Melatonin is an important endogenous hormone that modulates homeostasis in the microenvironment. Recent studies have indicated that serum melatonin levels are closely associated with the occurrence and development of osteoporosis in postmenopausal women. Exogenous melatonin could also improve bone mass and increase skeletal strength. To determine the underlying mechanisms of melatonin in the prevention and treatment of postmenopausal osteoporosis, we performed this review to analyze the role of melatonin in bone metabolism according to its physiological functions. Serum melatonin is related to bone mass, the measurement of which is a potential method for the diagnosis of osteoporosis. Melatonin has a direct effect on bone remodeling by promoting osteogenesis and suppressing osteoclastogenesis. Melatonin also regulates the biological rhythm of bone tissue, which benefits its osteogenic effect. Additionally, melatonin participates in the modulation of the bone microenvironment. Melatonin attenuates the damage induced by oxidative stress and inflammation on osteoblasts and prevents osteolysis from reactive oxygen species and inflammatory factors. As an alternative drug for osteoporosis, melatonin can improve the gut ecology, remodel microbiota composition, regulate substance absorption and maintain metabolic balance, all of which are beneficial to the health of bone structure. In conclusion, our review systematically demonstrates the effects of melatonin on bone metabolism. Based on the evidence in this review, melatonin will play a more important role in the diagnosis, prevention and treatment of postmenopausal osteoporosis.

Based on the positive correlation between bone mineral density and melatonin levels in blood, this study confirmed that melatonin supplementation prevents postmenopausal osteoporosis. We further confirmed that melatonin promotes an increase in intracellular calcium concentrations through the STIM1/ORAI1 pathway, thereby inducing the proliferation of osteoblasts.Introduction: Osteoporosis (OP) is a progressive, systemic bone disease that is one of the main causes of disability and death in elderly female patients. As an amine hormone produced by the human pineal gland, melatonin plays an important role in regulating bone metabolism. This study intends to investigate the relationship between melatonin levels in human blood and bone density and to suggest the efficacy of melatonin in treating osteoporosis by performing in vivo and in vitro experiments.Methods: We used liquid chromatography-tandem mass spectrometry to determine the serum melatonin levels in postmenopausal women with osteoporosis and young women with a normal bone mass. The bone density, BV/TV, Tb.Th, Tb.Sp and other indicators of postmenopausal osteoporosis and mice with a normal bone mass were detected by measuring bone density and micro-CT. The intracellular calcium ion concentration was detected using fluorescence microscopy and a full-wavelength multifunctional microplate reader, and the expression of SOCE-related genes and STIM1/ORAI1 proteins was detected using PCR and WB.Results: This study confirmed that bone density positively correlates with the melatonin level in human blood. In the animal model, melatonin supplementation reverses postmenopausal osteoporosis. We explored the internal mechanism of melatonin treatment of osteoporosis. Melatonin promotes an increase in intracellular calcium ion concentrations through the STIM1/ORAI1 pathway to induce osteoblast proliferation.Conclusions: This study provides an important theoretical basis for the clinical application of melatonin in patients with osteoporosis and helps to optimize the diagnosis and treatment of postmenopausal osteoporosis.

Accumulation of lipid substances decreased the activity of osteoblasts. Trehalose is a typical stress metabolite to form a protective membrane on cell surface which has been demonstrated to regulate lipid metabolism. This activity of Trehalose indicates the potential effect of osteoporosis treatment. Our study aimed to determine the therapeutic effect of Trehalose in high fat-induced osteoporosis. We used palmitic acid (PA) to mimic the state of high fat and observed the apoptosis ratio of osteoblasts increased. After adding Trehalose, the apoptosis ratio decreased obviously. Autophagy is a regulatory means involved in the process of apoptosis.We detected the autophagy protein and found that the expression of Beclin-1, Atg5, and LC3 II increased, and p62 decreased after Trehalose treatment. When adding an autophagy inhibitor (3-MA), the expression of Beclin-1, Atg5, and LC3 II decreased, and p62 increased. These results indicated autophagy was an important factor involved in the preventive effect of Trehalose in PA-induced apoptosis. SIRT3 is a mitochondrial gene that can inhibit apoptosis, which has been reported to promote autophagy. We used SIRT3-siRNA to silence the expression of SIRT3 and found the effect of Trehalose was counteracted. The apoptosis ratio increased and the expression of Beclin-1, Atg5, and LC3 II decreased, p62 increased. Additionally, we also fed the mice with a high-fat diet (HFD) and intragastrical Trehalose. The results showed that Trehalose could inhibit the bone mass loss with HFD. Our study revealed the effect and mechanism of Trehalose in the treatment of osteoporosis.