OARSI recommendations for the management of hip and knee osteoarthritis, part I: critical appraisal of existing treatment guidelines and systematic review of current research evidence.

PURPOSE: As a prelude to developing updated, evidence-based, international consensus recommendations for the management of hip and knee osteoarthritis (OA), the Osteoarthritis Research Society International (OARSI) Treatment Guidelines Committee undertook a critical appraisal of published guidelines and a systematic review (SR) of more recent evidence for relevant therapies. METHODS: Sixteen experts from four medical disciplines (primary care two, rheumatology 11, orthopaedics one and evidence-based medicine two), two continents and six countries (USA, UK, France, Netherlands, Sweden and Canada) formed the guidelines development team. Three additional experts were invited to take part in the critical appraisal of existing guidelines in languages other than English. MEDLINE, EMBASE, Science Citation Index, CINAHL, AMED, Cochrane Library, seven Guidelines Websites and Google were searched systematically to identify guidelines for the management of hip and/or knee OA. Guidelines which met the inclusion/exclusion criteria were assigned to four groups of four appraisers. The quality of the guidelines was assessed using the AGREE (Appraisal of Guidelines for Research and Evaluation) instrument and standardised percent scores (0-100%) for scope, stakeholder involvement, rigour, clarity, applicability and editorial independence, as well as overall quality, were calculated. Treatment modalities addressed and recommended by the guidelines were summarised. Agreement (%) was estimated and the best level of evidence to support each recommendation was extracted. Evidence for each treatment modality was updated from the date of the last SR in January 2002 to January 2006. The quality of evidence was evaluated using the Oxman and Guyatt, and Jadad scales for SRs and randomised controlled trials (RCTs), respectively. Where possible, effect size (ES), number needed to treat, relative risk (RR) or odds ratio and cost per quality-adjusted life year gained (QALY) were estimated. RESULTS: Twenty-three of 1462 guidelines or consensus statements retrieved from the literature search met the inclusion/exclusion criteria. Six were predominantly based on expert opinion, five were primarily evidence based and 12 were based on both. Overall quality scores were 28%, 41% and 51% for opinion-based, evidence-based and hybrid guidelines, respectively (P=0.001). Scores for aspects of quality varied from 18% for applicability to 67% for scope. Thirteen guidelines had been developed for specific care settings including five for primary care (e.g., Prodigy Guidance), three for rheumatology (e.g., European League against Rheumatism recommendations), three for physiotherapy (e.g., Dutch clinical practice guidelines for physical therapy) and two for orthopaedics (e.g., National Institutes of Health consensus guidelines), whereas 10 did not specify the target users (e.g., Ontario guidelines for optimal therapy). Whilst 14 guidelines did not separate hip and knee, eight were specific for knee but only one for hip. Fifty-one different treatment modalities were addressed by these guidelines, but only 20 were universally recommended. Evidence to support these modalities ranged from Ia (meta-analysis/SR of RCTs) to IV (expert opinion). The efficacy of some modalities of therapy was confirmed by the results of RCTs published between January 2002 and 2006. These included exercise (strengthening ES 0.32, 95% confidence interval (CI) 0.23, 0.42, aerobic ES 0.52, 95% CI 0.34, 0.70 and water-based ES 0.25, 95% CI 0.02, 0.47) and nonsteroidal anti-inflammatory drugs (NSAIDs) (ES 0.32, 95% CI 0.24, 0.39). Examples of other treatment modalities where recent trials failed to confirm efficacy included ultrasound (ES 0.06, 95% CI -0.39, 0.52), massage (ES 0.10, 95% CI -0.23, 0.43) and heat/ice therapy (ES 0.69, 95% CI -0.07, 1.45). The updated evidence on adverse effects also varied from treatment to treatment. For example, while the evidence for gastrointestinal (GI) toxicity of non-selective NSAIDs (RR=5.36, 95% CI 1.79, 16.10) and for increased risk of myocardial infarction associated with rofecoxib (RR=2.24, 95% CI 1.24, 4.02) were reinforced, evidence for other potential drug related adverse events such as GI toxicity with acetaminophen or myocardial infarction with celecoxib remained inconclusive. CONCLUSION: Twenty-three guidelines have been developed for the treatment of hip and/or knee OA, based on opinion alone, research evidence or both. Twenty of 51 modalities of therapy are universally recommended by these guidelines. Although this suggests that a core set of recommendations for treatment exists, critical appraisal shows that the overall quality of existing guidelines is sub-optimal, and consensus recommendations are not always supported by the best available evidence. Guidelines of optimal quality are most likely to be achieved by combining research evidence with expert consensus and by paying due attention to issues such as editorial independence, stakeholder involvement and applicability. This review of existing guidelines provides support for the development of new guidelines cognisant of the limitations in existing guidelines. Recommendations should be revised regularly following SR of new research evidence as this becomes available.

