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.
Murray
W J
WJ
Thrombosis Research Institute, London, UK.
Lindo
V S
VS
Kakkar
V V
VV
Melissari
E
E
D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D006493:Heparin / Q000008:administration & dosage / Q000633:toxicity*; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000633:toxicity*; D007279:Injections, Subcutaneous; D008297:Male; D008970:Molecular Weight; D010024:Osteoporosis / Q000139:chemically induced*; D011817:Rabbits; D013131:Spine / Q000187:drug effects; D013997:Time Factors
D006495:Heparin, Low-Molecular-Weight; D006493:Heparin