The Bone Clock: Circadian Rhythm, Melatonin, and Their Convergent Roles in Osteoporosis

Osteoporosis arises when bone resorption persistently exceeds bone formation, leading to reduced bone mass, microarchitectural deterioration, and increased fracture risk. Evidence from human and experimental studies indicates that skeletal remodeling is temporally organized by the circadian system. The suprachiasmatic nucleus coordinates peripheral clocks in osteoblasts, osteoclasts, osteocytes, and mesenchymal stromal cells through neural, endocrine, behavioral, and metabolic cues, whereas cell‐autonomous CLOCK–BMAL1, PER–CRY, REV‐ERB, and ROR loops regulate osteogenic differentiation and osteoclastogenesis. Sleep restriction, shift work, light at night, and irregular feeding can desynchronize these oscillators and produce negative uncoupling, in which formation is suppressed relative to resorption. Melatonin links central timekeeping to bone by promoting osteoblast differentiation, restraining RANKL‐dependent osteoclastogenesis, and limiting oxidative and mitochondrial injury. This review integrates molecular, epidemiological, and experimental evidence connecting circadian disruption and melatonin insufficiency with osteoporosis and evaluates the opportunities and limitations of chronobiology‐informed prevention and treatment.