diabetes, hypertension, body mass index, and smoking status.
A HAQ walking score of 2 was associated with an adjusted hazard ratio of 1.69, which was actually greater than that associated with preexisting cardiovascular disease or diabetes, she said.
For the composite CVD outcome, there was also a significant association with HAQ walking score (adjusted HR, 1.17; P = .001).
Sensitivity analyses performed in 402 patients (18%) receiving postbaseline total joint arthroplasty (TJA ) showed that controlling for TJA did not change the effect of baseline disability but was protective for both all-cause death (HR, 0.62; P less than .001) and CVD events (HR, 0.66; P less than .001), Dr. Hawker said at the meeting sponsored by the Osteoarthritis Research Society International.
Although the data were not dichotomized, she noted that there was "beautiful discrimination" when they looked at the outcomes based on whether or not patients used a walking aid.
"Obviously, it’s nice to see a dose-response, but simply knowing that someone’s using a walking aid and getting them to the point where they’ve got improved walking ability, could go a long way," she said.
Though the study was not designed to address potential mechanisms, Dr. Hawker said she’s long argued that physical activity and mobility are a key player of downstream effects on fitness, blood pressure, glucose control, and ability to participate in self-management activities and physician visits. The potential role for pain, mood, and stress also can not be excluded.
One audience member asked whether walking disability may be a "cheap and dirty version" of the stress test.
Dr. Hawker responded that walking disability is a proxy for a lot of things and is definitely OA-related, adding, "Yes, I think it is a very cheap and dirty stress test. It’s a lovely thing that if we focused more explicitly on it in randomized trials, for instance as a primary outcome, or in rehabilitation strategies, it would have global benefit."
The authors reported no competing interests.
PARIS – Greater walking disability is an independent predictor of all-cause death and major cardiovascular events in patients with symptomatic hip or knee osteoarthritis, according to a population-based study that confirms previous research.
For the composite cardiovascular disease (CVD) outcome of hospitalization for angina, acute myocardial infarction, coronary revascularization, congestive heart failure, stroke, or transient ischemic attack, the risk associated with a Health Assessment Questionnaire (HAQ) walking disability score of 2 was the same as that of diabetes and pre-existing CVD.
Total joint replacement reduced those risks by about 40%, Dr. Gillian A. Hawker said at the World Congress on Osteoarthritis (OA).
"I think the key piece here is that these data at least suggest that walking disability is a cardiovascular risk factor similar to diabetes," she said. "When we’re talking about risk assessment for cardiovascular outcomes, which everyone does pretty routinely in medicine, walking disability, which is really osteoarthritis, is one of the risk factors that they should be assessing ... If we can just start asking, hopefully it will get us thinking about, ‘Wow, this person has OA,’ and we need to start assessing it."
Session comoderator Ana M. Valdes, Ph.D., of the University of Nottingham (England) commented that the results are fascinating because this is not the first study to identify these associations. In 2011, British investigators reported that all-cause mortality, particularly due to CVD causes, was significantly related to baseline walking disability in patients with knee or hip OA (Br. Med. J. 2011;342:d1165).
"One of the things that happens often with OA is that it’s seen as just pain and if we can give them plenty of relief, they’ll be OK, but it’s actually life-threatening because if we do not address their disability, they are at risk of dying," Dr. Valdes said in an interview. "I think this should be put on the front pages of the weekly medical journals, so that people are aware of the dangers of not treating osteoarthritis properly."
Comorbidity is a barrier to OA care, and 90% of those aged 65 years and older with OA have at least one other chronic condition, such as diabetes and heart disease, observed Dr. Hawker, professor of medicine at the University of Toronto and physician-in-chief of medicine, Women’s College Hospital in Toronto.
Her group reported in a separate presentation at the meeting that walking disability also raises the risk for diabetes complications in those with both OA and diabetes.
For the current population-based study, the investigators linked provincial health administrative databases to baseline surveys from a population cohort of 2,156 patients with symptomatic moderate to severe OA who were recruited in 1996-1998 through a screening survey in Ontario.
Their mean age was 71 years (all were 55 years or older), 72% were female, 34% obese, 20% had diabetes, and 40% had prebaseline CVD. Their average HAQ walking disability score was 2 on a 3-point scale, and they had a mean WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) summary score of 41. Overall, 44% used a walking aid. (A walking disability score of 2 corresponds with walking outdoors on flat ground with much difficulty, whereas a score of 3 means the person is unable to do it.)
After a median follow-up period of 13.2 years, 57% of patients had died, and 38% experienced the composite CVD outcome with a median of 9.2 years follow-up.
In multivariable analysis, there was a very clear dose-response, where increased walking disability was associated with increasing risk of all-cause death, Dr. Hawker said. The adjusted hazard ratio per unit increase in HAQ walking score was 1.30 (P less than .001), after controlling for confounders including age, sex, preexisting CVD, diabetes, hypertension, body mass index, and smoking status.
A HAQ walking score of 2 was associated with an adjusted hazard ratio of 1.69, which was actually greater than that associated with preexisting cardiovascular disease or diabetes, she said.
For the composite CVD outcome, there was also a significant association with HAQ walking score (adjusted HR, 1.17; P = .001).
Sensitivity analyses performed in 402 patients (18%) receiving postbaseline total joint arthroplasty (TJA ) showed that controlling for TJA did not change the effect of baseline disability but was protective for both all-cause death (HR, 0.62; P less than .001) and CVD events (HR, 0.66; P less than .001), Dr. Hawker said at the meeting sponsored by the Osteoarthritis Research Society International.
Although the data were not dichotomized, she noted that there was "beautiful discrimination" when they looked at the outcomes based on whether or not patients used a walking aid.
"Obviously, it’s nice to see a dose-response, but simply knowing that someone’s using a walking aid and getting them to the point where they’ve got improved walking ability, could go a long way," she said.
Though the study was not designed to address potential mechanisms, Dr. Hawker said she’s long argued that physical activity and mobility are a key player of downstream effects on fitness, blood pressure, glucose control, and ability to participate in self-management activities and physician visits. The potential role for pain, mood, and stress also can not be excluded.
One audience member asked whether walking disability may be a "cheap and dirty version" of the stress test.
Dr. Hawker responded that walking disability is a proxy for a lot of things and is definitely OA-related, adding, "Yes, I think it is a very cheap and dirty stress test. It’s a lovely thing that if we focused more explicitly on it in randomized trials, for instance as a primary outcome, or in rehabilitation strategies, it would have global benefit."
The authors reported no competing interests.
PARIS – Greater walking disability is an independent predictor of all-cause death and major cardiovascular events in patients with symptomatic hip or knee osteoarthritis, according to a population-based study that confirms previous research.
For the composite cardiovascular disease (CVD) outcome of hospitalization for angina, acute myocardial infarction, coronary revascularization, congestive heart failure, stroke, or transient ischemic attack, the risk associated with a Health Assessment Questionnaire (HAQ) walking disability score of 2 was the same as that of diabetes and pre-existing CVD.
Total joint replacement reduced those risks by about 40%, Dr. Gillian A. Hawker said at the World Congress on Osteoarthritis (OA).
"I think the key piece here is that these data at least suggest that walking disability is a cardiovascular risk factor similar to diabetes," she said. "When we’re talking about risk assessment for cardiovascular outcomes, which everyone does pretty routinely in medicine, walking disability, which is really osteoarthritis, is one of the risk factors that they should be assessing ... If we can just start asking, hopefully it will get us thinking about, ‘Wow, this person has OA,’ and we need to start assessing it."
Session comoderator Ana M. Valdes, Ph.D., of the University of Nottingham (England) commented that the results are fascinating because this is not the first study to identify these associations. In 2011, British investigators reported that all-cause mortality, particularly due to CVD causes, was significantly related to baseline walking disability in patients with knee or hip OA (Br. Med. J. 2011;342:d1165).
"One of the things that happens often with OA is that it’s seen as just pain and if we can give them plenty of relief, they’ll be OK, but it’s actually life-threatening because if we do not address their disability, they are at risk of dying," Dr. Valdes said in an interview. "I think this should be put on the front pages of the weekly medical journals, so that people are aware of the dangers of not treating osteoarthritis properly."
Comorbidity is a barrier to OA care, and 90% of those aged 65 years and older with OA have at least one other chronic condition, such as diabetes and heart disease, observed Dr. Hawker, professor of medicine at the University of Toronto and physician-in-chief of medicine, Women’s College Hospital in Toronto.
Her group reported in a separate presentation at the meeting that walking disability also raises the risk for diabetes complications in those with both OA and diabetes.
For the current population-based study, the investigators linked provincial health administrative databases to baseline surveys from a population cohort of 2,156 patients with symptomatic moderate to severe OA who were recruited in 1996-1998 through a screening survey in Ontario.
Their mean age was 71 years (all were 55 years or older), 72% were female, 34% obese, 20% had diabetes, and 40% had prebaseline CVD. Their average HAQ walking disability score was 2 on a 3-point scale, and they had a mean WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) summary score of 41. Overall, 44% used a walking aid. (A walking disability score of 2 corresponds with walking outdoors on flat ground with much difficulty, whereas a score of 3 means the person is unable to do it.)
After a median follow-up period of 13.2 years, 57% of patients had died, and 38% experienced the composite CVD outcome with a median of 9.2 years follow-up.
In multivariable analysis, there was a very clear dose-response, where increased walking disability was associated with increasing risk of all-cause death, Dr. Hawker said. The adjusted hazard ratio per unit increase in HAQ walking score was 1.30 (P less than .001), after controlling for confounders including age, sex, preexisting CVD, diabetes, hypertension, body mass index, and smoking status.
A HAQ walking score of 2 was associated with an adjusted hazard ratio of 1.69, which was actually greater than that associated with preexisting cardiovascular disease or diabetes, she said.
For the composite CVD outcome, there was also a significant association with HAQ walking score (adjusted HR, 1.17; P = .001).
Sensitivity analyses performed in 402 patients (18%) receiving postbaseline total joint arthroplasty (TJA ) showed that controlling for TJA did not change the effect of baseline disability but was protective for both all-cause death (HR, 0.62; P less than .001) and CVD events (HR, 0.66; P less than .001), Dr. Hawker said at the meeting sponsored by the Osteoarthritis Research Society International.
Although the data were not dichotomized, she noted that there was "beautiful discrimination" when they looked at the outcomes based on whether or not patients used a walking aid.
"Obviously, it’s nice to see a dose-response, but simply knowing that someone’s using a walking aid and getting them to the point where they’ve got improved walking ability, could go a long way," she said.
Though the study was not designed to address potential mechanisms, Dr. Hawker said she’s long argued that physical activity and mobility are a key player of downstream effects on fitness, blood pressure, glucose control, and ability to participate in self-management activities and physician visits. The potential role for pain, mood, and stress also can not be excluded.
One audience member asked whether walking disability may be a "cheap and dirty version" of the stress test.
Dr. Hawker responded that walking disability is a proxy for a lot of things and is definitely OA-related, adding, "Yes, I think it is a very cheap and dirty stress test. It’s a lovely thing that if we focused more explicitly on it in randomized trials, for instance as a primary outcome, or in rehabilitation strategies, it would have global benefit."
The authors reported no competing interests.
AT OARSI 2014
Key clinical point: A study confirming previous research suggests that a high level of walking disability in OA patients should be considered a strong risk factor for CVD.
Major finding: The adjusted hazard ratio per unit increase in HAQ walking score was 1.30 (P less than .001) for all-cause mortality and 1.17 (P = .001) for composite CVD events.
Data source: A population-based, cohort study in 2,156 hip and knee OA patients.
Disclosures: The authors reported no competing interests.
Intraoperative wound anesthetic cut chronic pain after hip replacement
PARIS – Adding local anesthetic to the wound during total hip replacement surgery for osteoarthritis reduced chronic pain, according to a double-blind, randomized controlled trial.
At 12 months postoperative, the number of patients with severe pain was 8.6% with standard care, compared with 1.4% among those who also received 60 mL of 0.25% bupivacaine with lidocaine (Xylocaine) 1% with adrenaline 100 mcg/20 mL injected directly into the wound prior to closure.
