INTERMITTENT ADMINISTRATION OF BOVINE PTH-(1-34) INCREASES SERUM 1,25-DIHYDROXYVITAMIN-D CONCENTRATIONS AND SPINAL BONE-DENSITY IN SENILE (23 MONTH) RATS

We examined the effect of intermittent administration of bovine parathyroid hormone (1-34) (bPTH) on spinal bone mineral content (BMC) and bone mineral density (BMD), serum 1,25-dihydroxyvitamin D concentrations, and serum markers of osteoblast function in senile male and female rats (23 and 24 months of age, respectively). Sexually mature young (3 month) male rats were similarly treated for comparison. bPTH administration increased serum osteocalcin concentrations without changing serum inorganic phosphate or calcium concentrations in either group of old animals. In young animals, PTH administration increased the serum calcium and inorganic phosphate concentrations significantly (p < 0.05), although values remained within the normal range. In the vehicle-treated male rats, serum 1,25-dihydroxyvitamin D concentrations were lower in the senile than in the young animals (18 +/- 5 versus 47 +/- 6 pg/ml, p < 0.05). PTH administration resulted in significantly increased serum 1,25-dihydroxyvitamin D concentrations in the senile and young male animals (both, p < 0.05) and the final mean serum 1,25-dihydroxyvitamin D concentrations were not statistically different (68 +/- 9 versus 85 +/- 6 pg/ml respectively; p = NS). Serum 1,25-dihydroxy-vitamin D concentrations were significantly (p < 0.05) higher in the PTH-treated senile female rats than the sex-matched, vehicle-treated controls. The pretreatment spinal BMC and BMD as assessed by dual-energy x-ray absorptiometry (DEXA) were significantly higher in the senile male animals than in the young animals. Spinal BMC and BMD decreased in the vehicle-treated senile male rats (p < 0.05) over the 3 weeks of the study despite a gain in weight. bPTH administration prevented this fall in spinal BMC and increased spinal BMD (p < 0.05). Spinal BMC and BMD increased significantly (p < 0.05) in the young vehicle-treated rats, and PTH administration caused a further significant increase in both parameters of bone mass. Spinal BMD was significantly (p < 0.05) higher in the PTH-treated senile female rats than in vehicle-treated controls. These findings demonstrate that intermittent PTH administration increases serum 1,25-dihydroxyvitamin D concentrations of senile animals to the levels of PTH-treated, young, sexually mature animals. In addition, PTH administration arrests bone loss and increases spinal BMD of senile rats.