Context: Interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF-) 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: To determine the associations between serum markers of inflammation and changes in bone mineral density (BMD) and urinary pyridinoline/creatinine ratio (PYR/Cr) over 2.9 years in older adults.

Methods. A total of 168 randomly selected subjects (mean 63 years, range 52–78, 48% female) were studied. BMD was measured by DXA at baseline (mean T-score: -0.18 to -0.61) and 2.9 years later. Serum high-sensitivity C-reactive protein (hs-CRP), IL-6, TNF- and urinary PYR/Cr 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. Change in total body BMD was associated with baseline hs-CRP, IL-6 and TNF- as well as change in hs-CRP (: -0.41%/unit, 95% CI: -0.68%, -0.15%) and IL-6 (: -0.62%/unit, 95% CI: -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- (spine only). Lastly, change in PYR/Cr 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 targeted anti-inflammatory therapy has potential for the prevention of osteoporosis.