Long-term changes in bone mineral and biomechanical properties of vertebrae and femur in aging, dietary calcium restricted, and/or estrogen-deprived/-replaced rats

Abstract

To study the long-term effect of aging, low calcium diet (LCD) and/or ovariectomy (OVX), and estrogen replacement therapy (+E) on rat bone quality of both trabecular and cortical bone, 150 female Wistar rats of 4.5 months were divided into baseline, sham-operation (sham), sham + LCD, OVX, OVX + E, OVX + LCD, OVX + LCD + E, and were observed for 3, 6, and 9 months postsurgery. The bone mineral density (BMD) of the lumbar spine L1-L4, the femoral neck, the midshaft, and the distal metaphysis were determined using dual-energy X-ray absorptiometry (DXA) in vitro. Biomechanical tests of the L1 vertebral body and the left femur were performed. The right femoral midshaft and neck were processed undecalcified for determining cross-sectional moments of inertia (CSMIs). BMD in all groups increased rapidly with aging in the femoral midshaft composed only of cortical bone at 3 months post-OVX and stabilized or decreased thereafter, but decreased at all observation periods in the distal femoral metaphysis, consisting mostly of trabecular bone. L1 maximum compressive strength and stiffness increased as a function of aging in sham and sham + LCD but not in OVX and OVX + LCD. The order of loss in BMD at all sites and in L1 strength and stiffness was: OVX + LCD > OVX > LCD. LCD reduced while OVX improved the total femoral area, CSMIs in the femoral midshaft, and the torsional strength. Estrogen treatment preserved BMD and prevented OVX-induced loss in L1 strength. The BMD and biomechanical properties were greater in OVX + E than in OVX + LCD + E. Loss in BMD and CSMIs was greater in the femoral neck than in the midshaft. The data suggest that rat cortical bone might not be matured until 7.5 months of age. It would be more appropriate to consider rats at peak bone mass as a model of mature rat and to perform OVX at that time. LCD and OVX have a great potential for weakening the bone quality of cortical bone and trabecular bone, respectively, and have an additive effect when combined. Estrogen prevents only OVX-induced bone loss.