Melatonin effects on bone: experimental facts and clinical perspectives

Abstract

Bone formation proceeds through a remodeling process that runs continuously, involving the resorption of old bone by osteoclasts, and the subsequent formation of new bone by osteoblasts. This is controlled by growth factors and cytokines produced in bone marrow microenvironment and by the action of systemic hormones, like parathyroid hormone, estradiol or growth hormone (GH). One candidate for hormonal modulation of osteoblast and osteoclast formation is melatonin. Because circulating melatonin declines with age, its possible involvement in post-menopausal and senescence osteoporosis is considered. This review article discusses early studies on melatonin-bone relationships and recent data that suggest a direct effect of melatonin on bone. Melatonin could act as an autacoid in bone cells as it is present in high quantities in bone marrow, where precursors of bone cells are located. Melatonin dose-dependently augmented proteins that are incorporated into the bone matrix, like procollagen type I c-peptide. Osteoprotegerin, an osteoblastic protein that inhibits the differentiation of osteoclasts is also augmented by melatonin in vitro. Another possible target cell for melatonin is the osteoclast, which degrades bone partly by generating free radicals. Melatonin through its free radical scavenger and antioxidant properties may impair osteoclast activity and bone resorption. At least in one study melatonin was both inhibitory to osteoclastic and osteoblastic cells. Therefore, the documented bone-protecting effect of melatonin in ovariectomized rats can depend in part on the free radical scavenging properties of melatonin. Additionally, melatonin may impair development of osteopenia associated with senescence by improving non-rapid eye movement sleep and restoring GH secretion. Whether melatonin can be used as a novel mode of therapy for augmenting bone mass in diseases deserves to be studied.

Antioxidant effects of melatonin in heart tissue after induction of experimental periodontitis in rats

“…Melatonin has various biological effects, including antioxidant and immunity-enhancing ones (15)(16)(17)(18). It exhibits high lipophilicity, and easily reaches the cell membrane and mitochondria.…”

Superficies bioactivas en implantología: una nueva perspectiva

“…La melatonina, a través de su acción antioxidante y depuradora de radicales libres, podría interferir en esta función del osteoclasto e inhibir de esta forma la reabsorción ósea (27). Esta inhibición en la reabsorción ósea se vería potenciada por otra acción de la indolamina a nivel de la osteoclastogénesis, ya que Koyama et al han observado que la aplicación de melatonina en rangos de 5 a 500 µM disminuye de manera dosis-dependiente la expresión de mRNA de RANK y aumenta tanto los niveles de OPG como de mRNA de OPG en líneas celulares preosteoblásticas MC3T3-E 1 (28).…”

“…Todos estos datos confirman un efecto osteogénico de la melatonina que puede ser clínicamente importante, ya que podría ser usada como potencial agente terapéutico en situaciones en las que sea deseable un aumento de la formación ósea, como cicatrización de fracturas u osteoporosis, o su uso como, una superficie bioactiva en implantología (31).…”

Seasonal fluctuations in birth weight and neonatal limb length; does prenatal vitamin D influence neonatal size and shape?

“…There is also evidence suggesting that the maternal environment may influence the dprogrammingT of the fetal suprachiasmatic nucleus, which is involved in the generation of circadian rhythms [36,37]. Because of the links between melatonin, growth hormone and bone remodelling [38], these mechanisms require further scrutiny.…”