[Atherosclerosis and rheumatoid arthritis]. / Athérome et polyarthrite rhumatoïde.

AIMS: To identify studies which have shown that rheumatoid arthritis (RA) is associated with an increase in cardiovascular morbidity and mortality. To identify the different factors that may be involved. To consider what management would decrease the cardiovascular morbidity and mortality of RA. RESULTS: Epidemiological studies have shown that the risk of a cardiovascular event is increased twofold in RA patients irrespective of the traditional cardiovascular risk factors. Non-invasive methods have shown that RA patients have endothelial dysfunction, decreased arterial compliance and increased intima-media thickers, predictive factors for cardiovascular events in comparison to controls after controlling for traditional cardiovascular risk factors. The increased cardiovascular risk is directly mediated by inflammatory syndrome, which also indirectly increases the risk by inducing dyslipidemia and insulin resistance. Treatments also have a hamful effect, whether it be corticosteroid therapy, non-steroidal anti-inflammatory drugs (NSAIDs), or methotrexate (MTX), which leads to hyperhromocysteinemia. CONCLUSION: It should be possible to decrease cardiovascular morbidity and mortality by a strict control of the disease's activity. We should also take measures to combat other cardiovascular risk factors: as low a dose as possible for corticosteroid therapy, limited prescription of NSAIDs, systematic supplementation of MTX with folic acid encouragement of smoking cessation, regular lipid tests and prescription of statins treatment for hyperlipemia in accordance with current recommendations.

Increase in bone mineral density of patients with spondyloarthropathy treated with anti-tumour necrosis factor alpha.

OBJECTIVE: To determine the changes in bone mineral density (BMD) in patients with spondyloarthropathy (SpA) treated with infliximab. PATIENTS AND METHODS: 29 patients (six women; 23 men) aged 22-68 years, with persistently active SpA despite a high dose of non-steroidal anti-inflammatory drug and/or treatment with methotrexate or sulfasalazine, were studied. Median duration of disease was 13 years (range 3-30). Twenty five patients were treated with 5 mg/kg and four with 3 mg/kg of infliximab at weeks 0, 2, 6 and then received either no infusion (n=3), or additional infusion of infliximab every other month (n=6), and the remainder received one infusion only in the case of a relapse. Lumbar and femoral BMD was measured by dual energy x ray absorptiometry at baseline and six months later. Serum osteocalcin and urinary deoxypyridinoline were measured in 19 patients at weeks 0, 2, 24, and in 13 patients at all visits. RESULTS: In six months there was a significant increase in BMD at the spine (3.6%, p=0.001), total hip (2.2%, p=0.0012), and trochanter (2.3%, p=0.0012). A trend for increase (1.1%) was observed at the femoral neck. There was an increase in osteocalcin between baseline and week 6 (third infusion)-median 1.45 micro g/l (p=0.013). No change in marker of bone resorption was observed at the same time. There was no change in biochemical markers between baseline and final visits. There was a trend for a correlation between the decrease at six months in erythrocyte sedimentation rate, and lumbar spine BMD change (r(s)=-0.35, p=0.06). CONCLUSION: These data suggest that a benefit of anti-tumour necrosis factor alpha therapy on BMD in patients with SpA may be through an uncoupling effect on bone cells.

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.

[1,25-(OH)2-D3 treatment of hypophosphoremic osteomalacia associated with villonodular synovitis]. / Traitement par le 1,25 (OH)2 D3 d'une ostéomalacie hypophosphorémique associée à une synovite villonodulaire.

The authors report a case of hypophosphoremic osteomalacia due to a soft tissue tumor. This case confirm 1,25 (OH)2 cholecalciferol deficiency. Treatment with phosphorus and 1,25 (OH)2 cholecalciferol cured osteomalacia. Accountable tumor (villonodular synovitis) had never been described previously.