Biological age acceleration predicts osteoporosis and reduced longevity in a large prospective cohort.

Abstract

Osteoporosis is a major age-related musculoskeletal condition, yet chronological age does not fully capture individual risk. Biological age acceleration (BAA), as a biomarker of systemic aging, may offer greater predictive value for osteoporosis and lifespan loss. We analyzed data from 293,224 participants in the UK Biobank cohort who were free of osteoporosis at baseline. BAA was estimated using two validated models-Klemera-Doubal Method Biological Age (KDM-BA) and PhenoAge. Polygenic risk scores (PRS) were used to account for genetic susceptibility. Multivariable Cox models examined associations of BAA and PRS with incident osteoporosis and all-cause mortality. Over a median follow-up of 8.5 years, 9780 participants developed osteoporosis. Each one standard deviation (SD) increase in KDM-BA and PhenoAge acceleration was associated with a 22.6 % (95 % CI: 1.11, 1.36) and 19.3 % (95 % CI: 1.12, 1.36) higher risk of osteoporosis, respectively. Participants in the highest tertile of BAA had a 38-43 % increased risk compared to those in the lowest tertile. Individuals with both high BAA and high PRS had nearly threefold higher osteoporosis risk, indicating a strong additive effect. Accelerated aging was also linked to a 1.3-1.8-year reduction in life expectancy at age 45, independent of osteoporosis status. Accelerated biological aging is an independent predictor of osteoporosis and premature mortality. Integration of BAA into clinical assessment could enhance early identification of at-risk individuals and support aging-targeted interventions for skeletal health.