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.Bone and muscle are interacting tissues,and clinically,sarcopenia and osteoporosis often appear at the same time.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 GWAS and the GEnetic Factors for OSteoporosis(GEFOS)datasets.We used various methods including inverse-variance weighted(IVW),MR-Egger,weighted median,Robust Adjusted Profile Score(RAPS),and Mendelian Randomization Pleiotropy RESidual Sum and Outlier(MR-PRESSO)to estimate and cross-validate the potential causal relationship in this study.We found that BMD was positively and potentially causally associated with hand grip strength(lefthand grip strength,β = 0.017,p-value = 0.001;β in the results represents the effect value of IVs on outcomes),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,pvalue = 0.001;left-hand grip strength,β = 0.358,p-value = 3.97×10-4).However,sarcopenia-related traits were not causally associated with the fracture.In conclusion,osteoporosis may be one of the risk factors for sarcopenia-related traits and muscle strength may have a site-specific effect on BMD.