The difference was statistically significant (P = .004; odds ratio, 10.19), but the confidence intervals were wide (95% C.I., 2.10-49.55) because of the small number of patients with severe pain, Vikki Wylde, Ph.D., said at the World Congress on Osteoarthritis.
She noted that 7%-23% of patients report moderate to severe chronic pain in the long term after total hip replacement, according to a recent systematic review (BMJ Open 2012:2:e000435), and that the severity of postoperative pain is a known risk factor for chronic postsurgical pain.
Local anesthetic wound infiltration has been shown to be effective at reducing the severity of acute postoperative pain after total hip replacement (J. Am Coll. Surg. 2006:203:914-32), but this is the first double-blind trial to assess its long-term effects.
Investigators at high-volume orthopedic centers in the United Kingdom randomly assigned 322 patients undergoing total hip replacement for osteoarthritis to standard care (spinal anesthesia with or without general anesthesia) alone or with local anesthetic infiltration. The primary outcome was WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) pain scale scores at 12 months postoperatively.
Use of in-patient analgesia or length of hospitalization did not differ between the groups, said Dr. Wylde, a research associate with the University of Bristol, England. Acute postoperative pain severity was also similar, except that patients in the intervention group reported less severe pain on postoperative night 2 (P = .008). This was unexpected, but the study was not powered to detect differences in these secondary measures, and no conclusions can be drawn from these data, she said at the meeting, sponsored by the Osteoarthritis Research Society International.
There were no differences in other secondary measures including the WOMAC function or stiffness scales or in ICOAP (Intermittent and Constant Osteoarthritis Pain) scores.
Local anesthetic infiltration, however, significantly reduced neuropathic pain at 12 months, as assessed using the PainDETECT questionnaire, Dr. Wylde said.
"Our study suggests that local anesthetic infiltration is unlikely to change long-term pain outcomes for the majority of patients, but potentially can improve pain relief for a small number of patients who may otherwise go on to develop severe long-term pain after surgery," she concluded.
In a separate interview, Dr. Jeffrey Katz, codirector, Brigham Spine Center, Brigham & Women’s Hospital and professor at Harvard Medical School, both in Boston, said the study was very interesting mechanistically and potentially interesting from a public health standpoint because there are about 400,000 hips done a year in the United States and thus 4,000 or so of these patients are having chronic pain. Moreover, the problem of chronic pain after surgery is even more common in the knee than in the hip.
"The difference in severe pain of 8% vs. 1% or 2% is a striking difference, but it’s a small incidence, and so it does bear replication," he added. "I thought it was a very exciting study and think it’s important information for folks to begin to work with and might change practice."
Dr. Wylde reported funding from the National Institute for Health Research, London.
PARIS – Adding local anesthetic to the wound during total hip replacement surgery for osteoarthritis reduced chronic pain, according to a double-blind, randomized controlled trial.
At 12 months postoperative, the number of patients with severe pain was 8.6% with standard care, compared with 1.4% among those who also received 60 mL of 0.25% bupivacaine with lidocaine (Xylocaine) 1% with adrenaline 100 mcg/20 mL injected directly into the wound prior to closure.
The difference was statistically significant (P = .004; odds ratio, 10.19), but the confidence intervals were wide (95% C.I., 2.10-49.55) because of the small number of patients with severe pain, Vikki Wylde, Ph.D., said at the World Congress on Osteoarthritis.
She noted that 7%-23% of patients report moderate to severe chronic pain in the long term after total hip replacement, according to a recent systematic review (BMJ Open 2012:2:e000435), and that the severity of postoperative pain is a known risk factor for chronic postsurgical pain.
Local anesthetic wound infiltration has been shown to be effective at reducing the severity of acute postoperative pain after total hip replacement (J. Am Coll. Surg. 2006:203:914-32), but this is the first double-blind trial to assess its long-term effects.
Investigators at high-volume orthopedic centers in the United Kingdom randomly assigned 322 patients undergoing total hip replacement for osteoarthritis to standard care (spinal anesthesia with or without general anesthesia) alone or with local anesthetic infiltration. The primary outcome was WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) pain scale scores at 12 months postoperatively.
Use of in-patient analgesia or length of hospitalization did not differ between the groups, said Dr. Wylde, a research associate with the University of Bristol, England. Acute postoperative pain severity was also similar, except that patients in the intervention group reported less severe pain on postoperative night 2 (P = .008). This was unexpected, but the study was not powered to detect differences in these secondary measures, and no conclusions can be drawn from these data, she said at the meeting, sponsored by the Osteoarthritis Research Society International.
There were no differences in other secondary measures including the WOMAC function or stiffness scales or in ICOAP (Intermittent and Constant Osteoarthritis Pain) scores.
Local anesthetic infiltration, however, significantly reduced neuropathic pain at 12 months, as assessed using the PainDETECT questionnaire, Dr. Wylde said.
"Our study suggests that local anesthetic infiltration is unlikely to change long-term pain outcomes for the majority of patients, but potentially can improve pain relief for a small number of patients who may otherwise go on to develop severe long-term pain after surgery," she concluded.
In a separate interview, Dr. Jeffrey Katz, codirector, Brigham Spine Center, Brigham & Women’s Hospital and professor at Harvard Medical School, both in Boston, said the study was very interesting mechanistically and potentially interesting from a public health standpoint because there are about 400,000 hips done a year in the United States and thus 4,000 or so of these patients are having chronic pain. Moreover, the problem of chronic pain after surgery is even more common in the knee than in the hip.
"The difference in severe pain of 8% vs. 1% or 2% is a striking difference, but it’s a small incidence, and so it does bear replication," he added. "I thought it was a very exciting study and think it’s important information for folks to begin to work with and might change practice."
Dr. Wylde reported funding from the National Institute for Health Research, London.
PARIS – Adding local anesthetic to the wound during total hip replacement surgery for osteoarthritis reduced chronic pain, according to a double-blind, randomized controlled trial.
At 12 months postoperative, the number of patients with severe pain was 8.6% with standard care, compared with 1.4% among those who also received 60 mL of 0.25% bupivacaine with lidocaine (Xylocaine) 1% with adrenaline 100 mcg/20 mL injected directly into the wound prior to closure.
The difference was statistically significant (P = .004; odds ratio, 10.19), but the confidence intervals were wide (95% C.I., 2.10-49.55) because of the small number of patients with severe pain, Vikki Wylde, Ph.D., said at the World Congress on Osteoarthritis.
She noted that 7%-23% of patients report moderate to severe chronic pain in the long term after total hip replacement, according to a recent systematic review (BMJ Open 2012:2:e000435), and that the severity of postoperative pain is a known risk factor for chronic postsurgical pain.
Local anesthetic wound infiltration has been shown to be effective at reducing the severity of acute postoperative pain after total hip replacement (J. Am Coll. Surg. 2006:203:914-32), but this is the first double-blind trial to assess its long-term effects.
Investigators at high-volume orthopedic centers in the United Kingdom randomly assigned 322 patients undergoing total hip replacement for osteoarthritis to standard care (spinal anesthesia with or without general anesthesia) alone or with local anesthetic infiltration. The primary outcome was WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) pain scale scores at 12 months postoperatively.
Use of in-patient analgesia or length of hospitalization did not differ between the groups, said Dr. Wylde, a research associate with the University of Bristol, England. Acute postoperative pain severity was also similar, except that patients in the intervention group reported less severe pain on postoperative night 2 (P = .008). This was unexpected, but the study was not powered to detect differences in these secondary measures, and no conclusions can be drawn from these data, she said at the meeting, sponsored by the Osteoarthritis Research Society International.
There were no differences in other secondary measures including the WOMAC function or stiffness scales or in ICOAP (Intermittent and Constant Osteoarthritis Pain) scores.
Local anesthetic infiltration, however, significantly reduced neuropathic pain at 12 months, as assessed using the PainDETECT questionnaire, Dr. Wylde said.
"Our study suggests that local anesthetic infiltration is unlikely to change long-term pain outcomes for the majority of patients, but potentially can improve pain relief for a small number of patients who may otherwise go on to develop severe long-term pain after surgery," she concluded.
In a separate interview, Dr. Jeffrey Katz, codirector, Brigham Spine Center, Brigham & Women’s Hospital and professor at Harvard Medical School, both in Boston, said the study was very interesting mechanistically and potentially interesting from a public health standpoint because there are about 400,000 hips done a year in the United States and thus 4,000 or so of these patients are having chronic pain. Moreover, the problem of chronic pain after surgery is even more common in the knee than in the hip.
"The difference in severe pain of 8% vs. 1% or 2% is a striking difference, but it’s a small incidence, and so it does bear replication," he added. "I thought it was a very exciting study and think it’s important information for folks to begin to work with and might change practice."
Dr. Wylde reported funding from the National Institute for Health Research, London.
AT OARSI 2014
Major finding: Severe pain at 12 months was reduced from 8.6% with standard care to 1.4% with the addition of local anesthetic wound infiltration (P = .004).
Data source: Double-blind, randomized controlled trial in 322 patients undergoing total hip replacement for osteoarthritis.
Disclosures: Dr. Wylde reported funding from the National Institute for Health Research, London.
PCPs waffle in referrals for total joint replacement
PARIS – Primary care physicians are only moderately confident about which patients to refer for total hip or knee replacement, according to cross-sectional survey of 218 physicians.
One-quarter (27.4%) were unsure about the risks of total joint arthroplasty (TJA), and 44.3% reported they were discouraged from referring patients for TJA because of a lack of clarity about surgical indications.
When asked how confident they were in deciding which patients should be referred to orthopedic surgery for consideration of hip or knee replacement, the average response was 6.9 on a 10-point scale from "not at all" to "highly confident," indicating a moderate level of confidence, Esther* Waugh, Ph.D., reported at the World Congress on Osteoarthritis.
"The results suggest the need for increased guidance for primary care physicians regarding which patient, and when, total joint arthroplasty should be considered," she concluded. "While lack of confidence does not necessarily equate with decreased competence, additional clarity may result in enhanced physician confidence, improved decision making, and ultimately better surgical outcomes through better patient selection of appropriate candidates."
A total of 376 primary care physicians (PCPs) were recruited from among those providing care to participants of an established community cohort with symptomatic hip or knee osteoarthritis (OA) in Ontario, Canada, with 218 (58%) completing the standardized questionnaire by mail or online.
One-third reported seeing more than 10 moderate to severe hip/knee OA patients in the previous 2 weeks.
Most had been in practice for more than 15 years (77%), were in group practice (63%), and were older than age 50 years (65%). One-third practiced in a rural location, and 31% had more than 10 TJA referrals per year.
Interestingly, total hip and total knee arthroplasty was perceived as "very effective" by 53% and 40% of physicians, respectively, according to Dr. Waugh of the physical therapy department at the University of Toronto.
Still, TJA was viewed as carrying high risks of death by 11.3%, of complications by 35%, and need for revision surgery by 12.3%.
Lower confidence in referring patients for TJA was independently associated with lack of clarity about surgical indications (P less than .0001; parameter estimate, –1.02) and female sex (P = .02; parameter estimate, –0.54), in multiple linear regression analysis.
Both factors were associated with fewer years of practice, she noted. Female physicians were significantly more likely to report fewer years of practice (P less than .0001), fewer OA patients (P = .0004), practicing in a group practice (P = .003), urban practice location (P = .003), and being unsure about risks (P = .02).
Confidence was not associated with uncertainty of TJA risks, volume of OA patients in the prior 2 weeks, group practice, years of practice, or rural practice setting, Dr. Waugh reported at the meeting, sponsored by the Osteoarthritis Research Society International.
Prior research by the University of Toronto team demonstrated underuse of total joint arthroplasty, but concerns have recently been raised regarding possible overuse, particularly in younger patients. In Canada, PCPs are responsible for referrals to orthopedic surgery for TJA. Thus, "inappropriate under- or overuse of TJA may be a consequence of uncertainty among PCPs about indications for TJA," the authors noted in the poster presentation
Conflict of interest disclosures were not available at press time.
