Genetic variation in the RANKL/RANK/OPG signaling pathway is associated with bone turnover and bone mineral density in men
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The aim of this study was to determine if single-nucleotide polymorphisms (SNPs) in RANKL, RANK, and OPG influence bone turnover and bone mineral density (BMD) in men. Pairwise tag SNPs (r2 ≥ 0.8) were selected for RANKL, RANK, and OPG and their 10-kb flanking regions. Selected tag SNPs plus five SNPs near RANKL and OPG, associated with BMD in published genome-wide association studies (GWAS), were genotyped in 2653 men aged 40 to 79 years of age recruited for participation in a population-based study of male aging, the European Male Ageing Study (EMAS). N-terminal propeptide of type I procollagen (PINP) and C-terminal cross-linked telopeptide of type I collagen (CTX-I) serum levels were measured in all men. BMD at the calcaneus was estimated by quantitative ultrasound (QUS) in all men. Lumbar spine and total-hip areal BMD (BMDa) was measured by dual-energy X-ray absorptiometry (DXA) in a subsample of 620 men. Multiple OPG, RANK, and RANKL SNPs were associated with bone turnover markers. We also identified a number of SNPs associated with BMD, including rs2073618 in OPG and rs9594759 near RANKL. The minor allele of rs2073618 (C) was associated with higher levels of both PINP (β = 1.83, p = .004) and CTX-I (β = 17.59, p = 4.74 × 10−4), and lower lumbar spine BMDa (β = −0.02, p = .026). The minor allele of rs9594759 (C) was associated with lower PINP (β = −1.84, p = .003) and CTX-I (β = −27.02, p = 6.06 × 10−8) and higher ultrasound BMD at the calcaneus (β = 0.01, p = .037). Our findings suggest that genetic variation in the RANKL/RANK/OPG signaling pathway influences bone turnover and BMD in European men. © 2010 American Society for Bone and Mineral Research
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The RANKL-RANK-OPG pathway exerts a crucial role in osteoclast differentiation and bone resorption.
“It has been shown that the receptor activator of nuclear factor-kappa B ligand (RANKL)-RANK-osteoprotegerin (OPG) (RANKL-RANK-OPG) pathway exerts a crucial role in osteoclast differentiation and bone resorption [87,88,89].”
From An Overlooked Bone Metabolic Disorder: Cigarette Smoking-Induced Osteoporosis (2022) · cites this paper as [89]
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- Authors
- Roshandel, D., Holliday, K. L., Pye, S. R., Boonen, S., Borghs, H., Vanderschueren, D., Huhtaniemi, I. T., Adams, J. E., Ward, K. A., Bartfai, G., Casanueva, F., Finn, J. D., Forti, G., Giwercman, A., Han, T. S., Kula, K., Lean, M. E., Pendleton, N., Punab, M., Silman, A. J., Wu, F. C., Thomson, W., O'Neill, T. W., & and the EMAS Study Group
- Affiliations
- Manchester Academic Health Science Centre (GB)
- KU Leuven (BE)
- Imperial College London (GB)
- MRC Elsie Widdowson Laboratory (GB)
- Department of Obstetrics, Gynaecology and Andrology, Albert Szent-Gyorgy Medical University, Szeged, Hungary
- Complejo Hospitalario Universitario de Santiago (ES)
- University of Florence (IT)
- Lund University (SE)
- University of Glasgow (GB)
- Medical University of Lodz (PL)
- Tartu University Hospital (EE)
- Arthritis Research UK, Epidemiology Unit, The University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom
- Corresponding author
- Holliday, Kate L
- ORCID
- Venue
- Journal of Bone and Mineral Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-07-30
- Volume
- 25
- Issue
- 8
- Pages
- 1830-1838
- ISSN
- 0884-0431 (ISSN-L)
- 1523-4681
- OpenAlex
- W2079316695
- Cited by
- 66
- References
- 44
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 1 · 2020: 5 · 2019: 8 · 2018: 5 · 2017: 2 · 2016: 3 · 2015: 4 · 2014: 6 · 2013: 4 · 2012: 7
- FWCI
- 7.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Journal of Bone and Mineral Research (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Funders
- Vlaamse regering
- Versus Arthritis
- Topics
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- RANKL, RANK, OPG, bone turnover markers, bone mineral density, single nucleotide polymorphisms, tag SNPs, P1NP, C-terminal telopeptide of type I collagen, men, aging, genetic association, quantitative ultrasound, European Male Ageing Study
- MeSH terms
- Adult, Aged, Bone and Bones, Europe, Genetic Markers, Genotype, Humans, Male, Middle Aged, Ultrasonography, Genetic Variation, Signal Transduction, Absorptiometry, Photon, Bone Density, Bone Remodeling, Polymorphism, Single Nucleotide, Osteoprotegerin, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B, Genetic Association Studies
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