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Inflammatory Markers and the Risk of Hip Fracture: The Women's Health Initiative

Barbour, Kamil Elie (2012) Inflammatory Markers and the Risk of Hip Fracture: The Women's Health Initiative. Master's Thesis, University of Pittsburgh.

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    Abstract

    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, the most devastating consequence of osteoporosis. The public health significance of hip fractures is substantial; the one-year mortality rate after a hip fracture in women is estimated to range from 17-22%. Thus, preventing hip fractures is a public health imperative. We tested whether high receptor levels of pro-inflammatory cytokines are associated with an increased risk of hip fracture in older women. The Women’s Health Initiative Observational Study (WHI-OS)is a nested case-control study among 400 cases with physician adjudicated incident hip fractures and 400 age, race, and date of blood draw matched controls. Subjects were selected from 39,795 postmenopausal women without previous hip fractures, not using estrogens or other bone-active therapies. Conditional logistic regression was used to estimate the risk ratios for hip fracture. Incident hip fractures (median follow-up 7.1 years) were verified by review of radiological, magnetic resonance imaging, or operative reports and confirmed by blinded central adjudicators. Hip fractures with a pathological cause were excluded.In multivariate models, the risk ratio (95% CIs) of hip fracture for subjects with the highest inflammatory markers (quartile 4) compared with those with lower inflammatory markers (quartiles 1, 2, and 3) was 1.43 (0.98, 2.07) for interleukin-6 receptor (IL-6 SR) and 1.41 (0.97, 2.05) for tumor necrosis factor receptor 1 (TNF SR1) and 1.57 (1.09-2.25) for tumor necrosis factor receptor 2 (TNF SR2). In subjects with all three high inflammatory markers, the risk ratio of fracture was 2.27 (1.04, 4.93) in comparison with subjects with 0 or 1 elevated marker(s) (p trend = 0.042). Inflammatory markers may be one of the strongest risk factors of hip fracture to date. Future clinical trials should test whether interventions to decrease inflammatory marker levels reduces hip fractures.


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    Item Type: University of Pittsburgh ETD
    ETD Committee:
    ETD Committee TypeCommittee MemberEmailORCID
    Committee ChairYouk, Adaayouk@pitt.edu
    Committee MemberCauley, JaneJCauley@edc.pitt.edu
    Committee MemberBoudreau, RobertBoudreauR@edc.pitt.edu
    Title: Inflammatory Markers and the Risk of Hip Fracture: The Women's Health Initiative
    Status: Published
    Abstract: 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, the most devastating consequence of osteoporosis. The public health significance of hip fractures is substantial; the one-year mortality rate after a hip fracture in women is estimated to range from 17-22%. Thus, preventing hip fractures is a public health imperative. We tested whether high receptor levels of pro-inflammatory cytokines are associated with an increased risk of hip fracture in older women. The Women’s Health Initiative Observational Study (WHI-OS)is a nested case-control study among 400 cases with physician adjudicated incident hip fractures and 400 age, race, and date of blood draw matched controls. Subjects were selected from 39,795 postmenopausal women without previous hip fractures, not using estrogens or other bone-active therapies. Conditional logistic regression was used to estimate the risk ratios for hip fracture. Incident hip fractures (median follow-up 7.1 years) were verified by review of radiological, magnetic resonance imaging, or operative reports and confirmed by blinded central adjudicators. Hip fractures with a pathological cause were excluded.In multivariate models, the risk ratio (95% CIs) of hip fracture for subjects with the highest inflammatory markers (quartile 4) compared with those with lower inflammatory markers (quartiles 1, 2, and 3) was 1.43 (0.98, 2.07) for interleukin-6 receptor (IL-6 SR) and 1.41 (0.97, 2.05) for tumor necrosis factor receptor 1 (TNF SR1) and 1.57 (1.09-2.25) for tumor necrosis factor receptor 2 (TNF SR2). In subjects with all three high inflammatory markers, the risk ratio of fracture was 2.27 (1.04, 4.93) in comparison with subjects with 0 or 1 elevated marker(s) (p trend = 0.042). Inflammatory markers may be one of the strongest risk factors of hip fracture to date. Future clinical trials should test whether interventions to decrease inflammatory marker levels reduces hip fractures.
    Date: 30 January 2012
    Date Type: Completion
    Defense Date: 20 October 2011
    Approval Date: 30 January 2012
    Submission Date: 14 November 2011
    Release Date: 30 January 2012
    Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
    Patent pending: No
    Number of Pages: 33
    Institution: University of Pittsburgh
    Thesis Type: Master's Thesis
    Refereed: Yes
    Degree: MS - Master of Science
    Uncontrolled Keywords: Inflammation, hip fractures, cytokines, women, osteoporosis, nested case-control
    Schools and Programs: Graduate School of Public Health > Biostatistics
    Date Deposited: 30 Jan 2012 13:52
    Last Modified: 04 Jun 2013 10:09

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