Biomedical subjects

M C Hochberg

Publications and source records attributed to M C Hochberg.

At least 19 recordsLinked to original sources

PubMed2006

Hip and non-spine fracture risk reductions differ among antiresorptive agents: Evidence from randomised controlled trials.

A number of antiresorptive agents reduce the risk of vertebral fractures, but few have shown consistent effects on hip and other non-spine fractures. Meta-analysis provides a more precise estimate than individual trials when results are consistent across pooled trials. Earlier meta-analyses summarised the results for vertebral and non-spine fractures. New data have emerged for hormone therapy (HT), alendronate (ALN), risedronate (RIS) and ibandronate (IBN). We surveyed recent reports of randomised, placebo-controlled trials with non-spine and/or hip fracture data, and used meta-analysis where appropriate to test for heterogeneity and derive pooled estimates. The magnitude of effect on hip fracture appears to be similar to that for non-spine fracture for each drug, but differs among drugs. Based on the current data, ALN reduces the risk of hip and non-spine fracture by 49-55%, HT by 25-36% and RIS by 26-27%. There is insufficient and/or inconsistent evidence of an effect on these fractures for IBN, calcitonin and raloxifene.

Aged↗

PubMed2006

Women with hip fracture have a greater rate of decline in bone mineral density than expected: another significant consequence of a common geriatric problem.

INTRODUCTION: Hip fracture is a major public health problem, annually affecting over 350,000 persons in the United States and 1.6 million worldwide. Consequences include decreased survival, loss of independence, and increased risk of subsequent fractures. A substantial decline in bone mineral density (BMD) also occurs, yet the magnitude of the decline specifically attributable to hip fracture has not been documented. METHODS: To determine the amount of BMD decline attributable to hip fracture, the rate of decline in BMD in a cohort of hip fracture patients was compared with that in a cohort of women of similar age and BMD but without hip fracture. All subjects were community dwelling when enrolled. Hip fracture patients in the Baltimore Hip Studies (BHS) came from two hospitals in Baltimore, Maryland, from 1992 through 1995; comparison subjects came from the Study of Osteoporotic Fracture (SOF) enrolled in four areas of the United States during the same period. Eighty-four white, female hip fracture patients 65 years and older from the BHS were compared with 168 SOF participants matched on age, race, and BMD at baseline. BMD of the femoral neck and total hip was measured by dual-energy x-ray absorptiometry. RESULTS: Hip fracture patients had a greater decline in BMD during the 12-month postfracture follow-up than that expected on the basis of the nonfracture cohort: 4.9% vs. 0.4% at the femoral neck and 3.5% vs. 0.7% for the total hip. The decline in BMD in hip fracture patients was 11.8 times the amount expected at the femoral neck (matched on age and baseline BMD and adjusted for between-cohort differences in smoking prevalence) and 4.9 times that expected for the total hip at the end of 1 year after the hip fracture. CONCLUSION: In this sample of older women, bone loss over the year following hip fracture far exceeded that expected and is an important clinical management concern.

