Effects of Short-Term Zoledronic Acid Treatment on Bone Remodeling and Healing at Surgical Sites in the Maxilla and Mandible of Aged Dogs

Abstract

It is unknown whether zoledronic acid (ZA) interferes with initial bone healing at extraction and implant sites. The goal of this study was to examine the effect of short-duration ZA on bone remodeling and healing after surgical insult in an aged dog model. Four 2- to 3-year-old male dogs were administered ZA (0.1 mg/kg per month for 4 months), and 3 age-matched untreated dogs received no drug. In both groups, after the ZA-treated group had completed receiving the drug, the third premolar was extracted unilaterally and 2 orthodontic mini-implants per jaw per dog were placed on the ipsilateral side. After a 6-week healing period, a pair of calcein bone labels were administered. Bone sections from the mandible, maxilla, rib, and femur were obtained. The percent necrosis in the alveolar and basal regions of tooth-supporting bone was assayed by lactate dehydrogenase, and dynamic histomorphometric parameters were quantified and analyzed by use of mixed models. All extraction sites healed uneventfully, and no lesions resembling osteonecrosis were detected. The total percent necrosis was limited to less than 1% for all the bone sites examined. The ZA reduced bone remodeling at both surgical sites (extraction sites and mini-implant site) and nonsurgical sites. Although there was a significant (P < .05) increase in bone formation rate at the surgical sites in the untreated group, this increase was not significant (P = .3) in the ZA-treated group. Bone remodeling occurs in ZA-treated animals at surgical sites. ZA dramatically reduced bone turnover, but no exposed lesions resembling osteonecrosis developed at extraction and mini-implant sites after the 4-month drug duration.