title: High-sensitivity C-reactive protein is an independent risk factor for non-vertebral fractures in women and men: The Tromsø Study.
abstract: Low-grade inflammation is associated with fractures, while the relationship between inflammation and bone mineral density (BMD) is less clear. Moreover, any gender differences in the sensitivity to inflammation are still poorly elucidated. We therefore tested the hypothesis that high-sensitivity C-reactive protein (CRP) is an independent risk factor for low BMD and non-vertebral fractures, in both genders, and whether there are gender differences in these associations. CRP levels and BMD at the total hip and femoral neck were measured in 1902 women and 1648 men between 55 and 74 years of age, at baseline in the Tromsø Study, Norway, in 2001-2002. Non-vertebral fractures were registered from hospital X-ray archives during an average of 7.2 years follow-up. Linear regression analyses were used for CRP association with BMD and Cox proportional hazards model for fracture prediction by CRP. During 25 595 person-years follow-up, 366 (19%) women and 126 (8%) men suffered a non-vertebral fracture. There was no association between CRP and BMD in women, but an inverse association in men (p=0.001) after adjustment for age and body mass index. Each standard deviation (SD) increase in log-CRP was associated with an increased risk for non-vertebral fracture by 13% in women and 22% in men (hazard ratios (HRs) 1.13, 95% confidence interval (CI) 1.02-1.26, p=0.026 and 1.22, 95% CI=1.00-1.48, p=0.046, respectively). After adjustment for BMD and other risk factors, women with CRP in the upper tertile exhibited 39% higher risk for fracture than those in the lowest tertile of CRP (HR = 1.39, 95% CI = 1.06-1.83, p = 0.017), while men in the upper tertile exhibited 80% higher risk (HR=1.80, 95% CI=1.10-2.94, p=0.019). In summary, CRP was not associated with BMD in women but inversely associated in men, and predicted fractures in both genders. We infer that inflammation influence fracture risk in both women and men, although the biological mechanisms may differ between the genders.
authors.affiliation: Department of Health and Care Sciences, UiT-The Arctic University of Norway, Tromsø, Norway.
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Dahl
authors.affiliation: Department of Health and Care Sciences, UiT-The Arctic University of Norway, Tromsø, Norway.
authors.forename: Luai Awad
authors.initials: LA
authors.lastname: Ahmed
authors.affiliation: Department of Clinical Medicine, UiT-The Arctic University of Norway, Tromsø, Norway; Department of Internal Medicine, University Hospital of North Norway, Tromsø, Norway.
authors.forename: Ragnar Martin
authors.initials: RM
authors.lastname: Joakimsen
authors.affiliation: Department of Health and Care Sciences, UiT-The Arctic University of Norway, Tromsø, Norway.
authors.forename: Lone
authors.initials: L
authors.lastname: Jørgensen
authors.affiliation: Department of Community Medicine, UiT, The Arctic University of Norway, Tromsø, Norway.
authors.forename: Anne Elise
authors.initials: AE
authors.lastname: Eggen
authors.affiliation: Department of Clinical Endocrinology, Oslo University Hospital, Oslo, Norway.
authors.forename: Erik Fink
authors.initials: EF
authors.lastname: Eriksen
authors.affiliation: Department of Health and Care Sciences, UiT-The Arctic University of Norway, Tromsø, Norway. Electronic address: ashild.bjornerem@uit.no.
authors.forename: Åshild
authors.initials: Å
authors.lastname: Bjørnerem
mesh_terms: D000368:Aged; D015519:Bone Density; D002097:C-Reactive Protein / Q000378:metabolism*; D005260:Female; D050723:Fractures, Bone / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology*; D006801:Humans; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D009664:Norway / Q000453:epidemiology; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012737:Sex Factors; D011795:Surveys and Questionnaires
chemical_list: D002097:C-Reactive Protein
keywords: Bone mineral density; Gender differences; Non-vertebral fracture; hs-CRP