Activities of Daily Living↗

PubMed2006

Acetaminophen for osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is the most common form of arthritis. Published guidelines and expert opinion are divided over the relative role of acetaminophen (also called paracetamol or Tylenol) and non-steroidal anti-inflammatory drugs (NSAIDs) as first-line pharmacologic therapy. The comparative safety of acetaminophen and NSAIDs is also important to consider. This update to the original 2003 review includes nine additional RCTs. OBJECTIVES: To assess the efficacy and safety of acetaminophen versus placebo and versus NSAIDs (ibuprofen, diclofenac, arthrotec, celecoxib, naproxen, rofecoxib) for treating OA. SEARCH STRATEGY: We searched MEDLINE (up to July 2005), EMBASE (2002-July 2005), Cochrane Central Register of Controlled Trials (CENTRAL), ACP Journal Club, DARE, Cochrane Database of Systematic Reviews (all from 1994 to July 2005). Reference lists of identified RCTs and pertinent review articles were also hand searched. SELECTION CRITERIA: Published randomized controlled trials (RCTs) evaluating the efficacy and safety of acetaminophen alone in OA were considered for inclusion. DATA COLLECTION AND ANALYSIS: Pain, physical function and global assessment outcomes were reported. Results for continuous outcome measures were expressed as standardized mean differences (SMD). Dichotomous outcome measures were pooled using relative risk (RR) and the number needed to treat (NNT) was calculated. MAIN RESULTS: Fifteen RCTs involving 5986 participants were included in this review. Seven RCTs compared acetaminophen to placebo and ten RCTs compared acetaminophen to NSAIDs. In the placebo-controlled RCTs, acetaminophen was superior to placebo in five of the seven RCTs and had a similar safety profile. Compared to placebo, a pooled analysis of five trials of overall pain using multiple methods demonstrated a statistically significant reduction in pain (SMD -0.13, 95% CI -0.22 to -0.04), which is of questionable clinical significance. The relative percent improvement from baseline was 5% with an absolute change of 4 points on a 0 to 100 scale. The NNT to achieve an improvement in pain ranged from 4 to 16. In the comparator-controlled RCTs, acetaminophen was less effective overall than NSAIDs in terms of pain reduction, global assessments and in terms of improvements in functional status. No significant difference was found overall between the safety of acetaminophen and NSAIDs, although patients taking traditional NSAIDS were more likely to experience an adverse GI event (RR 1.47, (95% CI 1.08 to 2.00). 19% of patients in the traditional NSAID group versus 13% in the acetaminophen group experienced an adverse GI event. However, the median trial duration was only 6 weeks and it is difficult to assess adverse outcomes in a relatively short time period. AUTHORS' CONCLUSIONS: The evidence to date suggests that NSAIDs are superior to acetaminophen for improving knee and hip pain in people with OA. The size of the treatment effect was modest, and the median trial duration was only six weeks, therefore, additional considerations need to be factored in when making the decision between using acetaminophen or NSAIDs. In OA subjects with moderate-to-severe levels of pain, NSAIDs appear to be more effective than acetaminophen.

Acetaminophen↗

PubMed2005

Glucosamine therapy for treating osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is the most common form of arthritis, and it is often associated with significant disability and an impaired quality of life. OBJECTIVES: To review all randomized controlled trials (RCTs) evaluating the effectiveness and toxicity of glucosamine in OA. SEARCH STRATEGY: We searched MEDLINE, PREMEDLINE, EMBASE, AMED, ACP Journal Club, DARE, CDSR, and the CCTR. We also wrote letters to content experts, and hand searched reference lists of identified RCTs and pertinent review articles. All searches were updated in January 2005. SELECTION CRITERIA: Relevant studies met the following criteria: 1) RCTs evaluating the effectiveness and safety of glucosamine in OA, 2) Both placebo controlled and comparative studies were eligible, 3) Both single blinded and double blinded studies were eligible. DATA COLLECTION AND ANALYSIS: Data abstraction was performed independently by two investigators and the results were compared for degree of agreement. Gotzsche's method and a validated tool (Jadad 1996) were used to score the quality of the RCTs. Continuous outcome measures were pooled using standardized mean differences (SMD) as the measure of effect size. Dichotomous outcome measures were pooled using relative risk ratios (RR). MAIN RESULTS: Analysis restricted to eight studies with adequate allocation concealment failed to show benefit of glucosamine for pain and WOMAC function. Collectively, the 20 analyzed RCTs found glucosamine favoured placebo with a 28% (change from baseline) improvement in pain (SMD -0.61, 95% CI -0.95, -0.28) and a 21% (change from baseline) improvement in function using the Lequesne index (SMD -0.51 95% CI -0.96, -0.05). However, the results are not uniformly positive, and the reasons for this remain unexplained. WOMAC pain, function and stiffness outcomes did not reach statistical significance. In the 10 RCTs in which the Rotta preparation of glucosamine was compared to placebo, glucosamine was found to be superior for pain (SMD -1.31, 95% CI -1.99, -0.64) and function using the Lequesne index (SMD -0.51, 95% CI -0.96, -0.05). Pooled results for pain (SMD -0.15, 95% CI -0.35, 0.05) and function using the WOMAC index (SMD 0.03, 95% CI -0.18, 0.25) in those RCTs in which a non-Rotta preparation of glucosamine was compared to placebo did not reach statistical significance. In the four RCTs in which the Rotta preparation of glucosamine was compared to an NSAID, glucosamine was superior in two, and equivalent in two. Two RCTs using the Rotta preparation showed that glucosamine was able to slow radiological progression of OA of the knee over a three year period (SMD 0.24, 95% CI 0.04, 0.43). Glucosamine was as safe as placebo in terms of the number of subjects reporting adverse reactions (RR=0.97, 95% CI, 0.88, 1.08). AUTHORS' CONCLUSIONS: This update includes 20 studies with 2570 patients. Pooled results from studies using a non-Rotta preparation or adequate allocation concealment failed to show benefit in pain and WOMAC function while those studies evaluating the Rotta preparation show that glucosamine was superior to placebo in the treatment of pain and functional impairment resulting from symptomatic OA. WOMAC outcomes of pain, stiffness and function did not show a superiority of glucosamine over placebo for both Rotta and non-Rotta preparations of glucosamine. Glucosamine was as safe as placebo.

