Influence of Polymorphisms in the RANKL-RANK-OPG Signaling Pathway on Volumetric Bone Mineral Density and Bone Geometry at the Forearm in MenReport as inadecuate




Influence of Polymorphisms in the RANKL-RANK-OPG Signaling Pathway on Volumetric Bone Mineral Density and Bone Geometry at the Forearm in Men - Download this document for free, or read online. Document in PDF available to download.

Calcified Tissue International

, Volume 89, Issue 6, pp 446–455

First Online: 02 October 2011Received: 08 March 2011Accepted: 19 July 2011

Abstract

We sought to determine the influence of single-nucleotide polymorphisms SNPs in RANKL, RANK, and OPG on volumetric bone mineral density vBMD and bone geometry at the radius in men. Pairwise tag SNPs r ≥ 0.8 for RANKL n = 8, RANK n = 44, and OPG n = 22 and five SNPs near RANKL and OPG strongly associated with areal BMD in genomewide association studies were previously genotyped in men aged 40–79 years in the European Male Ageing Study EMAS. Here, these SNPs were analyzed in a subsample of men n = 589 who had peripheral quantitative computed tomography pQCT performed at the distal 4% and mid-shaft 50% radius. Estimated parameters were total and trabecular vBMD mg-mm and cross-sectional area mm at the 4% site and cortical vBMD mg-mm; total, cortical, and medullary area mm; cortical thickness mm; and stress strain index SSI mm at the 50% site. We identified 12 OPG SNPs associated with vBMD and-or geometric parameters, including rs10505348 associated with total vBMD β 95% CI = 9.35 2.12–16.58, P = 0.011, cortical vBMD β 95% CI = 5.62 2.10–9.14, P = 0.002, cortical thickness β 95% CI = 0.08 0.03–0.13, P = 0.002, and medullary area β 95% CI = −2.90 −4.94 to −0.86, P = 0.005 and rs2073618 associated with cortical vBMD β 95% CI = −4.30 −7.78 to −0.82, P = 0.015 and cortical thickness β 95% CI = −0.08 −0.13 to −0.03, P = 0.001. Three RANK SNPs were associated with vBMD, including rs12956925 associated with trabecular vBMD β 95% CI = −7.58 −14.01 to −1.15, P = 0.021. There were five RANK SNPs associated with geometric parameters, including rs8083511 associated with distal radius cross-sectional area β 95% CI = 8.90 0.92–16.88, P = 0.029. No significant association was observed between RANKL SNPs and pQCT parameters. Our findings suggest that genetic variation in OPG and RANK influences radius vBMD and geometry in men.

KeywordsOsteoporosis Genetic association Genetic polymorphism Male QCT T. W. O’Neill and W. Thomson equally contributed to this study.

F. C. W. Wu is the coordinator for the European Male Ageing Study EMAS.

The EMAS Study Group: Florence Gianni Forti, Luisa Petrone, Glovanni Corona; Leuven Dirk Vanderschueren, Steven Boonen, Herman Borghs; Lodz Krzysztof Kula, Jolanta Slowikowska-Hilczer, Renata Walczak-Jedrzejowska; London Ilpo Huhtaniemi; Malmö Aleksander Giwercman; Manchester Frederick Wu, Alan Silman, Terence O’Neill, Joseph Finn, Philip Steer, Abdelouahid Tajar, David Lee, Stephen Pye; Santiago Felipe Casanueva, Mary Lage; Szeged Gyorgy Bartfai, Imre Földesi, Imre Fejes; Tartu Margus Punab, Paul Korrovitz; Turku Min Jiang.

The authors have stated that they have no conflict of interest.

Electronic supplementary materialThe online version of this article doi:10.1007-s00223-011-9532-y contains supplementary material, which is available to authorized users.

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Author: Delnaz Roshandel - Kate L. Holliday - Stephen R. Pye - Kate A. Ward - Steven Boonen - Dirk Vanderschueren - Herman Borgh

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