LRP5 polymorphisms and response to risedronate treatment in osteoporotic men

Marcin Kruk, Stuart H. Ralston, Omar Al Bagha

Research output: Contribution to journalArticle

29 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)171-179
Number of pages9
JournalCalcified Tissue International
Volume84
Issue number3
DOIs
Publication statusPublished - Mar 2009
Externally publishedYes

Fingerprint

Bone Density
Pelvic Bones
Genotype
Therapeutics
Diphosphonates
Osteoporosis
Placebos
Risedronate Sodium
Bone Remodeling
Femur Neck
Femur
Spine
Biomarkers
Genes

Keywords

  • Bone
  • Bone density
  • LRP5
  • Osteoporosis
  • Polymorphism

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine
  • Endocrinology

Cite this

LRP5 polymorphisms and response to risedronate treatment in osteoporotic men. / Kruk, Marcin; Ralston, Stuart H.; Al Bagha, Omar.

In: Calcified Tissue International, Vol. 84, No. 3, 03.2009, p. 171-179.

Research output: Contribution to journalArticle

@article{03ce12f0bab94dd6ba168fa7ffc03f6c,
title = "LRP5 polymorphisms and response to risedronate treatment in osteoporotic men",
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, Bone density, LRP5, Osteoporosis, Polymorphism",
author = "Marcin Kruk and Ralston, {Stuart H.} and {Al Bagha}, Omar",
year = "2009",
month = "3",
doi = "10.1007/s00223-008-9207-5",
language = "English",
volume = "84",
pages = "171--179",
journal = "Calcified Tissue International",
issn = "0171-967X",
publisher = "Springer New York",
number = "3",

}

TY - JOUR

T1 - LRP5 polymorphisms and response to risedronate treatment in osteoporotic men

AU - Kruk, Marcin

AU - Ralston, Stuart H.

AU - Al Bagha, Omar

PY - 2009/3

Y1 - 2009/3

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.

AB - 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.

KW - Bone

KW - Bone density

KW - LRP5

KW - Osteoporosis

KW - Polymorphism

UR - http://www.scopus.com/inward/record.url?scp=62349136652&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=62349136652&partnerID=8YFLogxK

U2 - 10.1007/s00223-008-9207-5

DO - 10.1007/s00223-008-9207-5

M3 - Article

C2 - 19148563

AN - SCOPUS:62349136652

VL - 84

SP - 171

EP - 179

JO - Calcified Tissue International

JF - Calcified Tissue International

SN - 0171-967X

IS - 3

ER -