Leptin is a major hormonal product of the adipocyte which regulates appetite and reproductive function through its hypothalamic receptors. It has now become clear that leptin receptors are much more widely distributed than just the hypothalamus, and the skeleton has emerged as an important site of action of leptin.

The signalling form of the leptin receptor has been found in several cell types including human osteoblasts, rat osteoblasts and human chondrocytes. In vitro we have shown leptin to an anabolic factor, stimulating osteoblast proliferation and inhibiting osteoclastogenesis. Leptin increases bone mass and reduces bone fragility when administered peripherally but has an indirect inhibitory effect on bone mass via the hypothalamus when administered directly into the central nervous system.

Data from animal models where there is an absence of either leptin production (ob/ob) or its receptor (db/db) have been contradictory. In this study we compared the bone phenotype of leptin receptor-deficient (db/db) and wild-type (WT) mice. Micro-CT analysis was done on proximal tibiae using a Skyscan 1172 scanner. Db/db mice had significantly reduced trabecular bone volume, trabecular thickness and trabecular number and a higher degree of trabecular separation. Cortical bone was also significantly lower in db/db animals in volume, cross-sectional thickness and perimeter.

These results demonstrate that in the absence of leptin signalling there is reduced bone mass indicating that leptin indeed acts in vivo as a bone anabolic factor, mimicking the in vitro results.