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.
Brommage
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Department of Physiology, Chicago College of Osteopathic Medicine, Downers Grove, Illinois.
Baxter
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DC
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects* / Q000502:physiology; D001862:Bone Resorption / Q000378:metabolism* / Q000503:physiopathology; D004002:Clodronic Acid / Q000494:pharmacology*; D005260:Female; D007774:Lactation / Q000187:drug effects* / Q000502:physiology; D008903:Minerals / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains
D008903:Minerals; D004002:Clodronic Acid