title: Taxonomy of rare genetic metabolic bone disorders.
abstract: 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.
  
  
  BACKGROUND
  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.
authors.affiliation: Metabolic Bone Diseases Unit, Department of Surgery and Translational Medicine, University Hospital of Florence, University of Florence, Florence, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Masi
authors.affiliation: Eli Lilly and Co., Florence, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Agnusdei
authors.affiliation: College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: J
authors.initials: J
authors.lastname: Bilezikian
authors.affiliation: GEROM Groupe Etudes Remodelage Osseux et bioMatériaux-LHEA, IRIS-IBS Institut de Biologie en Santé, LUNAM Université, Angers, France.
authors.forename: D
authors.initials: D
authors.lastname: Chappard
authors.affiliation: INSERM UMR 1033, Department of Rheumatology, Université de Lyon, Hospices Civils de Lyon, Lyon, France.
authors.forename: R
authors.initials: R
authors.lastname: Chapurlat
authors.affiliation: Metabolic Bone Diseases Unit, Department of Surgery and Translational Medicine, University Hospital of Florence, University of Florence, Florence, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Cianferotti
authors.affiliation: Departement de Medicine Interne, Cliniques Universitaires UCL de Saint Luc, Brussels, Belgium.
authors.forename: J-P
authors.initials: JP
authors.lastname: Devolgelaer
authors.affiliation: Service de Rhumatologie, Hôpital Militaire Mohammed V, Rabbat, Morocco.
authors.forename: A
authors.initials: A
authors.lastname: El Maghraoui
authors.affiliation: Division of Bone Diseases, Faculty of Medicine, Geneva University Hospital, Geneva, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Ferrari
authors.affiliation: Oxford NIHR Musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK.
authors.forename: M K
authors.initials: MK
authors.lastname: Javaid
authors.affiliation: Department of Endocrinology, Ghent University Hospital, Gent, Belgium.
authors.forename: J-M
authors.initials: JM
authors.lastname: Kaufman
authors.affiliation: Department of Physiology and Pharmacology and the Felsenstein Medical Research Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: U A
authors.initials: UA
authors.lastname: Liberman
authors.affiliation: Laboratory for the Research of Musculoskeletal System, University of Athens, Athens, Greece.
authors.forename: G
authors.initials: G
authors.lastname: Lyritis
authors.affiliation: Colorado Center for Bone Research, University of Colorado Health Sciences Center, Lakewood, CO, USA.
authors.forename: P
authors.initials: P
authors.lastname: Miller
authors.affiliation: Division of Endocrinology and Diabetes, Università Campus Bio-Medico di Roma, Rome, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Napoli
authors.affiliation: Department of Clinical Pharmacology, Gador SA, Buenos Aires, Argentina.
authors.forename: E
authors.initials: E
authors.lastname: Roldan
authors.affiliation: Center for Bone Quality, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: S
authors.initials: S
authors.lastname: Papapoulos
authors.affiliation: Mercy Health Osteoporosis and Bone Health Services, Cincinnati, OH, USA.
authors.forename: N B
authors.initials: NB
authors.lastname: Watts
authors.affiliation: Metabolic Bone Diseases Unit, Department of Surgery and Translational Medicine, University Hospital of Florence, University of Florence, Florence, Italy. marialuisa.brandi@unifi.it.
authors.forename: M L
authors.initials: ML
authors.lastname: Brandi
mesh_terms: D001848:Bone Diseases, Developmental / Q000145:classification* / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D001851:Bone Diseases, Metabolic / Q000145:classification* / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D010006:Osteoblasts / Q000502:physiology; D010010:Osteoclasts / Q000502:physiology; D010011:Osteocytes / Q000502:physiology; D010641:Phenotype; D011509:Proteoglycans / Q000378:metabolism; D035583:Rare Diseases / Q000145:classification / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism
chemical_list: D011509:Proteoglycans
keywords: Bone metabolism; Genetic bone diseases; Metabolic bone diseases; Rare bone diseases; Taxonomy