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

Publication Type:

Journal Article

Source:

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research (2012)

Keywords:

April 2012, Center-Authored Paper, e-pub, Public Health Sciences Division

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. We tested whether high receptor levels of pro-inflammatory 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 age, race, and date of blood draw matched controls. 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% CI, 0.98 to 2.07) for IL-6 SR and 1.41 (95% CI, 0.97 to 2.05) for TNF SR1 and 1.57 (95% CI, 1.09 to 2.25) for TNF SR2. In subjects with all three markers in the highest quartile, the risk ratio of fracture was 2.27 (95% CI to 1.04 to 4.93) in comparison with subjects with 0 or 1 elevated marker(s) (p trend = 0.042). Elevated levels of inflammatory markers for all 3 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.