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  • Clinical Implications
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Clinical Implication

Pharmacogenomic approaches to osteoporosis

The Pharmacogenomics Journal volume 3, pages 261–263 (2003)Cite this article

Osteoporosis is a common bone disease inflicting about 40% of women and 12% of men at some point during life.1 It is mainly characterized by the unbalanced loss of bone mass with decreased density and deteriorated bone microarchitecture, leading to osteoporotic fracture. The social economic burden of osteoporosis is so large that its etiology, prevention and treatment have become an urgent issue that needs to be coped with worldwide.

It is generally believed that many genetic and environmental factors and the ways in which they interact with each other underlie the development of osteoporosis.2 However, the exact genetic pathogenesis remains unclear although a large number of candidate genes and their proteins are known to be involved in bone metabolism.3

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References

  1. Ralston SH . The genetics of osteoporosis. Q J Med 1997; 90: 247–251.

    Article  CAS  Google Scholar 

  2. Recker RR, Deng HW . Role of genetics in osteoporosis. Endocrine 2002; 17: 55–66.

    Article  CAS  Google Scholar 

  3. Ho NC et al. A skeletal gene database. J Bone Miner Res 2000; 15: 2095–2122.

    Article  CAS  Google Scholar 

  4. Altkorn D, Vokes T . Treatment of postmenopausal osteoporosis. JAMA 2001; 285: 1415–1418.

    Article  CAS  Google Scholar 

  5. Liu YZ et al. Molecular studies of identification of genes for osteoporosis: the 2002 update. J Endocrinol 2003; 177: 147–196.

    Article  CAS  Google Scholar 

  6. Kiel DP et al. The BsmI vitamin D receptor restriction fragment length polymorphism (bb) influences the effect of calcium intake on bone mineral density. J Bone Miner Res 1997; 12: 1049–1057.

    Article  CAS  Google Scholar 

  7. Dawson-Hughes B et al. Calcium absorption on high and low calcium intakes in relation to vitamin D receptor genotype. J Clin Endocrinol Metab 1995; 80: 3657–3661.

    CAS  PubMed  Google Scholar 

  8. Matsuyama T et al. Vitamin D receptor genotypes and bone mineral density. Lancet 1995; 345: 1238–1239.

    Article  CAS  Google Scholar 

  9. Kurabayashi T et al. Association of vitamin D and estrogen receptor gene polymorphism with the effect of hormone replacement therapy on bone mineral density in Japanese women. Am J Obstetr Gynecol 1999; 180: 1115–1120.

    Article  CAS  Google Scholar 

  10. Ferrari SL et al. Do dietary calcium and age explain the controversy surrounding the relationship between bone mineral density and vitamin D receptor gene polymorphisms? J Bone Miner Res 1998; 13: 363–370.

    Article  CAS  Google Scholar 

  11. Graafmans WC et al. The effect of vitamin D supplementation on the bone mineral density of the femoral neck is associated with vitamin D receptor genotype. J Bone Miner Res 1997; 12: 1241–1245.

    Article  CAS  Google Scholar 

  12. Marc J et al. VDR genotype and response to etidronate therapy in late postmenopausal women. Osteoporos Int 1999; 10: 303–306.

    Article  CAS  Google Scholar 

  13. Palomba S et al. Raloxifene administration in post-menopausal women with osteoporosis: effect of different BsmI vitamin D receptor genotypes. Hum Reprod 2003; 18: 192–198.

    Article  CAS  Google Scholar 

  14. Tofteng CL et al. Two polymorphisms in the vitamin D receptor gene—association with bone mass and 5-year change in bone mass with or without hormone-replacement therapy in postmenopausal women: the Danish Osteoporosis Prevention Study. J Bone Miner Res 2002; 17: 1535–1544.

    Article  CAS  Google Scholar 

  15. Deng HW et al. Change of bone mass in postmenopausal Caucasian women with and without hormone replacement therapy is associated with vitamin D receptor and estrogen receptor genotypes. Hum Genet 1998; 103: 576–585.

