Title: Influence of Polymorphisms in the RANKL/RANK/OPG Signaling Pathway on Volumetric Bone Mineral Density and Bone Geometry at the Forearm in Men
Authors: Roshandel, Delnaz ×
Holliday, Kate L
Pye, Stephen R
Ward, Kate A
Boonen, Steven
Vanderschueren, Dirk
Borghs, Herman
Huhtaniemi, Ilpo T
Adams, Judith E
Bartfai, Gyorgy
Casanueva, Felipe F
Finn, Joseph D
Forti, Gianni
Giwercman, Aleksander
Han, Thang S
Kula, Krzysztof
Lean, Michael E
Pendleton, Neil
Punab, Margus
Silman, Alan J
Wu, Frederick C
Thomson, Wendy
O'Neill, Terence W
The EMAS Study Group #
Issue Date: Dec-2011
Publisher: Springer-Verlag
Series Title: Calcified Tissue International vol:89 issue:6 pages:446-455
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 (2) ≥ 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(3)) and cross-sectional area (mm(2)) at the 4% site and cortical vBMD (mg/mm(3)); total, cortical, and medullary area (mm(2)); cortical thickness (mm); and stress strain index (SSI) (mm(3)) 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.
ISSN: 0171-967X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Clinical and Experimental Endocrinology
Gerontology and Geriatrics
× corresponding author
# (joint) last author

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