Background: It remains unclear whether an increased risk of type 2 diabetes (T2D) affects the risk of osteoarthritis (OA). Methods: Here, we used two-sample Mendelian randomization (MR) to obtain non-confounded estimates of the effect of T2D and glycemic traits on hip and knee OA. We identi ed single nucleotide polymorphisms (SNPs) strongly associated with T2D, fasting glucose (FG) and 2-hour postprandial glucose (2hGlu) from genome-wide association studies (GWAS). We used MR inverse variance weighted (IVW), the MR-Egger method, the weighted median (WM) and Robust Adjusted Pro le Score (MR.RAPS) to reveal the associations of T2D, FG and 2hGlu with hip and knee OA risk. Sensitivity analyses were also conducted to verify whether heterogeneity and pleiotropy can bias the MR results. Results: We did not nd statistically signi cant causal effects of genetically increased T2D risk, FG and 2hGlu on hip and knee OA (e.g., T2D and hip OA, MR-Egger OR=0.9536, 95% CI 0.5585 to 1.6283, p=0.8629). It was con rmed that horizontal pleiotropy was unlikely to bias the causality (e.g., T2D and hip OA, MR-Egger, intercept=-0.0032, p=0.8518). No evidence of heterogeneity was found between the genetic variants (e.g., T2D and hip OA, MR-Egger Q=40.5481, I 2 =0.1368, p=0.2389). Conclusions: Our MR study did not support causal effects of a genetically increased T2D risk, FG and 2hGlu on hip and knee OA risk.

Over 2 years, cartilage defects tend to progress in people with symptomatic OA, with only a small percentage decreasing in severity. Increasing age and increased bone area are risk factors for progression. Interventions aimed at preventing cartilage defects from occurring and reducing their severity may result in a reduction in the severity of OA, by reducing loss of articular cartilage and subsequent requirement for knee joint replacement.

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Introduction Total joint replacement is considered a surrogate measure for symptomatic end-stage osteoarthritis. It is unknown whether the adipose mass and the distribution of adipose mass are associated with the risk of primary knee and hip replacement for osteoarthritis. The aim of the present investigation was to examine this in a cohort study.

Objective. It is unclear whether physical activity that is beneficial for the cardiovascular system is detrimental to knee structures. We examined the association between intensity, frequency, and duration of physical activity and knee structures in a community-based population. Methods. A total of 297 healthy adults ages 50 -79 years with no history of knee injury or disease were recruited from an existing study on healthy aging. Each subject underwent knee magnetic resonance imaging (MRI) to measure tibial cartilage volume, tibiofemoral cartilage defects, and bone marrow lesions. Physical activity and anthropometric data were obtained via questionnaire during 1990 -1994 and 2003-2004. Results. Tibial cartilage volume increased with frequency (P ‫؍‬ 0.01) and duration (P ‫؍‬ 0.001) of vigorous activity (activity leading to diaphoresis or dyspnea) reported 10 years previously, as well as recent vigorous activity in the 7 days prior to MRI (P ‫؍‬ 0.05). Recent weight-bearing vigorous activity increased with tibial cartilage volume (P ‫؍‬ 0.02) and was inversely associated with cartilage defects (P ‫؍‬ 0.02). A reduced risk of bone marrow lesions was associated with regular walking (P ‫؍‬ 0.04). Conclusion.Vigorous physical activity appears to have a beneficial effect on knee articular cartilage in healthy, community-based adults with no history of knee injury or disease. Regular walking reduces the risk of bone marrow lesions in the knee. This study provides further support for a beneficial effect of physical activity for diseases associated with aging and suggests that exercise that is good for the heart is also good for the knees.

The female predisposition toward knee OA may, at least in part, be due to gender differences in cartilage health, even before the onset of clinical knee disease. Understanding the mechanism for these gender differences may provide a means to reduce the risk of knee OA in women.

Background: Although obesity is widely accepted as a risk factor for knee osteoarthritis, whether weight per se or the specific components of body composition are the major determinants of properties of articular knee cartilage is unclear. Objective: To examine associations between anthropometric and body composition measures and knee cartilage properties in healthy adults. Methods: 297 healthy adults with no clinical knee osteoarthritis were recruited from an existing communitybased cohort. Anthropometric measures and body composition, including fat-free mass and fat mass assessed using bioelectrical impedance analysis, were measured at baseline (1990-4) and current follow-up (2003-4). Tibial cartilage volume and tibiofemoral cartilage defects were assessed using MRI at follow-up. Results: After adjustment for potential confounders, baseline and current fat-free mass, independent of fat mass, were positively associated with tibial cartilage volume (all p,0.001). Increased fat-free mass over the time period was positively associated with tibial cartilage volume (p,0.001). Current fat mass was negatively associated with tibial cartilage volume (p = 0.004). Baseline and current fat mass were weakly associated with increased tibiofemoral cartilage defects (p = 0.06 and p = 0.07, respectively), independent of fat-free mass. Conclusion: The findings suggest a beneficial effect of fat-free mass, but a deleterious effect of fat mass, on knee cartilage properties in healthy adults. This suggests that weight-loss programmes aimed at reducing fat mass but maintaining muscle mass may be important in preventing the onset and/or progression of knee osteoarthritis.

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