    Article  CAS  Google Scholar 

  16. Salmen T et al. The protective effect of hormone-replacement therapy on fracture risk is modulated by estrogen receptor alpha genotype in early postmenopausal women. J Bone Miner Res 2000; 15: 2479–2486.

    Article  CAS  Google Scholar 

  17. Ongphiphadhanakul B et al. Oestrogen-receptor-alpha gene polymorphism affects response in bone mineral density to oestrogen in postmenopausal women. Clin Endocrinol 2000; 52: 581–585.

    Article  CAS  Google Scholar 

  18. Ongphiphadhanakul B et al. Association of a T262C transition in exon 1 of estrogen-receptor-alpha gene with skeletal responsiveness to estrogen in post-menopausal women. J Endocrinol Invest 2001; 24: 749–755.

    Article  CAS  Google Scholar 

  19. Yoneda K et al. Influence of adjuvant tamoxifen treatment on bone mineral density and bone turnover markers in postmenopausal breast cancer patients in Japan. Cancer Lett 2002; 186: 223–230.

    Article  CAS  Google Scholar 

  20. Qureshi AM . COLIA1 Sp1 polymorphism predicts response of femoral neck bone density to cyclical etidronate therapy. Calcif Tissue Int 2002; 70: 158–163.

    Article  CAS  Google Scholar 

  21. Mann V et al. A COL1A1 Sp1 binding site polymorphism predisposes to osteoporotic fracture by affecting bone density and quality. J Clin Invest 2001; 107: 899–907.

    Article  CAS  Google Scholar 

  22. Efstathiadou Z et al. Association of collagen I alpha 1 Sp1 polymorphism with the risk of prevalent fractures: a meta-analysis. J Bone Miner Res 2001; 16: 1586–1592.

    Article  CAS  Google Scholar 

  23. Zhao H et al. Haplotype analysis in population genetics and association studies. Pharmacogenomics 2003; 4: 171–178.

    Article  Google Scholar 

  24. Cardon LR, Abecasis GR . Using haplotype blocks to map human complex trait loci. Trends Genet 2003; 19: 135–140.

    Article  CAS  Google Scholar 

  25. Shilling PD, Kelsoe JR . Functional genomics approaches to understanding brain disorders. Pharmacogenomics 2002; 3: 31–45.

    Article  CAS  Google Scholar 

  26. Schadt EE et al. A new paradigm for drug discovery: integrating clinical, genetic, genomic and molecular phenotype data to identify drug targets. Biochem Soc Trans 2003; 31: 437–443.

    Article  CAS  Google Scholar 

  27. Dvornyk V et al. Gene expression studies of osteoporosis: implications for microarray research. Osteoporos Int 2003; 14: 451–461.

    Article  CAS  Google Scholar 

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Acknowledgements

The study was partially supported by grants from the Health Future Foundation of the USA, grants from the National Institute of Health (K01 AR02170-01, R01 GM60402-01 A1), grants from the State of Nebraska Cancer and Smoking Related Disease Research Program (LB595) and the State of Nebraska Tobacco Settlement Fund (LB692), and US Department of Energy grant (DE-FG03-00ER63000/A00).

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Author notes

  1. D-H Xiong and J-R Long: These two authors contributed equally to this article.

Authors and Affiliations

  1. Osteoporosis Research Center, Creighton University Medical Center, Omaha, NE, USA

    D-H Xiong, J-R Long, R R Recker & H-W Deng

  2. Department of Biomedical Sciences, Creighton University, Omaha, NE, USA

    D-H Xiong & H-W Deng

  3. Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, Hunan, People's Republic of China

    H-W Deng

Authors
  1. D-H Xiong
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  2. J-R Long
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  3. R R Recker
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  4. H-W Deng
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Corresponding author

Correspondence to H-W Deng.

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DUALITY OF INTEREST

None declared.

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Xiong, DH., Long, JR., Recker, R. et al. Pharmacogenomic approaches to osteoporosis. Pharmacogenomics J 3, 261–263 (2003). https://doi.org/10.1038/sj.tpj.6500199

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