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Calcified Tissue International

, Volume 92, Issue 5, pp 467–476 | Cite as

Polymorphisms of Muscle Genes Are Associated with Bone Mass and Incident Osteoporotic Fractures in Caucasians

  • T. HarsløfEmail author
  • M. Frost
  • T. L. Nielsen
  • L. B. Husted
  • M. Nyegaard
  • K. Brixen
  • A. D. Børglum
  • L. Mosekilde
  • M. Andersen
  • L. Rejnmark
  • B. L. Langdahl
Original Research

Abstract

The interaction between muscle and bone is complex. The aim of this study was to investigate if variations in the muscle genes myostatin (MSTN), its receptor (ACVR2B), myogenin (MYOG), and myoD1 (MYOD1) were associated with fracture risk, bone mineral density (BMD), bone mineral content (BMC), and lean body mass. We analyzed two independent cohorts: the Danish Osteoporosis Prevention Study (DOPS), comprising 2,016 perimenopausal women treated with hormone therapy or not and followed for 10 years, and the Odense Androgen Study (OAS), a cross-sectional, population-based study on 783 men aged 20–29 years. Nine tag SNPs in the four genes were investigated. In the DOPS, individuals homozygous for the variant allele of the MSTN SNP rs7570532 had an increased risk of any osteoporotic fracture, with an HR of 1.82 (95 % CI 1.15–2.90, p = 0.01), and of nonvertebral osteoporotic fracture, with an HR of 2.02 (95 % CI 1.20–3.41, p = 0.01). The same allele was associated with increased bone loss (BMC) at the total hip of 4.1 versus 0.5 % in individuals either heterozygous or homozygous for the common allele (p = 0.006), a reduced 10-year growth in bone area at the total hip of 0.4 versus 2.2 and 2.3 % in individuals heterozygous or homozygous for the common allele, respectively (p = 0.01), and a nonsignificantly increased 10-year loss of total-hip BMD of 4.4 versus 2.7 and 2.9 % in individuals heterozygous or homozygous for the common allele, respectively (p = 0.08). This study is the first to demonstrate an association between a variant in MSTN and fracture risk and bone loss. Further studies are needed to confirm the findings.

Keywords

Osteoporosis Genetics Muscle Fracture Polymorphism 

Notes

Acknowledgments

The OAS was supported by the World Anti-Doping Agency, Novo Nordisk, The Novo Nordisk Foundation, The Danish Ministry of Culture, and the Clinical Institute at University of Southern Denmark. Genotyping was supported by a grant from The Villum Kann Rasmussen Foundation, Jacob Madsen and Spouse Olga Madsens Foundation, The Family Hede Nielsen Foundation, The Danish Osteoporosis Foundation, The Brothers Hartmann Foundation, and The A.P. Møller Foundation.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • T. Harsløf
    • 1
    • 2
    Email author
  • M. Frost
    • 3
    • 4
  • T. L. Nielsen
    • 3
  • L. B. Husted
    • 1
  • M. Nyegaard
    • 5
    • 6
  • K. Brixen
    • 3
  • A. D. Børglum
    • 5
    • 7
  • L. Mosekilde
    • 1
  • M. Andersen
    • 3
  • L. Rejnmark
    • 1
  • B. L. Langdahl
    • 1
  1. 1.Department of Endocrinology and Internal MedicineTHG, Aarhus University HospitalAarhusDenmark
  2. 2.Department of MedicineRegional Hospital RandersRandersDenmark
  3. 3.Department of EndocrinologyOdense University HospitalOdenseDenmark
  4. 4.Department of MedicineKolding HospitalKoldingDenmark
  5. 5.Department of BiomedicineAarhus UniversityAarhusDenmark
  6. 6.Department of HaematologyAarhus University HospitalAalborgDenmark
  7. 7.Centre for Psychiatric ResearchAarhus University HospitalAarhusDenmark

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