Bone Abstracts

Adaptive responses of the skeleton to loading changes architecture and physical properties in order to optimise strength for function. However, bone is subjected to many local and circulating osteotropic factors, most acting on G-protein coupled receptors. Receptor activity modifying protein-3 is a single trans-membrane domain receptor accessory protein, which aids in trafficking of calcitonin and calcitonin-like receptors to the cell surface and changes ligand selectivity. As RAMP3^−/− mice have a high bone mass phenotype, we hypothesised that their bones would respond less to mechanical loading than wild types as they already have a skeleton that is adapted to supra-physiological loads. We applied cyclical dynamic loads to left tibiae of RAMP3^−/− (n=8) and WT (n=7) male mice, using a trapezoidal waveform, with peak compressive loads of 13N, engendering high physiological strain magnitudes at 180 000 microstrain per second on alternate days for two weeks. Right tibiae were internal non-loaded controls. In WT mice, whole bone volume was increased by 18% in the loaded tibia (P=0.03) when compared to a 15% increase in the RAMP3^−/− group (P=0.05). Loading induced significant changes in cortical bone volume of both groups compared with contra-lateral non-loaded tibiae, but there was no difference between the two groups (WTs: 11%, increased cortical volume, P≤0.0001 compared with 10% increase in RAMP3^−/− mice, P=0.0168). Analysis of surface properties of bones in the two groups using a reference point micro-indentation device showed that there was no difference in the surface mechanical properties of loaded bones in the two groups (total indentation distance in RAMP3^−/− mice: 36±9 μm compared with 30±7 μm in WTs). These results are consistent with an ability of RAMP3 to exert an inhibitory effect on bone formation, not through a change in sensitivity to mechanical loading, but through a receptor mediated endocrine or paracrine response.