Long-term administration of heparin and heparin fractions and osteoporosis in experimental animals.

To test whether heparin-induced osteoporosis is influenced by the molecular weight of heparin, 24 male rabbits received single daily subcutaneous injections of either physiological saline (controls, n = 5), low molecular weight heparin (LMWH, n = 7), conventional heparin (UFH, n = 7) or high molecular weight heparin (HMWH, n = 6). Heparin was administered in supratherapeutic daily dosages for 120 days (750 anti-FXa units/kg for 90 days and 1500 anti-FXa units/kg for another 30 days). Studied variables were: serial analysis of serum calcium, albumin, phosphate and alkaline phosphatase, measurement of the cortical thickness of the femur (radiographically), tibial and trabecular bone density (both by cross-sectional analysis) and femoral fragility. Observed changes in blood biochemistry associated with bone metabolism were not correlated to any of the treatments. Compared with the controls, a reduction in cortical and trabecular bone density was seen with UFH (P < 0.05) and HMWH (P < 0.01) but not with LMWH. Femoral fragility was also significantly increased (P < 0.002) by HMWH. In conclusion, LMWH did not cause toxic skeletal effects as opposed to HMWH which clearly did, and UFH which induced some osteoporotic changes.