Melatonin is a signal molecule that modulates the biological circadian rhythms of
vertebrates. Melatonin deficiency is thought to be associated with several disorders,
including insomnia, cancer, and cardiovascular and neurodegenerative diseases. Accumulating
evidence has also indicated that melatonin may be involved in the homeostasis of bone
metabolism. Age-related reductions in melatonin are considered to be critical factors
in bone loss and osteoporosis with aging. Thus, serum melatonin levels might serve
as a biomarker for the early detection and prevention of osteoporosis. Compared to
conventional antiosteoporosis medicines, which primarily inhibit bone loss, melatonin
both suppresses bone loss and promotes new bone formation. Mechanistically, by activating
melatonin receptor 2 (MT2), melatonin upregulates the gene expression of alkaline
phosphatase (ALP), bone morphogenetic protein 2 (BMP2), BMP6, osteocalcin, and osteoprotegerin
to promote osteogenesis while inhibiting the receptor activator of NF-kB ligand (RANKL)
pathway to suppress osteolysis. In view of the distinct actions of melatonin on bone
metabolism, we hypothesize that melatonin may be a novel remedy for the prevention
and clinical treatment of osteoporosis.
