Heparin and osteoporosis
Heparin as a drug

Author: alessandra di liberto
Date: 26/03/2009


Heparin Induced Osteoporosis

Long-term heparin treatment causes osteoporosis through an as not well defined mechanism. In a work published in 1996 (Histomorphometric analysis of the effects of standard heparin on trabecular bone in vivo) you can notice that biochemical markers of bone turnover showed that heparin treatment produced a dose-dependent decrease in serum alkaline phosphatase and a transient increase in urinary PYD thus confirming the decreasing in trabecular bone volume of histomorphometric data: heparin decreases the rate of bone formation and increases the rate of bone resorption

provate a vedere se la cosa si può spiegare col fatto che l'eparina aumenta l'efficacia e la durata d'azione dei growth factors e quindi stimola la degradazione dell'osso per fornire il P per la sintesi del DNA, ad es dei globuli bianchi.
Come è l'eparina dell'ospite nei linfomi? e come è l'osso?
Come sono i GB dopo eparina? leucocitosi?

The exact pathomechanism is unclear, but there are many hypothesis:

  • In Handschin AE’s work (Clin Appl Thromb Hemost. 2006 Oct;12) Cbfa-1 (Runx-2) and osteocalcin expression by human osteoblasts in heparin osteoporosis in vitro is showed that in vitro data suggest an impaired osteoblast function. The transcription axis of Cbfa-1 and osteocalcin is crucial in maintaining an equilibrium of bone formation and resorption in vivo At high doses, dalteparin caused a significant inhibition of both osteocalcin and Cbfa-1 expression in vitro
  • Vik A, Brodin E, Sveinbjørnsson B, Hansen JB in Heparin induces mobilization of osteoprotegerin into the circulation studied the role of Osteoprotegerin (OPG), a glycoprotein with a heparin-binding site, that is a decoy receptor for RANKL which is responsible for osteoclast development and prompt increases after bolus injection of UFH iv. Subcutaneous administration of LMWH causes a modest, but significant increase in plasma OPG similar to the mobilization by UFH sc, but the LMWH treatment caused a three-fold higher anti-Xa activity. We conclude that UFH causes a more pronounced vascular mobilization of OPG than LMWH, indicating that UFH has a higher affinity for OPG than LMWH.
    • This article gives prominence to another question: can also LMWH induce osteoporosis?
      Recent clinical trials have shown that the risk of developing osteoporosis is substantially lower when low molecular weight heparins (LMWHs) are used in place of unfractionated heparin. While the reason(s) for this difference has not been fully elucidated, studies with animals have suggested that heparin causes bone loss by both decreasing bone formation and increasing bone resorption. In contrast, LMWHs appear to cause less bone loss because they only decrease bone formation. (The effects of heparin and low molecular weight heparins on bone Rajgopal R, Bear M, Butcher MK, Shaughnessy SG, Department of Pathology and Molecular Medicine, McMaster University and the Henderson Research Centre, Hamilton, Ontario, Canada)
      Another work of Shaughnessy SG, Young E, Deschamps P, Hirsh J shows that unfractionated heparin stimulates the process of bone resorption and that the low molecular weight heparins (LMWHs), enoxaparin, fragmin, logiparin, and ardeparin produce significantly less calcium loss than unfractionated heparin, but more than 50-fold higher LMWH concentrations were required to obtain an equivalent effect to unfractionated heparin. Size and sulfation are major determinants of heparin's ability to promote bone resorption and that the risk of heparin-induced osteoporosis may be reduced by the use of LMWH preparations.
  • Handschin AE, Trentz OA, Hoerstrup SP, Kock HJ, Wanner GA, Trentz O.(Division of Trauma Surgery and Research Division, University of Zurich, Zurich Switzerland and Section of Accident and Reconstructive Surgery, University of Heidelberg, Heidelberg, Germany) published a work to compare heparin and fondaparinux: 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. The conclusion is that Fondaparinux does not inhibit osteoblast proliferation in vitro and may reduce the risk of heparin-induced osteoporosis associated with long-term heparin administration.
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