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] ex erts unique biologic effects on bone, we examined the effects of the v itamin 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 mo del 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/k g/day of 1 alpha,25(OH)(2)D-3, or vehicle alone, given daily for 28 da ys by intraperitoneal injection. 24R,25(OH)(2)D-3 at doses of 1-1000 m u g/kg/day had dose-dependent effects in increasing bone size, dry bon e weight, and bone mineral content without causing hypercalcemia. 1 al pha,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 r esorption 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 mi neral content, as did 1000 mu g/kg/day of 24R,25(OH)(2)D-3. These find ings suggest that 24R,25(OH)(2)D-3 exerts unique activity in the Hyp m ouse rather than merely mimicking the activity of 1 alpha,25(OH)(2)D-3 .