Therapeutic Potential of Melatonin in Osteoarticular Diseases and Musculoskeletal Medicine: A Narrative Review

Background and Objectives: Melatonin is traditionally recognized as a central regulator of circadian rhythms, but it is also a pleiotropic molecule with antioxidant, anti-inflammatory, mitochondrial-protective and immunomodulatory properties. These mechanisms are biologically relevant to degenerative, inflammatory and traumatic disorders of the musculoskeletal system. Materials and Methods: This narrative review summarizes evidence from PubMed/MEDLINE, Scopus and Web of Science regarding the role of melatonin in bone metabolism, cartilage homeostasis, osteoarthritis, muscle injury, tendon and ligament healing, spine disorders, sports medicine and musculoskeletal rehabilitation. Preclinical studies, translational investigations, clinical trials, systematic reviews and relevant mechanistic papers were considered. Results: Experimental evidence suggests that melatonin promotes osteoblast differentiation, limits osteoclastogenesis, protects chondrocytes from oxidative stress and apoptosis, modulates nuclear factor kappa B and nuclear factor erythroid 2-related factor 2 signaling, supports mitochondrial homeostasis and may influence autophagy, mitophagy and ferroptosis. These effects have potential implications for osteoporosis, fracture healing, osteoarthritis, tendinopathy, intervertebral disc degeneration and recovery after strenuous exercise. Clinical evidence remains promising but insufficient to define standardized orthopedic indications. Conclusions: Melatonin is a biologically plausible adjunct in musculoskeletal medicine, particularly where oxidative stress, low-grade inflammation and mitochondrial dysfunction contribute to disease progression. Well-designed randomized controlled trials are required to determine indications, timing, dose, route of administration and clinically meaningful outcomes.