1α-Hydroxyvitamin D 2 and 1α-hydroxyvitamin D 3 have anabolic effects on cortical bone, but induce intracortical remodeling at toxic doses in ovariectomized rats

Abstract

It is well established that vitamin D metabolites have anabolic properties on cancellous bone in rats. However, few data are available on cortical bone effects of vitamin D metabolites. In this study, we examined the effects of the synthetic vitamin D analogs 1α-hydroxyvitamin D 2 (1α(OH)D 2) and 1α-hydroxyvitamin D 3 (1α(OH)D 3) on cortical bone of the tibial shaft in ovariectomized (OVX) rats using bone histomorphometry. Six-month-old Fischer 344 rats were either OVX or sham-operated (SHAM). OVX rats received vehicle, 1α(OH)D 2 or 1α(OH)D 3 orally via the diet in a dose range from 0.025 to 0.2 μg/kg/day. All animals were killed 3 months postsurgery after in vivo fluorochrome labeling. Relative to SHAM rats, vehicle-treated OVX rats showed a reduction in cortical bone area (%) due to expansion of the marrow cavity. Treatment of OVX rats with either 1α(OH)D 2 or 1α(OH)D 3 dose-dependently decreased marrow area, and increased cortical area, periosteal perimeter, and periosteal and endocortical bone formation rate compared with OVX vehicle controls. Interestingly, OVX animals receiving the highest doses showed intracortical resorption cavities, a phenomenon only exceptionally observed in rats. The intracortical hole area was significantly lower in 1α(OH)D 2-treated compared with 1α(OH)D 3-treated rats. We conclude that 1α(OH)D 2 and 1α(OH)D 3 prevent cortical bone loss in OVX rats and have anabolic effects on cortical bone at higher doses. However, very high, toxic doses of both vitamin D analogs induce intracortical remodeling as an untoward side effect.