title: Inflammatory Markers and the Risk of Hip and Vertebral Fractures in Men: the Osteoporotic Fractures in Men (MrOS).
abstract: Cytokines play major roles in regulating bone remodeling, but their relationship to incident fractures in older men is uncertain. We tested the hypothesis that men with higher concentrations of pro-inflammatory markers have a higher risk of fracture. We used a case-cohort design and measured inflammatory markers in a random sample of 961 men and in men with incident fractures including 120 clinical vertebral, 117 hip, and 577 non-spine fractures; average follow-up 6.13 years (7.88 years for vertebral fractures). We measured interleukin (IL)-6, C-reactive protein (CRP), tumor necrosis factor alpha (TNFα), soluble receptors (SR) of IL-6 (IL-6SR) and TNF (TNFαSR1 and TNFαSR2), and IL-10. The risk of non-spine, hip, and clinical vertebral fracture was compared across quartiles (Q) of inflammatory markers using Cox proportional hazard models with tests for linear trend. In multivariable-adjusted models, men with the highest (Q4) TNFa cytokine concentrations and their receptors had a 2.0-4.2-fold higher risk of hip and clinical vertebral fracture than men with the lowest (Q1). Results were similar for all non-spine fractures, but associations were smaller. There was no association between CRP and IL-6SR and fracture. Men in the highest Q of IL-10 had a 49% lower risk of vertebral fracture compared with men in Q1. Among men with ≥3 inflammatory markers in the highest Q, the hazard ratio (HR) for hip fractures was 2.03 (95% confidence interval [CI] 1.11-3.71) and for vertebral fracture 3.06 (1.66-5.63). The HRs for hip fracture were attenuated by 27%, 27%, and 15%, respectively, after adjusting for appendicular lean mass (ALM), disability, and bone density, suggesting mediating roles. ALM also attenuated the HR for vertebral fractures by 10%. There was no association between inflammation and rate of hip BMD loss. We conclude that inflammation may play an important role in the etiology of fractures in older men. © 2016 American Society for Bone and Mineral Research.
authors.affiliation: Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Jane A
authors.initials: JA
authors.lastname: Cauley
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA, USA.
authors.forename: Kamil E
authors.initials: KE
authors.lastname: Barbour
authors.affiliation: California Pacific Medical Centre, San Francisco, CA, USA.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Harrison
authors.affiliation: Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Yona K
authors.initials: YK
authors.lastname: Cloonan
authors.affiliation: Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Danielson
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, MN, USA.|Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.|Center for Chronic Disease Outcomes Research, VA Health Care System, Minneapolis, MN, USA.
authors.forename: Kristine E
authors.initials: KE
authors.lastname: Ensrud
authors.affiliation: Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.|Center for Chronic Disease Outcomes Research, VA Health Care System, Minneapolis, MN, USA.|Geriatric Education and Clinical Center, VA Health Care System, Minneapolis, MN, USA.
authors.forename: Howard A
authors.initials: HA
authors.lastname: Fink
authors.affiliation: Bone and Mineral Unit, Oregon Health and Science University, Portland, OR, USA.
authors.forename: Eric S
authors.initials: ES
authors.lastname: Orwoll
authors.affiliation: Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Boudreau
mesh_terms: D015415:Biomarkers / Q000097:blood*; D001862:Bone Resorption / Q000150:complications / Q000453:epidemiology; D002097:C-Reactive Protein / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D006620:Hip Fractures / Q000097:blood* / Q000453:epidemiology*; D006801:Humans; D015994:Incidence; D007249:Inflammation / Q000097:blood*; D008297:Male; D058866:Osteoporotic Fractures / Q000097:blood*; D016016:Proportional Hazards Models; D012307:Risk Factors; D016103:Spinal Fractures / Q000097:blood* / Q000453:epidemiology*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D002097:C-Reactive Protein
keywords: AGING; CYTOKINES; FRACTURE RISK ASSESSMENT; GENERAL POPULATION STUDIES; OSTEOPOROSIS