INDUCTION OF OSTEOPOROSIS IN RATS BY STANDARD HEPARIN AND LOW MOLECULAR WEIGHT HEPARIN

Long-term treatment with heparin can induce osteoporosis. This complication is suspected to be related to the dosage of heparin rather than to duration of therapy, but the mechanism by which heparin induces osteoporosis is unknown. In a previous study we reported the same degree of reduction in mineral bone mass in rats after treatment with 2 IU heparm/g bw for 33 and 65 days (Thromb Haemostas 1986,56:293-4). Using the same animal model we compared the effect of a high-dose standard heparin (SH) and a low molecular weight heparin (LMWH) in a high and a low dose on the mineral bone mass in the femur of rats. Method: 60 female Wistar rats (207±1.8 g) were randomly allocated to treatment with either 2 Xal U/g bw of standard heparin (SH), 2 Xal U/g bw of LMWH ("high-dose"), 0.4 Xal U/g bw LMWH ("low-do-se") or placebo (saline). A standard sodium salt heparin of porcine origin was used, and the LMWH was an enzymatically depolymerized pork mucosal heparin (LHN-1, mean MW 4900 D). Treatment with s.c. injections was continued for 34 days. 24 hours after the last injection the rats were sacrificed and the carefully cleaned femora weighed in air and in water under standardized conditions. Volumes and densities were calculated from the weights. The bones were then incinerated for 48 hours at 600°C and weighed again to determine the ash content (expressed as ash weight per ml of unashed femur volume). Results: There was a significant decrease in ash content (p<0.01) and density (p<0.01) of the femora in all heparin treated groups as compared with controls. High-dose LMWH caused the same reduction in bone mineral mass as standard heparin. Treatment with low-dose LMWH resulted in a significantly less pronounced reduction in ash content (p<0.001) and density (p<0.05) of the femora when compared with high-dose standard heparin and high-dose LMWH. CONCLUSION: Daily injections of 2 Xal U/g body weight of standard heparin or low molecular weight heparin for 34 days causes the same degree of reduction of mineral bone mass in rats. The reduction of mineral bone mass in rats by treatment with low molecular weight heparin is dose dependent.