The effect of zoledronate during bone healing

Abstract

Background: Bisphosphonates have become the treatment of choice for a variety of bone diseases in which excessive osteoclastic activity is an important pathologic feature. However, inhibition of osteoclastic activity could lead to inhibition of remodeling during bone healing or repair. The objective of this study is to investigate the effect of zoledronate (the most potent bisphosphonate) in the biological process of bone healing.

Methods: Thirty immature male rabbits were divided into two groups (control and experimental) of 15 animals each. Both groups were submitted to fibular osteotomy. Only in the experimental group a single dose of zoledronate was administered. After 1, 2, and 4 weeks, animals of both groups were euthanized and the osteotomy site was histomorphometrically evaluated. The associated parameters analyzed were tissue volume (TV), fractional trabecular bone volume (BV/TV), fractional woven bone volume (WoV/TV), fractional periosteal fibrous volume (FbV/TV), and medullary fibrous volume (MaV/TV).

Results: The first week of healing was characterized by small callus area (experimental group) and less periosteal fibrosis. The second week was characterized by a large quantity of woven bone and marked decrease in periosteal fibrosis in the two groups. In the control group there was also a significant increase in trabecular bone. The fourth week was characterized by increased amount of woven bone and trabecular bone in the experimental group; there was increased medullary fibrosis in the two groups, while there continued to be significantly less periosteal fibrosis in the experimental group.

Conclusions: Zoledronate does not prevent bone healing. However, the effect of zoledronate was characterized by accentuated stimulation of primary bone production and probably inhibition of remodeling, leading to retention of trabecular bone.

Fig. 1

Histologic section of the callus in the control group during the fourth week of healing (HE, 100×)

Fig. 2

Histologic section of the callus in the experimental group during the fourth week, showing a large amount of woven bone compared with the control group (HE, 100×)