Melatonin as a chronobiotic/cytoprotective agent in bone: doses involved

• Autores: Cardinali, Daniel Pedro
• Año de publicación: 2023
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Journal of Pineal Research. 2023, 76 (1).
• Materia: ALOMETRIA; FISIOLOGIA OSEA; CRONOBIOTICA; RITMOS CIRCADIANOS; CITOPROTECTOR; MELATONINA; OSTEOPOROSIS; ESTRES OXIDATIVO
• Institución: Pontificia Universidad Católica Argentina

Fil: Cardinali, Daniel Pedro. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Cardinali, Daniel Pedro: Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas; Argentina
Abstract: Because the chronobiotic and cytoprotective molecule melatonin diminishes with age, its involvement in postmenopausal and senescence pathology has been considered since long. One relevant melatonin target site in aging individuals is bone where melatonin chronobiotic effects mediated by MT1 and MT2 receptors are demonstrable. Precursors of bone cells located in bone marrow are exposed to high quantities of melatonin and the possibility arises that melatonin acts a cytoprotective compound via an autacoid effect. Proteins that are incorporated into the bone matrix, like procollagen type I c‐peptide, augment after melatonin exposure. Melatonin augments osteoprotegerin, an osteoblastic protein that inhibits the differentiation of osteoclasts. Osteoclasts are target cells for melatonin as they degrade bone partly by generating free radicals. Osteoclast activity and bone resorption are impaired via the free radical scavenger properties of melatonin. The administration of melatonin in chronobiotic doses (less than 10 mg daily) is commonly used in clinical studies on melatonin effect on bone. However, human equivalent doses allometrically derived from animal studies are in the 1–1.5 mg/kg/day range for a 75 kg human adult, a dose rarely used clinically. In view of the absence of toxicity of melatonin in phase 1 pharmacological studies with doses up to 100 mg in normal volunteers, further investigation is needed to determine whether high melatonin doses have higher therapeutic efficacy in preventing bone loss.