*Correction, 5/8/2014: An earlier version of this story misspelled Dr. Esther Waugh's name.
PARIS – Primary care physicians are only moderately confident about which patients to refer for total hip or knee replacement, according to cross-sectional survey of 218 physicians.
One-quarter (27.4%) were unsure about the risks of total joint arthroplasty (TJA), and 44.3% reported they were discouraged from referring patients for TJA because of a lack of clarity about surgical indications.
When asked how confident they were in deciding which patients should be referred to orthopedic surgery for consideration of hip or knee replacement, the average response was 6.9 on a 10-point scale from "not at all" to "highly confident," indicating a moderate level of confidence, Esther* Waugh, Ph.D., reported at the World Congress on Osteoarthritis.
"The results suggest the need for increased guidance for primary care physicians regarding which patient, and when, total joint arthroplasty should be considered," she concluded. "While lack of confidence does not necessarily equate with decreased competence, additional clarity may result in enhanced physician confidence, improved decision making, and ultimately better surgical outcomes through better patient selection of appropriate candidates."
A total of 376 primary care physicians (PCPs) were recruited from among those providing care to participants of an established community cohort with symptomatic hip or knee osteoarthritis (OA) in Ontario, Canada, with 218 (58%) completing the standardized questionnaire by mail or online.
One-third reported seeing more than 10 moderate to severe hip/knee OA patients in the previous 2 weeks.
Most had been in practice for more than 15 years (77%), were in group practice (63%), and were older than age 50 years (65%). One-third practiced in a rural location, and 31% had more than 10 TJA referrals per year.
Interestingly, total hip and total knee arthroplasty was perceived as "very effective" by 53% and 40% of physicians, respectively, according to Dr. Waugh of the physical therapy department at the University of Toronto.
Still, TJA was viewed as carrying high risks of death by 11.3%, of complications by 35%, and need for revision surgery by 12.3%.
Lower confidence in referring patients for TJA was independently associated with lack of clarity about surgical indications (P less than .0001; parameter estimate, –1.02) and female sex (P = .02; parameter estimate, –0.54), in multiple linear regression analysis.
Both factors were associated with fewer years of practice, she noted. Female physicians were significantly more likely to report fewer years of practice (P less than .0001), fewer OA patients (P = .0004), practicing in a group practice (P = .003), urban practice location (P = .003), and being unsure about risks (P = .02).
Confidence was not associated with uncertainty of TJA risks, volume of OA patients in the prior 2 weeks, group practice, years of practice, or rural practice setting, Dr. Waugh reported at the meeting, sponsored by the Osteoarthritis Research Society International.
Prior research by the University of Toronto team demonstrated underuse of total joint arthroplasty, but concerns have recently been raised regarding possible overuse, particularly in younger patients. In Canada, PCPs are responsible for referrals to orthopedic surgery for TJA. Thus, "inappropriate under- or overuse of TJA may be a consequence of uncertainty among PCPs about indications for TJA," the authors noted in the poster presentation
Conflict of interest disclosures were not available at press time.
*Correction, 5/8/2014: An earlier version of this story misspelled Dr. Esther Waugh's name.
PARIS – Primary care physicians are only moderately confident about which patients to refer for total hip or knee replacement, according to cross-sectional survey of 218 physicians.
One-quarter (27.4%) were unsure about the risks of total joint arthroplasty (TJA), and 44.3% reported they were discouraged from referring patients for TJA because of a lack of clarity about surgical indications.
When asked how confident they were in deciding which patients should be referred to orthopedic surgery for consideration of hip or knee replacement, the average response was 6.9 on a 10-point scale from "not at all" to "highly confident," indicating a moderate level of confidence, Esther* Waugh, Ph.D., reported at the World Congress on Osteoarthritis.
"The results suggest the need for increased guidance for primary care physicians regarding which patient, and when, total joint arthroplasty should be considered," she concluded. "While lack of confidence does not necessarily equate with decreased competence, additional clarity may result in enhanced physician confidence, improved decision making, and ultimately better surgical outcomes through better patient selection of appropriate candidates."
A total of 376 primary care physicians (PCPs) were recruited from among those providing care to participants of an established community cohort with symptomatic hip or knee osteoarthritis (OA) in Ontario, Canada, with 218 (58%) completing the standardized questionnaire by mail or online.
One-third reported seeing more than 10 moderate to severe hip/knee OA patients in the previous 2 weeks.
Most had been in practice for more than 15 years (77%), were in group practice (63%), and were older than age 50 years (65%). One-third practiced in a rural location, and 31% had more than 10 TJA referrals per year.
Interestingly, total hip and total knee arthroplasty was perceived as "very effective" by 53% and 40% of physicians, respectively, according to Dr. Waugh of the physical therapy department at the University of Toronto.
Still, TJA was viewed as carrying high risks of death by 11.3%, of complications by 35%, and need for revision surgery by 12.3%.
Lower confidence in referring patients for TJA was independently associated with lack of clarity about surgical indications (P less than .0001; parameter estimate, –1.02) and female sex (P = .02; parameter estimate, –0.54), in multiple linear regression analysis.
Both factors were associated with fewer years of practice, she noted. Female physicians were significantly more likely to report fewer years of practice (P less than .0001), fewer OA patients (P = .0004), practicing in a group practice (P = .003), urban practice location (P = .003), and being unsure about risks (P = .02).
Confidence was not associated with uncertainty of TJA risks, volume of OA patients in the prior 2 weeks, group practice, years of practice, or rural practice setting, Dr. Waugh reported at the meeting, sponsored by the Osteoarthritis Research Society International.
Prior research by the University of Toronto team demonstrated underuse of total joint arthroplasty, but concerns have recently been raised regarding possible overuse, particularly in younger patients. In Canada, PCPs are responsible for referrals to orthopedic surgery for TJA. Thus, "inappropriate under- or overuse of TJA may be a consequence of uncertainty among PCPs about indications for TJA," the authors noted in the poster presentation
Conflict of interest disclosures were not available at press time.
*Correction, 5/8/2014: An earlier version of this story misspelled Dr. Esther Waugh's name.
AT OARSI 2014
Major finding: Lack of clarity about indications thwarted 44.3% of primary care physicians from referring patients for arthroplasty.
Data source: A cross-sectional survey of 218 primary care physicians.
Disclosures: Conflict of interest disclosures were not available at press time.
Men have more major complications after hip, knee replacement
PARIS – After total hip or knee replacement, men are at higher risk than women for heart attack, infection, and revision surgery, according to a large database analysis.
The elevated risk was particularly apparent following total knee arthroplasty (TKA), Dr. Gillian Hawker said at the World Congress on Osteoarthritis.
Prior research suggests that younger patients and males who have joint replacement are at higher risk of certain complications such as early revision, and that joint replacement is underutilized in women.
Based on the current study, underuse of total joint arthroplasty among women versus men does not appear to be explained by higher surgical risk, she said.
The investigators used administrative databases to analyze 97,445 patients who underwent primary, elective total joint arthroplasty in Ontario, Canada, between 2002 and 2009. In all, 59,564 patients (39% male) underwent TKA and 37,881 patients (46% male) had total hip arthroplasty.
Knee arthroplasty
Men had more acute myocardial infarctions within 90 days of undergoing TKA than did women (1.1% vs. 0.8%), more infection within 2 years of surgery (1.1% vs. 0.7%), and more revision TKA within 2 years (1.5% vs. 1%), said Dr. Hawker, professor of medicine at the University of Toronto and physician-in-chief of medicine, Women’s College Hospital, Toronto.
At baseline, the men were similar in age to women, but less likely to be frail (4% vs. 6.7%) and more likely to have a Charlson Comorbidity Index score of 2 or more (5.7% vs. 3.4%).
In Cox regression analysis, the risk for acute MI was significantly increased (hazard ratio, 1.79; P less than .0001) after adjustment for age, sex, income quartile, rurality, frailty, Charlson score, and hospital volume, she said.
Men were also at significantly increased risk for infection (HR, 1.67; P less than .0001) and revision TKA within 2 years (HR, 1.49; P less than .0001), after further adjustment for surgeon volume.
The investigators, led by colleague and orthopedic surgery resident Bheeshma Ravi, Ph.D., postulate that the increased risk of infection and revision among men is due to the high-impact activities that men may engage in after their prosthesis.
No sex differences were found for venous thromboembolism within 90 days or periprosthetic fracture within 2 years.
Hip arthroplasty
Men undergoing total hip replacement had higher rates of early acute MI than women (0.9% vs. 0.7%), but lower rates of periprosthetic fracture within 2 years (0.3% vs. 0.5%), Dr. Hawker said.
At baseline, male patients were younger than their female counterparts (65 years vs. 70 years) and less likely to be frail (3.5% vs. 6.6%), but more likely to have a Charlson score of 2 or more (5.3% vs. 3.7%).
After full adjustment, men were at significantly increased risk for acute MI (HR, 1.64; P less than .0001) and reduced risk for periprosthetic fracture (HR, 0.52; P = .0005), Dr. Hawker said at the meeting, which was sponsored by the Osteoarthritis Research Society International.
"We think the potential explanations for acute MI after both hip and knee replacement may be additional cardiovascular risk factors," she said. "We did not control for preexisting cardiovascular risk; that is something we are doing now."
The study excluded patients who had a pre–joint replacement fragility fracture, but because of the quality of the data postoperatively and the availability of drug benefit data, "we don’t feel we have adequate control for the presence of osteoporosis," Dr. Hawker observed.
No differences were found between sexes in the hip replacement cohort for infection, death, venous thromboembolism, dislocation, or revision.
Session comoderator Dr. Martin Englund, of Lund (Sweden) University, commented that the study was well conducted and the findings very interesting, but he cautioned against generalizing the results too broadly.
"We have seen before, that results from Sweden are not necessarily the same as in North America," he said in an interview. "I’m sure these results are probably very generalizable in Canada and in that type of health care setting, but may not be the same elsewhere. ... These are also things that might change over time. So we just need to keep monitoring outcomes and repeating these studies and adjust our treatment to what we find."
Dr. Ravi reported fellowship support from the University of Toronto, Canadian Institutes of Health Research, and Women’s College Research Institute.
PARIS – After total hip or knee replacement, men are at higher risk than women for heart attack, infection, and revision surgery, according to a large database analysis.
The elevated risk was particularly apparent following total knee arthroplasty (TKA), Dr. Gillian Hawker said at the World Congress on Osteoarthritis.
Prior research suggests that younger patients and males who have joint replacement are at higher risk of certain complications such as early revision, and that joint replacement is underutilized in women.
Based on the current study, underuse of total joint arthroplasty among women versus men does not appear to be explained by higher surgical risk, she said.
The investigators used administrative databases to analyze 97,445 patients who underwent primary, elective total joint arthroplasty in Ontario, Canada, between 2002 and 2009. In all, 59,564 patients (39% male) underwent TKA and 37,881 patients (46% male) had total hip arthroplasty.
Knee arthroplasty
Men had more acute myocardial infarctions within 90 days of undergoing TKA than did women (1.1% vs. 0.8%), more infection within 2 years of surgery (1.1% vs. 0.7%), and more revision TKA within 2 years (1.5% vs. 1%), said Dr. Hawker, professor of medicine at the University of Toronto and physician-in-chief of medicine, Women’s College Hospital, Toronto.
At baseline, the men were similar in age to women, but less likely to be frail (4% vs. 6.7%) and more likely to have a Charlson Comorbidity Index score of 2 or more (5.7% vs. 3.4%).
In Cox regression analysis, the risk for acute MI was significantly increased (hazard ratio, 1.79; P less than .0001) after adjustment for age, sex, income quartile, rurality, frailty, Charlson score, and hospital volume, she said.
Men were also at significantly increased risk for infection (HR, 1.67; P less than .0001) and revision TKA within 2 years (HR, 1.49; P less than .0001), after further adjustment for surgeon volume.
The investigators, led by colleague and orthopedic surgery resident Bheeshma Ravi, Ph.D., postulate that the increased risk of infection and revision among men is due to the high-impact activities that men may engage in after their prosthesis.
No sex differences were found for venous thromboembolism within 90 days or periprosthetic fracture within 2 years.
