Bone responses at various skeletal sites to human parathyroid hormone in ovariectomized rats: effects of long-term administration, withdrawal, and readministration

Abstract

This study was undertaken to examine bone responses to human parathyroid hormone (hPTH) at various skeletal sites. Forty 6-month-old female Wistar rats were divided into four groups, and bilateral ovariectomy (ovx) was performed in three of the four groups (n=30). The other group (n=10) received sham surgery (sham). Four weeks after the ovx, hPTH(1-34) administration was started. The ovx rats received 5 microg/kg per day of PTH (PTH-5; n=10), 10 microg/kg per day of PTH (PTH-10; n=10), or vehicle (PTH-v; n=10), three times a week for 24 weeks. Thereafter, PTH was withdrawn for 16 weeks followed by readministration at the same dosage for 8 weeks. The bone mineral content (BMC) at the whole skeleton and the bone mineral density (BMD) at the lumbar vertebrae, caudal vertebrae, distal femur, diaphysis of the femur, proximal tibia, and skull were longitudinally measured by dual-energy x-ray absorptiometry (DXA) at 4-week intervals during the experimental period. Thirteen rats that died during the experimental period were excluded from the analysis. As a result, the whole skeleton showed an increase in BMC during the PTH administration, whereas no withdrawal or readministration effects were observed. The metaphysis showed a highly sensitive bone response, while the lumbar vertebrae and diaphysis showed a moderate magnitude of changes in bone mass during the PTH administration. The skull and the caudal vertebrae did not show sensitive responses to PTH. After withdrawal, the BMD was markedly decreased at the sites that showed marked increases in BMD after PTH administration. The PTH readministration increased the BMD again at the sites that showed sensitive responses after the initial administration. Strength tests were also performed when the readministration was completed. The ultimate loads for the femur and vertebral body in the PTH-treated groups were significantly higher than those in the vehicle-treated group. In conclusion, the response to PTH in ovx rats varied among skeletal sites; withdrawal-related decreases were marked at the sites showing marked increases in bone mass related to PTH administration, and PTH readministration may be sufficiently effective.