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Zolendronate may cause ONJ if periodontitis is present



DOI:10.1038/bonekey.2012.176

This study uses the rice rat model, in which rats are fed a high sucrose and casein diet to accelerate periodontitis. Simultaneously, groups of the mice were also treated with different bisphosphonates (BPs). One group received alendronate (15 μg/kg; subcutaneous injection twice each week), while two other groups were given zoledronic acid (ZOL; low dose (8 μg/kg) and high dose (80 μg/kg), given as monthly intravenous injections). The high dose ZOL mimics the human dose given to cancer patients.

The progression of periodontitis, the status of the alveolar bone in the underlying jaw (including the level of bone formation/resorption), the level of vascularisation, and also the level of viable osteocytes present, were assessed at 6, 12, 18 and 24 weeks. At the two latter time points, only the high-dose ZOL group exhibited clear lesions resembling osteonecrosis of the jaw (ONJ). Bone formation was inhibited, the vascularity of the jaw was decreased and osteocyte numbers were significantly lowered.

Editor's comment: The rice rat was a model reported in the mid fifties to investigate the development of periodontal disease. In 1981, Gotcher and Jee demonstrated that severe periodontitis, that is local infection and inflammation, could lead to the destruction of alveolar bone with the appearance of necrotic bone remnants. Clodronate prevented alveolar bone loss but also increased the amount of alveolar bone protruding in the oral cavity, suggesting a vicious circle by which necrotic bone caused by severe periodontitis/osteomyelitis and not being removed as a result of low bone turnover would further promote inflammatory/infectious sockets and bone necrosis. The new study by Aguirre et al. is a repetition of the same with zoledronate, only this time the lesions are characterized as ONJ. Whether BPs can induce ONJ in absence of preexisting injury/inflammation/infection remains to be determined.


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