Adult↗

PubMed2005

Tumor necrosis factor-alpha polymorphism, bone strength phenotypes, and the risk of fracture in older women.

TNFalpha is a proinflammatory cytokine that promotes osteoclastic bone resorption. We evaluated the association between a G-308A polymorphism (rs1800629) at the TNFA locus and osteoporosis phenotypes in 4306 older women participating in the Study of Osteoporotic Fractures. Femoral neck bone mineral density (BMD) and structural geometry were measured using dual-energy x-ray absorptiometry and hip structural analysis. Incident fractures were confirmed by physician adjudication of radiology reports. Despite similar femoral neck BMD, women with the A/A genotype had greater subperiosteal width (P = 0.01) and endocortical diameter (P = 0.03) than those with the G/G genotype. The net result of these structural differences was that there was a greater distribution of bone mass away from the neutral axis of the femoral neck in women with the A/A genotype, resulting in greater indices of bone bending strength (cross-sectional moment of inertia: P = 0.004; section modulus: P = 0.003). Among 376 incident hip fractures during 12.1 yr of follow-up, a 22% decrease in the risk of hip fracture was seen per copy of the A allele (relative risk 0.78; 95% confidence interval 0.63, 0.96), which was not influenced by adjustments for potential confounding factors, BMD, or bone strength indices. The G-308A polymorphism was not associated with a reduced risk of other fractures. These results suggest a potential role of genetic variation in TNFalpha in the etiology of osteoporosis.

Absorptiometry, Photon↗

PubMed2005

Type I collagen alpha1 Sp1 transcription factor binding site polymorphism is associated with reduced risk of hip osteoarthritis defined by severe joint space narrowing in elderly women.

OBJECTIVE: A common G/T substitution at an Sp1 binding site in intron 1 of the COL1A1 gene has been reported to be associated with reduced bone mineral density and increased risk of osteoporotic fracture. The purpose of this study was to examine whether there is an association between COL1A1 Sp1 polymorphism and radiographic osteoarthritis (OA) of the hip in elderly women in the Study of Osteoporotic Fractures. METHODS: Radiographic hip OA status of subjects was defined by the presence of 1 of the following criteria in either hip: a joint space narrowing (JSN) score of >/=3, a Croft summary grade of >/=3, or both definite (score >/=2) osteophytes and JSN in the same hip. Cases of radiographic OA of the hip were further subdivided into those with JSN score >/=3 and those with a femoral osteophyte score >/=2 and JSN score </=2. The COL1A1 Sp1 polymorphism was genotyped using allele-specific kinetic polymerase chain reaction in 4,746 women. Multivariate logistic regression was performed to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Radiographic OA of the hip was present in 571 women (12%). Of these patients, 325 (57%) had severe JSN (score >/=3), and 131 (23%) had moderate or moderate-to-severe femoral osteophytosis (score >/=2). There was no association of the T/T genotype with either radiographic hip OA or radiographic hip OA characterized by osteophytosis. For radiographic OA of the hip characterized by moderate-to-severe JSN, the odds of disease were significantly reduced among subjects with the T/T compared with the G/G genotype (OR 0.30, 95% CI 0.11-0.81, P = 0.02) and did not change after adjustment for potential confounders (OR 0.36, 95% CI 0.13-0.99, P = 0.048). CONCLUSION: The T/T genotype of the COL1A1 Sp1 polymorphism was associated with a reduced risk of radiographic OA of the hip characterized by JSN. This association should be confirmed in other populations to determine if mechanistic studies are warranted.

