Summary
We have previously demonstrated that heparin produces cancellous bone loss in rats
due in part to a decrease in the number of osteoblasts lining the trabecular bone
surface. In the present study, we use a stromal-derived cell culture system together
with measurements of alkaline phosphatase (ALP) activity, to compare the effects of
heparin and the low molecular weight heparin (LMWH), Fragmin, on osteoblast differentiation
in vitro. In addition, we examined the possibility that both heparin and LMWH can induce adipogenesis
in our stromal cell culture system. Both heparin and LMWH were found to produce a
statistically significant (P <0.01) and concentration-dependent decrease in the number
of osteoblasts while increasing the number of adipocytes. When the effects of gravimetrically
equivalent amounts of heparin and LMWH were compared, heparin had a 4-fold greater
effect than LMWH. In contrast to heparin, N-desulfated heparin was found to have minimal
effects on both osteoblast and adipocyte differentiation indicating that the heparin
effect is not only chain-length dependent but also charge-dependent. The observation
that LMWH has less of an effect on bone formation than heparin is compatible with
the results of clinical trials indicating that LMWH produces less bone loss after
long-term administration.
Keywords
Heparin - low molecular weight heparin - bone - osteoblastogenesis - adipogenesis