24R,25dihydroxyvitaminD(3)による骨形成促進作用―Hyp マウスにおける検討―

The biological role of 24R, 25(OH)(29D(3) is still controversial, although 24R, 25(OH)(2)D(3) has been reported to have peculiar effects particularly on the bone. To examine the biological effects of 24R, 25(OH)(2)D(3), we administered Hyp mouse, which is a model for familial X-linked hypophosphatemic rickets in man, 1-10000μg/kg/day of 24R, 25(OH)(2)D(3) or 0.01-10μg/kg/day of 1α,24R, 25(OH)(2)D(3) for 28 successive days by intraperitoneal injecton. 24R, 25(OH)(2)D(3) increased the body weight gain, bone size, bone formation and mineralization and reduced the serum alkaline-phosphatase activity, dose-dependnetly from 1 to 1000μg/kg/day without hypercalcemia. Severe bone resorption and hypercalcemia were caused by 1 and 10μg/kg/day of 1α, 25(OH)(2)D(3), which are considered to be equivalent to 1000μg/kg/day of 24R, 25(OH)(2)D(3) in the affinity to the receptor of 1α, 25(OH)(2)D(3). On the other hand, 0.1μg/kg/day of 1α, 25(OH)(2)D(3) increased bone size, bone formation and mineralization to a similar degree as 1000μg/kg/day of 24R, 25(OH)(2)D(3), but did not increase body weight gain, dry bone weight or bone mineral contents, did not reduce serum alkaline-phosphatase activity. At 0.1μg/kg/day, 1α, 25(OH)(2)D(3) increased not only bone formation and mineralization but also bone resorption on Hyp mice. These findings suggest that 24R, 25(OH)(2)D(3) has peculiar biological effects on Hyp mouse rather than merely mimicking that of 1α, 25(OH)(2)D(3) mediated by its receptor.