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Taxonomy of rare genetic metabolic bone disorders

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A Publisher's Erratum to this article was published on 14 September 2015

Abstract

Summary

This article reports a taxonomic classification of rare skeletal diseases based on metabolic phenotypes. It was prepared by The Skeletal Rare Diseases Working Group of the International Osteoporosis Foundation (IOF) and includes 116 OMIM phenotypes with 86 affected genes.

Introduction

Rare skeletal metabolic diseases comprise a group of diseases commonly associated with severe clinical consequences. In recent years, the description of the clinical phenotypes and radiographic features of several genetic bone disorders was paralleled by the discovery of key molecular pathways involved in the regulation of bone and mineral metabolism. Including this information in the description and classification of rare skeletal diseases may improve the recognition and management of affected patients.

Methods

IOF recognized this need and formed a Skeletal Rare Diseases Working Group (SRD-WG) of basic and clinical scientists who developed a taxonomy of rare skeletal diseases based on their metabolic pathogenesis.

Results

This taxonomy of rare genetic metabolic bone disorders (RGMBDs) comprises 116 OMIM phenotypes, with 86 affected genes related to bone and mineral homeostasis. The diseases were divided into four major groups, namely, disorders due to altered osteoclast, osteoblast, or osteocyte activity; disorders due to altered bone matrix proteins; disorders due to altered bone microenvironmental regulators; and disorders due to deranged calciotropic hormonal activity.

Conclusions

This article provides the first comprehensive taxonomy of rare metabolic skeletal diseases based on deranged metabolic activity. This classification will help in the development of common and shared diagnostic and therapeutic pathways for these patients and also in the creation of international registries of rare skeletal diseases, the first step for the development of genetic tests based on next generation sequencing and for performing large intervention trials to assess efficacy of orphan drugs.

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Acknowledgments

This paper was supported by the IOF.

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Metabolic Bone Diseases Unit, Department of Surgery and Translational Medicine, University Hospital of Florence, University of Florence, Florence, Italy

    L. Masi, L. Cianferotti & M. L. Brandi

  2. Eli Lilly and Co., Florence, Italy

    D. Agnusdei

  3. College of Physicians and Surgeons, Columbia University, New York, NY, USA

    J. Bilezikian

  4. GEROM Groupe Etudes Remodelage Osseux et bioMatériaux-LHEA, IRIS-IBS Institut de Biologie en Santé, LUNAM Université, Angers, France

    D. Chappard

  5. INSERM UMR 1033, Department of Rheumatology, Université de Lyon, Hospices Civils de Lyon, Lyon, France

    R. Chapurlat

  6. Departement de Medicine Interne, Cliniques Universitaires UCL de Saint Luc, Brussels, Belgium

    J.-P. Devolgelaer

  7. Service de Rhumatologie, Hôpital Militaire Mohammed V, Rabbat, Morocco

    A. El Maghraoui

  8. Division of Bone Diseases, Faculty of Medicine, Geneva University Hospital, Geneva, Switzerland

    S. Ferrari

  9. Oxford NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK

    M. K. Javaid

  10. Department of Endocrinology, Ghent University Hospital, Gent, Belgium

    J.-M. Kaufman

  11. Department of Physiology and Pharmacology and the Felsenstein Medical Research Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    U. A. Liberman

  12. Laboratory for the Research of Musculoskeletal System, University of Athens, Athens, Greece

    G. Lyritis

  13. Colorado Center for Bone Research, University of Colorado Health Sciences Center, Lakewood, CO, USA

    P. Miller

  14. Division of Endocrinology and Diabetes, Università Campus Bio-Medico di Roma, Rome, Italy

    N. Napoli

  15. Department of Clinical Pharmacology, Gador SA, Buenos Aires, Argentina

    E. Roldan

  16. Center for Bone Quality, Leiden University Medical Center, Leiden, The Netherlands

    S. Papapoulos

  17. Mercy Health Osteoporosis and Bone Health Services, Cincinnati, OH, USA

    N. B. Watts

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  1. L. Masi
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Footnote: In the tables, biochemical markers have been indicated with abbreviations as described in the Addendum section.

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Masi, L., Agnusdei, D., Bilezikian, J. et al. Taxonomy of rare genetic metabolic bone disorders. Osteoporos Int 26, 2529–2558 (2015). https://doi.org/10.1007/s00198-015-3188-9

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