Hip arthroplasty
Men undergoing total hip replacement had higher rates of early acute MI than women (0.9% vs. 0.7%), but lower rates of periprosthetic fracture within 2 years (0.3% vs. 0.5%), Dr. Hawker said.
At baseline, male patients were younger than their female counterparts (65 years vs. 70 years) and less likely to be frail (3.5% vs. 6.6%), but more likely to have a Charlson score of 2 or more (5.3% vs. 3.7%).
After full adjustment, men were at significantly increased risk for acute MI (HR, 1.64; P less than .0001) and reduced risk for periprosthetic fracture (HR, 0.52; P = .0005), Dr. Hawker said at the meeting, which was sponsored by the Osteoarthritis Research Society International.
"We think the potential explanations for acute MI after both hip and knee replacement may be additional cardiovascular risk factors," she said. "We did not control for preexisting cardiovascular risk; that is something we are doing now."
The study excluded patients who had a pre–joint replacement fragility fracture, but because of the quality of the data postoperatively and the availability of drug benefit data, "we don’t feel we have adequate control for the presence of osteoporosis," Dr. Hawker observed.
No differences were found between sexes in the hip replacement cohort for infection, death, venous thromboembolism, dislocation, or revision.
Session comoderator Dr. Martin Englund, of Lund (Sweden) University, commented that the study was well conducted and the findings very interesting, but he cautioned against generalizing the results too broadly.
"We have seen before, that results from Sweden are not necessarily the same as in North America," he said in an interview. "I’m sure these results are probably very generalizable in Canada and in that type of health care setting, but may not be the same elsewhere. ... These are also things that might change over time. So we just need to keep monitoring outcomes and repeating these studies and adjust our treatment to what we find."
Dr. Ravi reported fellowship support from the University of Toronto, Canadian Institutes of Health Research, and Women’s College Research Institute.
PARIS – After total hip or knee replacement, men are at higher risk than women for heart attack, infection, and revision surgery, according to a large database analysis.
The elevated risk was particularly apparent following total knee arthroplasty (TKA), Dr. Gillian Hawker said at the World Congress on Osteoarthritis.
Prior research suggests that younger patients and males who have joint replacement are at higher risk of certain complications such as early revision, and that joint replacement is underutilized in women.
Based on the current study, underuse of total joint arthroplasty among women versus men does not appear to be explained by higher surgical risk, she said.
The investigators used administrative databases to analyze 97,445 patients who underwent primary, elective total joint arthroplasty in Ontario, Canada, between 2002 and 2009. In all, 59,564 patients (39% male) underwent TKA and 37,881 patients (46% male) had total hip arthroplasty.
Knee arthroplasty
Men had more acute myocardial infarctions within 90 days of undergoing TKA than did women (1.1% vs. 0.8%), more infection within 2 years of surgery (1.1% vs. 0.7%), and more revision TKA within 2 years (1.5% vs. 1%), said Dr. Hawker, professor of medicine at the University of Toronto and physician-in-chief of medicine, Women’s College Hospital, Toronto.
At baseline, the men were similar in age to women, but less likely to be frail (4% vs. 6.7%) and more likely to have a Charlson Comorbidity Index score of 2 or more (5.7% vs. 3.4%).
In Cox regression analysis, the risk for acute MI was significantly increased (hazard ratio, 1.79; P less than .0001) after adjustment for age, sex, income quartile, rurality, frailty, Charlson score, and hospital volume, she said.
Men were also at significantly increased risk for infection (HR, 1.67; P less than .0001) and revision TKA within 2 years (HR, 1.49; P less than .0001), after further adjustment for surgeon volume.
The investigators, led by colleague and orthopedic surgery resident Bheeshma Ravi, Ph.D., postulate that the increased risk of infection and revision among men is due to the high-impact activities that men may engage in after their prosthesis.
No sex differences were found for venous thromboembolism within 90 days or periprosthetic fracture within 2 years.
Hip arthroplasty
Men undergoing total hip replacement had higher rates of early acute MI than women (0.9% vs. 0.7%), but lower rates of periprosthetic fracture within 2 years (0.3% vs. 0.5%), Dr. Hawker said.
At baseline, male patients were younger than their female counterparts (65 years vs. 70 years) and less likely to be frail (3.5% vs. 6.6%), but more likely to have a Charlson score of 2 or more (5.3% vs. 3.7%).
After full adjustment, men were at significantly increased risk for acute MI (HR, 1.64; P less than .0001) and reduced risk for periprosthetic fracture (HR, 0.52; P = .0005), Dr. Hawker said at the meeting, which was sponsored by the Osteoarthritis Research Society International.
"We think the potential explanations for acute MI after both hip and knee replacement may be additional cardiovascular risk factors," she said. "We did not control for preexisting cardiovascular risk; that is something we are doing now."
The study excluded patients who had a pre–joint replacement fragility fracture, but because of the quality of the data postoperatively and the availability of drug benefit data, "we don’t feel we have adequate control for the presence of osteoporosis," Dr. Hawker observed.
No differences were found between sexes in the hip replacement cohort for infection, death, venous thromboembolism, dislocation, or revision.
Session comoderator Dr. Martin Englund, of Lund (Sweden) University, commented that the study was well conducted and the findings very interesting, but he cautioned against generalizing the results too broadly.
"We have seen before, that results from Sweden are not necessarily the same as in North America," he said in an interview. "I’m sure these results are probably very generalizable in Canada and in that type of health care setting, but may not be the same elsewhere. ... These are also things that might change over time. So we just need to keep monitoring outcomes and repeating these studies and adjust our treatment to what we find."
Dr. Ravi reported fellowship support from the University of Toronto, Canadian Institutes of Health Research, and Women’s College Research Institute.
AT OARSI 2014
Major finding: Men had more acute MIs within 90 days after total knee arthroplasty than did women (1.1% vs. 0.8%), more infection within 2 years of surgery (1.1% vs. 0.7%), and more revision surgery within 2 years (1.5% vs. 1%). After total hip replacement, men had a higher rate of early acute MI (0.9% vs. 0.7%), but less periprosthetic fracture within 2 years (0.3% vs. 0.5%).
Data source: Database analysis of 97,445 patients who received primary, elective hip or knee arthroplasty.
Disclosures: Dr. Ravi reported fellowship support from the University of Toronto, Canadian Institutes of Health Research, and Women’s College Research Institute.
Sprifermin injections showed some benefits for cartilage loss in knee osteoarthritis
In patients with knee osteoarthritis, intra-articular injections of 100 micrograms sprifermin led to significant benefits in measures of lateral femorotibial cartilage loss and joint space narrowing in a double-blind, randomized, proof-of-concept trial.
But the study failed to meet its primary efficacy endpoint – a significant change in central medial femorotibial compartment cartilage thickness at 6 and 12 months on MRI, reported Dr. Stefan Lohmander of Lund University, Sweden, and his associates.
Reasons for the preferential effect on the lateral compartment were unclear, the investigators said. The medial compartment is more severely affected in osteoarthritis, which might limit the effectiveness of anabolic agents that target cartilage, they said. Higher loading of the medial compartment in patients with varus also might "overwhelm" attempts to regenerate cartilage or slow loss, they added.
Preclinical studies indicated that sprifermin (recombinant human fibroblast growth factor 18) binds to and specifically activates fibroblast growth factor receptor 3 in cartilage to stimulate chondrocyte proliferation, cartilage matrix formation, and cartilage repair in vitro and in vivo.
The researchers randomized 192 patients with knee osteoarthritis to intra-articular injections of placebo or single or multiple-ascending doses of intra-articular sprifermin at 10, 30, or 100 micrograms (Arthritis Rheumatol. 2014 April 17 [doi:10.1002/art.38614]).
At 12 months, patients treated with 100 micrograms sprifermin had lost significantly less total femorotibial cartilage (difference from placebo, 0.04 mm; P = .039) and lateral femorotibial compartment cartilage (difference from placebo, 0.08 mm; P = .032), and had improved joint space narrowing of the lateral femorotibial compartment (difference from placebo, 0.52 mm; P = .012).
The study identified no significant difference in serious adverse events, treatment-emergent adverse events, or acute inflammatory reactions. All groups improved on the Western Ontario McMaster Universities Osteoarthritis Index, but the difference was relatively small, said Dr. Lohmander and his associates. The study did not collect detailed symptom data, patients were allowed to use pain medications, and patients knew which dose cohort (single or multiple) they were in – all of which limited interpretability of patient-reported data, the investigators noted.
The study was funded by Merck Serono S.A., a subsidiary of Merck KGaA in Darmstadt, Germany. Dr. Lohmander and three coauthors reported receiving consulting fees from Merck Serono, and two coauthors reported former employment with the company.
In patients with knee osteoarthritis, intra-articular injections of 100 micrograms sprifermin led to significant benefits in measures of lateral femorotibial cartilage loss and joint space narrowing in a double-blind, randomized, proof-of-concept trial.
But the study failed to meet its primary efficacy endpoint – a significant change in central medial femorotibial compartment cartilage thickness at 6 and 12 months on MRI, reported Dr. Stefan Lohmander of Lund University, Sweden, and his associates.
Reasons for the preferential effect on the lateral compartment were unclear, the investigators said. The medial compartment is more severely affected in osteoarthritis, which might limit the effectiveness of anabolic agents that target cartilage, they said. Higher loading of the medial compartment in patients with varus also might "overwhelm" attempts to regenerate cartilage or slow loss, they added.
Preclinical studies indicated that sprifermin (recombinant human fibroblast growth factor 18) binds to and specifically activates fibroblast growth factor receptor 3 in cartilage to stimulate chondrocyte proliferation, cartilage matrix formation, and cartilage repair in vitro and in vivo.
The researchers randomized 192 patients with knee osteoarthritis to intra-articular injections of placebo or single or multiple-ascending doses of intra-articular sprifermin at 10, 30, or 100 micrograms (Arthritis Rheumatol. 2014 April 17 [doi:10.1002/art.38614]).
At 12 months, patients treated with 100 micrograms sprifermin had lost significantly less total femorotibial cartilage (difference from placebo, 0.04 mm; P = .039) and lateral femorotibial compartment cartilage (difference from placebo, 0.08 mm; P = .032), and had improved joint space narrowing of the lateral femorotibial compartment (difference from placebo, 0.52 mm; P = .012).
The study identified no significant difference in serious adverse events, treatment-emergent adverse events, or acute inflammatory reactions. All groups improved on the Western Ontario McMaster Universities Osteoarthritis Index, but the difference was relatively small, said Dr. Lohmander and his associates. The study did not collect detailed symptom data, patients were allowed to use pain medications, and patients knew which dose cohort (single or multiple) they were in – all of which limited interpretability of patient-reported data, the investigators noted.
The study was funded by Merck Serono S.A., a subsidiary of Merck KGaA in Darmstadt, Germany. Dr. Lohmander and three coauthors reported receiving consulting fees from Merck Serono, and two coauthors reported former employment with the company.
In patients with knee osteoarthritis, intra-articular injections of 100 micrograms sprifermin led to significant benefits in measures of lateral femorotibial cartilage loss and joint space narrowing in a double-blind, randomized, proof-of-concept trial.
But the study failed to meet its primary efficacy endpoint – a significant change in central medial femorotibial compartment cartilage thickness at 6 and 12 months on MRI, reported Dr. Stefan Lohmander of Lund University, Sweden, and his associates.
Reasons for the preferential effect on the lateral compartment were unclear, the investigators said. The medial compartment is more severely affected in osteoarthritis, which might limit the effectiveness of anabolic agents that target cartilage, they said. Higher loading of the medial compartment in patients with varus also might "overwhelm" attempts to regenerate cartilage or slow loss, they added.
Preclinical studies indicated that sprifermin (recombinant human fibroblast growth factor 18) binds to and specifically activates fibroblast growth factor receptor 3 in cartilage to stimulate chondrocyte proliferation, cartilage matrix formation, and cartilage repair in vitro and in vivo.
