Regulatory Polymorphisms and Osteoporosis

  • Huilin Jin
  • Stuart H. RalstonEmail author


Osteoporosis is a common disease characterized by low bone mass and micro-architectural deterioration of bone tissue which leads to an increased risk of fragility fracture. Genetic factors play an important role in regulating bone mineral density (BMD) and other phenotypes relevant to the pathogenesis of osteoporosis. It is currently believed that a large number of susceptibility alleles contribute to the risk of osteoporosis each with a small effect size. Very little is known about the molecular mechanisms by which these variants predispose to osteoporosis, but it is likely that many affect regulatory elements and act by altering gene expression. Here, we review the molecular mechanisms by which common variants at the ERS1, COL1A1 and VDR loci regulate gene expression and predispose to osteoporosis. The most extensively studied locus is COL1A1, where a specific haplotype encompassing polymorphisms in the promoter and intron 1 leads to over-expression of COL1A1 mRNA and an imbalance in production of the collagen type 1 α1 chain relative to the α2 chain. Polymorphisms in the regulatory regions of ESR1 and VDR have also been described which modulate gene expression, but the mechanisms by which these predispose to osteoporosis have not been fully investigated. Genome-wide association studies have identified several variants that are associated with the expression of these genes, but further work will be required to define the responsible mechanisms.


Osteoporosis Bone mineral density Estrogen receptor Type 1 collagen Vitamin D receptor 



Bone mineral density


Body mass index


Endoplasmic reticulum


Genome-wide association studies


Skeleton genometry


Low-density lipoprotein-related receptor-5 gene


Osteogenesis imperfecta


Standard deviation


Systemic sclerosis


Osteoporosis-pseudoglioma syndrome


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© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Kennedy Institute of RheumatologyUniversity of OxfordLondonUK
  2. 2.Molecular Medicine Centre, Institute of Genetics and Molecular MedicineWestern General HospitalEdinburghUK

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