Use of Low-Dose Alendronate Improves Cranial Bone Repair and Is Associated With an Increase of Osteocalcin: An Experimental Study

Abstract

Purpose: The objective of the present study was to evaluate cranial bone repair and remodeling after systemic application of alendronate (ALN), using histologic analysis, histometric analysis, and immunohistochemistry (osteocalcin).

Materials and methods: Female rabbits (n = 28) were randomly divided into 2 groups: control (C) and ALN treated (A). Group A received 3 systemic intraperitoneal injections of ALN weekly for 4 weeks, at a dose of 0.2 mg/kg. Group C received intraperitoneal injections of physiologic saline for the same period. After 4 weeks, all the rabbits underwent surgery to create 2 noncritical defects on the calvaria (5 mm in diameter). The groups were divided into 2 subgroups for sacrificing, at 15 and 60 postoperative days. After death, the analyses were performed. The data were also analyzed statistically.

Results: Histologic analysis of group C revealed healing in the dense connective tissue and trabecular bone, and the presence of compact bone with osteoblastic activity was noted in both 15- and 60-day subgroups. In group A, at 15 days, the presence of conjunctive tissue with osteoblastic activity and intense, compact, newly formed bone was observed. At 60 days, the created bone defect in group A showed a large amount of neoformed compact bone with a surface of dense modeled connective tissue and the presence of adipocytes and trabecular bone. The histometric analysis confirmed that a statistically significant difference was present between groups C and A when comparing the measured bone area and the area of connective tissue. Group A presented with a statistically significant larger amount of bone area in the 60-day subgroup than in the 15-day subgroup. The immunohistochemical analysis showed stronger immunostaining for osteocalcin in group A.

Conclusions: Within the limits of the present study, our results have shown that the systemic application of ALN, at a dose of 0.2 mg/kg, increased the repair and remodeling of cranial bone.