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Discriminating Fracture Status in Men and Women with Stage 3-5 Chronic Kidney Disease: Cytokines, Neuromuscular Function and Daily Activity Levels
chronic kidney disease; fractures; osteoprotegerin; neuromuscular function; daily activity
Bone disease and fractures are common in men and women with chronic kidney disease (CKD). The etiology of fractures in CKD is multi-factorial; identifying risk factors for fracture is important in CKD, so that patients who are at high risk can be treated before they fracture. The majority of studies have focused on risk factors associated with fracture in patients with stage 5 CKD on dialysis–there is a need for studies in pre-dialysis CKD. Three novel, non-radiological factors were assessed in 211 men and women with stage 3-5 CKD: cytokines osteoprotegerin (OPG) and receptor activator of nuclear factor kappa beta ligand (RANKL); tests of neuromuscular function including the timed up and go (TUG), 6 minute walk (6MW), and grip strength; and daily activity levels by accelerometry. Fractures were defined as self-reported low-trauma fractures since the age of 40 and/or prevalent vertebral fractures identified by morphometry. Logistic regression and receiver operating characteristic curves (ROC) were performed using STATA version 11.0. Those with fractures had elevated OPG compared to those without fractures (9.37±4.23 vs. 8.13±3.04 pmol/L, p=0.03), however, after adjusting for age OPG did not differ by fracture status. After adjusting for age, weight, and sex, impairments in both the TUG and 6MW tests were associated with fractures (TUG odds ratio (OR): 1.68, 95% confidence interval (CI): 1.40-2.02; 6MW OR: 0.53, 95% CI: 0.52-0.54). The diagnostic tests characteristics of the TUG and 6MW tests were excellent; both could discriminate fracture status (TUG AUROC: 0.90, 95% CI: 0.84-0.95; 6MW AUROC: 0.87, 95% CI: 0.84-0.95). Overall, subjects were primarily sedentary. After adjusting for stage of CKD, increased sedentary activity and decreased light intensity activity could discriminate fracture status (sedentary AUROC: 0.72, 95% CI: 0.56 to 0.87; light activity AUROC: 0.71, 95% CI: 0.55 to 0.87). In conclusion, non-radiological, novel factors including the TUG, the 6MW, and daily activity, but not OPG or RANKL were able to discriminate fracture status in men and women with stage 3-5 CKD.
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