Rheumatoid Cachexia Research Articles

Rheumatoid cachexia and cardiovascular disease

Both cachexia and cardiovascular disease are strongly associated with rheumatoid arthritis (RA) and linked to the chronic inflammatory process. Typically, rheumatoid cachexia occurs in individuals with normal or increased BMI (reduced muscle mass and increased fat mass). Classic cachexia (reduced muscle mass and reduced fat mass) is rare in RA but is associated with high inflammatory activity and aggressive joint destruction in patients with a poor cardiovascular prognosis. Conversely, obesity is linked to hypertension and dyslipidemia but, paradoxically, lower RA disease activity and less cardiovascular disease-related mortality. Rheumatoid cachexia might represent the 'worst of both worlds' with respect to cardiovascular outcome, but until diagnostic criteria for this condition are agreed upon, its effect on cardiovascular disease risk remains controversial.

Pharmacological modulation by celecoxib of cachexia associated with experimental arthritis and atherosclerosis in rabbits

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.

Contribution of rheumatoid arthritis disease activity and disability to rheumatoid cachexia

This cross-sectional study was done to show how nutritional indices influence each other and the contributions made by inflammation to the development of rheumatoid cachexia. We studied 295 female patients with rheumatoid arthritis (RA). We chose five nutritional indices: body mass index (BMI), arm muscle area (AMA), triceps skinfold thickness (TSF), which were obtained via anthropometric measurements, and serum albumin and cholesterol. Clinical indicators of RA included disease duration, C-reactive protein (CRP) and Disease Activity Score 28 (DAS28). We performed a bivariate correlation test between the nutritional indices and multiple regression analysis for each nutritional index. Mean AMA was low, 87.3% of the normal value, whereas TSF was not different. Muscle protein expressed by AMA decreased according to RA duration, whereas visceral protein indicated by serum albumin decreased with an increase in RA activity. The continuation of inflammation appears to be essential for a decrease in muscle protein in rheumatoid cachexia. DAS28 showed a positive contribution to BMI in the regression model, and the increase in RA disease activity causes an increase in BMI via an accumulation of tissue fat.

Effects of high‐intensity resistance training in patients with rheumatoid arthritis: A randomized controlled trial

To confirm, in a randomized controlled trial (RCT), the efficacy of high-intensity progressive resistance training (PRT) in restoring muscle mass and function in patients with rheumatoid arthritis (RA). Additionally, to investigate the role of the insulin-like growth factor (IGF) system in exercise-induced muscle hypertrophy in the context of RA. Twenty-eight patients with established, controlled RA were randomized to either 24 weeks of twice-weekly PRT (n = 13) or a range of movement home exercise control group (n = 15). Dual x-ray absorptiometry-assessed body composition (including lean body mass [LBM], appendicular lean mass [ALM], and fat mass); objective physical function; disease activity; and muscle IGFs were assessed at weeks 0 and 24. Analyses of variance revealed that PRT increased LBM and ALM (P < 0.01); reduced trunk fat mass by 2.5 kg (not significant); and improved training-specific strength by 119%, chair stands by 30%, knee extensor strength by 25%, arm curls by 23%, and walk time by 17% (for objective function tests, P values ranged from 0.027 to 0.001 versus controls). In contrast, body composition and physical function remained unchanged in control patients. Changes in LBM and regional lean mass were associated with changes in objective function (P values ranged from 0.126 to <0.0001). Coinciding with muscle hypertrophy, previously diminished muscle levels of IGF-1 and IGF binding protein 3 both increased following PRT (P < 0.05). In an RCT, 24 weeks of PRT proved safe and effective in restoring lean mass and function in patients with RA. Muscle hypertrophy coincided with significant elevations of attenuated muscle IGF levels, revealing a possible contributory mechanism for rheumatoid cachexia. PRT should feature in disease management.

Locomotion and muscle mass measures in a murine model of collagen-induced arthritis

