Objective: To examine the placebo effect and its potential determinants in the treatment of osteoarthritis (OA) via a systematic literature search of Medline, EMBASE, Scientific Citation Index, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Cochrane Library Methods: Randomised placebo controlled trials in OA were included The placebo effect was defined as the overall change from baseline in the placebo group It was estimated as the effect size (ES; the standard mean difference between baseline and endpoint) and this was compared with the ES obtained from untreated control ES for pain was the primary outcome Statistical pooling was undertaken as appropriate and 95% CIs were used for comparison Quality of trials was assessed and potential determinants of placebo effect were examined using multiple regression analysis The partial regression coefficient (β) was used to present the adjusted size of the association Results: We identified 198 trials with 193 placebo groups (16 364 patients) and 14 untreated control groups (1167 patients) that met our inclusion criteria These included a range of therapies (non-pharmacological, pharmacological and surgical treatments) Placebo was effective at relieving pain (ES 051, 95% CI 046 to 055 for the placebo group and 003, 95% CI –013 to 018 for untreated control) Placebo was also effective at improving function and stiffness The pain-relieving effect increased when the active treatment effect (β = 038, p Conclusion: Placebo is effective in the treatment of OA, especially for pain, stiffness and self-reported function The size of this effect is influenced by the strength of the active treatment, the baseline disease severity, the route of delivery and the sample size of the study

https://ard.bmj.com/content/annrheumdis/early/2008/06/09/ard.2008.092015.full.pdf

The placebo effect and its determinants in osteoarthritis – meta-analysis of randomised controlled trials

Objective To determine the effect of glucosamine, chondroitin, or the two in combination on joint pain and on radiological progression of disease in osteoarthritis of the hip or knee. Design Network meta-analysis. Direct comparisons within trials were combined with indirect evidence from other trials by using a Bayesian model that allowed the synthesis of multiple time points. Main outcome measure Pain intensity. Secondary outcome was change in minimal width of joint space. The minimal clinically important difference between preparations and placebo was prespecified at −0.9 cm on a 10 cm visual analogue scale. Data sources Electronic databases and conference proceedings from inception to June 2009, expert contact, relevant websites. Eligibility criteria for selecting studies Large scale randomised controlled trials in more than 200 patients with osteoarthritis of the knee or hip that compared glucosamine, chondroitin, or their combination with placebo or head to head. Results 10 trials in 3803 patients were included. On a 10 cm visual analogue scale the overall difference in pain intensity compared with placebo was −0.4 cm (95% credible interval −0.7 to −0.1 cm) for glucosamine, −0.3 cm (−0.7 to 0.0 cm) for chondroitin, and −0.5 cm (−0.9 to 0.0 cm) for the combination. For none of the estimates did the 95% credible intervals cross the boundary of the minimal clinically important difference. Industry independent trials showed smaller effects than commercially funded trials (P=0.02 for interaction). The differences in changes in minimal width of joint space were all minute, with 95% credible intervals overlapping zero. Conclusions Compared with placebo, glucosamine, chondroitin, and their combination do not reduce joint pain or have an impact on narrowing of joint space. Health authorities and health insurers should not cover the costs of these preparations, and new prescriptions to patients who have not received treatment should be discouraged.

https://www.bmj.com/content/bmj/341/bmj.c4675.full.pdf

Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis

Many physicians use oral chondroitin, a highly hydrophilic, gel-forming polysaccharide macromolecule, to treat osteoarthritis. Meta-analyses of clinical trials have described moderate to large bene...

/pdf/meta-analysis-chondroitin-for-osteoarthritis-of-the-knee-or-wt2kzcwja5.pdf

Meta-analysis: Chondroitin for Osteoarthritis of the Knee or Hip

Background Strontium ranelate is currently used for osteoporosis. The international, double-blind, randomised, placebo-controlled Strontium ranelate Efficacy in Knee OsteoarthrItis triAl evaluated its effect on radiological progression of knee osteoarthritis. Methods Patients with knee osteoarthritis (Kellgren and Lawrence grade 2 or 3, and joint space width (JSW) 2.5–5 mm) were randomly allocated to strontium ranelate 1 g/day (n=558), 2 g/day (n=566) or placebo (n=559). The primary endpoint was radiographical change in JSW (medial tibiofemoral compartment) over 3 years versus placebo. Secondary endpoints included radiological progression, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and knee pain. The trial is registered (ISRCTN41323372). Results The intention-to-treat population included 1371 patients. Treatment with strontium ranelate was associated with smaller degradations in JSW than placebo (1 g/day: −0.23 (SD 0.56) mm; 2 g/day: −0.27 (SD 0.63) mm; placebo: −0.37 (SD 0.59) mm); treatment-placebo differences were 0.14 (SE 0.04), 95% CI 0.05 to 0.23, p Conclusions Treatment with strontium ranelate 1 and 2 g/day is associated with a significant effect on structure in patients with knee osteoarthritis, and a beneficial effect on symptoms for strontium ranelate 2 g/day.

