Periodontal disease and bisphosphonates induce osteonecrosis of the jaws in the rat

Tara L. Aghaloo, Ben Kang, Eric C. Sung, Michael Shoff, Matthew Ronconi, Jack Gotcher, Olga Bezouglaia, Sarah M. Dry, Sotirios Tetradis

Research output: Contribution to journalArticle

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Abstract

Bisphosphonates (BPs) are medications used commonly to treat primary and metastatic bone cancer, as well as osteoporosis. Although BPs improve bone mineral density, reduce fracture risk, and reduce hypercalcemia of malignancy, some patients develop BP-related osteonecrosis of the jaws (BRONJ). This devastating complication is defined as clinically exposed bone in the maxillofacial region for more than 8 weeks. Despite an increasing number of BRONJ cases since first reported, the disease pathophysiology remains largely unknown. Since published studies suggest a significant role for dental disease in the pathophysiology of BRONJ, we developed a BRONJ animal model where aggressive periodontal disease is induced by ligature placement around the crown of the right maxillary first molar in the presence of vehicle (veh) or zoledronic acid (ZA), a potent BP. Ligature placement induced significant alveolar bone loss, which was attenuated by ZA treatment. Osteonecrosis was observed associated with ligature-induced periodontitis in the ZA-treated group. This was seen as sequestration and extensive periosteal alveolar bone formation on micro-computed tomography (μCT) in the ligated site of BP-treated animals. Histologic examination confirmed these findings, seen as necrotic bone with diffuse loss of osteocytes and empty lacunae, rimming of the necrotic bone by squamous epithelium and inflammation, and exposure to the oral cavity. Importantly, the rat lesions were strikingly similar to those of BRONJ patients. Our data suggest that dental disease and potent BP therapy are sufficient for BRONJ development in the rat.

Original languageEnglish (US)
Pages (from-to)1871-1882
Number of pages12
JournalJournal of Bone and Mineral Research
Volume26
Issue number8
DOIs
StatePublished - Aug 1 2011

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Bisphosphonate-Associated Osteonecrosis of the Jaw
Osteonecrosis
zoledronic acid
Periodontal Diseases
Jaw
Diphosphonates
Ligation
Stomatognathic Diseases
Bone and Bones
Alveolar Bone Loss
Osteocytes
Bone Neoplasms
Periodontitis
Hypercalcemia
Crowns
Osteogenesis
Bone Density
Osteoporosis
Mouth
Epithelium

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

Cite this

Aghaloo, T. L., Kang, B., Sung, E. C., Shoff, M., Ronconi, M., Gotcher, J., ... Tetradis, S. (2011). Periodontal disease and bisphosphonates induce osteonecrosis of the jaws in the rat. Journal of Bone and Mineral Research, 26(8), 1871-1882. https://doi.org/10.1002/jbmr.379

Periodontal disease and bisphosphonates induce osteonecrosis of the jaws in the rat. / Aghaloo, Tara L.; Kang, Ben; Sung, Eric C.; Shoff, Michael; Ronconi, Matthew; Gotcher, Jack; Bezouglaia, Olga; Dry, Sarah M.; Tetradis, Sotirios.

In: Journal of Bone and Mineral Research, Vol. 26, No. 8, 01.08.2011, p. 1871-1882.

Research output: Contribution to journalArticle

Aghaloo, TL, Kang, B, Sung, EC, Shoff, M, Ronconi, M, Gotcher, J, Bezouglaia, O, Dry, SM & Tetradis, S 2011, 'Periodontal disease and bisphosphonates induce osteonecrosis of the jaws in the rat', Journal of Bone and Mineral Research, vol. 26, no. 8, pp. 1871-1882. https://doi.org/10.1002/jbmr.379
Aghaloo, Tara L. ; Kang, Ben ; Sung, Eric C. ; Shoff, Michael ; Ronconi, Matthew ; Gotcher, Jack ; Bezouglaia, Olga ; Dry, Sarah M. ; Tetradis, Sotirios. / Periodontal disease and bisphosphonates induce osteonecrosis of the jaws in the rat. In: Journal of Bone and Mineral Research. 2011 ; Vol. 26, No. 8. pp. 1871-1882.
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