Bone quality and osteonecrosis of the jaw induced by bisphosphonates

Abstract

Osteonecrosis of the jaw (ONJ) is a complication of long-term bisphosphonates therapy whose etiology and pathogenesis are not fully understood. Our purpose was to assess the quality of bone in the jaws of control subjects, and osteoradionecrosis (ORN) and ONJ patients.Materials and methods: six jaw bone samples were taken from control patients. Eight jaw bone samples in patients with osteonecrosis (2 ORN and 6 ONJ) were also taken during conservative surgery. Histology was used to analyze cellular composition, microarchitecture and static variables of bone formation and resorption. Bone quality was also assessed using Vickers microindentation (measurement of microhardness) and quantitative microradiography [measurement of the mean degree of mineralization of bone (DMB) and of the heterogeneity index (HI) of the distribution of the mineralization].Results: compared to controls, the osteonecrotic bone was hypovascularized, eroded, poor in osteoblasts and contained numerous empty periosteocytic lacunae. DMB (control group 1.14 ± 0.13 g.cm –3 , ORN 1.25 ± 0.14 g.cm –3 and ONJ 1.11 ± 0.12 g.cm –3 ) and HI (control group 0.18 ± 0.08 g.cm –3 , ORN 0.17 ± 0.06 g.cm –3 and ONJ 0.24 ± 0.08 g.cm –3 ) in osteoradionecrosis and ONJ samples were not significantly different from controls. Hypermineralization was never observed in ONJ. Bone microhardness after osteoradionecrosis (50.04 ± 4.34 kg.mm –2 ) and ONJ (47.48 ± 4.10 kg.mm –2 ) was slightly decreased compared to controls (53.52 ± 6.46 kg.mm –2 ).In conclusion, bisphosphonates-induced ONJ was neither associated with modifications of secondary bone mineralization, nor changes in bone microhardness. Bone vessels and cellular changes appeared to play a major role in the development of ONJ.