J. Cornish, G. Williams, K. Callon, J. Lin, M. Watson, Y. Wang, J. Lam, A. Orpe, N. Broom, J. Costa, D. Naot, I. Reid

Fat mass impacts on both bone turnover and bone density, and is a critical risk factor for osteoporotic fractures. Adipocyte-derived hormones may contribute to this relationship, and adiponectin is the principal circulating adipokine. However, its effects on bone remain unclear. We have, therefore, investigated the direct effects of adiponectin on bone cells in vitro, and determined the bone phenotype of adiponectin-deficient mice. Adiponectin was dose-dependently mitogenic to primary osteoblasts (60% increase at 10 μg/mL), and markedly inhibited osteoclastogenesis (by 26% and 54% at 1 and 5 μg/mL, respectively). It had no effect on bone resorption in isolated mature osteoclast assays.

In adiponectin-knockout (AdKO) male C57BL/6J mice, trabecular bone volume and trabecular number (assessed by micro-computed tomography) were increased at 14 weeks of age, by 30% (p=0.02) and 38% (p=0.0009), respectively. Similar, non-significant trends were observed at 8 and 22 weeks of age. Biomechanical testing showed lower bone fragility and reduced cortical hardness at 14 weeks.We conclude that adiponectin acts directly on bone cells, but that these actions do not explain the bone phenotype of the knockout animals. Thus, it must also have indirect effects on bone, possibly through modulating growth factor action, or insulin sensitivity. Since adiponectin does influence bone mass in vivo, it is likely to be a contributor to the fat-bone relationship.

Disclosures: None