Age Factors↗

PubMed2003

Acetaminophen for osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is the most common form of arthritis. Published guidelines and expert opinion are divided over the relative role of acetaminophen (also called paracetamol or Tylenol) and non-steroidal anti-inflammatory drugs (NSAIDs) as first-line pharmacologic therapy. The comparative safety of acetaminophen and NSAIDs is important to consider as NSAIDs have the potential for serious gastrointestinal, renal, and cardiovascular toxicities, and acetaminophen in high dosages (greater than or equal to 2 grams per day), may also have the potential for serious upper gastrointestinal toxicity. OBJECTIVES: To assess the efficacy and safety of acetaminophen versus placebo and versus NSAIDs (ibuprofen, arthrotec, celecoxib,naproxen, rofecoxib) for treating OA. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (Issue 3, 2002), MEDLINE (up to July 2002), and Current Contents (up to March 2002). Reference lists of identified RCTs and pertinent review articles were also hand searched. SELECTION CRITERIA: Published randomized controlled trials (RCTs) evaluating the efficacy and safety of acetaminophen alone in OA were considered for inclusion. DATA COLLECTION AND ANALYSIS: Pain, physical function and global assessment outcomes were reported. Results for continuous outcome measures were expressed as standardized mean differences. Dichotomous outcome measures were pooled using relative risk and the number needed to treat was calculated. MAIN RESULTS: Six RCTs and 1689 participants were included in the review. One study compared acetaminophen to placebo, and five compared acetaminophen to NSAIDs. In the placebo-controlled RCT, acetaminophen was shown to be clearly superior to placebo with a similar safety profile. The number needed to treat to achieve an improvement in pain was three. In the comparator-controlled RCTs, acetaminophen was less effective overall than NSAIDs in terms of pain reduction and global assessments but both drugs had similar efficacy in terms of improvements in functional status. No significant difference was found between the safety of acetaminophen and NSAIDs, although patients taking NSAIDS were more likely to withdraw due to GI events. REVIEWER'S CONCLUSIONS: The evidence to date suggests that NSAIDs are superior to acetaminophen for improving knee and hip pain in people with OA but have not been shown to be superior in improving function. The size of the treatment effect was modest, and the mean trial duration was only six weeks, therefore, additional considerations need to be factored in when making the decision between using acetaminophen or NSAIDs. In OA subjects with moderate-to-severe levels of pain, NSAIDs appear to be more effective than acetaminophen.

Acetaminophen↗

PubMed2003

Comparison of the efficacy of the tumour necrosis factor alpha blocking agents adalimumab, etanercept, and infliximab when added to methotrexate in patients with active rheumatoid arthritis.

OBJECTIVE: To determine, using the method of adjusted indirect comparisons, whether there are differences in efficacy of tumour necrosis factor (TNF alpha) blocking agents, as measured by the rate ratios for American College of Rheumatology (ACR) 20, 50, and 70 responses, in patients with rheumatoid arthritis with an incomplete response to methotrexate. METHODS: A systematic review was performed to identify placebo controlled trials of 24-30 weeks' duration of combination therapy that used a step-up approach with the addition of TNF alpha blocking agents to methotrexate. The method of "adjusted indirect comparisons" was used to compare results across trials to determine the relative risk for an ACR20 or 50 response. RESULTS: Placebo controlled trials for adalimumab, etanercept, and infliximab provided data on ACR20 and 50 responses. Both the similarity of demographic and disease characteristics of patients at entry, and the homogeneity of response rates in the placebo groups across trials, suggested that comparing results across trials was valid. The relative risk for obtaining an ACR20 and 50 response derived from the adjusted indirect comparisons of the TNF alpha blocking agents did not significantly differ from unity. CONCLUSION: The analysis showed that the three currently marketed TNF alpha blocking agents have similarly efficacy when added to methotrexate in the treatment of patients with rheumatoid arthritis with active disease.

Adalimumab↗

PubMed2002

Serum cartilage oligomeric matrix protein and clinical signs and symptoms of potential pre-radiographic hip and knee pathology.

