Osteoporosis International

, Volume 26, Issue 10, pp 2529–2558 | Cite as

Taxonomy of rare genetic metabolic bone disorders

  • L. Masi
  • D. Agnusdei
  • J. Bilezikian
  • D. Chappard
  • R. Chapurlat
  • L. Cianferotti
  • J.-P. Devolgelaer
  • A. El Maghraoui
  • S. Ferrari
  • M. K. Javaid
  • J.-M. Kaufman
  • U. A. Liberman
  • G. Lyritis
  • P. Miller
  • N. Napoli
  • E. Roldan
  • S. Papapoulos
  • N. B. Watts
  • M. L. BrandiEmail author
Original Article



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.


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.


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.


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.


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.


Bone metabolism Genetic bone diseases Metabolic bone diseases Rare bone diseases Taxonomy 



This paper was supported by the IOF.

Conflicts of interest


Supplementary material

198_2015_3188_MOESM1_ESM.docx (63 kb)
ESM 1 (DOCX 63.0 KB)


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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2015

Authors and Affiliations

  • L. Masi
    • 1
  • D. Agnusdei
    • 2
  • J. Bilezikian
    • 3
  • D. Chappard
    • 4
  • R. Chapurlat
    • 5
  • L. Cianferotti
    • 1
  • J.-P. Devolgelaer
    • 6
  • A. El Maghraoui
    • 7
  • S. Ferrari
    • 8
  • M. K. Javaid
    • 9
  • J.-M. Kaufman
    • 10
  • U. A. Liberman
    • 11
  • G. Lyritis
    • 12
  • P. Miller
    • 13
  • N. Napoli
    • 14
  • E. Roldan
    • 15
  • S. Papapoulos
    • 16
  • N. B. Watts
    • 17
  • M. L. Brandi
    • 1
    Email author
  1. 1.Metabolic Bone Diseases Unit, Department of Surgery and Translational MedicineUniversity Hospital of Florence, University of FlorenceFlorenceItaly
  2. 2.Eli Lilly and Co.FlorenceItaly
  3. 3.College of Physicians and SurgeonsColumbia UniversityNew YorkUSA
  4. 4.GEROM Groupe Etudes Remodelage Osseux et bioMatériaux-LHEA, IRIS-IBS Institut de Biologie en SantéLUNAM UniversitéAngersFrance
  5. 5.INSERM UMR 1033, Department of RheumatologyUniversité de Lyon, Hospices Civils de LyonLyonFrance
  6. 6.Departement de Medicine InterneCliniques Universitaires UCL de Saint LucBrusselsBelgium
  7. 7.Service de RhumatologieHôpital Militaire Mohammed VRabbatMorocco
  8. 8.Division of Bone Diseases, Faculty of MedicineGeneva University HospitalGenevaSwitzerland
  9. 9.Oxford NIHR Musculoskeletal Biomedical Research UnitUniversity of OxfordOxfordUK
  10. 10.Department of EndocrinologyGhent University HospitalGentBelgium
  11. 11.Department of Physiology and Pharmacology and the Felsenstein Medical Research Center, Sackler School of MedicineTel Aviv UniversityTel AvivIsrael
  12. 12.Laboratory for the Research of Musculoskeletal SystemUniversity of AthensAthensGreece
  13. 13.Colorado Center for Bone ResearchUniversity of Colorado Health Sciences CenterLakewoodUSA
  14. 14.Division of Endocrinology and DiabetesUniversità Campus Bio-Medico di RomaRomeItaly
  15. 15.Department of Clinical PharmacologyGador SABuenos AiresArgentina
  16. 16.Center for Bone QualityLeiden University Medical CenterLeidenThe Netherlands
  17. 17.Mercy Health Osteoporosis and Bone Health ServicesCincinnatiUSA

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