Osteoporosis International

, Volume 19, Issue 4, pp 571–579

Estrogen receptor α CA dinucleotide repeat polymorphism is associated with rate of bone loss in perimenopausal women and bone mineral density and risk of osteoporotic fractures in postmenopausal women

  • B. M. H. Lai
  • C. L. Cheung
  • K. D. K. Luk
  • A. W. C. Kung
Original Article

DOI: 10.1007/s00198-007-0482-1

Cite this article as:
Lai, B.M.H., Cheung, C.L., Luk, K.D.K. et al. Osteoporos Int (2008) 19: 571. doi:10.1007/s00198-007-0482-1



The association between a newly identified CA repeat polymorphism of the estrogen receptor alpha gene (ESR1) with osteoporosis was investigated. Postmenopausal women with <18 CA repeats had low BMD, increased rate of bone loss and increased fracture risk.


Studies have shown that intronic dinucleotide repeat polymorphisms in some genes are associated with disease risk by modulating mRNA splicing efficiency. D6S440 is a newly identified intronic CA repeat polymorphism located downstream of the 5’-splicing site of exon 5 of ESR1.


The associations of D6S440 with bone mineral density (BMD), rate of bone loss and fracture risk were evaluated in 452 pre-, 110 peri- and 622 postmenopausal southern Chinese women using regression models.


Post- but not premenopausal women with less CA repeats had lower spine and hip BMD. The number of CA repeats was linearly related to hip BMD in postmenopausal women (β = 0.008; p = 0.004). Postmenopausal women with CA repeats <18 had higher risks of having osteoporosis (BMD T-score<−2.5 at the spine: OR 2.46, 95% CI 1.30–4.65; at the hip: OR 3.79(1.64–8.74)) and low trauma fractures (OR 2.31(1.29–4.14)) than those with ≥18 repeats. Perimenopausal women with <18 CA repeats had significantly greater bone loss in 18 months at the hip than those with ≥18 repeats (−1.96% vs. −1.61%, p = 0.029).


ESR1 CA repeat polymorphism is associated with BMD variation, rate of bone loss and fracture risk, and this may be a useful genetic marker for fracture risk assessment.


Association BMD Estrogen receptor alpha Fracture Osteoporosis Polymorphism 

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2007

Authors and Affiliations

  • B. M. H. Lai
    • 1
  • C. L. Cheung
    • 1
  • K. D. K. Luk
    • 2
  • A. W. C. Kung
    • 1
  1. 1.Department of MedicineThe University of Hong KongHong KongChina
  2. 2.Department of Orthopaedics and TraumatologyThe University of Hong KongHong KongChina

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