Osteoarthritis is a leading cause of disability with no cure. The incidence of osteoarthritis is sexually dimorphic: women have a higher rate of osteoarthritis than men after the age of 50. Research has investigated the contribution of sex hormones, reproductive factors and hormone supplementation to osteoarthritis. It has been recognized that different joints are susceptible to different risk factors for osteoarthritis. We reviewed the evidence for the effect of endogenous sex hormones, reproductive factors and hormone supplementation on joint-specific osteoarthritis of the knee, hip and hand. Although the role of these hormonal factors in the pathogenesis of osteoarthritis is complex, data suggest that endogenous hormones and reproductive factors have a role in the pathogenesis of osteoarthritis, especially knee osteoarthritis, with uncertainty for the effect of exogenous hormones. From the available data, it is hard to conclude whether this is a direct effect of hormonal factors, or whether other factors related to these hormonal factors, i.e. obesity and inflammation, have a role in this association. Further studies should consider the mediation effect of body weight and inflammation, change in body weight throughout life, circulatory levels of all endogenous hormones and circulatory levels of hormones after hormone supplementation in this complex relationship.

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BackgroundNo disease-modifying drugs are currently available for the treatment of osteoarthritis (OA). Bone marrow lesions (BMLs) visualised on magnetic resonance imaging (MRI) have been identified as a promising therapeutic target. Our pilot study showed that a single infusion of zoledronic acid (ZA) reduced knee pain and BML size in knee OA patients over 6 months.1 A longer, larger study was required to assess whether these improvements can be reproduced in a larger multicentre design.ObjectivesTo compare the effect of once-yearly intravenous infusion of ZA to placebo on knee pain and BML size over 24 months in knee OA patients with significant knee pain and BMLs.MethodsThe Zoledronic Acid for Osteoarthritis Knee Pain (ZAP2) study is a multicentre, randomised, double-blinded, placebo-controlled trial over 24 months. Patients≥50 years who had significant knee pain (defined as a visual analogue scale (VAS)≥40 mm) and MRI-detected knee BML were randomised to receive either ZA (5 mg in 100 ml saline) or placebo (100 ml saline) once-yearly. Those with severe knee OA (joint space narrowing (JSN) on X-ray of Grade 3 using the Osteoarthritis Research Society International (OARSI) atlas) were excluded. Outcomes included knee pain and function by the Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC), knee pain by VAS and change in knee total BML size (sum of medial femoral, lateral femoral, medial tibial, lateral tibial and patellar sites) by proton density weighted MRI from baseline to 24 months. Effect modification of the absence or presence of radiographic OA (JSN grade 0 or grade 1–2) was pre-specified. Mixed effect modelling using an intent-to-treat design was performed for data analyses. Adjustment for baseline values were performed for knee pain and function outcomes due to baseline imbalances.Results223 patients (mean ±SD age 62.0±8.0 years, 117 females) were enrolled. At baseline, mean ±SD knee WOMAC pain (0–500), WOMAC function (0–1700) and VAS pain scores (0–100) were 200.0±105.0, 656.9±352.9 and 51.0±20.5, and median BML size was 489.6 mm2. After 24 months, there was no significant difference in changes in knee pain (WOMAC pain: −37.5 vs −58.0, p=0.205; VAS pain: −11.5 vs −16.8, p=0.17) or function scores (−134.9 vs −159.2, p=0.65), or knee BML size (−33.5 mm2 vs −11.7 mm2, p=0.68) between the ZA group and the placebo group. Pre-specified analyses consistently showed that ZA was more effective than placebo in patients without radiographic OA (JSN Grade 0) on changes in WOMAC pain (−88.3 vs −42.6, p=0.21), VAS pain (−21.8 to −8.3, p=0.11), WOMAC function (−296.9 vs −78.5, p=0.06) and BML size (−67.4 vs 98.2, p=0.14). Adverse events were more frequent in the ZA group, primarily flu-like symptoms and musculoskeletal pain and stiffness.ConclusionsOnce-yearly infusion of ZA did not significantly reduce knee pain or BML size overall in knee OA patients over 24 months but may have symptomatic benefit in milder disease.Reference[1] Laslett LL, et al. Ann Rheum Dis2012;71:1322–8.Disclosure of Inte...

The findings indicated that paternal psychopathology and family functioning should not be overlooked in child behaviour development. In addition, this study underscored the importance to investigate the different impact of father and mother on child development within a dyadic unit.

Conclusions:Patients who had an APM had a higher rate of JSN than matched controls with or without a meniscus tear who were treated non-surgically, and the rate of JSN was higher in the first 12 months after surgery. This suggests that APM results in a temporary increase in the rate of radiographic narrowing compared to non-surgical management of meniscus tear with OA. The precise timing of joint space loss following APM is still unclear, as the first postoperative radiograph occurred at varying times during the first year. Multiple factors may contribute to joint space narrowing following APM including loss of interposed meniscus, increased contact stress in the knee, or inflammation induced by surgery. Further study of the relationship between APM and joint space narrowing is merited, including whether this increased narrowing is associated with worsening symptoms or increased progression to total knee replacement.

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