BackgroundRheumatoid arthritis (RA) is characterized by chronic poly-arthritis, synovial hyperplasia, erosive synovitis, progressive cartilage and bone destruction accompanied by a loss of body cell mass. This loss of cell mass, known as rheumatoid cachexia, predominates in the skeletal muscle and can in part be explained by a decreased physical activity. The murine collagen induced arthritis (CIA) model has been proven to be a useful model in RA research since it shares many immunological and pathological features with human RA. The present study explored the interactions between arthritis development, locomotion and muscle mass in the CIA model.MethodsCIA was induced in male DBA/1 mice. Locomotion was registered at different time points by a camera and evaluated by a computerized tracing system. Arthritis severity was detected by the traditionally used semi-quantitative clinical scores. The muscle mass of the hind-legs was detected at the end of the study by weighing. A methotrexate (MTX) intervention group was included to study the applicability of the locomotion and muscle mass for testing effectiveness of interventions in more detail.ResultsThere is a strong correlation between clinical arthritis and locomotion. The correlations between muscle mass and locomotion or clinical arthritis were less pronounced. MTX intervention resulted in an improvement of disease severity accompanied by an increase in locomotion and muscle mass.ConclusionThe present data demonstrate that registration of locomotion followed by a computerized evaluation of the movements is a simple non invasive quantitative method to define disease severity and evaluate effectiveness of therapeutic agents in the CIA model.

Sarcopenia da caquexia reumatoide: conceituação, mecanismos, consequências clínicas e tratamentos possíveis

A caquexia relacionada à artrite reumatoide é conceituada como perda involuntária de massa magra, predominantemente de músculo esquelético, que também ocorre em vísceras e sistema imune, com massa gorda estável ou um pouco elevada e com pequena ou nenhuma perda de peso. A causa é multifatorial, incluindo a produção acentuada de citocinas, principalmente TNF± e IL-1², diminuição da ação periférica da insulina e pouca atividade física. A caquexia se faz presente em doentes com AR ativa ou mesmo inativa. Neste artigo discutem-se aspectos relacionados à patogenia, implicações clínicas e possíveis opções terapêuticas.

Rheumatoid cachexia, central obesity and malnutrition in patients with low-active rheumatoid arthritis: feasibility of anthropometry, Mini Nutritional Assessment and body composition techniques

The concurrent decrease in fat free mass (FFM) and increase in fat mass (FM), including central obesity, in patients with rheumatoid arthritis (RA) may be related to increased cardiovascular morbidity as well as to functional decline. The objectives of this study were to evaluate body composition and nutritional status in patients with RA and the feasibility of bioelectrical impedance (BIA) to detect rheumatoid cachexia. Eighty RA outpatients (76% women), mean age 61 (range 22-80) years and with mean disease duration of 6 (range 1-52) years, were assessed by body mass index (BMI), waist circumference (WC), whole-body dual-energy X-ray absorptiometry (DXA), BIA and the Mini Nutritional Assessment (MNA). Fat free mass index (FFMI; kg/m(2)) was low in 26% of the women and in 21% of the men. About every fifth patient displayed concomitant low FFMI and elevated fat mass index (FMI; kg/m(2)), i.e. rheumatoid cachexia. BMI and MNA were not able to detect this condition. Sixty-seven percent had increased WC. Reduced FFM was independently related to age (p = 0.022), disease duration (p = 0.027), ESR (p = 0.011) and function trendwise (p = 0.058). There was a good relative agreement between DXA and BIA (FM r (2) = 0.94, FFM r (2) = 0.92; both p < 0.001), but the limits of agreement were wide for each variable, i.e. for FM -3.3 to 7.8 kg; and for FFM -7.9 to 3.7 kg. Rheumatoid cachexia and central obesity were common in patients with RA. Neither BMI nor MNA could detect this properly. There was a good relative agreement between DXA and BIA, but the limits of agreement were wide, which may restrict the utility of BIA in clinical practice.

Rheumatoid cachexia: a complication of rheumatoid arthritis moves into the 21st century

Rheumatoid cachexia, loss of muscle mass and strength and concomitant increase in fat mass, is very common in patients with rheumatoid arthritis (RA). Despite great advances in the treatment of RA, it appears that rheumatoid cachexia persists even after joint inflammation improves. Rheumatoid cachexia may be an important risk factor for cardiovascular disease and excess mortality in RA. In this issue of Arthritis Research & Therapy, Elkan and colleagues demonstrate a link between rheumatoid cachexia and metabolic syndrome, further reinforcing the need for therapy directed beyond inflammation and at the metabolic consequences of RA.

Rheumatoid cachexia is associated with dyslipidemia and low levels of atheroprotective natural antibodies against phosphorylcholine but not with dietary fat in patients with rheumatoid arthritis: a cross-sectional study.

