The potential benefits of melatonin in the prevention and treatment of bone loss in response to microgravity.

Exposure to microgravity during spaceflight is known to be associated with rapid and drastic bone loss in humans, which can increase the risks of fragility fracture and renal stone formation. Furthermore, the recovery of bone loss may require a relatively long time after returning back to Earth. Therefore, bone loss has become a substantial obstacle to human exploration of outer space. Currently, the therapeutic effects of the countermeasures related to microgravity-induced bone loss, including exercise, pharmacological intervention and supplementation, are not sufficient. Moreover, each class of pharmacological drugs has potential side effects. Hence, it is urgent to find more safer and effective drugs to alleviate microgravity-induced bone loss. Melatonin is a tryptophan-derived methoxyindole synthetized and released principally from the pineal gland. The secondary source of melatonin are bone marrow, retina, gut and skin. The production of melatonin occurs almost exclusively during the night, so exposure to light at night can reduce its production. Through receptor-mediated and receptor-independent actions, melatonin functions pleiotropic physiological actions in vertebrate. Due to its production and secretion are closely related to the environmental light/dark cycle, the key function of melatonin is to regulate circadian rhythm. Moreover, there is credible evidence that melatonin possesses antioxidant, anti-aging, anti-inflammatory and anticancer properties. Interestingly, melatonin is capable of chelating metals, such as iron, aluminum, cadmium, copper, lead and zinc. It is worth noting that melatonin has high safety profile and positive effects on osteoporosis, including microgravity-induced bone loss. As an attractive multitasking molecule, in the present review we shed light on the potential benefits of melatonin in the prevention and treatment of microgravity-induced bone loss. • Circadian disruption, oxidative stress and elevated iron levels are main risk factors for microgravity-induced bone loss. • We discuss the potential utility of melatonin for microgravity-induced bone loss. • Melatonin may act as a circadian rhythm modulator against microgravity-induced bone loss. • Melatonin may act as a powerful antioxidant against microgravity-induced bone loss. • Melatonin may act as an iron-chelator against microgravity-induced bone loss. [ABSTRACT FROM AUTHOR]