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Inflammatory markers and the risk of hip fracture: The women's health initiative

Barbour, KE and Boudreau, R and Danielson, ME and Youk, AO and Wactawski-Wende, J and Greep, NC and LaCroix, AZ and Jackson, RD and Wallace, RB and Bauer, DC and Allison, MA and Cauley, JA (2012) Inflammatory markers and the risk of hip fracture: The women's health initiative. Journal of Bone and Mineral Research, 27 (5). 1167 - 1176. ISSN 0884-0431

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Cytokines play a major role in bone remodeling in vitro and in animal models, with evidence supporting the involvement of inflammatory markers in the pathogenesis of osteoporosis. However, less is known about the longitudinal association of inflammatory markers with hip fracture. We tested whether high receptor levels of proinflammatory cytokines are associated with an increased risk of hip fracture in older women. We used a nested case-control study design from the Women's Health Initiative Observational Study (WHI-OS) and selected 400 cases with physician-adjudicated incident hip fractures and 400 controls matched on age, race, and date of blood draw. Participants were chosen from 39,795 postmenopausal women without previous hip fractures, not using estrogens or other bone-active therapies. Incident hip fractures (median follow-up 7.1 years) were verified by review of radiographs and confirmed by blinded central adjudicators. Hip fractures with a pathological cause were excluded. In multivariable models, the risk of hip fracture for subjects with the highest levels of inflammatory markers (quartile 4) compared with those with lower levels (quartiles 1, 2, and 3) was 1.43 (95% confidence interval [CI], 0.98-2.07) for interleukin-6 (IL-6) soluble receptor (SR), 1.40 (95% CI, 0.97-2.03) for tumor necrosis factor (TNF) SR1, and 1.56 (95% CI, 1.09-2.22) for TNF SR2. In subjects with all three markers in the highest quartile, the risk ratio of fracture was 2.76 (95% CI, 1.22-6.25) in comparison with subjects with 0 or 1 elevated marker(s) (p trend=0.018). Elevated levels of inflammatory markers for all three cytokine-soluble receptors were associated with an increased risk of hip fractures in older women. Future clinical trials should test whether interventions to decrease inflammatory marker levels reduces hip fractures. © 2012 American Society for Bone and Mineral Research.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Barbour, KE
Boudreau, Rrob21@pitt.eduROB21
Danielson, MEDanielsonM@edc.pitt.eduEPIDMED
Youk, AOayouk@pitt.eduAYOUK
Wactawski-Wende, J
Greep, NC
LaCroix, AZ
Jackson, RD
Wallace, RB
Bauer, DC
Allison, MA
Cauley, JAJCauley@edc.pitt.eduJCAULEY
Date: 1 May 2012
Date Type: Publication
Journal or Publication Title: Journal of Bone and Mineral Research
Volume: 27
Number: 5
Page Range: 1167 - 1176
DOI or Unique Handle: 10.1002/jbmr.1559
Schools and Programs: School of Public Health > Epidemiology
Refereed: Yes
ISSN: 0884-0431
Date Deposited: 03 Apr 2015 01:31
Last Modified: 02 Jul 2022 10:56


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