OBJECTIVE: To examine the cross-sectional relationship between serum cartilage oligomeric matrix protein (COMP) and hip and knee clinical signs and symptoms in a sample of adults without radiographic hip or knee osteoarthritis (OA). DESIGN: A total of 145 persons with available sera and no evidence of radiographic hip or knee OA (Kellgren-Lawrence grade 0) were randomly selected from the Caucasian participants of the Johnston County Osteoarthritis Project. COMP was quantified by a competitive ELISA assay with a monoclonal antibody 17-C10. Hip and knee clinical signs and symptoms were assessed by physical examination and interview, and their associations with Ln COMP analysed with general linear models. RESULTS: After adjustment for age, gender, body mass index (BMI), and other symptomatic joints, mean Ln COMP was statistically significantly higher among persons with hip-related clinical signs (P=0.018), among those with hip-related symptoms (P=0.046), and among individuals meeting American College of Rheumatology clinical criteria for hip OA (P=0.021). There were no statistically significant associations between any of the knee-related clinical signs and symptoms and Ln COMP. CONCLUSION: Serum COMP may be useful as a biomarker of pre-radiographic hip joint pathology; its utility as a biomarker of pre-radiographic knee joint pathology is unclear.

Aged↗

PubMed2001

Widespread musculoskeletal pain and the progression of disability in older disabled women.

BACKGROUND: Widespread musculoskeletal pain is a poorly understood but common problem in older adults. Little is known about the progression of disability related to this condition. OBJECTIVE: To determine whether widespread musculoskeletal pain increases the risk for worsening disability in older women with disabilities. DESIGN: Prospective cohort study. SETTING: The Women's Health and Aging Study. PARTICIPANTS: 1002 community-dwelling women 65 years of age or older with disability. MEASUREMENTS: Widespread musculoskeletal pain was defined as pain in the upper and lower extremities and axial pain with moderate or severe pain in at least one of the three regions. Worsening disability was defined as progression from no or mild difficulty to severe difficulty or inability to perform activities of daily living (ADLs), walk one-quarter mile, or lift 10 lbs. RESULTS: At baseline, 24% of participants had widespread pain and 25% had no pain or only mild pain in a single site. Women with widespread pain were 2.5 to 3.5 times more likely to have severe difficulty with ADLs, walking, or lifting at baseline compared with women who had no or mild pain. In women without severe difficulty initially, widespread pain nearly doubled the risk for progression to severe difficulty in each of the tasks, after adjustment for age, body mass index, comorbid illness, and other confounders. CONCLUSION: Widespread musculoskeletal pain is frequent among community-dwelling older women with disability and appears to predict the progression of disability. Efforts to better understand the cause of this pain and its treatment might reduce the overall burden of disability.

Activities of Daily Living↗

PubMed2001

The role of acetaminophen in the management of patients with osteoarthritis.

Both the incidence and prevalence of osteoarthritis increase with advancing age. Management of osteoarthritis in older adults focuses on reducing pain and other symptoms, minimizing functional limitation and disability from the disease, and avoiding the side effects associated with pharmacologic therapy. This article first briefly reviews the clinical pharmacology of acetaminophen and then summarizes the evidence supporting the use of acetaminophen in the management of patients with osteoarthritis. We conclude that acetaminophen, when given at full doses of 4,000 mg/day, is more efficacious than placebo and has comparable efficacy to ibuprofen in the management of patients with osteoarthritis of the knee who have mild to moderate pain. Thus, acetaminophen merits a trial as initial therapy based on its cost-effectiveness and safety profile relative to NSAIDs.

Acetaminophen↗

PubMed2001

Glucosamine therapy for treating osteoarthritis.

Double-Blind Method↗

PubMed2001

What a difference a year makes: reflections on the ACR recommendations for the medical management of osteoarthritis.