The researchers randomized 192 patients with knee osteoarthritis to intra-articular injections of placebo or single or multiple-ascending doses of intra-articular sprifermin at 10, 30, or 100 micrograms (Arthritis Rheumatol. 2014 April 17 [doi:10.1002/art.38614]).
At 12 months, patients treated with 100 micrograms sprifermin had lost significantly less total femorotibial cartilage (difference from placebo, 0.04 mm; P = .039) and lateral femorotibial compartment cartilage (difference from placebo, 0.08 mm; P = .032), and had improved joint space narrowing of the lateral femorotibial compartment (difference from placebo, 0.52 mm; P = .012).
The study identified no significant difference in serious adverse events, treatment-emergent adverse events, or acute inflammatory reactions. All groups improved on the Western Ontario McMaster Universities Osteoarthritis Index, but the difference was relatively small, said Dr. Lohmander and his associates. The study did not collect detailed symptom data, patients were allowed to use pain medications, and patients knew which dose cohort (single or multiple) they were in – all of which limited interpretability of patient-reported data, the investigators noted.
The study was funded by Merck Serono S.A., a subsidiary of Merck KGaA in Darmstadt, Germany. Dr. Lohmander and three coauthors reported receiving consulting fees from Merck Serono, and two coauthors reported former employment with the company.
FROM ARTHRITIS & RHEUMATOLOGY
Major Finding: At 12 months, patients who received intra-articular injections of 100 micrograms sprifermin had significantly less total and lateral femorotibial compartment cartilage loss and less narrowing of the lateral femorotibial compartment, compared with placebo-treated patients.
Data Source: Double-blind, proof-of-concept trial of 192 patients with knee osteoarthritis randomized to placebo or to single or multiple-ascending doses of intra-articular sprifermin at 10, 30, or 100 micrograms.
Disclosures: The study sponsor was Merck Serono S.A., a subsidiary of Merck KGaA in Darmstadt, Germany. Dr. Lohmander and three coauthors reported receiving consulting fees from Merck Serono. Two authors reported former employment with the company.
Milk may slow knee OA progression in women
Milk consumption was associated with a slowing of the structural progression of knee osteoarthritis among women who participated in the longitudinal Osteoarthritis Initiative study.
From a group of 4,796 adults aged 45-79 years with established knee OA or major risk factors for OA who had been enrolled in the study in 2004, Dr. Bing Lu of the division of rheumatology, immunology, and allergy at Brigham and Women’s Hospital and Harvard Medical School, Boston, and his associates identified 2,148 of these adults with 3,064 affected knees. They followed the patients using annual plain radiographs at 1, 2, 3, and 4 years after enrollment.
The investigators measured changes in joint space width between the medial femur and tibia to quantify OA progression, as well as Osteoarthritis Research Society International grading as a semiquantitative measure of progression. Milk consumption and intake of dairy products, other foods, and dietary supplements were assessed with a food frequency questionnaire.
Among women only, a significant inverse dose-response relationship was found between milk intake and the rate of decline in joint space width, beginning at the relatively low "dose" of seven or fewer glasses of milk per week. Every increase of 10 glasses per week was associated with 0.06 mm less decline in joint space width over 48 months, compared with women who drank no milk.
This association remained robust after the data were adjusted to account for alcohol consumption and the intake of cheese and yogurt, and it was not affected by the participants’ race, smoking status, level of physical activity, vitamin D intake, and the presence or absence of obesity. A sensitivity analysis that accounted for dietary calcium intake reduced the effect of milk consumption in women by 25% (Arthritis Care Res. 2014 April 7 [doi: 10.1002/acr.22297]).
The reason for this association remains unclear, and it also isn’t known why milk intake didn’t correlate with OA progression in men. Moreover, causality has not been established because this was an observational study and the participants were not randomized to consume different quantities of milk, Dr. Lu and his associates wrote.
This study was supported by the National Heart, Lung and Blood Institute. The Osteoarthritis Initiative is a public-private partnership funded by the National Institutes of Health, Pfizer, Novartis, Merck, and GlaxoSmithKline. Dr. Lu and his associates reported no financial conflicts of interest.
This is the first large, prospective study to examine the association between milk intake and progression of knee OA, and although the results are "intriguing," they do not yet warrant a change in clinical practice. So don’t start advising patients to drink more milk quite yet, said Shivani Sahni, Ph.D., and Robert R. McLean, D.Sc.
If these findings are replicated in further studies, the current dietary guidelines for milk intake should be sufficient to delay the progression of OA. Moreover, it is not yet clear whether the beneficial radiographic effect observed in this study translates into meaningful clinical outcomes such as decreased pain, improved function, or avoidance of joint replacement, they noted.
Shivani Sahni, Ph.D., and Robert R. McLean, D.Sc., are at the Institute for Aging Research at Beth Israel Deaconess Medical Center, Boston. They reported no financial conflicts of interest. These remarks were taken from their editorial accompanying Dr. Lu and colleagues’ report (Arthritis Care Res. 2014 April 7 [doi: 10.1002/acr.22334]).
This is the first large, prospective study to examine the association between milk intake and progression of knee OA, and although the results are "intriguing," they do not yet warrant a change in clinical practice. So don’t start advising patients to drink more milk quite yet, said Shivani Sahni, Ph.D., and Robert R. McLean, D.Sc.
If these findings are replicated in further studies, the current dietary guidelines for milk intake should be sufficient to delay the progression of OA. Moreover, it is not yet clear whether the beneficial radiographic effect observed in this study translates into meaningful clinical outcomes such as decreased pain, improved function, or avoidance of joint replacement, they noted.
Shivani Sahni, Ph.D., and Robert R. McLean, D.Sc., are at the Institute for Aging Research at Beth Israel Deaconess Medical Center, Boston. They reported no financial conflicts of interest. These remarks were taken from their editorial accompanying Dr. Lu and colleagues’ report (Arthritis Care Res. 2014 April 7 [doi: 10.1002/acr.22334]).
This is the first large, prospective study to examine the association between milk intake and progression of knee OA, and although the results are "intriguing," they do not yet warrant a change in clinical practice. So don’t start advising patients to drink more milk quite yet, said Shivani Sahni, Ph.D., and Robert R. McLean, D.Sc.
If these findings are replicated in further studies, the current dietary guidelines for milk intake should be sufficient to delay the progression of OA. Moreover, it is not yet clear whether the beneficial radiographic effect observed in this study translates into meaningful clinical outcomes such as decreased pain, improved function, or avoidance of joint replacement, they noted.
Shivani Sahni, Ph.D., and Robert R. McLean, D.Sc., are at the Institute for Aging Research at Beth Israel Deaconess Medical Center, Boston. They reported no financial conflicts of interest. These remarks were taken from their editorial accompanying Dr. Lu and colleagues’ report (Arthritis Care Res. 2014 April 7 [doi: 10.1002/acr.22334]).
Milk consumption was associated with a slowing of the structural progression of knee osteoarthritis among women who participated in the longitudinal Osteoarthritis Initiative study.
From a group of 4,796 adults aged 45-79 years with established knee OA or major risk factors for OA who had been enrolled in the study in 2004, Dr. Bing Lu of the division of rheumatology, immunology, and allergy at Brigham and Women’s Hospital and Harvard Medical School, Boston, and his associates identified 2,148 of these adults with 3,064 affected knees. They followed the patients using annual plain radiographs at 1, 2, 3, and 4 years after enrollment.
The investigators measured changes in joint space width between the medial femur and tibia to quantify OA progression, as well as Osteoarthritis Research Society International grading as a semiquantitative measure of progression. Milk consumption and intake of dairy products, other foods, and dietary supplements were assessed with a food frequency questionnaire.
Among women only, a significant inverse dose-response relationship was found between milk intake and the rate of decline in joint space width, beginning at the relatively low "dose" of seven or fewer glasses of milk per week. Every increase of 10 glasses per week was associated with 0.06 mm less decline in joint space width over 48 months, compared with women who drank no milk.
This association remained robust after the data were adjusted to account for alcohol consumption and the intake of cheese and yogurt, and it was not affected by the participants’ race, smoking status, level of physical activity, vitamin D intake, and the presence or absence of obesity. A sensitivity analysis that accounted for dietary calcium intake reduced the effect of milk consumption in women by 25% (Arthritis Care Res. 2014 April 7 [doi: 10.1002/acr.22297]).
The reason for this association remains unclear, and it also isn’t known why milk intake didn’t correlate with OA progression in men. Moreover, causality has not been established because this was an observational study and the participants were not randomized to consume different quantities of milk, Dr. Lu and his associates wrote.
This study was supported by the National Heart, Lung and Blood Institute. The Osteoarthritis Initiative is a public-private partnership funded by the National Institutes of Health, Pfizer, Novartis, Merck, and GlaxoSmithKline. Dr. Lu and his associates reported no financial conflicts of interest.
Milk consumption was associated with a slowing of the structural progression of knee osteoarthritis among women who participated in the longitudinal Osteoarthritis Initiative study.
From a group of 4,796 adults aged 45-79 years with established knee OA or major risk factors for OA who had been enrolled in the study in 2004, Dr. Bing Lu of the division of rheumatology, immunology, and allergy at Brigham and Women’s Hospital and Harvard Medical School, Boston, and his associates identified 2,148 of these adults with 3,064 affected knees. They followed the patients using annual plain radiographs at 1, 2, 3, and 4 years after enrollment.
The investigators measured changes in joint space width between the medial femur and tibia to quantify OA progression, as well as Osteoarthritis Research Society International grading as a semiquantitative measure of progression. Milk consumption and intake of dairy products, other foods, and dietary supplements were assessed with a food frequency questionnaire.
Among women only, a significant inverse dose-response relationship was found between milk intake and the rate of decline in joint space width, beginning at the relatively low "dose" of seven or fewer glasses of milk per week. Every increase of 10 glasses per week was associated with 0.06 mm less decline in joint space width over 48 months, compared with women who drank no milk.
This association remained robust after the data were adjusted to account for alcohol consumption and the intake of cheese and yogurt, and it was not affected by the participants’ race, smoking status, level of physical activity, vitamin D intake, and the presence or absence of obesity. A sensitivity analysis that accounted for dietary calcium intake reduced the effect of milk consumption in women by 25% (Arthritis Care Res. 2014 April 7 [doi: 10.1002/acr.22297]).
The reason for this association remains unclear, and it also isn’t known why milk intake didn’t correlate with OA progression in men. Moreover, causality has not been established because this was an observational study and the participants were not randomized to consume different quantities of milk, Dr. Lu and his associates wrote.
This study was supported by the National Heart, Lung and Blood Institute. The Osteoarthritis Initiative is a public-private partnership funded by the National Institutes of Health, Pfizer, Novartis, Merck, and GlaxoSmithKline. Dr. Lu and his associates reported no financial conflicts of interest.
FROM ARTHRITIS CARE AND RESEARCH
Major finding: Beginning at the relatively low "dose" of 7 or fewer glasses of milk per week, every increase of 10 glasses per week was associated with 0.06 mm less decline in joint space width over 48 months, compared with women who drank no milk.
Data source: An observational cohort study involving 2,148 adults with OA in 3,064 knees who underwent knee radiography annually for 4 years.
Disclosures: This study was supported by the National Heart, Lung and Blood Institute. The Osteoarthritis Initiative is a public-private partnership funded by the National Institutes of Health, Pfizer, Novartis, Merck, and GlaxoSmithKline. Dr. Lu and his associates reported no financial conflicts of interest.
Glucosamine no better than placebo for knee osteoarthritis
Glucosamine supplements were no better than placebo at improving cartilage damage in patients with knee osteoarthritis in a randomized trial that was described by study investigators as the first "to evaluate the benefit of glucosamine on joint health using two different MRI parameters to measure outcomes."
Dr. C. Kent Kwoh of the University of Pittsburgh and the University of Arizona, Tucson, and his associates randomly assigned 201 patients to receive 6 months of either 1,500 mg daily oral glucosamine hydrochloride in the form of a diet lemonade drink (98 patients) or a matching placebo (103 patients). The study participants, aged 35-65 years, all had mild to moderate chronic, frequent knee pain typical of osteoarthritis (OA).
