BONE-FORMING ABILITY OF 24R,25-DIHYDROXYVITAMIN D-3 IN THE HYPOPHOSPHATEMIC MOUSE

To determine whether 24R,25-dihydroxyvitamin D-3 [24R,25(OH)(2)D-3] exerts unique biologic effects on bone, we examined the effects of the vitamin D metabolites, 24R,25(OH)(2)D-3 and 1 alpha,25-dihydroxyvitamin D-3 [1 alpha,25(OH)(2)D-3], on the hypophosphatemic (Hyp) mouse, a model for X-linked hypophosphatemic rickets in humans. The Hyp mice were administered 1-10,000 mu g/kg/day of 24R,25(OH)(2)D-3, 0.01-10 mu g/kg/day of 1 alpha,25(OH)(2)D-3, or vehicle alone, given daily for 28 days by intraperitoneal injection. 24R,25(OH)(2)D-3 at doses of 1-1000 mu g/kg/day had dose-dependent effects in increasing bone size, dry bone weight, and bone mineral content without causing hypercalcemia. 1 alpha,25(OH)(2)D-3 at doses of 1 or 10 mu g/kg/day, which we considered to have activity similar to that of 1000 mu g/kg/day of 24R,25(OH)(2)D-3 with respect to cell differentiation activity, caused severe bone resorption and hypercalcemia. At 0.1 mu g/kg/day, 1 alpha,25(OH)(2)D-3 increased bone size, similarly to a dose of 1000 mu g/kg/day of 24R,25(OH)(2)D-3, without significantly affecting dry bone weight or bone mineral content, as did 1000 mu g/kg/day of 24R,25(OH)(2)D-3. These findings suggest that 24R,25(OH)(2)D-3 exerts unique activity in the Hyp mouse rather than merely mimicking the activity of 1 alpha,25(OH)(2)D-3.