Effects of pregnancy and lactation on bone in cynomolgus macaques: histomorphometric analysis of iliac biopsies

Abstract

The effects of pregnancy and lactation on bone histomorphometry have been studied extensively in rats and dogs. However, these models differ greatly in reproductive physiology compared with women. The purpose of this study was to evaluate histomorphometric changes in iliac crest bone biopsies taken from cynomolgus monkeys (Macaca fascicularis), animals similar to women both skeletally and reproductively. After fluorochrome labeling, paired iliac crest bone biopsies were collected and subjected to structural and dynamic histomorphometric analyses during the third trimester and 3 months postpartum in one group (n=16), at 3 and 9 months postpartum in the second group (n=14), and at 4 month intervals in a nonpregnant control group (n=6). Serum was collected at the time of surgery to measure total alkaline phosphatase (ALP), bone gla-protein (BGP), calcium, and estradiol. Trabecular thickness increased significantly between 3 and 9 months postpartum. Bone formation rates did not differ between control and pregnant monkeys, but were significantly increased during lactation (3 months postpartum) and remained elevated at 9 months postpartum. ALP and BGP levels were elevated at 3 months postpartum, compared with levels during pregnancy, and remained elevated at 9 months postpartum. Estradiol concentrations were greatly elevated during pregnancy, dropped below normal nonpregnant levels by 3 months postpartum, and remained suppressed at 9 months postpartum. These results suggest that, during the third trimester, the rate of bone turnover was not altered, but lactational demands for calcium were met in part by increased bone turnover.