Organic Bone Matrix Component Type I and V Collagen Are Not Destructed in Bisphosphonate-Associated Osteonecrosis of the Jaws

Abstract

Background and objectives: The investigation of the pathophysiology behind medication-related osteonecrosis (MRONJ) of the jaw mostly focuses on alterations in osteoclast and osteoblast cell activity, but changes in the organic and inorganic bone matrix have rarely been studied. The aim of this study was to investigate whether collagen, the main organic component of extracellular bone matrix, is destructed in osteonecrosis of the jaw secondary to antiresorptive medication. Material and methods: Bone samples of patients with MRONJ (n = 15, control group n = 3) were demineralized, and collagen fragments were separated from intact collagen pellets by ultrafiltration. The quantification of mature collagen cross-links hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) in pellets and ultrafiltrates was performed by high-performance liquid chromatography (HPLC). The detection of hydroxyproline (Hyp) was carried out using a spectrophotometric assay. In addition, collagen chains were analyzed by sodium dodecylsulfate-polyacrylamide gel (SDS-PAGE). Results: The results revealed significantly higher concentrations of HP, LP and Hyp in pellet samples. In addition, there were no significant differences between samples from MRONJ patients and those of the control group. These results were paralleled by SDS- PAGE. Conclusion: These findings suggest that MRONJ does not involve the destruction of type I and V collagen molecules, in contrast to previously reported destruction by osteoradionecrosis.