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Myelodysplastic syndromes and bone loss in mice and men

Leukemia volume 31, pages 1003–1007 (2017)Cite this article

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Myelodysplastic syndromes (MDS) are clonal disorders of the hematopoietic stem and progenitor cells (HSPC) that predominantly occur in the elderly. MDS are characterized by cytopenia due to ineffective hematopoiesis in the bone marrow and a propensity to transform into acute myeloid leukemia.1 Alterations of the bone microenvironment, where bone precursors and HSPC interact, have been recently linked to the pathophysiology of MDS.2, 3, 4, 5 In fact, this crosstalk within the osteo-hematopoietic niche is mandatory for the maintenance of HSPC which are precursors of circulating blood cells and bone-resorbing osteoclasts. Besides osteoclasts, bone-forming osteoblasts and their precursors, mesenchymal stem/progenitor cells (MSC) are present in this niche, regulate bone homeostasis,6 and were shown to be functionally altered in MDS.1 How the disturbed interaction of HSPC with MSC within the osteo-hematopoietic niche affects bone homeostasis in MDS is not well defined. Thus, we assessed the bone phenotype in a murine model of MDS and validated our observations in a well-defined large insurance-based cohort of elderly patients.

To assess a potential link between MDS and bone loss in humans, we used the AOK PLUS health services research database that includes comprehensive information on the administrative data from in- and outpatient care of ~49% of all inhabitants of the German federal state of Saxony. Further information on the data, including IRB approval has been described elsewhere.9, 10 The cross-sectional analysis was restricted to the data between 2008 and 2014, and included insured persons being born before 1950. Internal case validation methods based on ICD-10-GM, the German Procedure Classification (‘Operationen- und Prozedurenschlüssel’, OPS), the Uniform Value Scale (‘Einheitlicher Bewertungsmaßstab’, EBM), the Anatomical Therapeutic Chemical Classification System (ATC) and the profession of the treating physician were applied to identify prevalent cases with MDS (ICD-10-GM D46; with concurrent bone marrow puncture [OPS 1-424/EBM 02341]; treating physician: hematologist) and prevalent osteoporosis (ICD-10 M80—M82; with concurrent prescription of bisphosphonate (ATC M05BA) or denosumab (ATC M05BX04, trade name Prolia, Amgen, Thousand Oak, CA, USA)).

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Acknowledgements

This work was supported by the José Carreras foundation to MR and UP (DJCLS R 13/15), a grant from the Deutsche Forschungsgemeinschaft (DFG SFB-655) to LCH and UP, a grant of the Elsbeth Bonhoff foundation to UP and LCH, and the Deutsche Konsortium für Translationale Krebsforschung (DKTK) to LCH, MB and UP. The authors thank T Datzmann and F Tesch for the statistical analysis of the human data. We thank the Saxony Health Insurance AOK PLUS for the cooperation in data utilisation and for providing technical support.

Author contributions

HW, MR, LCH and UP designed the study. HW, FT, JS, MR, EB and UB performed experiments and analyzed the results. LCH, MB and CK contributed tools, HW, MR, LCH and UP wrote the manuscript and all authors critically read and approved the letter.

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Authors and Affiliations

  1. Department of Medicine I, Technische Universität Dresden, Dresden, Germany

    H Weidner, E Balaian, A Mies, S Helas, M Bornhäuser & U Platzbecker

  2. Department of Medicine III, Technische Universität Dresden, Dresden, Germany

    M Rauner, U Baschant & L C Hofbauer

  3. Center for Healthy Aging, Technische Universität Dresden, Dresden, Germany

    M Rauner, U Baschant & L C Hofbauer

  4. National Center for Tumor Diseases (NCT), partner site Dresden and German Cancer Research Center (DKFZ), Dresden, Germany

    F Trautmann & J Schmitt

  5. Center for Evidence-Based Healthcare (ZEGV), Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany

    F Trautmann & J Schmitt

  6. Department of Hematology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Duisburg, Germany

    C Khandanpour

  7. German Cancer Consortium (DKTK), partner site Dresden and German Cancer Research Center (DKFZ), Heidelberg, Germany

    M Bornhäuser, L C Hofbauer & U Platzbecker

Authors
  1. H Weidner
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  2. M Rauner
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  3. F Trautmann
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  4. J Schmitt
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  5. E Balaian
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  6. A Mies
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  7. S Helas
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  8. U Baschant
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  9. C Khandanpour
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  10. M Bornhäuser
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  11. L C Hofbauer
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  12. U Platzbecker
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Corresponding author

Correspondence to U Platzbecker.

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The authors declare no conflict of interest.

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Weidner, H., Rauner, M., Trautmann, F. et al. Myelodysplastic syndromes and bone loss in mice and men. Leukemia 31, 1003–1007 (2017). https://doi.org/10.1038/leu.2017.7

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