HISTOMORPHOMETRIC ANALYSIS OF THE EFFECTS OF STANDARD HEPARIN ON TRABECULAR BONE IN-VIVO

Long-term heparin treatment causes osteoporosis through an as yet unde fined mechanism. To investigate this phenomenon, we treated rats with once daily subcutaneous injections of heparin (in doses ranging from 0 .25 to 1.0 U/g) or saline for 8 to 32 days and monitored the effects o n bone both histomorphometrically and by serial measurements of urinar y type I collagen cross linked-pyridinoline (PYD) and serum alkaline p hosphatase, markers of bone resorption and formation, respectively, Hi stomorphometric analysis of the distal third of the right femur in the region proximal to the epiphyseal growth plate showed that heparin in duces both a time- and dose-dependent decrease in trabecular bone volu me, with the majority of trabecular bone loss occurring within the fir st 8 days of treatment. Thus, heparin doses of 1.0 U/g/d resulted in a 32% loss of trabecular bone, Heparin-treated rats also showed a 37% d ecrease in osteoblast surface as well as a 75% decrease in osteoid sur face. In contrast, heparin treatment had the opposite effect on osteoc last surface, which was 43% higher in heparin-treated rats, as compare d with that in control rats. Biochemical markers of bone turnover show ed that heparin treatment produced a dose-dependent decrease in serum alkaline phosphatase and a transient increase in urinary PYD, thus con firming the histomorphometric data, Based on these observations, we co nclude that heparin decreases trabecular bone volume both by decreasin g the rate of hone formation and increasing the rate of bone resorptio n. (C) 1996 by The American Society of Hematology.