Use of local melatonin with xenogeneic bone graft to treat critical-size bone defects in rats with osteoporosis: a randomized study

The aim of this study was to evaluate the effect of local administration of melatonin (MLT) on molecular biomarkers and calvaria bone critical defects in female rats with or without osteoporosis, associated or not with a xenogeneic biomaterial. Forty-eight female rats were randomly divided into two groups: (O) ovariectomized and (S) placebo groups. After 45 days of osteoporosis induction, two critical-size defects (5 mm diameter) were created on the calvaria. The groups were subdivided according to the following treatment: (C) Clot, MLT, MLT associated with Bio-Oss ^® (MLTBO), and Bio-Oss ^® (BO). After 45 days, the defect samples were collected and processed for microtomography, histomorphometry, and biomolecular analysis (Col-I, BMP-2, and OPN). All animals had one femur harvested to confirm the osteoporosis. Microtomography analysis demonstrated a bone mineral density reduction in the O group. Regarding bone healing, the S group presented greater filling of the defects than the O group; however, in the O group, the defects treated with MLT showed higher mineral filling than the other treatments. There was no difference between the treatments performed in the S group (p = 0.05). Otherwise, O-MLT had neoformed bone higher than in the other groups (p = 0.05). The groups that did not receive biomaterial demonstrated lower levels of Col-I secretion; S-MLT and S-MLTBO presented higher levels of OPN, while O-C presented statistically lower results (p < 0.05); O-BO showed greater BMP-2 secretion (p < 0.05). In the presence of ovariectomy-induced osteoporosis, MLT treatment increased the newly formed bone area, regulated the inflammatory response, and increased OPN expression.