Low-molecular-weight heparin (dalteparin) demonstrated a weaker effect on rat bone metabolism compared with heparin.
We studied the pharmacological effects of dalteparin (low-molecular-weight heparin) and heparin on bone metabolism in rats. After their 28 days of consecutive intravenous injections, significant loss of bone weight and mineral contents was observed in the heparin-treated rats, whereas dalteparin slightly reduced bone mass. By the end of the experiment, the femora of 7 out of 8 rats fractured in the heparin (10,000 U/kg/day)-treated group, but none had broken in the control and dalteparin-treated groups. Serum osteocalcin levels were significantly decreased in the former group. The growth plate width of the tibia was increased in a dose-dependent manner, especially in the heparin-treated group. Histomorphometric assessment of tibia showed that the osteoid surface and mineral apposition rates were significantly reduced in the heparin-treated group, whereas the eroded surface was significantly increased in the heparin-treated group. The above results suggest that heparin not only augments bone resorption but also suppressed bone formation and that dalteparin has a weaker suppressive effect on bone formation compared with heparin.
Nishiyama
M
M
Central Research Laboratories, Kissei Pharmaceutical Co., Ltd., Nagano, Japan.
Itoh
F
F
Ujiie
A
A
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D015519:Bone Density / Q000187:drug effects; D001853:Bone Marrow / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D003720:Densitometry; D005264:Femoral Fractures / Q000473:pathology; D006493:Heparin / Q000494:pharmacology*; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D008297:Male; D008903:Minerals / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D015675:Osteocalcin / Q000378:metabolism; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000378:metabolism
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D008903:Minerals; D016212:Transforming Growth Factor beta; D015675:Osteocalcin; D006493:Heparin