The role of 1,25-dihydroxyvitamin D in the inhibition of bone formation induced by skeletal unloading.
Skeletal unloading results in osteopenia. To examine the involvement of vitamin D in this process, the rear limbs of growing rats were unloaded, and alterations in bone calcium and bone histology were related to changes in serum calcium (Ca), inorganic phosphorus, 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D [24,25-(OH)2D], and 1,25-dihydroxyvitamin D [1,25-(OH)2D]. Acute skeletal unloading induced a transitory inhibition of Ca accumulation in unloaded bones. This was accompanied by a transitory rise in serum Ca, a 21% decrease in longitudinal bone growth (P less than 0.01), a 32% decrease in bone surface lined with osteoblasts (P less than 0.05), no change in bone surface lined with osteoclasts, and a decrease in circulating 1,25-(OH)2D from 130 +/- 10 to 53 +/- 11 pg/ml. No significant changes in the serum concentrations of inorganic phosphorus, 25-hydroxyvitamin D, or 24,25-(OH)2D were observed. After 2 weeks of unloading, bone Ca stabilized at approximately 70% of control values, and serum Ca and 1,25-(OH)2D returned to control values. Maintenance of a constant serum 1,25-(OH)2D concentration by chronic infusion of 1,25-(OH)2D (Alza osmotic minipump) throughout the study period did not prevent the bone changes induced by acute unloading. These results suggest that acute skeletal unloading in the growing rat produces a transitory inhibition of bone formation, which, in turn, produces a transitory hypercalcemia, leading to a temporary decrease in serum 1,25-(OH)2D. No evidence could be found for a direct involvement of 1,25-(OH)2D in the bone changes induced by skeletal unloading.
D015650:24,25-Dihydroxyvitamin D 3; D001842:Bone and Bones / Q000378:metabolism*; D002112:Calcifediol / Q000378:metabolism; D002117:Calcitriol / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D004100:Dihydroxycholecalciferols / Q000378:metabolism; D008954:Models, Biological; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism; D013131:Spine / Q000166:cytology / Q000378:metabolism; D013314:Stress, Mechanical; D013977:Tibia / Q000166:cytology / Q000378:metabolism
D004100:Dihydroxycholecalciferols; D015650:24,25-Dihydroxyvitamin D 3; D002117:Calcitriol; D002112:Calcifediol; D002118:Calcium