Introduction : ONJ risk factors include the exposure to the long term doses of intra-venous bisphosphonates, concomitant use of corticosteroids (combined therapy) and a surgical dental procedure. The aim of this study was to characterize a clinical, histological and microarchitectural bone phenotype after an adapted long-term single or combined therapy in mice.
Materials and methods 24 C3H/HeN adult mice (6 mice per group) were systemically treated (i.p) by 56 days with a single (Zoledronic Acid–ZOL [100 μg/kg twice/week] or Dexamethasone – DX [2,5 mg/kg twice/week]), an adapted combined protocol (ZOL + DX) or saline solution (NaCl). A left first maxillary molar was extracted in all mice at day 21 of treatment. A clinical, histomorphometric (Bone Surface [BS], number of TRAP (+) cells) and a micro-CT assessment (Bone volume [BV]) were performed at the end of experience.
Results : No bone exposition was confirmed. The single use of DX significantly decreased alveolar BS. The single use of ZOL exhibited a protective effect of bone loss. No change in BS was observed with combined therapy. The single or combined use of DX induced a significant activation of osteoclasts, however a single use of ZOL does not increased the number of osteoclast activated. The single use of ZOL increased the volume of alveolar bone. On the contrary, the single or combined use of DX does not modify the alveolar bone volume.
Conclusions : The single use of ZOL or DX induced a sclerotic or osteopenic alveolar bone phenotype, respectively. This bone changes were osteoclasts-dependent, suggesting a key role of osteoclasts in the pathogenesis of ONJ. Otherwise, combined therapy showed an intermediate response without induces significant changes in alveolar bone, suggesting a compensatory effect of both drugs tested in this model.