Calcified Tissue International

, Volume 84, Issue 3, pp 171–179 | Cite as

LRP5 Polymorphisms and Response to Risedronate Treatment in Osteoporotic Men

  • Marcin Kruk
  • Stuart H. Ralston
  • Omar M. E. Albagha
Article

Abstract

Genetic factors are important in the pathogenesis of osteoporosis, but little is known about the genetic determinants of treatment response. Previous studies have shown that polymorphisms of the LRP5 gene are associated with bone mineral density (BMD), but the relationship between LRP5 polymorphisms and response to bisphosphonate treatment in osteoporosis has not been studied. In this study we investigated LRP5 polymorphisms in relation to treatment response in a group of 249 osteoporotic or osteopenic men who participated in a 24-month randomized double blind placebo-controlled trial of risedronate treatment. BMD and biochemical markers of bone turnover were measured at baseline and after 6, 12, and 24 months of follow-up. We analyzed two coding polymorphisms of LRP5, which have previously been associated with BMD, V667M (rs4988321) and A1330V (rs3736228), and found a significant association between the A1330V polymorphism and hip BMD at baseline. Subjects with the 1330 Val/Val genotype had 8.4% higher total-hip BMD compared with the other genotype groups (P = 0.009), and similar associations were observed at the femoral neck (P = 0.01) and trochanter (P = 0.002). There was no association between A1330V and spine BMD, however, or between the V667M polymorphism and BMD at any site. The difference in hip BMD between A1330V genotype groups remained significant throughout the study, but there was no evidence of a genotype–treatment interaction in either risedronate- or placebo-treated patients. In conclusion, the LRP5 A1330V polymorphism is associated with hip BMD in osteoporotic men, but allelic variations in LRP5 do not appear to be associated with response to bisphosphonate treatment.

Keywords

Bone LRP5 Osteoporosis Polymorphism Bone density 

Notes

Acknowledgments

The study was supported by a research grant from Procter & Gamble Pharmaceuticals. O. M. E. A. is funded by the Arthritis Research Campaign UK (15389 and 16303). S. H. R. acted as a consultant for Novartis, Procter & Gamble, and Sanofi Aventis pharmaceuticals.

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Marcin Kruk
    • 1
  • Stuart H. Ralston
    • 1
  • Omar M. E. Albagha
    • 1
  1. 1.Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, Western General HospitalUniversity of EdinburghEdinburghUK

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