Aminobisphosphonate-treated ewes as a model of osteonecrosis of the jaw and of dental implant failure

J Periodontol. 2020 May;91(5):628-637. doi: 10.1002/JPER.19-0213. Epub 2019 Dec 15.

Abstract

Background: Bisphosphonate (BP)-related osteonecrosis of the jaw (BRONJ) and dental implant failure are two negative side effects of chronic aminoBP treatment.

Methods: Eleven ovariectomized (OVX) ewes and four ewes subjected to sham surgery (SHAM) were treated as follows: OVX (n = 5): OVX plus saline solution; zoledronic acid-treated group (ZOL) (n = 6): OVX plus ZOL; SHAM (n = 4): SHAM plus saline solution. Extraction of the first upper molar was performed at 1 year, dental implant placement at 2 years, and sacrifice at 28 months.

Results: Implants remained in place in SHAM and OVX ewes but were lost in all ZOL ewes. ZOL sheep (2/6) showed inflammation and necrotic bone at mandibular region. No differences in serum calcium (Ca), inorganic phosphate (Pi) or 25-hydroxyvitamin D were observed, whereas bone alkaline phosphatase levels decreased in the three studied groups (P < 0.05). The significantly lowest levels of carboxy-terminal telopeptide of type I collagen were observed in ZOL (P < 0.05), and showed no differences between SHAM and OVX. OVX showed the lowest and ZOL the highest Ca and Pi contents in femur and maxilla (P < 0.05). Bone volume (BV/TV%) and iliac crest were similar at baseline and at month 4. At the end of the study, BV/TV%, proximal femur and hemi-mandible bone mineral content and bone mineral density, and trabeculae number were similar in SHAM and ZOL, and lower in OVX (P < 0.05).

Conclusion: All ZOL-treated ewes on a schedule similar to that used in cancer patients showed extensive suppression of bone remodeling and implant failure. Some of the ZOL ewes developed BRONJ.

Keywords: bisphosphonate-associated osteonecrosis of the jaw; dental implants; metabolic bone diseases; osteoporosis; zoledronic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Density
  • Bone Density Conservation Agents*
  • Dental Implants*
  • Diphosphonates
  • Female
  • Humans
  • Imidazoles
  • Osteonecrosis*
  • Ovariectomy
  • Sheep

Substances

  • Bone Density Conservation Agents
  • Dental Implants
  • Diphosphonates
  • Imidazoles