The Composite OrthoAge Score Index (COASI) for Estimating Musculoskeletal Biological Age Acceleration in Older Adults

AIM: Chronological age does not adequately reflect musculoskeletal biological aging. Although individual biomarkers capture specific processes, a unified quantitative measure of musculoskeletal biological age gap is lacking. This study aimed to develop and evaluate a multidomain composite biomarker index, the Composite OrthoAge Score Index (COASI), to estimate biological age gap in older adults. METHODS: This cross-sectional case-control study included 126 individuals with radiologically confirmed musculoskeletal disorders and 117 age- and sex-matched asymptomatic controls recruited from orthopedic outpatient clinics and community sources in Kolkata, India. Serum levels of 14 biomarkers across six domains were quantified using enzyme-linked immunosorbent assays. Domain-specific scores were calculated using standardized effect size-based weighting and integrated into COASI. Calibration against chronological age was performed in controls, with internal validation using 10-fold cross-validation. RESULTS: COASI showed a significant positive association with chronological age in controls (R² = 0.578, p < 0.001), with cross-validation demonstrating consistent performance (mean R² = 0.54 ± 0.06). Individuals with musculoskeletal disorders exhibited a significantly greater biological age gap than controls (+26.7 years; SE ±4.34; p < 0.001). Sensitivity analyses confirmed robustness (+24.9 years; SE ±4.61; p < 0.001). No significant subgroup differences were observed (p = 0.18). Muscle-extracellular matrix and bone-cartilage turnover were dominant contributors. CONCLUSIONS: COASI is a multidomain, biomarker-derived index estimating musculoskeletal biological age and its gap relative to chronological age. It may support early risk stratification; however, it remains exploratory and hypothesis-generating. Further longitudinal validation, external replication in diverse populations, and integration with standardized geriatric functional outcomes (e.g., frailty, physical performance, fall risk) are required prior to any clinical application.