Since the publication in 2000 of the updated American College of Rheumatology (ACR) recommendations for the medical management of patients with lower limb osteoarthritis (OA), additional recommendations, newer epidemiologic studies, systematic reviews, and clinical trials have been published. The results of these reviews, studies, and trials, which highlight the greater efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) for controlling pain and the potential serious upper gastrointestinal toxicity of acetaminophen, require us to reassess the use of acetaminophen as the first-line pharmacologic agent for all patients with knee OA. Furthermore, the documented efficacy of glucosamine for pain relief and function improvement in patients with knee OA, with an effect size that is comparable with that of NSAIDs, requires us to reassess the use of glucosamine as a potential first-line agent at least for patients with knee OA who have mild-to-moderate pain. The availability of the cyclo-oxygenase 2 (COX-2)-specific inhibitors and their documented greater safety relative to traditional dual-inhibitor NSAIDs with regard to serious upper gastrointestinal toxicity lead us to reassess the use of traditional NSAIDs in patients with OA, especially in those at increased risk for such adverse events. The COX-2-specific inhibitors cost less than the combination of a generic NSAID plus a proton-pump inhibitor. The results of ongoing and future studies, especially of structure-modifying anti- osteoarthritis drugs, will lead to further reassessment and updating of recommendations for the medical management of patients with knee OA. Hopefully, the use of such recommendations will improve the outcomes for patients with this debilitating chronic condition.

Acetaminophen↗

PubMed2001

Exercise rehabilitation improves functional outcomes and peripheral circulation in patients with intermittent claudication: a randomized controlled trial.

OBJECTIVE: To determine the effects of a 6-month exercise program on ambulatory function, free-living daily physical activity, peripheral circulation, and health-related quality of life (QOL) in disabled older patients with intermittent claudication. DESIGN: Prospective, randomized controlled trial. SETTING: University Medical (Center and Veterans Affairs Medical Center, Baltimore, Maryland. PARTICIPANTS: Thirty-one of 61 patients with Fontaine stage II peripheral arterial occlusive disease (PAOD) were randomized to exercise rehabilitation and 30 to usual-care control. Three patients from the exercise group and six patients from the control group dropped out, leaving 28 and 24 patients, respectively, completing the study in each group. INTERVENTION: Six months of exercise rehabilitation. MEASUREMENTS: Treadmill distance walked to onset of claudication and to maximal claudication, ambulatory function, peripheral circulation, perceived QOL, and daily physical activity. RESULTS: Compliance with the exercise program was 73% of the possible sessions. Exercise rehabilitation increased treadmill distance walked to onset of claudication by 134% (P < .001) and to maximal claudication by 77% (P < .001), walking economy by 12% (P = .003), 6-minute walk distance by 12% (P < .001), and maximal calf blood flow by 30% (P < .001). Changes in distance walked to maximal pain correlated with changes in walking economy (r = -.50, P = .013) and changes in maximal calf blood flow (r = .38, P = .047). Exercise rehabilitation increased accelerometer-derived daily physical activity by 38% (P < .001); this change correlated with the change in distance walked to maximal pain (r = .45, P = .020). These improvements were significantly better than the changes in the control group (P < .05). CONCLUSION: Improvements in claudication following exercise rehabilitation in older PAOD patients are dependent on improvements in peripheral circulation and walking economy. Improvement in treadmill claudication distances in these patients translated into increased accelerometer-derived physical activity in the community, which enabled the patients to become more functionally independent.

Activities of Daily Living↗

PubMed2001

Pharmacological therapy of osteoarthritis.

In 2000, both the American College of Rheumatology (ACR) and the European League of Associations of Rheumatology (EULAR) published recommendations for the use of pharmacological therapy in the treatment of patients with lower limb osteoarthritis. These recommendations are based on the level of evidence observed in systematic reviews and/or meta-analyses of published randomized controlled trials as well as expert opinion. Acetaminophen (paracetamol) is considered as first-line oral therapy for symptomatic lower limb osteoarthritis with mild to moderate pain because it is more efficacious than placebo and is generally considered to be safe and well tolerated. Data obtained in recent trials and the results of a meta-analysis, however, show that acetaminophen is not as efficacious as non-steroidal anti-inflammatory drugs (NSAIDs) for pain at rest and pain on motion. Furthermore, data from a recent epidemiological study suggest that use of high-dose acetaminophen (>2 g/day) may convey the same magnitude of increased risk for serious upper gastrointestinal adverse events as NSAIDs.NSAIDs have demonstrated efficacy superior to placebo in patients with osteoarthritis. The newer cyclo-oxygenase (COX)-2-specific inhibitors (coxibs) have comparable efficacy to traditional dual inhibitor NSAIDs and have demonstrated a better gastrointestinal safety profile. Thus, for patients who have severe pain and/or signs of inflammation or who have failed to respond to acetaminophen, the use of a coxib should be considered, especially if the patient is at increased risk for serious upper gastrointestinal adverse events from a traditional NSAID.Compounds different from pure analgesics and NSAIDs are also used for the management of patients with osteoarthritis. Recent clinical trials have demonstrated statistically significant efficacy of such compounds (e.g. chondroitin sulphate, diacerhein, glucosamine sulphate) with the following characteristics: (1) the effect size seems to be of slightly lower magnitude than that seen for NSAIDs; (2) the onset of action is delayed for approximately 4 to 6 weeks; and (3) the symptomatic effect is maintained after stopping the treatment for periods of 4 to 8 weeks.The methodology for evaluating the possible structure-modifying effect of drugs has dramatically improved during the past decade. Two agents have demonstrated a beneficial structural effect: glucosamine sulphate in osteoarthritis of the knee, and diacerhein in osteoarthritis of the hip. The clinical relevance of such an effect needs to be further evaluated in long-term outcome studies.

