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dc.contributor.authorApalset, Ellen M.en_US
dc.contributor.authorGjesdal, Clara Gramen_US
dc.contributor.authorUeland, Per Magneen_US
dc.contributor.authorØyen, Jannikeen_US
dc.contributor.authorMeyer, Klausen_US
dc.contributor.authorMidttun, Øivinden_US
dc.contributor.authorEide, Geir Egilen_US
dc.contributor.authorTell, Grethe Seppolaen_US
dc.description.abstractSummary The cytokine interferon gamma (IFN-γ) stimulates neopterin release and tryptophan degradation into kynurenines through the kynurenine pathway. High levels of neopterin were associated with increased hip fracture risk, as were some of the kynurenines, suggesting a role of IFN-γ-mediated inflammation in the processes leading to hip fracture. Introduction Low-grade systemic inflammation has been associated with bone loss and risk of fractures. Interferon gamma (IFN-γ) initiates macrophage release of neopterin and also stimulates degradation of tryptophan along the kynurenine pathway as part of cell-mediated immune activation. Plasma neopterin and the kynurenine/tryptophan ratio (KTR) are thus markers of IFN-γ-mediated inflammation. Risk of hip fracture was investigated in relation to markers of inflammation and metabolites in the kynurenine pathway (kynurenines). Methods Participants (71 to74 years, N = 3,311) in the community-based Hordaland Health Study (HUSK) were followed for hip fractures from enrolment (1998–2000) until 31 December 2009. Plasma C-reactive protein (CRP), neopterin, KTR, and six kynurenines were investigated as predictors of hip fracture, using Cox proportional hazards regression analyses. Results A hazard ratio (HR) of 1.9 (95 % confidence interval (CI) 1.3–2.7) for hip fracture was found in the highest compared to the lowest quartile of neopterin (p trend across quartiles <0.001). CRP and KTR were not related to hip fracture risk. Among the kynurenines, a higher risk of fracture was found in the highest compared to the lowest quartiles of anthranilic acid and 3-hydroxykynurenine. For subjects in the highest quartiles of neopterin, CRP, and KTR compared to those in no top quartiles, HR was 2.5 (95 % CI 1.6–4.0). Conclusions This may indicate a role for low-grade immune activation in the pathogenic processes leading to hip fracture.en_US
dc.rightsAttribution-NonCommercial CC BY-NCeng
dc.subjectHip fractureeng
dc.subjectKynurenine pathwayeng
dc.titleInterferon gamma (IFN-γ)-mediated inflammation and the kynurenine pathway in relation to risk of hip fractures: The Hordaland Health Studyen_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderCopyright 2014 The Authors
dc.source.journalOsteoporosis International
dc.subject.nsiVDP::Medical sciences: 700::Clinical medical sciences: 750::Rheumatology: 759eng
dc.subject.nsiVDP::Medisinske fag: 700::Klinisk medisinske fag: 750::Reumatologi: 759nob

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