Calcium absorption and osseous organ-, tissue-, and envelope-specific changes following ovariectomy in rats

Abstract

Because cancellous bone loss occurs following ovariectomy (OVX) in rats, this has become a popular model to explore therapeutic modalities for postmenopausal bone loss in humans. The purpose of this study was to determine intestinal calcium absorption in situ and organ-, tissue-, envelope-, and site-specific changes in osseous tissues at six weeks after OVX in rats using chemical, biochemical, absorptiometric, microradiographic, and morphometric methods. There were no changes in intestinal absorption of calcium, but duodenal weight per length was significantly increased in the OVX animals compared with age-matched, sham-operated controls. There was an increase in wet bone weight, but decreases in ash/dry bone weight, total bone Ca, and Ca per ash weight in the OVX animals. There were significant decreases in the OVX animals in metaphyseal bone mineral content, as determined by photon absorptiometry and metaphyseal cancellous bone volume. The perimeter to area ratio of the metaphyseal cancellous bone in the OVX animals was increased compared with controls. Endochondral growth rates were increased in the OVX animals, attributable to an increased growth plate hypertrophic cell size and rate of chondrocyte proliferation. In the OVX animals there was an increase in modeling in the formation mode of the periosteal surface at the tibio-fibular junction. Increased periosteal modeling in the formation mode was also observed in the body of the mandible, suggesting that the changes in periosteal bone formation are not strictly coupled with changes in endochondral growth. There was an increase in modeling in the resorption mode of the endocortical surface at the tibio-fibular junction in the OVX animals. There was increased bone turnover in the OVX animals compared with controls on the endosteal surface, as indicated by increases in both formation and resorption indices, including an increase in the osteoclast population. In the long bones, OVX results in larger bones due to increases in endochondral growth and modeling in the formation mode at the periosteal surfaces, with a loss of cancellous bone and total bone calcium due to increased resorption on the endocortical surfaces and turnover (increased formation and resorption) on endosteal surfaces. This study emphasizes that osseous tissue changes following OVX in rats are tissue-specific, envelop-specific, and site-specific.