Effects of melatonin on bone: a case control study
Keywords:Melatonin, Bone mineral density, Osteopenia, Osteoporosis, Postmenopausal
Background: There is a stereotypical notion of estrogen being the most relevant parameter for bone health in post-menopausal females, but apart from estrogen; advances in research have presented ample evidence that melatonin may also play a critical role in bone health outcomes.
Methods: Our study consisted of 48 post-menopausal females, 24 subjects in the case group and 24 in control groups, to study the differences of certain parameters existing between the two. Serum Melatonin was calculated using ELISA test and Bone Mineral Density (BMD) was evaluated using a portable Ultrasound Bone Densitometer Testing Machine.
Results: A strong Positive Pearson correlation exists between BMD and serum melatonin levels. Pearson correlation coefficient value (r) of 0.96 and 0.95 for the Control and Osteopenic group respectively. Linear regression for control group is (r2) 0.92. Linear regression for osteopenic group is (r2) 0.90.
Conclusions: The results of our study exhibited strong interdependence between the serum melatonin levels and their effects on BMD. Osteopenic subjects who had a lower BMD were also found to have relatively lower levels of serum melatonin. Aligning with the results, similarly control group with normal BMD was found to have relatively higher level of serum melatonin.
Claustrat B, Brun J, Chazot G. The basic physiology and pathophysiology of melatonin. Sleep Med Rev. 2005;9:11-24
Aulinas A. Physiology of the pineal gland and melatonin. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, Herder WW, Dhatariya K, et al, eds. South Dartmouth: MD Text; 2000.
Bubenik GA. Gastrointestinal melatonin: localization, function, and clinical relevance. Dig Dis Sci. 2002;47: 2336-48.
Hardeland R. Antioxidative protection by melatonin: multiplicity of mechanisms from radical detoxification to radical avoidance. Endocrine. 2002; 27:119-30.
Jan JE, Reiter RJ, Wasdell MB, Bax M. The role of the thalamus in sleep, pineal melatonin production, and circadian rhythm sleep disorders. J Pineal Res. 2009;46:1-7.
Sack RL, Auckley D, Auger RR. Circadian rhythm sleep disorders: part I, basic principles, shift work and jet lag disorders. An American academy of sleep medicine review. Sleep. 2007;30:1460-83.
Schulz P, Steimer T. Neurobiology of circadian systems. CNS Drugs. 2009;23:3-13.
Zhdanova IV, Wurtman RJ. Efficacy of melatonin as a sleep-promoting agent. J Biol Rhythms. 2009;112: 644-50.
Brzezinski A. Melatonin in humans. N Engl J Med. 1997;336:186-95.
Hadjidakis DJ, Androulakis II. Bone remodeling. Ann NY Acad Sci. 2006;1092:385-96.
Suzuki N, Hattori A. Melatonin suppresses osteoclastic and osteoblastic activities in the scales of goldfish. J Pineal Res. 2002;33(4):253-8.
Nakade O, Koyama H, Ariji H, Yajima A, Kaku T. Melatonin stimulates proliferation and type I collagen synthesis in human bone cells in vitro. J Pineal Res. 1999;27(2):106-10.
Karasek M. Melatonin, human aging, and age-related diseases. Exp Gerontol. 2004;39(11-12):1723-9.
Reiter RJ, Tan DX, Manchester LC, Qi W. Biochemical reactivity of melatonin with reactive oxygen and nitrogen species: a review of the evidence. Cell Biochem Biophys. 2001;34:237-56.
Reiter RJ, Tan DX, Allegra M. Melatonin: Reducing molecular pathology and dysfunction due to free radicals and associated reactants. Neuroendocrinol Lett. 2002;23(l):3-8.
Okatani Y, Wakatsuki A, Reiter RJ, Miyahara Y. Melatonin reduces oxidative damage of neural lipids and proteins in senescence-accelerated mouse. Neurobiol Aging. 2002;23:639-44.
Kennaway DJ, Stamp GE, Goble FC. Development of melatonin production in infants and the impact of prematurity. J Clin Endocrinol Metab. 1992;75(2): 367-9.
Waldhauser F, Weiszenbacher G, Frisch H, Zeitlhuber U, Waldhauser M, Wurtman RJ. Fall in nocturnal serum melatonin during prepuberty and pubescence. Lancet. 1984;1(8373):362-5.
Wetterberg L, Bergiannaki JD, Paparrigopoulos T, von Knorring L, Eberhard G, Bratlid T, et al. Normative melatonin excretion: a multinational study. Psycho-neuroendocrinology. 1999;24(2):209-26.
Kennaway DJ, Lushington K, Dawson D, Lack L, van den Heuvel C, Rogers N. Urinary 6-sulfatoxymelatonin excretion and aging: new results and a critical review of the literature. J Pineal Res. 1999;27(4):210-20.
Scholtens RM, van Munster BC, van Kempen MF, de Rooij SE. Physiological melatonin levels in healthy older people: A systematic review. J Psychosom Res. 2016;86:20-7.
Manolagas SC. Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev. 2000;21(2):115-37.
Sack RL, Lewy AJ, Erb DL, Vollmer WM, Singer CM. Human melatonin production decreases with age. J Pineal Res. 1986;3(4):379-88.
Kanis JA, Melton LJ, Christiansen C, Johnston CC, Khaltaev N. The diagnosis of osteoporosis. J Bone Miner Res. 1994;9(8):1137-41.
Kenkre JS, Bassett J. The bone remodelling cycle. Ann Clin Biochem. 2018;55(3):308-27.
Tian L, Yang R, Wei L, Liu J, Yang Y, Shao F, et al. Prevalence of osteoporosis and related lifestyle and metabolic factors of postmenopausal women and elderly men: A cross-sectional study in Gansu province, Northwestern of China. Medicine. 2017; 96(43):e8294.
Erdem M, Gulabi D, Sen C, Sahin SA, Bozdag E. Effects of caffeic acid phenethyl ester and melatonin on distraction osteogenesis: an experimental study. Springerplus. 2014;3:8.
Man GC, Wang WW, Yim AP. A review of pinealectomy induced melatonin deficient animal models for the study of etiopathogenesis of adolescent idiopathic scoliosis. Int J Mol Sci. 2014;15(9):16484-99.
Aota Y, Terayama H, Saito T, Itoh M. Pinealectomy in a broiler chicken model impairs endochondral ossification and induces rapid cancellous bone loss. Spine J. 2013;13(11):1607-16.
Kono H, Machida M, Saito M. Mechanism of osteoporosis in adolescent idiopathic scoliosis: experimental scoliosis in pinealectomized chickens. J Pineal Res. 2011;51(4):387-93.
Theodoros G, Savvidou O. Melatonin the "light of night" in human biology and adolescent idiopathic scoliosis. Scoliosis. 2007;2:6-10.