Roubenoff R, Roubenoff RA, Ward LM, Holland SM, Hellmann DB. Rheumatoid cachexia: depletion of lean body mass in rheumatoid arthritis. Possible association with tumor necrosis factor. J Rheumatol 19, 1505-1510
To investigate body composition and serum tumor necrosis factor (TNF) levels in a series of 24 patients with rheumatoid arthritis (RA).
Body composition assessment by anthropometric measures and bioelectrical impedance. Cytokine determination in serum by ELISA:
When compared to United States population norms, 16 of the subjects (67%) were cachectic. In regression models, lean body mass (LBM) was inversely associated with the number of swollen joints (p < 0.025). Elevated TNF-alpha was found in 3 of 5 flaring patients vs 0 of 18 patients with less active disease (p = 0.001). These 3 were all cachectic, while the 2 flaring patients without detectable TNF had normal LBM (p < 0.03). Among the whole group, there was a trend toward increasing disability with decreased LBM after adjusting for joint pain and disease duration (p < 0.07).
Cachexia is common in RA, and may be cytokine driven. Given the prognostic impact of LBM wasting in other diseases, the effect of rheumatoid cachexia on outcome in RA deserves further study.
"The lack of association between REE and disease activity can be explained as follows. Enhanced REE in RA patients is thought to be caused by cytokine-induced hypermetabolism [3,5,6] and, therefore, TNF-blocking agents should decrease REE. Marcora et al.  enrolled 26 RA patients and randomized them into MTX or etanercept groups. "
[Show abstract][Hide abstract] ABSTRACT: Background/Aims
Increased resting energy expenditure (REE) in rheumatoid arthritis (RA) patients is thought to be caused by hypermetabolism associated with production of proinflammatory cytokines. Our aim in the present study was to explore the possible association between REE and disease activity in females with RA.
A total of 499 female RA patients were recruited to this cross-sectional study assessing REE scores on disease activity indices (the routine assessment of patient index data 3 [RAPID3], the disease activity score 28, and the clinical/simplified disease activity index [CDAI/SDAI]) and the levels of RA-associated autoantibodies (rheumatoid factor and anticyclic citrullinated peptide [anti-CCP] antibodies). Age-matched healthy female controls (n = 131) were also enrolled.
REE did not differ between RA patients (all patients, and those in remission or not) and controls, or between RA patients in remission or not (p > 0.05 for all comparisons). Increased REE in total RA patients was associated with younger age and a higher body mass index (BMI) (p < 0.001 and p < 0.001, respectively), but not with disease activity index scores on any of RAPID3, CDAI, or SDAI. BMI was the only clinical parameter exhibiting a significant relationship with REE quartiles (Q1 to Q4; p < 0.001); none of disease duration, functional status, or anti-CCP antibody titer in RA patients was significantly related to REE, based on analysis of covariance.
We found no association between REE and disease activity in RA patients, implying that energy metabolism in RA patients might be independent of RA-associated systemic inflammation.
The Korean Journal of Internal Medicine 07/2014; 29(4):516-24. DOI:10.3904/kjim.2014.29.4.516 · 1.43 Impact Factor
"In addition, adipose tissue can exert both endocrine and immune effects on multiple other organs through the release of adipocytokines , which are suspected to contribute to the pathogenesis of several inflammatory conditions, including rheumatoid arthritis (RA) . Even if to date and to our knowledge, the role of fat tissue has not been widely investigated in ankylosing spondylitis (AS), several indirect results suggest a possible link between the AS-related inflammation and fat tissue excess: (a) weight loss and subsequent lower BMI are linked to a high RA activity ; and (b) a significant increase in body weight and fat mass has been observed in AS patients receiving anti-tumor necrosis factor (TNF)-α treatment . "
[Show abstract][Hide abstract] ABSTRACT: The excess of adipose tissue in obese individuals may have immunomodulating properties and pharmacokinetic consequences. The aim of this study was to determine whether body mass index (BMI) affects response to infliximab (IFX) in ankylosing spondylitis (AS) patients.
In 155 patients retrospectively included with active AS, the BMI was calculated before initiation of IFX treatment (5 mg/kg intravenously). After 6 months of treatment, changes from baseline in BASDAI, Visual Analogue Scale (VAS) pain, C-reactive protein (CRP) level, and total dose of nonsteroidal antiinflammatory drug (NSAID) were dichotomized with a threshold corresponding to a decrease of 50% of initial level of the measure, into binary variables assessing response to IFX (BASDAI50, VAS50, CRP50, NSAID50). Whether the BMI was predictive of the response to IFX therapy according to these definitions was assessed with logistic regression.
Multivariate analysis found that a higher BMI was associated with a lower response for BASDAI50 (P = 0.0003; OR, 0.87; 95% CI (0.81 to 0.94)), VAS50 (P < 0.0001; OR, 0.87; 95% CI (0.80 to 0.93)); CRP50 (P = 0.0279; OR, 0.93; 95% CI (0.88 to 0.99)), and NSAID50 (P = 0.0077; OR, 0.91; 95% CI (0.85 to 0.97)), criteria. According to the three WHO BMI categories, similar results were found for BASDAI50 (77.6%, 48.9%, and 26.5%; P < 0.0001), VAS50 (72.6%, 40.4%, and 16.7%; P < 0.0001); CRP50 (87.5%, 65.7%, and 38.5%; P = 0.0001), and NSAID50 (63.2%, 51.5%, and 34.6%; P = 0.06).
This study provides the first evidence that a high BMI negatively influences the response to IFX in AS. Further prospective studies, including assessment of the fat mass, pharmacokinetics, and adipokines dosages are mandatory to elucidate the role of obesity in AS IFX response.
"Unfortunately, both reduced muscle mass and elevated adiposity, termed " rheumatoid cachexia " (Roubenoff et al., 1992), are characteristic of RA. Muscle wasting due to RA was first observed by Sir James Paget in 1873 and has been consistently reported in recent decades (see Summers et al., 2008 for a review); most prolifically and notably by Ronenn Roubenoff's group (Rall & Roubenoff, 1996, 2004; Rall et al., 1996a, 2002; Roubenoff, 2000; Roubenoff et al., 1992, 1994, 2002; Walsmith & Roubenoff, 2002; Walsmith et al., 2004). "
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