Cachexia in rheumatoid arthritis is associated with inflammatory activity, physical disability, and low bioavailable insulin-like growth factor

Objectives: To examine the impact of inflammation, insulin-like growth factor (IGF-1) and its regulating binding protein (IGFBP-1) on lean body mass (LBM) in patients with rheumatoid arthritis (RA). Methods: In 60 inpatients (50 women), inflammatory activity was measured by Disease Activity Score 28 (DAS28), C-reactive protein (CRP), and interleukin (IL)-6, and physical disability by the Health Assessment Questionnaire (HAQ). LBM was assessed by dual-energy X-ray absorptiometry (DXA) and fat free mass index (FFMI; kg/m(2)) and fat mass index (FMI; kg/m(2)) were calculated. Results: Median age was 65 years and disease duration 13 years. Fifty per cent of the patients had FFMI below the 10th percentile of a reference population and 45% had FMI above the 90th percentile, corresponding to the condition known as rheumatoid cachexia (loss of muscle mass in the presence of stable or increased FM). DAS28, CRP, and IL-6 correlated negatively with LBM (p=0.001, 0.001, and 0.018, respectively), as did HAQ (p=0.001). Mean (confidence interval) IGF-1 was in the normal range, at 130 (116-143) g/L. IGFBP-1 levels were elevated in patients (median 58 g/L in women and 59 g/L in men) compared with a normal population (33 g/L in women and 24 g/L in men). The ratio IGF-1/IGFBP-1, which reflects bioavailable IGF-1, was low (2.0 g/L) and was positively correlated with LBM (p=0.015). In multiple regression analysis, 42% of the LBM variance was explained by IGF-1/IGFBP-1, HAQ score, and DAS28. Conclusion: A large proportion of RA inpatients, mainly women, had rheumatoid cachexia. The muscle wasting was explained by inflammatory activity and physical disability as well as low bioavailable IGF-1.