Osteoporosis International

, Volume 15, Issue 10, pp 820–826

Interleukin-6 promoter polymorphism is associated with bone quality assessed by calcaneus ultrasound and previous fractures in a cohort of 75-year-old women

  • Anna Nordström
  • Paul Gerdhem
  • Helena Brändström
  • Fredrik Stiger
  • Ulf H. Lerner
  • Mattias Lorentzon
  • Karl Obrant
  • Peter Nordström
  • Kristina Åkesson
Original Article

Abstract

Interleukin 6 (IL-6) is a multifunctional cytokine and a potent stimulator of bone resorption and has been implicated in the pathogenesis of osteoporosis in postmenopausal women. The aim of this study was to investigate if a functional IL-6 promoter polymorphism (−174) was related to bone mass and fractures in a cohort consisting of 964 postmenopausal Caucasian women aged 75 years. Bone mineral density (BMD; g/cm2) of the femoral neck, lumbar spine and total body was measured using dual energy X-ray absorptiometry (DXA). Quantitative ultrasound (QUS) was also measured in the calcaneus and quantified as speed of sound (SOS; m/s), broadband ultrasound attenuation (BUA; dB/MHz), and stiffness index (SI). IL-6 genotypes was determined by restriction fragment length polymorphism (RFLP) using the restriction enzyme NlaIII. The frequencies of the different IL-6 genotypes were 27.5% (GG), 47.9% (GC), 24.6% (CC). The IL-6 polymorphism (presence of G) was independently related to a lower stiffness (β=−0.07; P=0.03) and BUA (β=−0.08; P=0.02), but not to BMD at any site measured by DXA. In the cohort, 420 subjects (44%) reported at least one fracture during their lifetime, and 349 (36%) reported at least one fracture after the age of 50. Using binary logistic regression, the IL-6 polymorphism (presence of G) was significantly related to an increased risk of a previous fracture during life (odds ratio 1.46, 95% CI 1.08–1.97) and to an increased risk of a fracture occurring after 50 years of age (odds ratio 1.37, 95% CI 1.004–1.88). The risk was further increased for fractures grouped as osteoporotic fractures (odds ratio 1.67, 95% CI 1.14–2.45), including forearm fractures (odds ratio 1.59, 95% CI 1.05–2.40). In conclusion, presence of G allele in the IL-6 promoter polymorphism at position –174 is independently related to previous fractures in postmenopausal women. This association may be related primarily to an altered bone quality identified by QUS and not a lower bone mass. This is also the first demonstration of association of IL-6 gene polymorphism to calcaneal QUS.

Keywords

Fractures IL-6 polymorphism Postmenopausal women QUS 

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2004

Authors and Affiliations

  • Anna Nordström
    • 1
  • Paul Gerdhem
    • 2
  • Helena Brändström
    • 3
  • Fredrik Stiger
    • 3
  • Ulf H. Lerner
    • 4
  • Mattias Lorentzon
    • 1
  • Karl Obrant
    • 2
  • Peter Nordström
    • 1
    • 5
  • Kristina Åkesson
    • 2
  1. 1.Sports Medicine, Department of Surgical and Perioperative SciencesUmeå University HospitalUmeåSweden
  2. 2.Department of OrthopaedicsMalmö University HospitalSweden
  3. 3.Department of Medical SciencesUppsala UniversitySweden
  4. 4.Department of Oral Cell BiologyUmeå UniversityUmeåSweden
  5. 5.Department of Geriatric MedicineUmeå University HospitalUmeåSweden

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