Circulating levels of inflammatory markers predict change in bone mineral density and resorption in older adults: A longitudinal study

Context: IL-1, IL-6, and TNF-alpha play an important role in the pathogenesis of osteoporosis in animals; however, evidence that these play a similar role in bone loss in human studies is limited. Objective: Our objective was to determine the associations between serum markers of inflammation and changes in bone mineral density (BMD) and urinary pyridinoline (PYR) to creatinine (Cr) ratio over 2.9 yr in older adults. Methods: A total of 168 randomly selected subjects (mean 63 yr, range 52-78, 48% female) was studied. BMD was measured by dual-energy x-ray absorptiometry at baseline (mean T score: -0.18 to -0.61) and 2.9 yr later. Serum high-sensitivity (hs) C-reactive protein (CRP), IL-6, TNF-alpha, and the urinary PYR/Cr ratio were measured on both occasions. Results: The mean annual loss of BMD was 0.15, 0.15, and 0.34% at total body, spine, and hip, respectively. Changein total body BMD was associated with baseline hs-CRP, IL-6, and TNF-alpha, as well as change in hs-CRP (beta: -0.41%/ U, 95% confidence interval -0.68%, -0.15%) and IL-6 (beta: -0.62%/ U, 95% confidence interval -1.01%, -0.23%). If these markers were put in the same predictive model, only IL-6 remained largely unchanged. Changes in other BMD sites were significantly predicted by IL-6 (hip and spine) and TNF-alpha(spine only). Finally, change in the PYR/Cr ratio was positively associated baseline IL-6, hs-CRP, and their changes (all P < 0.05) in women, but not men. Conclusions: Variation within the low levels of inflammatory markers observed in this study, especially IL-6, predicts bone loss and resorption, suggesting that targeted antiinflammatory therapy has potential for the prevention of osteoporosis.