Molecular alterations of bone quality in sequesters of bisphosphonates-related osteonecrosis of the jaws

Abstract

Compared to healthy bone, the intrinsic bone materials properties in the pre-existing lamellar bone are altered in jaw bone sequesters of bisphosphonates (BP)-related osteonecrosis. The aim of this study was to evaluate the human jaw bone quality, especially intrinsic bone material properties among sequesters of osteonecrosis of the jaw (ONJ) induced by BP. Bone sequesters were obtained from 24 patients suffering from ONJ following a BP treatment. Within BP-exposed bone samples, benign-BP and malignant-BP groups were distinguished in relation to the underlying disease: osteoporosis and bone metastases or multiple myeloma, respectively. Healthy cadaveric cortical jaw bone samples were used as controls. The physicochemical parameters of bone samples - mineral/organic ratio, relative proteoglycan content, crystallinity, monohydrogen phosphate content, and type-B carbonate substitution - were evaluated by Raman microspectroscopy. Representative Raman spectral features of bones control and BP-exposed bone sequesters were identified with the Partial-Least-Square Discriminant Analysis (PLS-DA). BP-exposed bone sequesters are characterized by a significant increase of mineral to organic ratio (+12 %) and a significant decrease of relative proteoglycan content (-35 %), thus regulating initial collagen matrix mineral deposition. Structural changes on mineral components are revealed by a significant decrease of both crystallinity (-2 %) and mineral maturation (-41 %) in the BP-exposed bone sequesters compared to healthy bones. These modifications were also observed distinctly in both benign-BP and malignant-BP groups. In addition, a shift of the phosphate ν1 band was highlighted by PLS-DA between bones control and BP-exposed bone sequesters, revealing a disruption of the apatitic phosphate environment in the jaw bone sequesters. The present data show that jaw bone quality can be altered with an overmineralization and ultrastructural modifications of apatitic mineral in bone sequesters of BP-related ONJ.