Combined effect of MASLD and low muscle strength on the risk of osteoporotic fractures: A UK Biobank cohort study

BACKGROUND: The relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and osteoporotic fractures risk remains controversial. LMS, a key component of sarcopenia and an established fracture risk factor, frequently coexists with MASLD; however, its combined effect on skeletal health is unclear. This study examined the individual and combined effects of MASLD and LMS on osteoporotic fracture risk. METHODS: This large-scale cohort study utilized UK Biobank data. MASLD was defined as a fatty liver index ≥60 plus at least one metabolic risk factor. LMS was defined as a maximum handgrip strength Z-score <-0.5, standardized for age and sex. Participants were categorized into: (1) control (no MASLD/no LMS), (2) LMS only, (3) MASLD only, and (4) MASLD with LMS. The primary outcome was incident osteoporotic fractures. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: A total of 191 176 participants were included. Over a median follow-up of 13.4 years, 4919 fracture events occurred (median age: 57 years; women: 52.1%). Compared with controls, MASLD alone was not associated with higher fracture risk (adjusted hazard ratio [aHR]: 1.00, 95% CI: 0.90-1.10), unlike LMS alone (aHR: 1.14, 95% CI: 1.06-1.22). Participants with both MASLD and LMS, particularly women, had the greatest fracture risk (aHR: 1.23, 95% CI: 1.10-1.38). CONCLUSION: Fracture risk in individuals with MASLD was increased only when LMS coexisted. These findings highlight the importance of incorporating muscle health assessment into the clinical evaluation of MASLD to improve risk stratification.