Top

Published in:

01-02-2016 | Short Communication

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

Authors: J. I. Barzilay, P. Bůžková, J. R. Kizer, L. Djoussé, J. H. Ix, H. A. Fink, D. S. Siscovick, J. A. Cauley, K. J. Mukamal

Published in: Osteoporosis International | Issue 2/2016

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.

Available only for authorised users

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

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

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):195–210CrossRefPubMed

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

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):583–589PubMedCentralCrossRefPubMed

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):263–276CrossRefPubMed

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):260–268CrossRefPubMed

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

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):366–374PubMedCentralCrossRefPubMed

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 423:116–121CrossRefPubMed

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):39–52PubMedCentralCrossRefPubMed

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):1754–1764CrossRefPubMed

14.

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

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):693–699PubMedCentralCrossRefPubMed

16.

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

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):513–520CrossRefPubMed

Title: Fibrosis markers, hip fracture risk, and bone density in older adults
Authors: J. I. Barzilay
P. Bůžková
J. R. Kizer
L. Djoussé
J. H. Ix
H. A. Fink
D. S. Siscovick
J. A. Cauley
K. J. Mukamal
Publication date: 01-02-2016
Publisher: Springer London
Published in: Osteoporosis International / Issue 2/2016
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-015-3269-9

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

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

Abstract

Summary

Introduction

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Summary

Introduction

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 2/2016

Relationship of sarcopenia and body composition with osteoporosis

Predictors of trabecular bone score in school children

Bilateral distal fibula fractures in a woman on long-term bisphosphonate therapy

Genetic influence on the association between bone mineral density and testosterone in Korean men

Validity of parental recall of children’s fracture: implications for investigation of childhood osteoporosis

Impact of hip fracture on hospital care costs: a population-based study