At least 10 observational studies have examined the association of inflammatory markers with bone loss and fracture risk in humans. Most included only older women, and most of these subjects were white, says Centers for Disease Control and Prevention epidemiologist and researcher Kamil Barbour, PhD, MPH, who led 3 of the studies examining inflammation and osteoporosis-related fractures while at the University of Pittsburgh. But despite this limitation, he says, the studies offer compelling evidence that inflammation could be a significant risk factor for bone loss and fracture in aging.
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In addition, Dr. Barbour noted that renal function appeared to be a significant mediating factor in the inflammation, hip fracture pathway. In both the 2014 study and a 2012 trial that included data from the Women’s Health Initiative (WHI), controlling for cystatin C led to the largest attenuation of hip fracture risk among women with the highest inflammatory burden: decreases of 19% and 15%, respectively.4
“It appears that poor kidney function leads to greater inflammation and bone loss, while greater inflammation leads to kidney damage and bone loss,” Dr. Barbour says. “We need to understand this possible bidirectional association better when we explore possible interventions.”
IL-6 shows strongest association
Dr. Barbour’s 2012 study also involved a nested case-control study design.5 The researchers selected 400 cases of incident hip fractures from the WHI data and 400 controls matched for age, race, and date of blood draw from 39,795 postmenopausal women without previous hip fractures. Median follow-up was 7 years.
Subjects with the highest levels of inflammatory burden for 3 markers examined (IL-6 SR, TNF SR1, and TNF SR2) had an almost threefold (2.76; 95% CI 1.22-6.25) increase in hip fracture risk compared to those with the lowest burden.5
One of the first studies to examine the possible impact of inflammation on bone status in humans is also one of the only studies to include men. In 2008, researchers in Australia reported the results of their longitudinal study, which was the first to show an association between baseline inflammatory markers, change in these markers, and bone loss and resorption in older adults.6
The most consistent associations were for IL-6 in both sexes, with less consistency for high-sensitivity C-reactive protein (hs-CRP) and TNF-α.6
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