Objectives: We have demonstrated that daily I.P. injection of melatonin could increase cancellous bone mass in young growing mice in vivo, mostly through suppressing bone resorption. Further, we have recently shown that melatonin suppresses osteoclast formation, in part, throughupregulation of osteoprotegrin production in vitro. Methods: The present study was to determine whether melatonin could prevent bone loss in ovariectomized (OVX) rats in vivo. Female rats were sham-operated or OVX at 6 months of age and treated for 8 weeks with vehicle or melatonin. Sham-operated control rats and one group of OVX rats were injected I.P. with vehicle between 3 and 5 p.m. The remaining OVX rats were injected I.P. with 5, 10 or 50 mg melatonin / kg BW / day at the same time with vehicle-injected groups. The proximal tibiae were used to examine the effect melatonin on bone mineral density(BMD) and bone histomorphometry. Results: Melatonin treatment itself did not significantly affect body weight, and the weight of internal organs. There were no pathologic changes in internal organs in any groups. Vehicle-treated OVX rats were osteopenic with low bone density at 54% and a cancellous bone volume at 58 % of vehicle-treated control level. Compared to vehicle-treated OVX group, melatonin treatment significantly suppressed a decrease in BMD by 90% and in bone mass by 66%. This treatment significantly reduced bone resorption parameters (i.e., Oc.S/BS and N.Oc/BS), but did not significantly affect histomorphometric bone formation parameters (i.e., BFR/BS, MAR, OV/TV). Conclusions: These results indicate that melatonin treatment could prevent bone loss in OVX-rats through decreased bone resorption activity, indicating that melatonin could be a safe and potent agent to prevent postmenopausal osteoporosis.

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