Regulation of bone turnover and prevention of bone atrophy in ovariectomized beagle dogs by the administration of 24R, 25(OH)2D3

Summary In order to determine whether the administration of 24R,25(OH)₂D₃ had any beneficial effect on the regulation of bone turnover and the prevention of bone atrophy, we examined beagles for 31 months after ovariectomy (OVX). Fourteen beagle dogs (8.54±1.22 kg body wt-b.w.) were divided into four groups. Group 1 (n=3) was the sham, and Group 2 (n=3) served as the OVX control. In Group 3 (n=4) and Group 4 (n=4), 24,25-dihydroxyvitamin D₃(24R,25(OH)₂D₃) was given daily at dose levels of 2 and 10 mcg/kg B.W., respectively. In Group 4, the dose level was increased to 100 mcg/kg by 17 months. During the experiments, urinary hydroxyproline (U-HPr), serum chemistry, serum bone gla-protein (BGP), and vitamin D metabolite levels were monitored. At the end of the experiment, bone mineral content (BMC) in the 6th and 7th lumbar vertebrae and right femur was determined by single photon absorptiometry. The left iliac bone sample was obtained after tetracycline labeling, and undecalcified sections were observed. In Group 2, excretion of U-HPr increased after OVX and had reached a level of approximately twice the baseline values by 10 months; then it gradually came down to the original level. In Group 3, however, U-HPr excretion remained at the same level as the baseline value, as it did in Group 1. In Group 4, it was remarkably reduced down to 50–60% of the baseline values. Serum BGP level was markedly reduced in Group 4. Serum 24,25(OH)₂D levels were markedly increased in Groups 3 and 4. BMC levels of both vertebrae and epi-metaphyseal regions in the femur showed a significant reduction of approximately 25% in Group 2. In Groups 3 and 4, however, they remained at the same level as in Group 1. Histomorphometrical data showed a reduction in the parameters of osteoblast functions in Group 2. In Group 3, both kinetic and static parameters maintained the same level as in Group 1. In Group 4, eroded surface and osteoclast number decreased significantly, but mineral appositional rate and wall thickness maintained the same level as in Group 1. From these findings, it was concluded that, in beagle dogs, the administration of 24R,25(OH)₂D₃ inhibited the increase of bone turnover and prevented the reduction of cancellous bone mass after a long time postovariectomy.