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Fibrosis markers, hip fracture risk, and bone density in older adults

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Abstract

Summary

We examined whether blood levels of two markers of fibrosis (transforming growth factor beta one (TGF-β1) and procollagen type III N-terminal propeptide (PIIINP)) are related to hip fracture risk and to bone mineral density (BMD). TGF-β1 levels were associated with lower hip fracture risk in women and with lower BMD in men. PIIINP levels were not associated with either outcome.

Introduction

TGF-β1 serves several roles in bone formation and resorption. A consequence of TGF-β1 activation is the production of PIIINP, a marker of collagen III deposition. Here, we explore whether these two biomarkers are related to incident hip fracture and bone mineral density (BMD) and whether their associations are modified by systemic inflammation, as measured by C-reactive protein (CRP) levels.

Methods

Participants were from the Cardiovascular Health Study (mean age 78 years; mean follow-up 8.3 years). We included 1681 persons with measured levels of TGF-β1 (149 hip fractures) and 3226 persons with measured levels of PIIINP (310 hip fractures).

Results

Among women, higher TGF-β1 levels were associated with lower hip fracture risk (HR, per doubling, 0.78 [95 % CI 0.61, 0.91]). Among men, TGF-β1 levels were associated with hip fracture risk in a non-linear manner, but among those with elevated CRP levels, doubling was associated with increased risk of fracture (HR 2.22 [1.20, 4.08]) (p = 0.02, interaction between low and high CRP and TGF-β1 on fracture risk). TGF-β1 levels had no significant association with total hip or total body BMD in women but were significantly associated with lower BMD in men. There were no associations of PIIINP levels with hip fracture risk or BMD in men or women.

Conclusions

TGF-β1 levels appear to be associated with bone-related phenotypes in a sex-specific manner. The reasons for these differences between men and women regarding TGF-β1 levels and hip fracture risk and bone density require further investigation.

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References

  1. Erlebacher A, Filvaroff EH, Ye JQ, Derynck R (1998) Osteoblastic responses to TGF-beta during bone remodeling. Mol Biol Cell 9(7):1903–1918

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Tang SY, Alliston T (2013) Regulation of postnatal bone homeostasis by TGFβ. Bonekey Rep 2:255. doi:10.1038/bonekey.2012.255

    Article  PubMed Central  PubMed  Google Scholar 

  3. Erlebacher A, Derynick R (1996) Increased expression of TGF-beta 2 in osteoblasts results in an osteoporosis-like phenotype. J Cell Biol 132(1–2):195–210

    Article  CAS  PubMed  Google Scholar 

  4. Sundström J, Vasan RS (2006) Circulating biomarkers of extracellular matrix remodeling and risk of atherosclerotic events. Curr Opin Lipidol 17(1):45–53

    Article  PubMed  Google Scholar 

  5. Agarwal I, Glazer NL, Barasch E, Biggs ML, Djousse L, Fitzpatrick AL, Gottdiener JS, Ix JH, Kizer JR, Rimm EB, Sicovick DS, Tracy RP, Mukamal KJ (2014) Fibrosis-related biomarkers and incident cardiovascular disease in older adults: The Cardiovascular Health Study. Circ Arrhythm Electrophysiol 7(4):583–589

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Fried LP, Borhani NO, Enright P, Furberg CD, Gardin JM, Kronmal RA, Kuller LH, Manolio TA, Mittelmark MB, Newman A (1991) The Cardiovascular Health Study: design and rationale. Ann Epidemiol 1(3):263–276

    Article  CAS  PubMed  Google Scholar 

  7. Fisher DM, Wong JM, Crowley C, Khan WS (2013) Preclinical and clinical studies on the use of growth factors for bone repair: a systematic review. Curr Stem Cell Res Ther 8(3):260–268

    Article  CAS  PubMed  Google Scholar 

  8. Grainger DJ, Mosedale DE, Metcalfe JC (2000) TGF-beta in blood: a complex problem. Cytokine Growth Factor Rev 11(1–2):133–145

    Article  CAS  PubMed  Google Scholar 

  9. Young RL, Weinberg J, Vieira V, Ozonoff A, Webster TF (2011) Generalized additive models and inflated type i error rates of smoother significance tests. Comput Stat Data Anal 55(1):366–374

    Article  PubMed Central  PubMed  Google Scholar 

  10. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. ISBN 3-900051-07-0, URL http://www.R-project.org

