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Elevated inflammatory markers may predict hip fracture risk in older adults
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In a cohort of older adults, higher interleukin-6 level and white blood cell count were predictive of a higher likelihood of hip fracture, according to an analysis of the Cardiovascular Health Study.
Danijela Stojanovic, PharmD, PhD, of the office of surveillance and epidemiology at the FDA, and colleagues analyzed data from 5,265 adults aged at least 65 years participating in the Cardiovascular Health Study, a population-based, prospective study of CV risk factors in a random sample of Medicare-eligible patients living in California, Maryland, North Carolina and Pennsylvania. Participants were enrolled between 1989 and 1993, with follow-up every 6 months for the first 10 years (clinic exams alternating with phone interviews) and phone interviews every 6 months thereafter. Researchers assessed baseline levels of inflammatory markers, including IL-6, C-reactive protein, white blood cell count and fibrinogen, collected during the 1992-1993 study visit. Primary outcome was incident hip fracture, identified through hospitalization records. Secondary outcome was a composite of incident fracture of the hip, pelvis, humerus and distal forearm measured in a composite fracture analysis cohort (n = 4,477). Participants were followed until incident fracture, death or July 30, 2009. Researchers used Kaplan-Meier curves to describe the association between high vs. low levels of inflammatory markers and time to incident fracture, and used Cox proportional hazard models to estimate HRs of incident fractures associated with a doubling of IL-6 and C-reactive protein, and with a unit increase in white blood cell count and fibrinogen.
In the hip fracture and composite fracture cohorts, median follow-up times were 11.2 years and 6.6 years, respectively, with 11% of participants developing a hip fracture and 19% of participants developing a composite fracture.
In the hip fracture cohort, researchers found that a doubling of IL-6 was associated with a higher risk for incident hip fractures that persisted after adjustment (HR = 1.15; 95% CI, 1.02-1.3). In analyses stratified by sex, the association persisted for women (HR = 1.17; 95%CI, 1.01-1.35), but not men.
In the composite fracture cohort, researchers did not observe an association between IL-6 levels and incident composite fractures.
Additionally, researchers found that for each unit increase in white blood cell count, there was a higher risk for incident hip fracture overall (HR = 1.04; 95%, CI 1.01-1.06) and in women in sex-stratified models (HR = 1.08; 95% CI, 1.03-1.14), but not in men. There were no observed associations between white blood cell count and incident composite fractures.
Researchers observed no association between a doubling of C-reactive protein level or fibrinogen and higher risk for either hip or composite fracture.
“Our findings support the direction of the association between IL-6 and hip fractures in other longitudinal studies and have allowed us to generate a more precise and statistically significant estimate of the IL-6 and fracture association,” the researchers wrote. “Although significant progress has been made in unraveling the complex role of the immune system in the pathophysiology of osteoporosis, the clinical implications of this relationship remain to be determined.” – by Regina Schaffer
Disclosures: The authors report no relevant financial disclosures.
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