The primary outcome was the inhibition of worsening cartilage damage in both knees, as assessed using detailed MRI examination of 14 articular subregions in each joint. Cartilage status declined in both groups to the same degree, and there was no evidence that glucosamine lessened the deterioration of knee cartilage. There was worsening in at least one knee subregion in 7.7% of glucosamine-treated knees and 10.7% of placebo-treated knees, and in at least two subregions in 5.1% of those treated with glucosamine and 4.4% of those treated with placebo.
Subchondral bone marrow lesions ("bone bruises"), another feature of cartilage damage, also showed either worsening or no change in both study groups. In fact, "changes in bone marrow lesions suggested that there was less worsening and more improvement in the control group as compared to the glucosamine group," the investigators wrote.
In addition to these assessments of structural changes, the investigators also examined a molecular biomarker of cartilage tissue degradation: the urinary level of C-terminal cross-linking telopeptide of type II collagen, which correlates with radiographic progression of OA. Again, there were no differences between the two study groups after 6 months of treatment. Similarly, the study participants indicated in subjective measures of knee pain and function that glucosamine yielded no benefits (Arthritis Rheumatol. 2014 March 11 [doi:10.1002/art.38314]).
The evidence concerning glucosamine’s effectiveness in improving joint health is "very conflicting," with independent studies showing no benefit while industry-sponsored studies show the opposite. Nevertheless, glucosamine is the second most commonly used nutraceutical in the United States, and a 2007 study showed that more than 10% of American adults take it. "Global sales of glucosamine supplements increased over 60% between 2003 ($1.3 billion) and 2010 (over $2.1 billion)," Dr. Kwoh and his associates wrote.
This study was funded by the Coca-Cola Beverage Institute for Health & Wellness and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. No other financial conflicts of interest were reported.
Glucosamine supplements were no better than placebo at improving cartilage damage in patients with knee osteoarthritis in a randomized trial that was described by study investigators as the first "to evaluate the benefit of glucosamine on joint health using two different MRI parameters to measure outcomes."
Dr. C. Kent Kwoh of the University of Pittsburgh and the University of Arizona, Tucson, and his associates randomly assigned 201 patients to receive 6 months of either 1,500 mg daily oral glucosamine hydrochloride in the form of a diet lemonade drink (98 patients) or a matching placebo (103 patients). The study participants, aged 35-65 years, all had mild to moderate chronic, frequent knee pain typical of osteoarthritis (OA).
The primary outcome was the inhibition of worsening cartilage damage in both knees, as assessed using detailed MRI examination of 14 articular subregions in each joint. Cartilage status declined in both groups to the same degree, and there was no evidence that glucosamine lessened the deterioration of knee cartilage. There was worsening in at least one knee subregion in 7.7% of glucosamine-treated knees and 10.7% of placebo-treated knees, and in at least two subregions in 5.1% of those treated with glucosamine and 4.4% of those treated with placebo.
Subchondral bone marrow lesions ("bone bruises"), another feature of cartilage damage, also showed either worsening or no change in both study groups. In fact, "changes in bone marrow lesions suggested that there was less worsening and more improvement in the control group as compared to the glucosamine group," the investigators wrote.
In addition to these assessments of structural changes, the investigators also examined a molecular biomarker of cartilage tissue degradation: the urinary level of C-terminal cross-linking telopeptide of type II collagen, which correlates with radiographic progression of OA. Again, there were no differences between the two study groups after 6 months of treatment. Similarly, the study participants indicated in subjective measures of knee pain and function that glucosamine yielded no benefits (Arthritis Rheumatol. 2014 March 11 [doi:10.1002/art.38314]).
The evidence concerning glucosamine’s effectiveness in improving joint health is "very conflicting," with independent studies showing no benefit while industry-sponsored studies show the opposite. Nevertheless, glucosamine is the second most commonly used nutraceutical in the United States, and a 2007 study showed that more than 10% of American adults take it. "Global sales of glucosamine supplements increased over 60% between 2003 ($1.3 billion) and 2010 (over $2.1 billion)," Dr. Kwoh and his associates wrote.
This study was funded by the Coca-Cola Beverage Institute for Health & Wellness and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. No other financial conflicts of interest were reported.
Glucosamine supplements were no better than placebo at improving cartilage damage in patients with knee osteoarthritis in a randomized trial that was described by study investigators as the first "to evaluate the benefit of glucosamine on joint health using two different MRI parameters to measure outcomes."
Dr. C. Kent Kwoh of the University of Pittsburgh and the University of Arizona, Tucson, and his associates randomly assigned 201 patients to receive 6 months of either 1,500 mg daily oral glucosamine hydrochloride in the form of a diet lemonade drink (98 patients) or a matching placebo (103 patients). The study participants, aged 35-65 years, all had mild to moderate chronic, frequent knee pain typical of osteoarthritis (OA).
The primary outcome was the inhibition of worsening cartilage damage in both knees, as assessed using detailed MRI examination of 14 articular subregions in each joint. Cartilage status declined in both groups to the same degree, and there was no evidence that glucosamine lessened the deterioration of knee cartilage. There was worsening in at least one knee subregion in 7.7% of glucosamine-treated knees and 10.7% of placebo-treated knees, and in at least two subregions in 5.1% of those treated with glucosamine and 4.4% of those treated with placebo.
Subchondral bone marrow lesions ("bone bruises"), another feature of cartilage damage, also showed either worsening or no change in both study groups. In fact, "changes in bone marrow lesions suggested that there was less worsening and more improvement in the control group as compared to the glucosamine group," the investigators wrote.
In addition to these assessments of structural changes, the investigators also examined a molecular biomarker of cartilage tissue degradation: the urinary level of C-terminal cross-linking telopeptide of type II collagen, which correlates with radiographic progression of OA. Again, there were no differences between the two study groups after 6 months of treatment. Similarly, the study participants indicated in subjective measures of knee pain and function that glucosamine yielded no benefits (Arthritis Rheumatol. 2014 March 11 [doi:10.1002/art.38314]).
The evidence concerning glucosamine’s effectiveness in improving joint health is "very conflicting," with independent studies showing no benefit while industry-sponsored studies show the opposite. Nevertheless, glucosamine is the second most commonly used nutraceutical in the United States, and a 2007 study showed that more than 10% of American adults take it. "Global sales of glucosamine supplements increased over 60% between 2003 ($1.3 billion) and 2010 (over $2.1 billion)," Dr. Kwoh and his associates wrote.
This study was funded by the Coca-Cola Beverage Institute for Health & Wellness and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. No other financial conflicts of interest were reported.
FROM ARTHRITIS & RHEUMATOLOGY
Major finding: There was worsening cartilage damage in at least one knee subregion in 7.7% of glucosamine-treated knees and 10.7% of placebo-treated knees, and in at least two subregions in 5.1% of those treated with glucosamine and 4.4% of those treated with placebo.
Data source: A randomized, controlled trial comparing the effect of 6 months of glucosamine supplementation against placebo for inhibiting the progression of knee OA and improving symptoms in 201 patients aged 35-65 years.
Disclosures: This study was funded by the Coca-Cola Beverage Institute for Health & Wellness and the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
Colchicine: Old drug with a new trick
SNOWMASS, COLO. – Colchicine, a venerable drug Hippocrates proposed as a gout remedy some 2,400 years ago, shows fresh potential as a novel treatment for osteoarthritis.
"I’m going out on a limb here: Could colchicine improve osteoarthritis pain and function? I won’t tell you to do it, but there are a couple of studies that say it may be of some value – and they are intriguing," Dr. Michael H. Pillinger said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.
Moreover, there is evidence of a biologically plausible mechanism of benefit because osteoarthritis, contrary to conventional wisdom, may actually be an inflammatory disease, added Dr. Pillinger, a rheumatologist at New York University.
Investigators at Tehran (Iran) University of Medical Sciences randomized 61 postmenopausal women with moderate to severe knee osteoarthritis (OA) and no evidence of calcium pyrophosphate deposition disease on x-ray to 0.5 mg twice daily of colchicine or placebo in a double-blind clinical trial. After 3 months of prospective follow-up, the colchicine-treated group showed a mean 11.1-point improvement on a 15-point patient global assessment visual analog scale, compared with a 3.1-point improvement in controls.
The colchicine group also had a 9.8-point improvement on the 15-point physician global assessment, compared with a 3.7-point gain among controls. The mean daily consumption of acetaminophen – used as a rescue analgesic – was 879 mg in the colchicine group and nearly twice as great in controls at 1,621 mg (Clin. Exp. Rheumatol. 2011;29:513-8).
The Iranian study recapitulates an earlier double-blind randomized trial conducted by investigators at King George’s Medical College in Lucknow, India. They randomized 36 patients on background nonsteroidal anti-inflammatory drug (NSAID) therapy for OA of the knee to colchicine at 0.5 mg twice daily or placebo. The coprimary outcomes were the proportions of patients showing at least a 30% improvement in symptoms at 20 weeks as measured by the total WOMAC (Western Ontario and McMaster Universities) osteoarthritis index and a visual analog scale for knee pain. That threshold was achieved on the WOMAC osteoarthritis index by 58% of the colchicine group, compared with 24% of controls, and on the knee pain score by 53% of colchicine-treated patients and 18% of controls (Arthritis Rheum. 2002;47:280-4).
Turning to colchicine’s putative mechanism of benefit in OA, Dr. Pillinger commented that the drug has well-established anti-inflammatory effects on neutrophils. It also curbs tumor necrosis factor–alpha receptor expression on both macrophages and endothelial cells, with resultant inhibition of TNF-alpha secretion. Calcium-containing crystals are common in patients with primary OA, and it has been hypothesized that they activate the inflammasome, which drives production of interleukin-1 (IL-1), a key mediator of cartilage breakdown in OA. Colchicine inhibits this calcium crystal–induced inflammation.
In addition, Dr. Pillinger noted, investigators at Duke University in Durham, N.C., have shown that synovial fluid uric acid levels in 159 patients with OA and no gout were strongly correlated with both synovial fluid IL-1 levels and OA severity. They have proposed that uric acid is released into diseased joints by damaged chondrocytes as a danger signal, and that this uric acid crystallizes at a microscopic level in joints and cartilage, promoting chronic subacute IL-1–mediated inflammation (Proc. Natl. Acad. Sci. U.S.A. 2011;108:2088-93).
Gout and OA appear to be fellow travelers, according to Dr. Pillinger. He cited a study by his New York University colleague Dr. Rennie G. Howard, who conducted a rigorous evaluation of OA in 25 patients who presented with gout, 25 others with hyperuricemia, and 25 controls. All were men over age 65. She found that the men with gout were twice as likely as controls to meet American College of Rheumatology (ACR) criteria for OA. They were also more likely to have bilateral knee OA by x-ray.
Dr. Pillinger reported receiving research grants from Savient and Takeda, which markets colchicine under the brand name Colcrys.
SNOWMASS, COLO. – Colchicine, a venerable drug Hippocrates proposed as a gout remedy some 2,400 years ago, shows fresh potential as a novel treatment for osteoarthritis.
"I’m going out on a limb here: Could colchicine improve osteoarthritis pain and function? I won’t tell you to do it, but there are a couple of studies that say it may be of some value – and they are intriguing," Dr. Michael H. Pillinger said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.
Moreover, there is evidence of a biologically plausible mechanism of benefit because osteoarthritis, contrary to conventional wisdom, may actually be an inflammatory disease, added Dr. Pillinger, a rheumatologist at New York University.
Investigators at Tehran (Iran) University of Medical Sciences randomized 61 postmenopausal women with moderate to severe knee osteoarthritis (OA) and no evidence of calcium pyrophosphate deposition disease on x-ray to 0.5 mg twice daily of colchicine or placebo in a double-blind clinical trial. After 3 months of prospective follow-up, the colchicine-treated group showed a mean 11.1-point improvement on a 15-point patient global assessment visual analog scale, compared with a 3.1-point improvement in controls.
The colchicine group also had a 9.8-point improvement on the 15-point physician global assessment, compared with a 3.7-point gain among controls. The mean daily consumption of acetaminophen – used as a rescue analgesic – was 879 mg in the colchicine group and nearly twice as great in controls at 1,621 mg (Clin. Exp. Rheumatol. 2011;29:513-8).