  11. Xie GQ, Lei DD, He HB, Gong JJ, Chen C, Chen P, Zhang H, Luo XH, Liao EY, Wu XP (2013) Relationship between serum TGF-β1, OPG levels and osteoporotic risk in native Chinese women. Clin Chim Acta 423:116–121

    Article  CAS  PubMed  Google Scholar 

  12. Braga M, Bhasin S, Jasuja R, Pervin S, Singh R (2012) Testosterone inhibits transforming growth factor-β signaling during myogenic differentiation and proliferation of mouse satellite cells: potential role of follistatin in mediating testosterone action. Mol Cell Endocrinol 350(1):39–52

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Borton AJ, Frederick JP, Datto MB, Wang XF, Weinstein RS (2001) The loss of Smad3 results in a lower rate of bone formation and osteopenia through dysregulation of osteoblast differentiation and apoptosis. J Bone Miner Res 16(10):1754–1764

    Article  CAS  PubMed  Google Scholar 

  14. Blobe GC, Schiemann WP, Lodish HF (2000) Role of transforming growth factor beta in human disease. N Engl J Med 342(18):1350–1358

    Article  CAS  PubMed  Google Scholar 

  15. Shull MM, Ormsby I, Kier AB, Pawlowski S, Diebold RJ, Yin M, Allen R, Sidman C, Proetzel G, Calvin D et al (1992) Targeted disruption of the mouse transforming growth factor-β 1 gene results in multifocal inflammatory disease. Nature 359(6397):693–699

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Levant S, Chari K, DeFrances CJ (2015) Hospitalizations for patients aged 85 and over in the United States, 2000–2010. NCHS Data Brief 182:1–8

    PubMed  Google Scholar 

  17. Cho TJ, Gerstenfeld LC, Einhorn TA (2002) Differential temporal expression of members of the transforming growth factor beta superfamily during murine fracture healing. J Bone Miner Res 17(3):513–520

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This research was supported by contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, and grant HL080295 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). This work was also funded in part by R01 HL094555 from the National Heart, Lung, and Blood Institute (to Drs. Djoussé, Ix, Kizer, and Mukamal). A full list of principal CHS investigators and institutions can be found at www.CHS-NHLBI.org.

Conflicts of interest

Joshua I. Barzilay, Petra Bůžková, Jorge R. Kizer, Luc Djoussé, Joachim H. Ix, Howard A. Fink, David S. Siscovick, Jane A. Cauley, and Kenneth J. Mukamal declare that they have no conflicts of interest.

Author information

Authors and Affiliations

  1. Kaiser Permanente of Georgia, Division of Endocrinology and the Division of Endocrinology, Emory University School of Medicine, Atlanta, GA, USA

    J. I. Barzilay

  2. Department of Biostatistics, University of Washington, Seattle, WA, USA

    P. Bůžková

  3. Department of Medicine and the Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA

    J. R. Kizer

  4. Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    L. Djoussé

  5. Division of Nephrology, University of California San Diego, San Diego VA Healthcare System, San Diego, CA, USA

    J. H. Ix

  6. Geriatric Research Education and Clinical Center, Veterans Affair Medical Center, Minneapolis, MN, USA

    H. A. Fink

  7. New York Academy of Sciences, New York, NY, USA

    D. S. Siscovick

  8. Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA

    J. A. Cauley

  9. Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA

    K. J. Mukamal

  10. 3650 Steve Reynolds Blvd, Duluth, GA, 30096, USA

    J. I. Barzilay

Authors
  1. J. I. Barzilay
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  2. P. Bůžková
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  3. J. R. Kizer
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  4. L. Djoussé
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  5. J. H. Ix
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  6. H. A. Fink
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  7. D. S. Siscovick
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  8. J. A. Cauley
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  9. K. J. Mukamal
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Corresponding author

Correspondence to J. I. Barzilay.

Appendix

Appendix

Table 2 Baseline characteristics of the cohort by whether the TGF-β1 and PIIINP levels are above the median level
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Barzilay, J.I., Bůžková, P., Kizer, J.R. et al. Fibrosis markers, hip fracture risk, and bone density in older adults. Osteoporos Int 27, 815–820 (2016). https://doi.org/10.1007/s00198-015-3269-9

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  • DOI: https://doi.org/10.1007/s00198-015-3269-9

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