Total and Regional Fat‐to‐Muscle Ratio ( FMR ) and Risk of Osteoporosis: Evidence From the UK Biobank Cohort

ABSTRACT Introduction Osteoporosis is a systemic skeletal disease whose prevalence and associated healthcare burden are increasing, particularly among women. Although BMI is commonly used to assess the relationship between body weight and bone health, it cannot distinguish fat mass from muscle mass, which may have different effects on bone health. The fat‐to‐muscle ratio (FMR) may capture the relative balance between adiposity and muscle reserve, but longitudinal evidence regarding the associations of regional FMR with incident osteoporosis remains limited. Objectives We aimed to evaluate the associations of total and regional FMR with bone mineral density (BMD) and the risk of incident osteoporosis. Methods We included 324 631 UK Biobank participants. Analyses were stratified by sex to account for potential sex‐specific associations. Linear regression models were used to examine the associations of total and regional FMR with BMD T‐scores for the whole body, heel, lumbar spine (L1–L4) and femoral neck. Cox proportional hazards models were applied to assess the associations between each FMR measure and incident osteoporosis. Results Among these participants, 9983 incident osteoporosis cases were identified during follow‐up. Among male participants, higher whole‐body, trunk and arm FMR values were associated with a higher risk of osteoporosis, with HRs of 1.66 (95% CI, 1.36–2.02), 1.43 (95% CI, 1.14–1.79) and 2.09 (95% CI, 1.67–2.62), respectively, for the highest versus lowest quintiles (Q5 versus Q1). By contrast, higher leg FMR was associated with a lower risk across Q2–Q5, with an HR of 0.64 (95% CI, 0.52–0.78) for Q5 versus Q1. Among female participants, higher whole‐body FMR and arm FMR were similarly associated with a higher risk of osteoporosis, with HRs for Q5 versus Q1 of 1.21 (95% CI, 1.08–1.37) for whole‐body FMR and 2.31 (95% CI, 1.94–2.75) for arm FMR, respectively, whereas higher leg and trunk FMR were associated with a lower risk, with HRs of 0.84 (95% CI, 0.73–0.97) and 0.57 (95% CI, 0.49–0.65), respectively, for the same comparison. Conclusion Distinct sex‐ and region‐specific associations were observed between total and regional FMR measures and osteoporosis risk. These findings suggest that regional variation in FMR may provide additional body‐composition information beyond BMI alone.