The Iranian study recapitulates an earlier double-blind randomized trial conducted by investigators at King George’s Medical College in Lucknow, India. They randomized 36 patients on background nonsteroidal anti-inflammatory drug (NSAID) therapy for OA of the knee to colchicine at 0.5 mg twice daily or placebo. The coprimary outcomes were the proportions of patients showing at least a 30% improvement in symptoms at 20 weeks as measured by the total WOMAC (Western Ontario and McMaster Universities) osteoarthritis index and a visual analog scale for knee pain. That threshold was achieved on the WOMAC osteoarthritis index by 58% of the colchicine group, compared with 24% of controls, and on the knee pain score by 53% of colchicine-treated patients and 18% of controls (Arthritis Rheum. 2002;47:280-4).
Turning to colchicine’s putative mechanism of benefit in OA, Dr. Pillinger commented that the drug has well-established anti-inflammatory effects on neutrophils. It also curbs tumor necrosis factor–alpha receptor expression on both macrophages and endothelial cells, with resultant inhibition of TNF-alpha secretion. Calcium-containing crystals are common in patients with primary OA, and it has been hypothesized that they activate the inflammasome, which drives production of interleukin-1 (IL-1), a key mediator of cartilage breakdown in OA. Colchicine inhibits this calcium crystal–induced inflammation.
In addition, Dr. Pillinger noted, investigators at Duke University in Durham, N.C., have shown that synovial fluid uric acid levels in 159 patients with OA and no gout were strongly correlated with both synovial fluid IL-1 levels and OA severity. They have proposed that uric acid is released into diseased joints by damaged chondrocytes as a danger signal, and that this uric acid crystallizes at a microscopic level in joints and cartilage, promoting chronic subacute IL-1–mediated inflammation (Proc. Natl. Acad. Sci. U.S.A. 2011;108:2088-93).
Gout and OA appear to be fellow travelers, according to Dr. Pillinger. He cited a study by his New York University colleague Dr. Rennie G. Howard, who conducted a rigorous evaluation of OA in 25 patients who presented with gout, 25 others with hyperuricemia, and 25 controls. All were men over age 65. She found that the men with gout were twice as likely as controls to meet American College of Rheumatology (ACR) criteria for OA. They were also more likely to have bilateral knee OA by x-ray.
Dr. Pillinger reported receiving research grants from Savient and Takeda, which markets colchicine under the brand name Colcrys.
SNOWMASS, COLO. – Colchicine, a venerable drug Hippocrates proposed as a gout remedy some 2,400 years ago, shows fresh potential as a novel treatment for osteoarthritis.
"I’m going out on a limb here: Could colchicine improve osteoarthritis pain and function? I won’t tell you to do it, but there are a couple of studies that say it may be of some value – and they are intriguing," Dr. Michael H. Pillinger said at the Winter Rheumatology Symposium sponsored by the American College of Rheumatology.
Moreover, there is evidence of a biologically plausible mechanism of benefit because osteoarthritis, contrary to conventional wisdom, may actually be an inflammatory disease, added Dr. Pillinger, a rheumatologist at New York University.
Investigators at Tehran (Iran) University of Medical Sciences randomized 61 postmenopausal women with moderate to severe knee osteoarthritis (OA) and no evidence of calcium pyrophosphate deposition disease on x-ray to 0.5 mg twice daily of colchicine or placebo in a double-blind clinical trial. After 3 months of prospective follow-up, the colchicine-treated group showed a mean 11.1-point improvement on a 15-point patient global assessment visual analog scale, compared with a 3.1-point improvement in controls.
The colchicine group also had a 9.8-point improvement on the 15-point physician global assessment, compared with a 3.7-point gain among controls. The mean daily consumption of acetaminophen – used as a rescue analgesic – was 879 mg in the colchicine group and nearly twice as great in controls at 1,621 mg (Clin. Exp. Rheumatol. 2011;29:513-8).
The Iranian study recapitulates an earlier double-blind randomized trial conducted by investigators at King George’s Medical College in Lucknow, India. They randomized 36 patients on background nonsteroidal anti-inflammatory drug (NSAID) therapy for OA of the knee to colchicine at 0.5 mg twice daily or placebo. The coprimary outcomes were the proportions of patients showing at least a 30% improvement in symptoms at 20 weeks as measured by the total WOMAC (Western Ontario and McMaster Universities) osteoarthritis index and a visual analog scale for knee pain. That threshold was achieved on the WOMAC osteoarthritis index by 58% of the colchicine group, compared with 24% of controls, and on the knee pain score by 53% of colchicine-treated patients and 18% of controls (Arthritis Rheum. 2002;47:280-4).
Turning to colchicine’s putative mechanism of benefit in OA, Dr. Pillinger commented that the drug has well-established anti-inflammatory effects on neutrophils. It also curbs tumor necrosis factor–alpha receptor expression on both macrophages and endothelial cells, with resultant inhibition of TNF-alpha secretion. Calcium-containing crystals are common in patients with primary OA, and it has been hypothesized that they activate the inflammasome, which drives production of interleukin-1 (IL-1), a key mediator of cartilage breakdown in OA. Colchicine inhibits this calcium crystal–induced inflammation.
In addition, Dr. Pillinger noted, investigators at Duke University in Durham, N.C., have shown that synovial fluid uric acid levels in 159 patients with OA and no gout were strongly correlated with both synovial fluid IL-1 levels and OA severity. They have proposed that uric acid is released into diseased joints by damaged chondrocytes as a danger signal, and that this uric acid crystallizes at a microscopic level in joints and cartilage, promoting chronic subacute IL-1–mediated inflammation (Proc. Natl. Acad. Sci. U.S.A. 2011;108:2088-93).
Gout and OA appear to be fellow travelers, according to Dr. Pillinger. He cited a study by his New York University colleague Dr. Rennie G. Howard, who conducted a rigorous evaluation of OA in 25 patients who presented with gout, 25 others with hyperuricemia, and 25 controls. All were men over age 65. She found that the men with gout were twice as likely as controls to meet American College of Rheumatology (ACR) criteria for OA. They were also more likely to have bilateral knee OA by x-ray.
Dr. Pillinger reported receiving research grants from Savient and Takeda, which markets colchicine under the brand name Colcrys.
EXPERT ANALYSIS FROM THE WINTER RHEUMATOLOGY SYMPOSIUM
Hyaluronic acid injection for knee OA as effective as NSAIDs in short term
Treatment of osteoarthritis with intra-articular injections of hyaluronic acid over a 5-week period provided symptomatic relief that had noninferior efficacy and was safer than treatment with an oral NSAID in an open-label, multicenter randomized trial of older Japanese adults.
Intra-articular injections of hyaluronic acid (IA-HA) have been shown to reduce pain and improve joint function in knee osteoarthritis (OA), but studies also have reported a relatively slow speed of therapeutic onset and "considerable heterogeneity" in outcomes. NSAIDs have long been regarded as effective for symptomatic relief of knee OA, but carry the risk of serious gastrointestinal adverse events. The lack of data on the short-term effects of IA-HA compared with widely used NSAIDs spurred Dr. Muneaki Ishijima of Juntendo University, Tokyo, and colleagues to conduct the first trial to directly compare efficacy and safety of the two treatments for knee OA (Arthritis Res. Ther. 2014 Jan. 21 [doi:10.1186/ar4446]).
The investigators randomized 200 patients to 5 weeks of either weekly IA-HA or the nonselective cyclo-oxygenase inhibitor loxoprofen in three 60-mg tablets daily and evaluated patients’ percent change from baseline on the patient-reported Japanese Knee Osteoarthritis Measure (JKOM, primary endpoint) and their percent change from baseline in pain as rated on a 0- to 100-point visual analog scale (VAS, secondary endpoint). (Loxoprofen is not approved in the United States.)
After the 5 weeks of therapy, the investigators analyzed data from 98 patients who underwent IA-HA and 86 patients who received loxoprofen who had final JKOM scores available. In the IA-HA group, one patient withdrew consent before undergoing IA-HA, and one was lost to follow-up before the final JKOM analysis. In the NSAID group, six patients withdrew consent before receiving treatment, one patient was excluded because of duplicate entry into the trial before receiving treatment, and another seven were lost to follow-up before the final analysis.
The trial participants had a mean age of about 68 years, and approximately 72% were women. The patients had OA of the medial femorotibial joint with a Kellgren-Lawrence grade of 1-3.
The mean JKOM score declined 32.2% (from 32.0 to 22.0) with NSAID treatment and 34.7% (from 33.8 to 21.5) with IA-HA. This difference of –2.5% and its 95% confidence interval of –14.0% to 9.1% meant that the two treatments had similar efficacy based on the trial’s prespecified definition of noninferiority as a 10% difference or less in the upper limit of the confidence interval. The result did not change after adjustment for age, Kellgren-Lawrence grade, body mass index, and medical center.
Pain on the VAS dropped by 36.0% (from 55.5 to 31.9) with NSAID therapy and by 41.2% (from 60.1 to 31.8) with IA-HA, a nonsignificant difference.
There also were no differences in the percentage of responders in each group based on Outcome Measures in Rheumatology clinical trials and Osteoarthritis Research Society International (OMERACT-OARSI) response criteria, with 69.7% in the IA-HA group and 62.4% in the NSAID group. For this trial, the responder criteria were partly modified by use of the JKOM score. Response was defined as a decrease in joint pain or improvement in function based on at least a 50% reduction in score and a decrease of at least 20 mm on the VAS or clinical improvement on two of three measures: at least a 20% decline in joint pain and at least 10 mm on the VAS; functional improvement of at least 20% and a drop of at least 4 points on the 40-point JKOM functional subcategory scale; and a decrease of at least 20% on the patient’s global assessment score and a drop of at least 10 points from the total JKOM score.
No serious adverse events occurred in either group, but in the NSAID group, seven patients had symptoms related to a GI tract disorder, and three had allergy to loxoprofen, compared with one patient who received IA-HA who had stiffness in the treated knee after injection, a significant difference.
"The present study suggests that future randomized trials should thus be carried out with a longer duration of follow-up and larger samples, in order to identify optimal knee OA treatment alternatives," the investigators wrote.
They acknowledged the problems inherent with the potential of the trial’s open-label design to introduce bias into the results and the use of a 10% difference in the change in JKOM score to define noninferiority, although this margin was supported by a pilot study.
The authors reported no relevant financial disclosures.
In this interesting, multicenter, Japanese noninferiority trial, 200 patients with symptomatic knee osteoarthritis were randomized to either intra-articular hyaluronic acid (once per week for 5 weeks) or an oral NSAID (three times daily for 5 weeks). For both the primary (Japanese Knee Osteoarthritis Measure) and secondary (pain visual analog scale) outcomes, there was no significant difference in treatment response between the two groups. In addition, a similar proportion in each group (60%-70%) attained OMERACT-OARSI responder status.
There were fewer withdrawals in the IA-HA group, and no serious adverse events were seen in either arm. This trial was of very short duration with all outcomes assessed immediately after treatment at 5 weeks. There was no placebo arm, and the approximately 30% response rate for both treatments is similar to the placebo response in many clinical trials of OA, so while both therapies were equally efficacious, it may be that neither was more effective than placebo. In addition, there is no information in the literature regarding a minimal clinically important difference in the JKOM, making the 10-point difference before and after treatment difficult to interpret.
 |
|
Investigators and patients were masked to initial randomization, but not for actual treatment, which could also have introduced some bias. Finally, given the very short trial duration, no information is available regarding longer-term efficacy or adverse events.
This study supports a lack of difference between IA-HA and oral NSAIDs over a period of 5 weeks, and should be applauded for the attempt at direct comparison of two commonly used treatment modalities. However, the clinical relevance of this finding is unclear, as much of the difficulty in the treatment of OA stems from the need for safe treatments that are effective over the many years’ duration of this chronic condition.
