Bone Abstracts

Bone resorption and deposition occur in a tightly regulated fashion reflecting the coupled activities of osteoclasts and osteoblasts. Several pathological conditions perturb this balance between bone synthesis and resorption, including osteoporosis and skeletal metastases. The uncoupling of remodeling activities contributes to disseminated tumor cells homing to the bone and to tumor growth in bone. Therefore, a reliable marker of bone remodeling would be useful to provide a strong correlation with the extent of skeletal disease, evaluate the effectiveness of an intervention to suppress resorption associated with metastases or menopause and to predict future bone metastases in cancer patients without malignant spread. The purpose of this study is to determine if the fluorescent bisphosphonate imaging probe osteosense (Perkin Elmer) can predict bone turnover in ovariectomized and parathyroid hormone (PTH)-treated mice. While absolute fluorescence suggests a trend of decreased osteosense binding in ovariectomized mice, no statistical difference was observed. To determine whether bone affinity, rather than total binding capacity, could serve as a more reliable marker of bone minerlization, kinetic analysis of binding was measured. Regressional analysis suggests that decreases in bone mineralization caused by ovariectomy results in significant reductions in the rates of osteosense binding at the proximal tibia as compared to wild-type mice. This observation was found to be highly consistent between mice, showing little intra group variation. The utility of binding kinetics as a tool for monitoring changes in bone mineralization was further confirmed in a bone-gain model in which ovariectomized mice were treated intermittently with parathyroid hormone. Binding kinetics analysis revealed significant increases in osteosense binding in mice treated with PTH as compared to control mice. Our data suggests a highly reproducible and sensitive method for monitoring changes in bone mineralization using the binding kinetics of osteosense.