Rheumatoid cachexia: Depletion of lean body mass in rheumatoid arthritis. Possible association with tumor necrosis factor

Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD.
The Journal of Rheumatology (Impact Factor: 3.17). 11/1992; 19(10):1505-10.
Source: PubMed

ABSTRACT 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.

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    • "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). "
    Rheumatoid Arthritis - Treatment, 01/2012; , ISBN: 978-953-307-850-2
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    • "This complication, which appears early during the course of the disease, may not be evident on clinical examination as these changes in body composition are not usually followed by modifications in body mass index (Giles et al., 2008b). The average loss of body cell mass (BCM), which comprises lean tissue mass and, to a lesser extent, visceral and immune cell mass, in these patients ranges between 13% and 15% (Roubenoff et al., 1992; 1994). The mechanism underlying this complication in RA is not well understood, but a severe catabolic state driven by pro-inflammatory cytokines, particularly tumour necrosis factor (TNF)-a and interleukin (IL)-6, can be blamed for the loss of BCM seen in this condition (Roubenoff et al., 1994; Arshad et al., 2007). "
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    ABSTRACT: Non-steroidal anti-inflammatory drugs improve inflammatory cachexia in several conditions. Thus, we have explored inhibition of cyclooxygenase-2 (COX-2) in an experimental model of rheumatoid cachexia in rabbits. Chronic arthritis was induced in immunized rabbits by repeated intra-articular injections of ovalbumin. To increase the degree of systemic inflammation and also to induce atherosclerotic lesions, the animals were fed a hyperlipidaemic diet (2% cholesterol and 6% peanut oil) and were given an endothelial injury of the femoral artery. Rabbits were randomized to receive the COX-2 inhibitor celecoxib (10 mg·kg⁻¹ ·day⁻¹) or no treatment. After 4 weeks, sera, peripheral mononuclear cells and vessel specimens were collected. Inhibition of COX-2 by celecoxib modulated the systemic inflammatory response and increased total cholesterol and triglyceride levels. Celecoxib also minimized weight loss and prevented serum albumin fall. At a vascular level, celecoxib reduced COX-2 protein in the femoral arterial wall, but did not modify size or the macrophage infiltration of femoral lesions nor the percentage of rabbits with spontaneous aortic plaques. Our animal model induced a severe inflammatory cachexia, comparable to that of persistently active rheumatoid arthritis. The inhibition of COX-2 by celecoxib improves this state, suggesting that COX products play an important role in its development, without affecting the development or the progression of vascular lesions. Overall, these results suggest that celecoxib might be considered as a new therapeutic tool for the treatment of rheumatoid cachexia.
    British Journal of Pharmacology 11/2010; 161(5):1012-22. DOI:10.1111/j.1476-5381.2010.00957.x · 4.99 Impact Factor
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    • "Furthermore , chronic inflammation is known to increase energy expenditure as well. Indeed, it has repeatedly been shown that BMR is increased in patients with RA [8] [9]. In addition, De Carvalho et al. showed that during standardises walking on a treadmill, oxygen consumption and hence energy expenditure was significantly higher in patients with RA than healthy controls, as was the rate of perceived exertion [1]. "
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    ABSTRACT: Rheumatoid arthritis (RA) is a chronic inflammatory auto-immune disease, causing progressive damage to the musculoskeletal system. Many patients with RA also suffer from accelerated muscle loss or cachexia, which contributes to the loss of physical function and quality of life. Physical activity plays a central role in the management of the disease as it is essential to maintain muscle strength and endurance, range of motion and the ability to perform activities of daily life. On the other hand, given the nature of the disease, there is always an increased risk for injury. There is a large amount of literature investigating the effect of exercise interventions on muscle function and disease activity. These studies show that exercise clearly improves muscle function without affecting disease activity. Studies including radiographic evaluation of joint damage as an endpoint also show that there is no evidence that exercise, even high-intensity exercise, increases inflammation or joint damage, although care should be taken with patients with severe baseline damage. Regarding daily physical activity (exercise is only one component of physical activity) there is hardly any research done showing either that physical activity is indeed decreased in patients or whether or not there is a relation between daily physical activity and disease activity. The results from studies looking at the effect of exercise on muscle mass or the ability to prevent or reverse cachexia are somewhat contradictory, but it seems that when the training dose is sufficiently large, gains in muscle mass can be achieved.
    Physiology & Behavior 06/2008; 94(2):270-5. DOI:10.1016/j.physbeh.2007.12.012 · 3.03 Impact Factor
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