Melatonin: A Potential Therapy for Osteoporosis With Insights Into Molecular Mechanisms

ABSTRACT Melatonin is a versatile neurohormone with diverse molecular functions, including sleep regulation, inflammation reduction, antioxidant activity, immune modulation, and anticancer properties. In bone metabolism, it promotes osteoblast formation, inhibits osteoclast activity, and synchronizes skeletal tissue rhythms to support bone health. As melatonin is not yet clinically used for osteoporosis and concerns about the current treatments' side effects remain, this review highlights its role in modulating osteoblast and osteoclast interactions, particularly through regulation of the receptor activator of nuclear factor‐κB ligand and osteoprotegerin, to achieve bone‐forming and antiresorptive effects. These effects have been demonstrated across various concentrations in diverse cell types and In Vivo models. Furthermore, melatonin safeguards the bone microenvironment by mitigating oxidative stress and inflammation, protecting osteoblasts, preventing bone loss, and maintaining the gut microbiota and brain–gut–bone axis. These attributes underscore melatonin's potential as an effective alternative or complementary therapy for promoting bone health and managing osteoporosis. Future research is needed to determine optimal dosing and timing for maximum efficacy.