Abstract
<title>Abstract</title> <p> Background Chronic musculoskeletal disorders (MSDs) are a leading cause of disability worldwide, and long-term treatment with nonsteroidal anti-inflammatory drugs, corticosteroids, and opioids is frequently limited by adverse effects. We developed the <bold>Unified Musculoskeletal Dysfunction Index (UMDI)</bold> and <bold>Unified Musculoskeletal Aging Index (UMAI)</bold> as multidomain quantitative tools to assess musculoskeletal dysfunction and estimate model-derived musculoskeletal biological age. Methods In this 16-week randomized controlled trial, 180 adults with chronic MSDs were randomized (1:1) to receive either a standardized oral and topical multi-target phytotherapeutic intervention or standard management. The primary outcome was the change in UMDI. Physical domains, including symptom and functional disability, gait, structural asymmetry, mobility restriction, and anthropometric risk, together with biological domains comprising inflammation, muscle–cartilage degeneration, bone turnover, cardiometabolic status, and neurovascular function, were integrated into the Composite Musculoskeletal Dysfunction Index (CMDI) and Composite Biological Musculoskeletal Index (CBMI) using random-effects standardized mean differences (Cohen's <italic>d</italic> ). Weighted integration of CMDI and CBMI generated the UMDI, from which the UMAI and model-derived musculoskeletal biological age were estimated. Treatment effects were evaluated using mixed-effects models. Results Compared with standard management, the phytotherapeutic intervention significantly improved all primary and secondary outcomes (all <italic>P</italic> < 0.001), <bold>except suprapatellar, infrapatellar, and thigh girth measurements, which did not differ significantly between groups</bold> . CMDI and CBMI effect sizes were 0.73 and 0.92, respectively. UMDI decreased from 2.64 to 0.846, UMAI from 0.264 to 0.0846, and model-derived musculoskeletal biological age from 68.55 to 64.10 years, reducing the biological age acceleration gap by 67.9%. Conclusions A standardized oral and topical multi-target phytotherapeutic intervention significantly improved multidomain clinical function and biological biomarkers in adults with chronic MSDs. The newly developed UMDI and UMAI provide integrated quantitative measures of treatment response and estimated musculoskeletal biological age, supporting their use as multidimensional outcome measures in phytotherapy research and musculoskeletal medicine. </p>