fondaparinux and Osteoporosis

Unfractionated heparin (UFH) may lead to symptomatic vertebral fractures in up to 3 out of every 100 people on long-term therapy. Ten-times that many people will experience a significant reduction in bone density leading to osteopoenia or osteoporosis. Low molecular weight heparins (LMWH) have been shown to be as effective as UFH in the prevention and treatment of venous thromboembolism. Several well-established advantages of LMWH over UFH include increased bioavailability, more predictable dose response, less intensive coagulation monitoring, and a lower probability of causing immune-mediated thrombocytopenia. There is also some evidence that long-term LMWH therapy is less likely to cause osteoporotic fractures and significant reductions in bone mass than UFH. Both UFH and LMWH undergo pharmacokinetic changes during pregnancy, which sometimes necessitates dosage adjustments. Fondaparinux is a synthetic antithrombotic agent, which specifically binds to antithrombin. It has been shown to be comparable to, or even more effective than, LMWH in the management of both arterial and venous thrombosis. Fondaparinux does not appear to have a negative effect on bone metabolism. Therefore, fondaparinux may be a safe and effective alternative to UFH and LMWH in women who require anticoagulation during pregnancy.

Topics: Adult; Anticoagulants; Bone Density; Female; Fondaparinux; Heparin, Low-Molecular-Weight; Humans; Osteoporosis; Polysaccharides; Pregnancy; Pregnancy Complications; Risk Factors; Venous Thrombosis

The prolonged administration of heparin for prevention and treatment of venous thromboembolism has been associated with a risk of heparin-induced osteoporosis. Fondaparinux is a new antithrombotic drug that specifically inhibits factor Xa. Because of the known interactions of other antithrombotic agents with bone remodelling, the effects of fondaparinux on human osteoblasts were analysed in vitro.. Primary human osteoblast cell cultures were incubated with either the low molecular weight heparin dalteparin at concentrations of 30, 300 and 900 microg/ml or with fondaparinux at concentrations of 25, 50, 100, 150, 200 and 250 microg/ml. Cellular proliferation rate and protein synthesis were measured. Expression of genes encoding osteocalcin, collagen type I and alkaline phosphatase was examined by reverse transcriptase-polymerase chain reaction.. Incubation with dalteparin led to a significant, dose-dependent inhibition of osteoblast proliferation, inhibition of protein synthesis, and inhibited expression of phenotype markers (osteocalcin and alkaline phosphatase genes) after 3 and 7 days. No inhibitory effects were observed in the fondaparinux-treated cells.. Fondaparinux did not inhibit osteoblast proliferation in vitro and may reduce the risk of heparin-induced osteoporosis associated with long-term heparin administration.

Topics: Alkaline Phosphatase; Anticoagulants; Cells, Cultured; Dalteparin; Fluoresceins; Fondaparinux; Gene Expression; Humans; Osteoblasts; Osteocalcin; Osteoporosis; Polysaccharides; Reverse Transcriptase Polymerase Chain Reaction; Risk Factors; Thromboembolism