/pdf/efficacy-and-safety-of-strontium-ranelate-in-the-treatment-10mxx2vsw5.pdf

Efficacy and safety of strontium ranelate in the treatment of knee osteoarthritis: results of a double-blind, randomised placebo-controlled trial

Objective
Osteoarthritis (OA) of the knee causes significant morbidity and current medical treatment is limited to symptom relief, while therapies able to slow structural damage remain elusive. This study was undertaken to evaluate the effect of glucosamine and chondroitin sulfate (CS), alone or in combination, as well as celecoxib and placebo on progressive loss of joint space width (JSW) in patients with knee OA.

Methods
A 24-month, double-blind, placebo-controlled study, conducted at 9 sites in the United States as part of the Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT), enrolled 572 patients with knee OA who satisfied radiographic criteria (Kellgren/Lawrence [K/L] grade 2 or grade 3 changes and JSW of at least 2 mm at baseline). Patients with primarily lateral compartment narrowing at any time point were excluded. Patients who had been randomized to 1 of the 5 groups in the GAIT continued to receive glucosamine 500 mg 3 times daily, CS 400 mg 3 times daily, the combination of glucosamine and CS, celecoxib 200 mg daily, or placebo over 24 months. The minimum medial tibiofemoral JSW was measured at baseline, 12 months, and 24 months. The primary outcome measure was the mean change in JSW from baseline.

Results
The mean JSW loss at 2 years in knees with OA in the placebo group, adjusted for design and clinical factors, was 0.166 mm. No statistically significant difference in mean JSW loss was observed in any treatment group compared with the placebo group. Treatment effects on K/L grade 2 knees, but not on K/L grade 3 knees, showed a trend toward improvement relative to the placebo group. The power of the study was diminished by the limited sample size, variance of JSW measurement, and a smaller than expected loss in JSW.

Conclusion
At 2 years, no treatment achieved a predefined threshold of clinically important difference in JSW loss as compared with placebo. However, knees with K/L grade 2 radiographic OA appeared to have the greatest potential for modification by these treatments.

/pdf/the-effect-of-glucosamine-and-or-chondroitin-sulfate-on-the-5gqg5890xk.pdf

The effect of glucosamine and/or chondroitin sulfate on the progression of knee osteoarthritis: A report from the glucosamine/chondroitin arthritis intervention trial

Objective

To determine whether chondroitin sulfate (CS) is effective in inhibiting cartilage loss in knee osteoarthritis (OA).



Methods

In this randomized, double-blind, placebo-controlled trial, 300 patients with knee OA were recruited from an outpatient clinic, from private practices, and through advertisements. Study patients were randomly assigned to receive either 800 mg CS or placebo once daily for 2 years. The primary outcome was joint space loss over 2 years as assessed by a posteroanterior radiograph of the knee in flexion; secondary outcomes included pain and function.



Results

Of 341 patients screened, 300 entered the study and were included in the intent-to-treat analysis. The 150 patients receiving placebo had progressive joint space narrowing, with a mean ± SD joint space loss of 0.14 ± 0.61 mm after 2 years (P = 0.001 compared with baseline). In contrast, there was no change in mean joint space width for the 150 patients receiving CS (0.00 ± 0.53 mm; P not significant compared with baseline). Similar results were found for minimum joint space narrowing. The differences in loss of joint space between the two groups were significant for mean joint space width (0.14 ± 0.57 mm; P = 0.04) and for minimum joint space width (0.12 ± 0.52 mm; P = 0.05). CS was well tolerated, with no significant differences in rates of adverse events between the two groups.



Conclusion

While there was no significant symptomatic effect in this study, long-term treatment with CS may retard radiographic progression in patients with OA of the knee. However, the clinical relevance of the observed structural results has to be further evaluated, and further studies are needed to confirm the structural effects of CS.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.20867

Chondroitins 4 and 6 sulfate in osteoarthritis of the knee: A randomized, controlled trial

Background. The early detection of rheumatic diseases and the treatment to target have become of utmost importance to control the disease and improve its prognosis. However, establishing a diagnosis in early stages is challenging as many diseases initially present with similar symptoms and signs. Expert systems are computer programs designed to support the human decision making and have been developed in almost every field of medicine. Methods. This review focuses on the developments in the field of rheumatology to give a comprehensive insight. Medline, Embase, and Cochrane Library were searched. Results. Reports of 25 expert systems with different design and field of application were found. The performance of 19 of the identified expert systems was evaluated. The proportion of correctly diagnosed cases was between 43.1 and 99.9%. Sensitivity and specificity ranged from 62 to 100 and 88 to 98%, respectively. Conclusions. Promising diagnostic expert systems with moderate to excellent performance were identified. The validation process was in general underappreciated. None of the systems, however, seemed to have succeeded in daily practice. This review identifies optimal characteristics to increase the survival rate of expert systems and may serve as valuable information for future developments in the field.

/pdf/computer-based-diagnostic-expert-systems-in-rheumatology-1xpvn7luuj.pdf

Computer-Based Diagnostic Expert Systems in Rheumatology: Where Do We Stand in 2014?

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.10579

Pius Bruehlmann

Papers

Chondroitins 4 and 6 sulfate in osteoarthritis of the knee: A randomized, controlled trial

Computer-Based Diagnostic Expert Systems in Rheumatology: Where Do We Stand in 2014?

Osteoid osteoma of the capitate