Melatonin as a chronobiotic/cytoprotective agent in bone. Doses involved.
allometry
bone physiology
chronobiotic
circadian rhythms
cytoprotector
melatonin
osteoporosis
oxidative stress
Journal
Journal of pineal research
ISSN: 1600-079X
Titre abrégé: J Pineal Res
Pays: England
ID NLM: 8504412
Informations de publication
Date de publication:
11 Dec 2023
11 Dec 2023
Historique:
revised:
29
11
2023
received:
29
09
2023
accepted:
30
11
2023
medline:
12
12
2023
pubmed:
12
12
2023
entrez:
12
12
2023
Statut:
aheadofprint
Résumé
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.
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12931Informations de copyright
© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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