Review Article

Human Genetics

, Volume 127, Issue 3, pp 249-285

Genetics of osteoporosis: accelerating pace in gene identification and validation

  • Wen-Feng LiAffiliated withDepartment of Orthopaedics, The First Affiliated Hospital, General Hospital of the People’s Liberation Army
  • , Shu-Xun HouAffiliated withDepartment of Orthopaedics, The First Affiliated Hospital, General Hospital of the People’s Liberation Army Email author 
  • , Bin YuAffiliated withDepartment of Orthopaedic Trauma, Nanfang Hospital, Southern Medical University
  • , Meng-Meng LiAffiliated withDepartment of Orthopaedics, The First Affiliated Hospital, General Hospital of the People’s Liberation Army
  • , Claude FérecAffiliated withInstitut National de la Santé et de la Recherche Médicale (INSERM), U613Faculté de Médecine et des Sciences de la Santé, Université de Bretagne Occidentale (UBO)Etablissement Français du Sang (EFS), BretagneLaboratoire de Génétique Moléculaire et d’Histocompatibilité, Centre Hospitalier Universitaire (CHU), Hôpital Morvan
  • , Jian-Min ChenAffiliated withInstitut National de la Santé et de la Recherche Médicale (INSERM), U613Faculté de Médecine et des Sciences de la Santé, Université de Bretagne Occidentale (UBO)Etablissement Français du Sang (EFS), Bretagne Email author 

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Abstract

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.