Bone Abstracts

Bisphosphonates (BP) are used as anti-resorptive drugs in benign (osteoporosis) and malignant (myeloma, bone metastasis) bone diseases. Their high affinity for biominerals allows prolonged storage within bone. However information about molecular impact of BP on bone quality are missing. Better understanding of BP properties to optimize their clinical use is needed. The aim of this study was thus to investigate human bone physicochemical changes upon BP uptake.

Methods: Bone sequesters obtained from 24 patients (42–94 years old) suffering from BP-related osteonecrosis of the jaw were used and split into two groups: low-dose (BP_low group, n=8) and high-dose (BP_high group, n=16) therapies, respectively for benign and malignant bone diseases. The control group (CTL, n=24; 64–93 years old) was composed of cadaver mandibular samples. Raman microspectroscopy measured mineral/organic ratio, carbonate/phosphate ratio, cristallinity degree, and mineral and collagen maturities. Chemometric discriminant method was used to isolate spectral features of each group.

Results: In the BP_high group, mineralization, mineral and collagen maturities were increased significantly by 15, 43 and 57% respectively, compared to the CTL group (P<0.01). In contrast, cristallinity was lowered by 2.3% in the BP_high group (P<0.002). Similar trends were observed with the BP_low group. Chemometric distinguished the CTL group as characterized by organic components (amides and collagen) from BP groups, indicating a greater mineralization with BP. In addition, the ν₁ phosphate band shifted between CTL and BP groups, suggesting changes in apatitic crystal organization by BP.

Conclusion: This study highlights the modifications of bone quality in mandibular bone during BP treatment at a molecular level. These changes occur in both mineral and organic compartments of bone.