Dr. Amanda E. Nelson is with the division of rheumatology, allergy, and immunology at the Thurston Arthritis Research Center, University of North Carolina at Chapel Hill, and is an investigator in the Johnston County (N.C.) Osteoarthritis Project. She reported no relevant financial disclosures.
In this interesting, multicenter, Japanese noninferiority trial, 200 patients with symptomatic knee osteoarthritis were randomized to either intra-articular hyaluronic acid (once per week for 5 weeks) or an oral NSAID (three times daily for 5 weeks). For both the primary (Japanese Knee Osteoarthritis Measure) and secondary (pain visual analog scale) outcomes, there was no significant difference in treatment response between the two groups. In addition, a similar proportion in each group (60%-70%) attained OMERACT-OARSI responder status.
There were fewer withdrawals in the IA-HA group, and no serious adverse events were seen in either arm. This trial was of very short duration with all outcomes assessed immediately after treatment at 5 weeks. There was no placebo arm, and the approximately 30% response rate for both treatments is similar to the placebo response in many clinical trials of OA, so while both therapies were equally efficacious, it may be that neither was more effective than placebo. In addition, there is no information in the literature regarding a minimal clinically important difference in the JKOM, making the 10-point difference before and after treatment difficult to interpret.
|
|
Investigators and patients were masked to initial randomization, but not for actual treatment, which could also have introduced some bias. Finally, given the very short trial duration, no information is available regarding longer-term efficacy or adverse events.
This study supports a lack of difference between IA-HA and oral NSAIDs over a period of 5 weeks, and should be applauded for the attempt at direct comparison of two commonly used treatment modalities. However, the clinical relevance of this finding is unclear, as much of the difficulty in the treatment of OA stems from the need for safe treatments that are effective over the many years’ duration of this chronic condition.
Dr. Amanda E. Nelson is with the division of rheumatology, allergy, and immunology at the Thurston Arthritis Research Center, University of North Carolina at Chapel Hill, and is an investigator in the Johnston County (N.C.) Osteoarthritis Project. She reported no relevant financial disclosures.
In this interesting, multicenter, Japanese noninferiority trial, 200 patients with symptomatic knee osteoarthritis were randomized to either intra-articular hyaluronic acid (once per week for 5 weeks) or an oral NSAID (three times daily for 5 weeks). For both the primary (Japanese Knee Osteoarthritis Measure) and secondary (pain visual analog scale) outcomes, there was no significant difference in treatment response between the two groups. In addition, a similar proportion in each group (60%-70%) attained OMERACT-OARSI responder status.
There were fewer withdrawals in the IA-HA group, and no serious adverse events were seen in either arm. This trial was of very short duration with all outcomes assessed immediately after treatment at 5 weeks. There was no placebo arm, and the approximately 30% response rate for both treatments is similar to the placebo response in many clinical trials of OA, so while both therapies were equally efficacious, it may be that neither was more effective than placebo. In addition, there is no information in the literature regarding a minimal clinically important difference in the JKOM, making the 10-point difference before and after treatment difficult to interpret.
|
|
Investigators and patients were masked to initial randomization, but not for actual treatment, which could also have introduced some bias. Finally, given the very short trial duration, no information is available regarding longer-term efficacy or adverse events.
This study supports a lack of difference between IA-HA and oral NSAIDs over a period of 5 weeks, and should be applauded for the attempt at direct comparison of two commonly used treatment modalities. However, the clinical relevance of this finding is unclear, as much of the difficulty in the treatment of OA stems from the need for safe treatments that are effective over the many years’ duration of this chronic condition.
Dr. Amanda E. Nelson is with the division of rheumatology, allergy, and immunology at the Thurston Arthritis Research Center, University of North Carolina at Chapel Hill, and is an investigator in the Johnston County (N.C.) Osteoarthritis Project. She reported no relevant financial disclosures.
Treatment of osteoarthritis with intra-articular injections of hyaluronic acid over a 5-week period provided symptomatic relief that had noninferior efficacy and was safer than treatment with an oral NSAID in an open-label, multicenter randomized trial of older Japanese adults.
Intra-articular injections of hyaluronic acid (IA-HA) have been shown to reduce pain and improve joint function in knee osteoarthritis (OA), but studies also have reported a relatively slow speed of therapeutic onset and "considerable heterogeneity" in outcomes. NSAIDs have long been regarded as effective for symptomatic relief of knee OA, but carry the risk of serious gastrointestinal adverse events. The lack of data on the short-term effects of IA-HA compared with widely used NSAIDs spurred Dr. Muneaki Ishijima of Juntendo University, Tokyo, and colleagues to conduct the first trial to directly compare efficacy and safety of the two treatments for knee OA (Arthritis Res. Ther. 2014 Jan. 21 [doi:10.1186/ar4446]).
The investigators randomized 200 patients to 5 weeks of either weekly IA-HA or the nonselective cyclo-oxygenase inhibitor loxoprofen in three 60-mg tablets daily and evaluated patients’ percent change from baseline on the patient-reported Japanese Knee Osteoarthritis Measure (JKOM, primary endpoint) and their percent change from baseline in pain as rated on a 0- to 100-point visual analog scale (VAS, secondary endpoint). (Loxoprofen is not approved in the United States.)
After the 5 weeks of therapy, the investigators analyzed data from 98 patients who underwent IA-HA and 86 patients who received loxoprofen who had final JKOM scores available. In the IA-HA group, one patient withdrew consent before undergoing IA-HA, and one was lost to follow-up before the final JKOM analysis. In the NSAID group, six patients withdrew consent before receiving treatment, one patient was excluded because of duplicate entry into the trial before receiving treatment, and another seven were lost to follow-up before the final analysis.
The trial participants had a mean age of about 68 years, and approximately 72% were women. The patients had OA of the medial femorotibial joint with a Kellgren-Lawrence grade of 1-3.
The mean JKOM score declined 32.2% (from 32.0 to 22.0) with NSAID treatment and 34.7% (from 33.8 to 21.5) with IA-HA. This difference of –2.5% and its 95% confidence interval of –14.0% to 9.1% meant that the two treatments had similar efficacy based on the trial’s prespecified definition of noninferiority as a 10% difference or less in the upper limit of the confidence interval. The result did not change after adjustment for age, Kellgren-Lawrence grade, body mass index, and medical center.
Pain on the VAS dropped by 36.0% (from 55.5 to 31.9) with NSAID therapy and by 41.2% (from 60.1 to 31.8) with IA-HA, a nonsignificant difference.
There also were no differences in the percentage of responders in each group based on Outcome Measures in Rheumatology clinical trials and Osteoarthritis Research Society International (OMERACT-OARSI) response criteria, with 69.7% in the IA-HA group and 62.4% in the NSAID group. For this trial, the responder criteria were partly modified by use of the JKOM score. Response was defined as a decrease in joint pain or improvement in function based on at least a 50% reduction in score and a decrease of at least 20 mm on the VAS or clinical improvement on two of three measures: at least a 20% decline in joint pain and at least 10 mm on the VAS; functional improvement of at least 20% and a drop of at least 4 points on the 40-point JKOM functional subcategory scale; and a decrease of at least 20% on the patient’s global assessment score and a drop of at least 10 points from the total JKOM score.
No serious adverse events occurred in either group, but in the NSAID group, seven patients had symptoms related to a GI tract disorder, and three had allergy to loxoprofen, compared with one patient who received IA-HA who had stiffness in the treated knee after injection, a significant difference.
"The present study suggests that future randomized trials should thus be carried out with a longer duration of follow-up and larger samples, in order to identify optimal knee OA treatment alternatives," the investigators wrote.
They acknowledged the problems inherent with the potential of the trial’s open-label design to introduce bias into the results and the use of a 10% difference in the change in JKOM score to define noninferiority, although this margin was supported by a pilot study.
The authors reported no relevant financial disclosures.
Treatment of osteoarthritis with intra-articular injections of hyaluronic acid over a 5-week period provided symptomatic relief that had noninferior efficacy and was safer than treatment with an oral NSAID in an open-label, multicenter randomized trial of older Japanese adults.
Intra-articular injections of hyaluronic acid (IA-HA) have been shown to reduce pain and improve joint function in knee osteoarthritis (OA), but studies also have reported a relatively slow speed of therapeutic onset and "considerable heterogeneity" in outcomes. NSAIDs have long been regarded as effective for symptomatic relief of knee OA, but carry the risk of serious gastrointestinal adverse events. The lack of data on the short-term effects of IA-HA compared with widely used NSAIDs spurred Dr. Muneaki Ishijima of Juntendo University, Tokyo, and colleagues to conduct the first trial to directly compare efficacy and safety of the two treatments for knee OA (Arthritis Res. Ther. 2014 Jan. 21 [doi:10.1186/ar4446]).
The investigators randomized 200 patients to 5 weeks of either weekly IA-HA or the nonselective cyclo-oxygenase inhibitor loxoprofen in three 60-mg tablets daily and evaluated patients’ percent change from baseline on the patient-reported Japanese Knee Osteoarthritis Measure (JKOM, primary endpoint) and their percent change from baseline in pain as rated on a 0- to 100-point visual analog scale (VAS, secondary endpoint). (Loxoprofen is not approved in the United States.)
After the 5 weeks of therapy, the investigators analyzed data from 98 patients who underwent IA-HA and 86 patients who received loxoprofen who had final JKOM scores available. In the IA-HA group, one patient withdrew consent before undergoing IA-HA, and one was lost to follow-up before the final JKOM analysis. In the NSAID group, six patients withdrew consent before receiving treatment, one patient was excluded because of duplicate entry into the trial before receiving treatment, and another seven were lost to follow-up before the final analysis.
The trial participants had a mean age of about 68 years, and approximately 72% were women. The patients had OA of the medial femorotibial joint with a Kellgren-Lawrence grade of 1-3.
The mean JKOM score declined 32.2% (from 32.0 to 22.0) with NSAID treatment and 34.7% (from 33.8 to 21.5) with IA-HA. This difference of –2.5% and its 95% confidence interval of –14.0% to 9.1% meant that the two treatments had similar efficacy based on the trial’s prespecified definition of noninferiority as a 10% difference or less in the upper limit of the confidence interval. The result did not change after adjustment for age, Kellgren-Lawrence grade, body mass index, and medical center.
Pain on the VAS dropped by 36.0% (from 55.5 to 31.9) with NSAID therapy and by 41.2% (from 60.1 to 31.8) with IA-HA, a nonsignificant difference.
There also were no differences in the percentage of responders in each group based on Outcome Measures in Rheumatology clinical trials and Osteoarthritis Research Society International (OMERACT-OARSI) response criteria, with 69.7% in the IA-HA group and 62.4% in the NSAID group. For this trial, the responder criteria were partly modified by use of the JKOM score. Response was defined as a decrease in joint pain or improvement in function based on at least a 50% reduction in score and a decrease of at least 20 mm on the VAS or clinical improvement on two of three measures: at least a 20% decline in joint pain and at least 10 mm on the VAS; functional improvement of at least 20% and a drop of at least 4 points on the 40-point JKOM functional subcategory scale; and a decrease of at least 20% on the patient’s global assessment score and a drop of at least 10 points from the total JKOM score.
No serious adverse events occurred in either group, but in the NSAID group, seven patients had symptoms related to a GI tract disorder, and three had allergy to loxoprofen, compared with one patient who received IA-HA who had stiffness in the treated knee after injection, a significant difference.
"The present study suggests that future randomized trials should thus be carried out with a longer duration of follow-up and larger samples, in order to identify optimal knee OA treatment alternatives," the investigators wrote.
They acknowledged the problems inherent with the potential of the trial’s open-label design to introduce bias into the results and the use of a 10% difference in the change in JKOM score to define noninferiority, although this margin was supported by a pilot study.
The authors reported no relevant financial disclosures.
FROM ARTHRITIS RESEARCH & THERAPY
Major finding: The mean JKOM score declined 32.2% (from 32.0 to 22.0) with NSAID treatment and 34.7% (from 33.8 to 21.5) with IA-HA.
Data source: A multicenter, randomized, open-label noninferiority trial of 184 older Japanese adults with osteoarthritis.
Disclosures: The authors reported no relevant financial disclosures.
