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Autologous stem cell transplantation normalizes abnormal bone remodeling and sRANKL/osteoprotegerin ratio in patients with multiple myeloma

Leukemia volume 18, pages 1420–1426 (2004)Cite this article

Abstract

The osteoprotegerin (OPG)/receptor activator of NF-kappa B ligand (RANKL) system has a major role in the pathogenesis of bone disease in myeloma (MM). The effect of autologous stem cell transplantation (ASCT) on bone turnover in MM was evaluated in 51 patients (35M/16F). Markers of bone resorption (NTX, TRACP-5b), bone formation (bone-alkaline phosphatase (bALP), osteocalcin), OPG and sRANKL were measured pre- and every month post-ASCT. The median follow-up period was 12 months. Four patients were transplanted in CR, 44 were transplanted in PR and three patients had progressive/resistant disease. All patients received bisphosphonates both pre- and post-ASCT. At baseline the majority of patients had increased NTX, TRACP-5b levels, and sRANKL/OPG ratio, while markers of bone formation were strongly suppressed. ASCT produced a significant reduction of sRANKL/OPG ratio, with a concomitant decrease of NTX, and TRACP-5b levels, starting the second month post-ASCT. Bone formation markers, osteocalcin and bALP, started to increase after the 9th and 11th month post-ASCT, respectively, while the increase of OPG preceded this. These results provide biochemical evidence that ASCT normalizes the abnormal bone resorption in MM patients possibly through the decrease of RANKL/OPG ratio, while bone formation requires a longer period to return to normal.

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Authors and Affiliations

  1. Department of Hematology, Faculty of Medicine Imperial College London, Hammersmith Hospital, London, UK

    E Terpos, M Politou, R Szydlo, E Nadal, S Avery, E Olavarria, E Kanfer, J M Goldman, J F Apperley & A Rahemtulla

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  1. E Terpos
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  2. M Politou
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  3. R Szydlo
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  4. E Nadal
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  5. S Avery
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  6. E Olavarria
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  7. E Kanfer
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  8. J M Goldman
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  9. J F Apperley
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  10. A Rahemtulla
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Correspondence to A Rahemtulla.

Additional information

The paper has been presented as a poster presentation in the American Society of Hematology Annual Meeting 2003 in San Diego: ‘Autologous Stem Cell Transplantation normalizes abnormal bone resorption through the reduction of sRANKL/osteoprotegerin ratio in multiple myeloma’ (Blood 2003; 102: abstract no. 3658).

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Terpos, E., Politou, M., Szydlo, R. et al. Autologous stem cell transplantation normalizes abnormal bone remodeling and sRANKL/osteoprotegerin ratio in patients with multiple myeloma. Leukemia 18, 1420–1426 (2004). https://doi.org/10.1038/sj.leu.2403423

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