Acetaminophen↗

PubMed2001

Serum carotenoids and radiographic knee osteoarthritis: the Johnston County Osteoarthritis Project.

OBJECTIVE: Antioxidant intake has been associated with less progression of radiographic knee osteoarthritis (OA), but studies of carotenoid biomarkers and OA have not been done. We examined associations between serum concentrations of nine naturally occurring carotenoids and radiographic knee OA. DESIGN: The study design was matched case-control. Sera were analysed by high-performance liquid chromatography for nine carotenoids: lutein, zeaxanthin, alpha- and beta-cryptoxanthin, trans- and cis-lycopene, alpha-carotene, and trans- and cis-beta-carotene. Conditional logistic regression was used to estimate the association between tertiles of each carotenoid and radiographic knee OA, independent of body mass index, education, serum cholesterol, and the other carotenoids. SETTING: Johnston County, North Carolina, United States of America. SUBJECTS: Two-hundred cases with radiographic knee OA (Kellgren-Lawrence grades > or = 2) and 200 controls (Kellgren-Lawrence grade = 0) were randomly selected from the Johnston County Osteoarthritis Project, and were matched on age, gender and race. RESULTS: Participants with serum levels of lutein or beta-cryptoxanthin in the highest tertile were approximately 70% less likely to have knee OA than controls (odds ratio (OR) [95% confidence interval (CI)] = 0.28 [0.11, 0.73] and 0.36 [0.14, 0.95], respectively). Those in the highest tertile of trans-beta-carotene (OR = 6.40 [1.86, 22.1]) and zeaxanthin (OR = 3.06 [1.19, 7.85]) were more likely to have knee OA. CONCLUSIONS: While certain carotenoids may protect against knee OA, others may increase the odds of knee OA. Further study of carotenoids and knee OA are warranted before clinical recommendations about these substances and knee OA can be made.

Antioxidants↗

PubMed2001

Weight loss and exercise walking reduce pain and improve physical functioning in overweight postmenopausal women with knee osteoarthritis.

We conducted an uncontrolled pilot study to determine the effects of a weight loss and walking program on knee pain and physical function in overweight and obese (body mass index; BMI [kg/m] 25-29.9 and BMI > or = 30, respectively) postmenopausal women with knee osteoarthritis (OA). Forty-eight such women completed self-report (Western Ontario and McMaster University Osteoarthritis Index (WOMAC)) and performance-based measures of physical function ("up and go" test, 6-min walk) and enrolled in a 6-month intervention that included weekly nutrition classes and an exercise-walking program. The intervention produced an average weight loss of 5.6 +/- 4.0 kg in the 30 women who completed the program. There also were significant improvements in the 6-min walk and on VO(2max). Improvements in the timed up and go test and on the WOMAC pain and function scores, however, were restricted only to women who were classified as obese at baseline. These findings suggest that a 6-month weight loss and walking program improves measures of physical functioning and pain in overweight and obese postmenopausal women with knee OA. Among obese women, functional improvement correlated with weight loss, encouraging continued emphasis on weight loss for managing knee OA.

Journal Article↗

PubMed2001

"Stepping-up" from methotrexate: a systematic review of randomised placebo controlled trials in patients with rheumatoid arthritis with an incomplete response to methotrexate.

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Antibodies, Monoclonal↗