Objective The objective of this study was to investigate whether diacerein has comparable efficacy with celecoxib in pain reduction for treatment in symptomatic knee OA patients. Methods This randomized double-blind multicentre non-inferiority trial evaluated diacerein vs celecoxib treatment in patients with Kellgren–Lawrence grade 2–3 and pain scoring ≥4 (10-cm VAS). Patients were randomized to 6 months of treatment with diacerein 50 mg (n = 187) once daily for 1 month and twice daily thereafter, or celecoxib 200 mg (n = 193) once daily. The primary outcome was the change in WOMAC pain score (0–50 cm) at 6 months, and the secondary outcomes were WOMAC sub-scores, VAS pain score, and the OMERACT–OARSI responder rate. Results In the per protocol population, the adjusted mean change from baseline in the WOMAC pain score was –11.1 ( 0.9) with diacerein (n = 140) and –11.8 (0.9) with celecoxib (n = 148). The intergroup difference was 0.7 (95% CI: −1.8, 3.2; P = 0.597), meeting the non-inferiority margin. Supportive analysis of the intention-to-treat population gave similar results. Other outcomes showed no significant difference between treatment groups. The incidence of treatment-related adverse events was low and balanced between groups, but a greater incidence of diarrhoea occurred with diacerein (10.2% vs 3.7%). Diarrhoea was considered mild-to-moderate in all but one case with complete resolution. Conclusions Diacerein was non-inferior to celecoxib in reducing knee OA pain and improving physical function. Diacerein also demonstrated a good safety profile. Trial registration A multicentre study on the effect of DIacerein on Structure and Symptoms vs Celecoxib in Osteoarthritis is a National Institutes of Health (NCT02688400) and European Clinical Trial Database (2015–002933-23) registered phase III (Canada) or IV (Europe) study.
Objectives: The aim of this study was to investigate changes over time in osteoarthritis risk factors most closely associated with the occurrence of total knee arthroplasty (TKA). We hypothesize that the robustness of a longitudinal case–control study will provide new information on the association between changes in various clinical and structural parameters in different time frames before TKA. Methods: Cases (195; TKA after cohort entry) and controls (468) matched for age, gender, income, WOMAC pain, Kellgren–Lawrence grade and follow-up duration were from the Osteoarthritis Initiative cohort. Associations between changes in sociodemographic, clinical, imaging and osteoarthritis therapies with the occurrence of TKA were performed using conditional logistic regression analyses. Results: Worsening of WOMAC scores (cOR 1.02–1.20, p ⩽ 0.012), KOOS (1.02–1.04, p ⩽ 0.014), knee injuries sustained in the previous 30–40 years (women 2.70, p = 0.034) and valgus alignment (1.10, p = 0.052) were associated with the occurrence of TKA. Also associated with TKA was cartilage volume loss in the lateral (overall 1.76, p = 0.025; women 1.93, p = 0.047) and medial compartments (⩾10%, overall 1.54, p = 0.027; men 2.34, p = 0.008), occurrence of medial meniscal extrusion (overall 1.77, p = 0.046; men 2.86, p = 0.028), and increase in bone marrow lesions (BMLs) for women (1.09, p = 0.048). The association of risk factors with TKA was reinforced when both an increase in WOMAC pain and cartilage volume loss (1.85, p = 0.001) were combined. Pain medication usage, mainly narcotics and intra-articular steroid injections (IASI), was also associated with TKA, with no impact on changes in cartilage loss or structure. Conclusion: This study provides new information about gender differences in risk factors associated with the occurrence of TKA. Worsening of valgus alignment, cartilage volume loss in the lateral compartment, BMLs and older injuries are important risk factors in women, while medial compartment cartilage loss and meniscal extrusion are in men. The use of pain medication and IASI although associated was found not causal with TKA.
The hallmark of osteoarthritis (OA), the most prevalent musculoskeletal disease, is the loss of cartilage. By using machine learning (ML), we aimed to assess if baseline knee bone curvature (BC) could predict cartilage volume loss (CVL) at one year, and to develop a gender-based model. BC and cartilage volume were assessed on 1246 participants using magnetic resonance imaging. Variables included age, body mass index, and baseline values of eight BC regions. The outcome consisted of CVL at one year in 12 regions. Five ML methods were evaluated. Validation demonstrated very good accuracy for both genders (R ≥ 0.78), except the medial tibial plateau for the woman. In conclusion, we demonstrated, for the first time, that knee CVL at one year could be predicted using five baseline BC region values. This would benefit patients at risk of structural progressive knee OA.
Elite athletes are at greater risk of joint injuries linked to the subsequent risk of developing osteoarthritis (OA). Genetic factors such as mitochondrial (mt) DNA haplogroups have been associated with the incidence/progression of OA and athletic performance. This review highlights an area not yet addressed: is there a common pattern in the mtDNA haplogroups for OA occurrence in individuals and elite athletes of populations of the same descent? Haplotypes J and T confer a decreased risk of OA in Caucasian/European descent, while H and U increase this risk. Both J and T haplogroups are under-represented in Caucasian/European individuals and endurance athletes with OA, but power athletes showed a greater percentage of the J haplogroup. Caucasian/European endurance athletes had a higher percentage of haplogroup H, which is associated with increased athletic performance. In a Chinese population, haplogroup G appears to increase OA susceptibility and is over-represented in Japanese endurance athletes. In contrast, in Koreans, haplogroup B had a higher frequency of individuals with OA but was under-represented in the endurance athlete population. For Caucasian endurance athletes, it would be interesting to evaluate if those carrying haplotype H would be at an increased risk of accelerated OA, as well as the haplogroup G in Chinese and Japanese endurance athletes. The reverse might be studied for the Korean descent for haplogroup B. Knowledge of such genetic data could be used as a preliminary diagnosis to identify individuals at high risk of OA, adding prognostic information and assisting in personalising the early management of both populations.
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