Femoral Neck Trabecular Microstructure in Ovariectomized Ewes Treated With Calcitonin: MRI Microscopic Evaluation

Abstract

Ovariectomy induces deterioration of the trabecular structure in the femoral neck of ewes, as depicted by MR microscopic imaging. This structural deterioration is prevented by salmon calcitonin treatment. This study evaluated the trabecular (Tb) microarchitecture of an ovariectomy (OVX)-induced osteoporotic model in ewes and determined the effects of salmon calcitonin (sCT), an osteoclast inhibitor, on the Tb structure. This is the first report of OVX-induced changes in the Tb structure in the femoral neck in the ewes and effect of sCT on the microarchitecture. Ewes (5-8 years old, n = 28) were equally allocated into sham (Sham), OVX injected with vehicle, or OVX injected with sCT at 50 or 100 IU, three injections per week. They were killed 6 months after OVX. The femoral neck was examined with an MR imager at 9.4 T in axial, coronal, and sagittal planes. An internal calibration procedure as a means of standardizing image analysis was used to adjust the segmentation threshold. Data from all three planes were averaged. Compared with Sham, OVX induced significant changes (p < 0.0125) in the MRI-derived femoral neck Tb structure: Tb bone volume fraction (BV/TV), -18%; Tb number, -20%; Tb separation, +23%; number of free ends, +28%; number of nodes, -39%; number of Tb branches, -23%; mean length of Tb branches, -19%. Compared with OVX, treatment of sCT at 100 IU significantly improved all the Tb structural parameters to the Sham level (p < 0.0001 approximately p = 0.0281), whereas 50 IU significantly increased the Tb number and the mean length of the Tb branches. BV/TV explained 74% of the variation of compressive stress of the trabecular cylinder cores of the femoral neck. Combining all structural parameters in a multivariate regression analysis significantly improved the explanation to 84%, and adding BMD further improved the predictive ability of the model to 92%. We conclude that OVX induces deterioration of the MRI-derived Tb microstructure in the femoral neck of ewes. sCT treatment prevents OVX-induced changes. The femoral neck microarchitecture significantly correlates with its biomechanical properties. Combining microstructural parameters with BMD further improves the prediction of bone biomechanical properties. The effects of sCT on OVX ewes may help explain reduced fracture risk in postmenopausal osteoporotic women treated with sCT.