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Biological age acceleration predicts osteoporosis and reduced longevity in a large prospective cohort
Rui Zhang1, Wanyang Zhong1, Yuelan Gao2
1Center of Regenerative Medicine, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Background:
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.
Methods:
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.
Results:
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.
Conclusion:
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.
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