A bi-directional Mendelian randomization study of the sarcopenia-related traits and osteoporosis

Both sarcopenia and osteoporosis are common geriatric diseases causing huge socioeconomic burdens, and clinically, they often occur simultaneously. Observational studies have found a controversial correlation between sarcopenia and osteoporosis and their causal relationship is not clear. Therefore, we performed a bi-directional two-sample Mendelian randomization (MR) analysis to assess the potential causal relationship between sarcopenia-related traits (hand grip strength, lean mass, walking pace) and osteoporosis. Our analysis was performed by applying genetic variants obtained from the UK Biobank and the GEnetic Factors for OSteoporosis (GEFOS) datasets. We used inverse-variance weighted (IVW) and several sensitivity analyses to estimate and cross-validate the potential causal relationship in this study. We found that bone mineral density (BMD) was causally positively associated with left-hand grip strength (β = 0.017, p-value = 0.001), fat-free mass (FFM; right leg FFM, β = 0.014, p-value = 0.003; left arm FFM, β = 0.014, p-value = 0.005), but not walking pace. Higher hand grip strength was potentially causally associated with increased LS-BMD (right-hand grip strength, β = 0.318, p-value = 0.001; left-hand grip strength, β = 0.358, p-value = 3.97 × 10–4). In conclusion, osteoporosis may be a risk factor for sarcopenia-related traits and muscle strength may have a site-specific effect on BMD.