Increased bone volume and reduced bone turnover in vitamin D-replete rabbits by the administration of 24R,25-dihydroxyvitamin D3

Abstract

To study the effect of a large dose of 24R,25(OH)2D3 on bone metabolism, we treated vitamin D-replete rabbits with the agent for eight weeks. Fifteen rabbits 20 weeks of age were divided into three groups of five animals each. Group I received only the vehicle; groups II and III were given the agent at doses of 10 micrograms/kg/d, and 100 micrograms/kg/d, respectively. Through the dosing period, serum calcium, phosphorus, alkaline phosphatase, and creatinine levels were not altered. By the end of the experiment, serum 1,25(OH)2D or serum 25(OH)D levels did not change, nor did the PTH level. Serum 24,25(OH)2D levels for groups I, II, and III were 5.25 +/- 3.40, 76.16 +/- 19.90 (p less than .01), and 199.0 +/- 30.90 (p less than .01) ng/ml, respectively. The bone mineral content (BMC) significantly increased in group III. The percentages of BMC increase in group III over group I were 14.5% on the femur, 34.1% (p less than .01) on the sixth lumbar vertebra, and 23.3% (p less than .05) on the seventh lumbar vertebra. A marked increase of bone mineral densities in the cancellous bone-rich regions was seen in group III. Bone histomorphometry on the seventh lumbar vertebra demonstrated that both the eroded surface and the osteoclast number were reduced and the surfaces indicating bone formation such as the osteoid surface and the tetracycline double labeled surface were also reduced. However, both the osteoid thickness and the mineral apposition rate increased and the mineral formation rate at the tissue level remained approximately equal to that in the control.(ABSTRACT TRUNCATED AT 250 WORDS)