Contribution of the intra-specimen variations in tissue mineralization to PTH- and raloxifene-induced changes in stiffness of rat vertebrae

The intra-specimen spatial variation in mineralization of bone tissue can be changed by drug treatments that alter bone remodeling. However, the contribution of such changes to the overall biomechanical effect of a treatment on bone strength is not known. To provide insight into this issue, we used a rat model to determine the effects of ovariectomy, parathyroid hormone, and raloxifene (vs. sham) on the contribution of spatial variations in mineralization to treatment-induced changes in vertebral stiffness. Mineral density was measured from 6-µm voxel-sized quantitative micro-CT scans. Whole-vertebral and trabecular stiffness values were estimated using finite element analysis of these micro-CT scans, first including all intra-specimen variations in mineral density in the model and then excluding such variations by using a specimen-specific average density throughout each specimen. As expected, we found appreciable effects of treatment on overall bone stiffness, the effect being greater for the trabecular compartment (up to 52% reduction vs. sham, p < 0.0001) than the whole vertebra (p = 0.055). Intra-specimen mean mineralization was not changed with treatment but the intra-specimen variation in mineralization was, although the effect was small (4%). Intra-specimen spatial variations in mineralization accounted for 10–12% and 5–6% of overall stiffness of the trabecular compartment and whole vertebral body, respectively. However, after accounting for all treatment effects on bone geometry and trabecular microstructure, any treatment effects due to changes in mineralization were negligible (< 2%), although statistically detectable (p < 0.02). We conclude that, despite a role in the general biomechanical behavior of bone, the spatial variations in tissue mineralization, as measured by quantitative micro-CT, did not appreciably contribute to ovariectomy-, PTH-, or raloxifene-induced changes in stiffness of the whole bone or the trabecular compartment in these rat vertebrae.