Inhibition of bone mineral loss during lactation by Cl2MBP.

Pregnant rats were injected subcutaneously with either saline or the bisphosphonate Cl2MBP (dichloromethylenebisphosphonic acid) at a daily dose of 15 mg P/kg body weight on days 1 through 16 of gestation. Cl2MBP treatment did not influence maternal body weight nor the number of pups born. When analyzed 1 day after birth, pups from Cl2MBP-treated rats had a normal body weight but a 10% reduction in carcass calcium (Ca) content. The Cl2MBP injections were resumed on day 1 postpartum and led to a 10% reduction in pup body weight gain and carcass Ca content at 16 days of age. In saline-injected rats, lactation resulted in slight hypocalcemia, greatly elevated serum levels of 1,25(OH)2D3, and loss of bone mineral, as indicated by a reduction in femur ash weight. In non-lactating rats, Cl2MBP treatment produced slight hypercalcemia but had no effect on serum 1,25(OH)2D3 levels or bone mineral content. Compared to lactating rats receiving saline, Cl2MBP-treated lactating rats were more hypocalcemic and had higher serum 1,25(OH)2D3 levels. However, the lactation-induced loss of bone mineral was completely inhibited by Cl2MBP treatment.