Effects of short-term zoledronic acid treatment on bone remodeling and healing at surgical sites in the maxilla and mandible of aged dogs

J Oral Maxillofac Surg. 2011 Feb;69(2):418-27. doi: 10.1016/j.joms.2010.05.062. Epub 2010 Dec 3.

Abstract

Purpose: 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.

Materials and methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Alveolar Process / drug effects
  • Animals
  • Bicuspid / surgery
  • Bone Density Conservation Agents / pharmacology*
  • Bone Remodeling / drug effects*
  • Dental Implantation, Endosseous
  • Diphosphonates / pharmacology*
  • Dogs
  • Femur / drug effects
  • Fluoresceins
  • Fluorescent Dyes
  • Imidazoles / pharmacology*
  • L-Lactate Dehydrogenase / analysis
  • Male
  • Mandible / drug effects
  • Mandible / surgery*
  • Mandibular Diseases / etiology
  • Maxilla / drug effects
  • Maxilla / surgery*
  • Maxillary Diseases / etiology
  • Models, Animal
  • Orthodontic Anchorage Procedures / instrumentation
  • Osteogenesis / drug effects
  • Osteonecrosis / etiology
  • Random Allocation
  • Ribs / drug effects
  • Tooth Extraction
  • Wound Healing / drug effects
  • Zoledronic Acid

Substances

  • Bone Density Conservation Agents
  • Diphosphonates
  • Fluoresceins
  • Fluorescent Dyes
  • Imidazoles
  • Zoledronic Acid
  • L-Lactate Dehydrogenase
  • fluorexon