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LRP5 Polymorphisms and response to risedronate treatment in osteoporotic men.
Calcif Tissue Int. 2009 Mar; 84(3):171-9.CT

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.

Authors+Show Affiliations

Molecular Medicine Centre, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, UK.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19148563

Citation

Kruk, Marcin, et al. "LRP5 Polymorphisms and Response to Risedronate Treatment in Osteoporotic Men." Calcified Tissue International, vol. 84, no. 3, 2009, pp. 171-9.
Kruk M, Ralston SH, Albagha OM. LRP5 Polymorphisms and response to risedronate treatment in osteoporotic men. Calcif Tissue Int. 2009;84(3):171-9.
Kruk, M., Ralston, S. H., & Albagha, O. M. (2009). LRP5 Polymorphisms and response to risedronate treatment in osteoporotic men. Calcified Tissue International, 84(3), 171-9. https://doi.org/10.1007/s00223-008-9207-5
Kruk M, Ralston SH, Albagha OM. LRP5 Polymorphisms and Response to Risedronate Treatment in Osteoporotic Men. Calcif Tissue Int. 2009;84(3):171-9. PubMed PMID: 19148563.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - LRP5 Polymorphisms and response to risedronate treatment in osteoporotic men. AU - Kruk,Marcin, AU - Ralston,Stuart H, AU - Albagha,Omar M E, Y1 - 2009/01/16/ PY - 2008/08/11/received PY - 2008/11/29/accepted PY - 2009/1/17/entrez PY - 2009/1/17/pubmed PY - 2009/5/9/medline SP - 171 EP - 9 JF - Calcified tissue international JO - Calcif. Tissue Int. VL - 84 IS - 3 N2 - 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. SN - 1432-0827 UR - https://www.unboundmedicine.com/medline/citation/19148563/LRP5_Polymorphisms_and_response_to_risedronate_treatment_in_osteoporotic_men_ L2 - https://dx.doi.org/10.1007/s00223-008-9207-5 DB - PRIME DP - Unbound Medicine ER -