Bone Abstracts

Introduction: Bone metastasis pathophysiology is currently defined as a vicious circle. Indeed, tumor cells co-express RANK-L and its receptor, RANK, allowing their own proliferation and peritumoral bone resorption necessary to the lesion expansion. Odontogenic tumors, which occur within the jaw, seem to present the same pathophysiological characteristics. Thus, studying the impact on bone of RANK over-expression by the osteoclasts would permit a better understanding of those tumoral processes. We will here describe a part of our data, concerning the bone phenotype of a transgenic mice model over-expressing RANK in the monocyte-macrophage lineage.

Description of methods: Forty-one 6 weeks old mice were used for this study; they were analyzed according to their genotype and sex. For each mouse, right femur was used for histomorphometric analyses, and the left one for μCT. Mice were injected with tetracycline and calcein 72 and 24 h before sacrifice.

Results: At 6 weeks old, transgenic female had an increased BV/TV (+2%; P=0.0355), increased trabecular number (+19%; P=0.0106) and reduced trabecular separation (−18%; P=0.0454). Body weight, osteoclast and dynamic parameters were equivalent.

Concerning transgenic males, trabecular number was increased (+19%; P=0.0431), and also increased mineralizing surface (MS/BS) (+35%; P=0.0256), suggesting an increased osteoblastic activity.

Conclusion: This study is the first one describing bone phenotype of those transgenic mice. RANK over-expression in monocyte-macrophage lineage seems to induce different effects in male and female at 6 weeks. Interestingly, regarding central role of RANK in osteoclast differentiation, we do not observe any modification in osteoclast number and surface. This study will be completed by analyses of earlier and later stages for the long bones, and the same stages will be analyzed for mandibular bone.