Does Inflammation Increase Fracture Risk?

By Salynn Boyles
Reviewed by Vrunda Bhavsar Desai, MD, FACOG, Assistant Professor of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT

Aging is associated with chronic, low-grade, systemic inflammation characterized by an increase in circulating levels of inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and interleukin 1 (IL-1).

This pro-inflammatory response has been linked to a wide range of chronic conditions associated with aging, including cardiovascular disease,1 diabetes,2 and dementia.3 There’s mounting evidence implicating chronic systemic inflammation in osteoporosis and fracture risk in adults.

Most studies in older white women

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.

The trials conducted by the University of Pittsburgh research team showed a 1.5-fold to 2.5-fold greater risk for fracture in older women with the highest levels of inflammation compared to those with the lowest levels.

“Two of our studies looked at hip fractures and 1 examined nontraumatic fractures, and we did find very strong associations,” Dr. Barbour said. “In 2 of the 3 studies there was a 2.5-fold greater risk for hip fractures in women with high levels of inflammation.”

More study needed

While the majority of the studies suggest a causal role for inflammation in age-related bone loss and fracture risk, Dr. Barbour says more research is needed to strengthen the association, especially in men.

“I know a lot of people will remain skeptical and say inflammation is just a marker for frailty or something else,” he says. “But in our studies we controlled for frailty, and this did not change our results.”

Published: 06/03/2014

References:

  1. Pai JK, Pischon T, Ma J, et al. Inflammatory markers and the risk of coronary heart disease in men and women. N Engl J Med. 2004;351:2599-2610.
  2. Hu FB, Meigs JB, Li TY, et al. Inflammatory markers and risk of developing type 2 diabetes in women. Diabetes. 2004;53:693-700.
  3. Weaver JD, Huang MH, Albert M, et al. Interleukin-6 and risk of cognitive decline: MacArthur studies of successful aging. Neurology. 2002;59:371-378.
  4. Barbour KE, Lui LY, Ensrud KE, et al. Inflammatory markers and risk of hip fracture in older white women: The Study of Osteoporotic Fractures. J Bone Miner Res. 2014 Apr 9. [Epub ahead of print]
  5. BarbourKE,BoudreauR,DanielsonME,etal.Inflammatorymarkersandtheriskofhipfracture: the Women’s Health Initiative. J Bone Miner Res. 2012;27:1167-1176.
  6. Ding C, Parameswaran V, Udayan R, et al. Circulating levels of inflammatory markers predict change in bone mineral density and resorption in older adults: a longitudinal study. J Clin Endocrinol Metab. 2008;93:1952-1958.
  7. Pasco JA, Kotowicz MA, Henry MJ, et al. High-sensitivity C-reactive protein and fracture risk in elderly women. JAMA. 2006;296:1353-1355.
  8. NakamuraK,SaitoT,KobayashiR,etal.C-reactiveproteinpredictsincidentfracturein community-dwelling elderly Japanese women: the Muramatsu study. Osteoporos Int. 2011;22:2145- 2150.
  9. Ishii S, Cauley JA, Greendale GA, et al. C-reactive protein, bone strength, and nine-year fracture risk: data from the Study of Women’s Health Across the Nation (SWAN). J Bone Miner Res. 2013;28:1688-1698.

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