Osteoblast Growth Inhibition by Unfractionated Heparin and by Low Molecular Weight Heparins: An in-vitro Investigation

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Abstract
Osteoporosis is a rare but potentially severe complication under high-dose, long-term unfractionated heparin therapy. Low-molecular-weight heparins (LMWHs) have gained increased importance in antithrombotic therapy over the past decade. Whether this heterogeneous group of drugs carries a comparable risk of osteoporosis in long-term application is unknown. In a standardized in vitro model, the effects of 4 different low-molecular-weight heparins (nadroparin, enoxaparin, dalteparin, certoparin) on osteoblast growth were studied at the same dose (50,μg/mL). As control, the effect of unfractionated heparin (Liquemin) was tested on human osteoblasts in vitro at an equal dose. Human osteoblast cell cultures were incubated with equal doses of the heparins, and cell concentrations were measured after 48 and 96 hours. In addition, a fluorescence assay was performed to detect potential cytotoxic effect of heparins on bone cells. In comparison to control groups of non-incubated cell cultures, LMWHs caused a significant inhibition of osteoblast growth (p<0.05). Therefore, the risk of osteoporosis under long-term therapy with high doses of LMWHs cannot be excluded and should be further evaluated in clinical trials.