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

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

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)815-820
Number of pages6
JournalOsteoporosis International
Volume27
Issue number2
DOIs
StatePublished - Feb 1 2016

Fingerprint

Pelvic Bones
Hip Fractures
Bone Density
Fibrosis
Collagen Type III
C-Reactive Protein
Bone Resorption
Collagen Type I
Osteogenesis
Transforming Growth Factor beta
Hip
Collagen
Biomarkers
Inflammation
Phenotype
Bone and Bones

Keywords

  • Bone mineral density
  • Hip fracture
  • PIIINP
  • TGF-β

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

Cite this

Barzilay, J. I., Bůžková, P., Kizer, J., Djoussé, L., Ix, J. H., Fink, H. A., ... Mukamal, K. J. (2016). Fibrosis markers, hip fracture risk, and bone density in older adults. Osteoporosis International, 27(2), 815-820. https://doi.org/10.1007/s00198-015-3269-9

Fibrosis markers, hip fracture risk, and bone density in older adults. / Barzilay, J. I.; Bůžková, P.; Kizer, Jorge; Djoussé, L.; Ix, J. H.; Fink, H. A.; Siscovick, D. S.; Cauley, J. A.; Mukamal, K. J.

In: Osteoporosis International, Vol. 27, No. 2, 01.02.2016, p. 815-820.

Research output: Contribution to journalArticle

Barzilay, JI, Bůžková, P, Kizer, J, Djoussé, L, Ix, JH, Fink, HA, Siscovick, DS, Cauley, JA & Mukamal, KJ 2016, 'Fibrosis markers, hip fracture risk, and bone density in older adults', Osteoporosis International, vol. 27, no. 2, pp. 815-820. https://doi.org/10.1007/s00198-015-3269-9
Barzilay, J. I. ; Bůžková, P. ; Kizer, Jorge ; Djoussé, L. ; Ix, J. H. ; Fink, H. A. ; Siscovick, D. S. ; Cauley, J. A. ; Mukamal, K. J. / Fibrosis markers, hip fracture risk, and bone density in older adults. In: Osteoporosis International. 2016 ; Vol. 27, No. 2. pp. 815-820.
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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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AU - Ix, J. H.

AU - Fink, H. A.

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N2 - 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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