Osteoporosis International

, Volume 21, Issue 3, pp 467–477 | Cite as

The role of cigarette smoking and statins in the development of postmenopausal osteoporosis: a pilot study utilizing the Marshfield Clinic Personalized Medicine Cohort

  • P. F. GiampietroEmail author
  • C. McCarty
  • B. Mukesh
  • F. McKiernan
  • D. Wilson
  • A. Shuldiner
  • J. Liu
  • J. LeVasseur
  • L. Ivacic
  • T. Kitchner
  • N. Ghebranious
Original Article



A cohort of postmenopausal osteoporotic females and controls with normal bone mineral density, the interleukin 6 (IL6) −634G > C (rs1800796) C allele of the promoter region showed association with osteoporosis. The lipoprotein receptor-related protein 5 (LRP5) gene showed association between C135242T C/T alleles and osteoporosis only in smokers, suggesting a role for environmental interaction.


A nested case–control study within a population-based cohort was undertaken to assess the relative impact of cigarette smoking, statin use, genetic polymorphisms, and one-way interaction of these factors on development of osteoporosis in postmenopausal women.


Genotyping of 14 single-nucleotide polymorphisms (SNPs) corresponding to vitamin D receptor gene, estrogen receptor 1, collagen type 1 alpha 1, IL6, transcription growth factor beta, apolipoprotein E, and LRP5 genes was performed in cases (n = 309) with osteoporosis and controls (n = 293) with normal bone mineral density drawn from a homogeneous Caucasian population. SNPs were chosen based on known functional consequences or prior evidence for association and genotyped using matrix-assisted laser desorption ionization time-of-flight technology.


Cases differed from controls relative to body mass index, age, and smoking but not statin use. After adjusting for age, the IL6 −634G > C (rs1800796) allele showed association with osteoporosis (odds ratio (OR) for CC + CG = 2.51, p = 0.0047)), independent of statin use or smoking status. On stratification for smoking, association with LRP5 C135242T (rs545382) and osteoporosis emerged (OR 2.8 in smokers for CT alleles, p = 0.03)), suggestive of potential environmental interaction.


Evidence suggested a role for genetic variation in IL6 and LRP5 in conferring risk for osteoporosis in Caucasian women, with the latter manifest only in smokers.


Cigarette Gene–environment interaction IL6 LRP5 Osteoporosis Smoking 



The authors thank Adeline Kaam for her assistance with phenotyping and Ingrid Glurich, Alice Stargardt, and Marie Fleisner, Marshfield Clinic Research Foundation, Office of Scientific Writing, for their editorial assistance in the preparation of this manuscript.


Marshfield Clinic Research Foundation; Donors to Personalized Medicine and Rheumatology

Conflicts of interest



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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2009

Authors and Affiliations

  • P. F. Giampietro
    • 1
    • 8
    Email author
  • C. McCarty
    • 2
  • B. Mukesh
    • 3
  • F. McKiernan
    • 4
  • D. Wilson
    • 4
  • A. Shuldiner
    • 5
  • J. Liu
    • 5
  • J. LeVasseur
    • 6
    • 7
  • L. Ivacic
    • 2
  • T. Kitchner
    • 2
  • N. Ghebranious
    • 2
  1. 1.Marshfield Clinic, Department of Medical Genetic ServicesMarshfieldUSA
  2. 2.Marshfield Clinic Research Foundation, Center for Human GeneticsMarshfieldUSA
  3. 3.Alcon Research Ltd.Fort WorthUSA
  4. 4.Marshfield Clinic, Department of RheumatologyMarshfieldUSA
  5. 5.University of Maryland School of MedicineBaltimoreUSA
  6. 6.University of Wisconsin-MadisonMadisonUSA
  7. 7.Marshfield Clinic Research FoundationMarshfieldUSA
  8. 8.Department of PediatricsUniversity of Wisconsin-MadisonMadisonUSA

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