ABNORMAL MODULATION OF SERUM OSTEOCALCIN BY DIETARY PHOSPHATE AND 1,25-DIHYDROXYVITAMIN D-3 IN THE HYPOPHOSPHATEMIC MOUSE

We evaluated in normal and hypophosphatemic (Hyp) mice whether changes in serum levels of osteocalcin in response to dietary phosphate suppl ementation, parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D-3 (1 ,25(OH)(2)D-3) administration were related to perturbations in calcium phosphate homeostasis. In normal mice, serum osteocalcin levels mere not altered by phosphate supplementation. In contrast, phosphate suppl ementation in Hyp mice led to a 2-fold decrease in serum osteocalcin t o normal levels after 3 days and to an increase in osteocalcin levels after 14 days, The decrease in osteocalcin was associated with normoph osphatemia, severe hypocalcemia, and marked increases in circulating 1 ,25(OH)(2)D-3 levels, whereas the increase in osteocalcin levels was a ssociated with normophosphatemia and no change in serum calcium and 1, 25(OH)(2)D-3. Administration of PTH decreased serum osteocalcin in bot h genotypes. Infusion of 1,25(OH)(2)D-3 for 3 days elicited increases in serum osteocalcin and calcium levels in normal mice, whereas in Hyp mice it produced significant decreases in osteocalcin Levels and no c hange in serum calcium, However, with a more prolonged infusion of 1,2 5(OH)(2)D-3, hypercalcemia and increases in serum osteocalcin were ind uced in mutant mice, Our results suggest that the abnormal osteocalcin response of Hyp mice is not directly attributable to an osteoblast dy sfunction but is secondary, at least in part, to perturbations in fact ors that modulate the osteoblast activity, especially serum calcium an d/or PTH.