SKELETAL UNLOADING DECREASES PRODUCTION OF 1,25-DIHYROXYVITAMIN-D

The plasma concentration of 1,25-dihydroxyvitamin D [1,25(OH)2D] decre ases during skeletal unloading and increases when normal weight bearin g is restored. To determine whether these changes in plasma 1,25(OH)2D reflect changes in production, metabolic clearance, or both we measur ed the kinetics of 1,25(OH)2D metabolism in rats whose skeletons were normally loaded, unloaded, or reloaded after a period of nonweight bea ring. Skeletal unloading produced a transient but striking fall in the production (-73%) and plasma concentration (-72%) of 1,25(OH)2D witho ut having a significant effect (<20%) on metabolic clearance. Skeletal reloading returned production to normal. Bone formation predictably d ecreased during unloading and returned to normal after return to weigh t bearing. No consistent changes in blood ionized calcium, plasma immu noreactive parathyroid hormone (irPTH), or plasma phosphorus occurred. These data suggest that the changes in plasma 1,25(OH)2D associated w ith changes in skeletal weight bearing primarily reflect changes in 1, 25(OH)2D production. The data provide no evidence that the changes in 1,25(OH)2D production are a consequence of changes in blood ionized ca lcium, plasma irPTH, or phosphorus.