Bone Abstracts

Bisphosphonates (BPs) such as zoledronic acid (ZA) are widely used to treat bone diseases. The use of BPs can lead to osteonecrosis of the jaw (ONJ), but it is not clear why in particular the jaw bone is affected. Previously, it was shown that osteoclasts derived from different bone sites have different properties. We hypothesize that BPs have distinct effects on bone-site specific osteoclasts or precursors. To investigate this, female C57BL/6J mice were injected intraperitoneally with 0 5 mg/kg zoledronic acid (ZA) or saline once a week. At baseline and after 1, 3, and 6 months, jaw and long-bone marrow cells were isolated and osteoclastogenesis was induced in vitro. The number of multinucleated TRACP-positive cells was assessed. Bone volume and the degree of mineralization of bone (DMB) of the humeri and mandibles were assessed with microCT. After 6 months of treatment, fewer jaw bone marrow cells were isolated from ZA-treated mice than from controls. This effect was not seen for long bones. ZA treatment did not affect the osteoclastogenic potential of long-bone and jaw osteoclast precursors. ZA treatment significantly increased the bone volume and the DMB of both humeri and mandibles. In conclusion, these results indicate that ZA reduces the number of jaw bone marrow cells without affecting long-bone marrow cells. Our findings support the hypothesis that BPs have distinct effects on different osteoclast precursors and may help to gain more insight into the pathogenesis of BP-related ONJ.