LONG-TERM ADMINISTRATION OF HEPARIN AND HEPARIN FRACTIONS AND OSTEOPOROSIS IN EXPERIMENTAL-ANIMALS

To test whether heparin-induced osteoporosis is influenced by the mole cular weight of heparin, 24 male rabbits received single daily subcuta neous 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 admin istered in supratherapeutic daily dosages for 120 days (750 anti-FXa u nits/kg for 90 days and 1500 anti-FXa units/kg for another 30 days). S tudied variables were: serial analysis of serum calcium, albumin, phos phate and alkaline phosphatase, measurement of the cortical thickness of the femur (radiographically), tibial and trabecular bone density (b oth by cross-sectional analysis) and femoral fragility. Observed chang es in blood biochemistry associated with bone metabolism were not corr elated to any of the treatments. Compared with the controls, a reducti on 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 sig nificantly 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.