Alendronate Impairs Healing of Calvaria Critical Defects After Bone Graft With Different Bone Substitute Materials

Abstract

The aim of this preclinical study was to evaluate the healing of critical-sized defects (CSDs) in the calvarial bone of rats grafted with deproteinized bovine bone graft (DBB) and with a combination of hydroxyapatite (HA) and β-tricalcium phosphate (TCP) and bisphosphonate treatment. Eighty-four animals were randomly divided into 2 groups according to the type of solution administered: the control group (CTR, saline solution) and the test group (alendronate [ALD]; sodium alendronate-50μg/kg/day). Medications were administered via oral gavage starting 15days before the surgical procedure until the end of the experiment. A CSD (5mm in diameter) was made in the calvaria of each animal, and the rats were randomly allocated to 3 subgroups according to the biomaterial used to fill the defect: coagulum, DBB, and HA/TCP. The animals were sacrificed 15 and 60days after the surgical procedure (n=7 animals/period/subgroup). Microcomputed tomography was used to evaluate the percentage of mineralized tissues (volume). The amount of newly formed bone and remaining bone substitute material in the calvaria were analyzed by histomorphometry. There were no differences between the CTR and ALD groups with regard to the volume of mineralized tissues. The DBB and HA/TCP subgroups of CTR animals presented a significant increase in newly formed bone compared with these subgroups of ALD animals after 60days of healing. Collectively, our findings indicate that the use of oral ALD reduced bone formation in CSD in the calvaria of rats grafted with DBB and HA/TCP.