Human Genetics

, Volume 127, Issue 3, pp 249–285

Genetics of osteoporosis: accelerating pace in gene identification and validation

Review Article


Osteoporosis is characterized by low bone mineral density and structural deterioration of bone tissue, leading to an increased risk of fractures. It is the most common metabolic bone disorder worldwide, affecting one in three women and one in eight men over the age of 50. In the past 15 years, a large number of genes have been reported as being associated with osteoporosis. However, only in the past 4 years we have witnessed an accelerated pace in identifying and validating osteoporosis susceptibility loci. This increase in pace is mostly due to large-scale association studies, meta-analyses, and genome-wide association studies of both single nucleotide polymorphisms and copy number variations. A comprehensive review of these developments revealed that, to date, at least 15 genes (VDR, ESR1, ESR2, LRP5, LRP4, SOST, GRP177, OPG, RANK, RANKL, COLIA1, SPP1, ITGA1, SP7, and SOX6) can be reasonably assigned as confirmed osteoporosis susceptibility genes, whereas, another >30 genes are promising candidate genes. Notably, confirmed and promising genes are clustered in three biological pathways, the estrogen endocrine pathway, the Wnt/β-catenin signaling pathway, and the RANKL/RANK/OPG pathway. New biological pathways will certainly emerge when more osteoporosis genes are identified and validated. These genetic findings may provide new routes toward improved therapeutic and preventive interventions of this complex disease.


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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  1. 1.Department of Orthopaedics, The First Affiliated HospitalGeneral Hospital of the People’s Liberation ArmyBeijingChina
  2. 2.Department of Orthopaedic TraumaNanfang Hospital, Southern Medical UniversityGuangzhouChina
  3. 3.Institut National de la Santé et de la Recherche Médicale (INSERM), U613BrestFrance
  4. 4.Faculté de Médecine et des Sciences de la SantéUniversité de Bretagne Occidentale (UBO)BrestFrance
  5. 5.Etablissement Français du Sang (EFS), BretagneBrestFrance
  6. 6.Laboratoire de Génétique Moléculaire et d’HistocompatibilitéCentre Hospitalier Universitaire (CHU), Hôpital MorvanBrestFrance

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