["Geriatrics &Gerontology International, Volume 26, Issue 6, June 2026. ", "\nThe Composite OrthoAge Score Index (COASI) integrates 14 serum biomarkers across six pathophysiological domains to quantify the musculoskeletal biological age gap. Validated in 126 patients and 117 controls, COASI identified a +26.38‐year gap in musculoskeletal disorder patients, enabling early detection and clinical risk stratification.\n\nABSTRACT\n\nAim\nChronological 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.\n\n\nMethods\nThis 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.\n\n\nResults\nCOASI 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.\n\n\nConclusions\nCOASI 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.\n\n"]