Bisphosphonates (BPs) are widely used for treating osteoporosis and preventing osseous metastasis or hypercalcemia in cancers. However, osteonecrosis of the jaw in patients treated with BP after dentoalveolar surgery has been increasing, especially in those treated with strong BPs such as zoledronate (ZA). The pathobiology underlying the occurrence of osteonecrosis only in the jaw bone remains unclear. The objective of this study was to compare the effects of BPs on the in vivo osseous healing process between an extracted socket and a tibial defect. Rats were intravenously injected with 0.067 mg/kg of ZA, the weaker BP etidronate (EA), or vehicle once a week for six weeks. A mandibular molar was extracted, and a hole defect was created in the tibia 2 weeks after BP treatment. Bone healing was evaluated using microcomputed tomography and histological staining 1 and 4 weeks after defect creation. Pre-administration of ZA inhibited bone resorption at both extraction molar and tibia defect. The subsequent net result was impaired bone healing at the extraction socket versus excessive woven bone formation in the tibia. The healing process involved bone resorption before bone formation in the socket, whereas the opposite was true for tibia defect. However, the EA enhanced the in vivo bone healing of both areas and had minor anti-resorptive activity as like control. The activity on osteoclast activation in vivo was consistent with the in vitro effects of the two BPs on osteoclast differentiation. In conclusions, the anti-resorptive action of ZA had a negative effect on bone healing, particularly at the extraction socket in the jaw. These results suggest that the difference in healing process is another critical factor to the preferential osteonecrosis at the area of extracted teeth rather than tibial defect after pre-administration of a potent anti-resorptive BP.
14 May 2016 - 17 May 2016