Low-Molecular-Weight Heparin (Dalteparin) Demonstrated a Weaker Effect on Rat Bone Metabolism Compared with Heparin.

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  • Nishiyama Masahiko
    Central Research Laboratories, Kissei Pharmaceutical Co., Ltd.
  • Itoh Fumiaki
    Central Research Laboratories, Kissei Pharmaceutical Co., Ltd.
  • Ujiie Arao
    Central Research Laboratories, Kissei Pharmaceutical Co., Ltd.

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  • Low-Molecular-Weight Heparin Dalteparin

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Abstract

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.

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