Site specific effects of Zoledronic acid on vascularization in jaw bone versus femur

Abstract

Background: Medication-related osteonecrosis of the jaws (MRONJ) is a newly updated nomenclature after bisphosphonate-related osteonecrosis of the jaws, which is characterised clinically as an area of exposed bone in the maxilla or the mandible that has failed to heal within a period of six to eight weeks in a patient exposed to various drugs including bisphosphonate, denosumab, and antiangiogenic agents. Although all MRONJ presented as avascular lesions, the aetiology and pathogenesis have not been fully investigated. The reason why the necrosis was found in jaw bones only remains unknown. Objectives: This study aimed to compare the effects of bisphosphonates on angiogenesis in jawbone and long bones using a Sprague-Dawley (SD)-rat model. Methods: 72 SD-rats were treated with zoledronic acid (ZA; n = 36) or saline (n = 36) for four weeks and then subjected to tooth extractions on mandibles and maxillas and creations of bone defect on femurs. The rats then were treated with zoledronic acid till sacrifice at week two, four and eight. The site of tooth extraction on jaws, and the defect on femurs were analysed by histomorphometry and microcomputed tomography (micro-CT) examination. Findings and Conclusion: Micro-CT scanning showed higher bone density in ZA treated femur and jaw bones comparing with that in saline treated group. Necrotic bone was found only in the mandibles in ZA treated group. Vascular casts by micro-CT examination showed that the blood vessels in ZA treated group were denser but less structured than that in control group in jaw bones; however, the difference was not evident in femur site.