IntroductionPatients with rheumatoid arthritis (RA) have an increased risk for cardiovascular disease (CVD) independent of traditional risk factors. The aim of this study was to analyze the associations between diet, body composition, lipids and atheroprotective natural antibodies against phosphorylcholine (anti-PC) in patients with RA.MethodsA total of 80 RA patients (76% women), mean age (standard deviation (SD)) 61.4 (12) years and median disease duration of 6 years, were assessed by food frequency questionnaire (FFQ), fatty acid profile in adipose tissue and whole-body dual energy x ray absorptiometry (DXA). Rheumatoid cachexia was defined as fat free mass index below the 25th percentile and fat mass index above the 50th percentile of a reference population. Blood lipids, oxidized low-density lipoprotein (oxLDL) and anti-PC levels were determined.ResultsThe mean body mass index for the women and men was 25.0 and 27.0, respectively. Central obesity was found in 57% of the women (waist circumference >80 cm) and in 89% of the men (waist circumference >94 cm). In all, 18% of the women and 26% of the men had rheumatoid cachexia. These patients had significantly higher total cholesterol (P < 0.033), LDL (P < 0.029), and trendwise oxLDL (P = 0.056) as well as lower anti-PC IgM (P = 0.040), higher frequency of hypertension (69%) and metabolic syndrome (25%) than those without. The patients reported a high dietary intake of saturated fat, which partly correlated with fatty acid composition in adipose tissue and significantly with disease activity. However, patients with or without cachexia did not differ with respect to dietary fat intake or intake of Mediterranean-like diet. Additionally, patients on a Mediterranean-like diet had high levels of anti-PC (P < 0.001).ConclusionsAbout one in five patients with low-active RA displayed rheumatoid cachexia. This condition was associated with high levels of LDL cholesterol, low levels of atheroprotective anti-PC and high frequency of hypertension, which is of interest in the context of CVD in RA. The cachexia could not be related to diet fat intake. However, patients on a Mediterranean-like diet had high anti-PC levels in spite of similar frequency of cachexia. High anti-PC levels may provide some protection against CVD.

Metabolism in Patients with Rheumatoid Arthritis: Resting Energy Expenditure, Physical Activity and Diet-Induced Thermogenesis. Invited Review

Metabolism is one of the most important physiological functions. Resting energy expenditure, physical activity and diet are the main factors of total metabolism but the contribution of these components to total energy expenditure may be significantly changed with chronic inflammatory diseases such as rheumatoid arthritis (RA). RA is a disease that alters normal metabolism due to the overproduction of pro-inflammatory cytokines and may lead to rheumatoid cachexia. This review focuses on the individual components of total energy expenditure and discusses how physical activity and diet may influence resting metabolism both in the healthy population as well as patients with RA. Moreover, information is provided regarding the available patents (i.e. equipment and prediction equations) that may be used in order to predict metabolism in the normal population and RA patients.

Geriatrician Offers Simpler Frailty Assessment

Geriatrician Offers Simpler Frailty Assessment

Rheumatoid cachexia: a clinical perspective

Rheumatoid cachexia is under-recognized in clinical practice. The loss of lean body tissue, which characterizes cachexia, is often compensated for by gain in body fat-so called 'cachectic obesity'-so that 85% or more RA patients have a normal BMI. Severe cachexia with loss of weight leads to increased morbidity and premature mortality but loss of muscle bulk with a normal BMI also associates with poor clinical outcomes. Increasing BMI, even into the obese range, is associated with less joint damage and reduced mortality. Measurement of body composition using DXA and other techniques is feasible but the results must be interpreted with care. Newer techniques such as whole-body MRI will help define with more confidence the mass and distribution of fat and muscle and help elucidate the relationships between body composition and outcomes. Cachexia shows little response to diet alone but progressive resistance training and anti-TNF therapies show promise in tackling this potentially disabling extra-articular feature of RA.

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/m2) and fat mass index (FMI; kg/m2) 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) μg/L. IGFBP‐1 levels were elevated in patients (median 58 µg/L in women and 59 µg/L in men) compared with a normal population (33 µg/L in women and 24 µg/L in men). The ratio IGF‐1/IGFBP‐1, which reflects bioavailable IGF‐1, was low (2.0 µg/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.

Blockade of tumour necrosis factor- in rheumatoid arthritis: effects on components of rheumatoid cachexia

Rheumatoid arthritis (RA) is accompanied by increased resting energy expenditure (REE) and decreased fat-free mass (FFM). This is referred to as rheumatoid cachexia and is attributed to high levels of tumour necrosis factor-alpha (TNF-alpha). This study aimed to investigate the effects of anti-TNF-alpha therapy on REE, body composition, physical activity and protein intake in RA patients. Twenty RA patients [50% female; age: (mean +/- s.d.) 61.1 +/- 6.8 yrs; body mass index (BMI): 28.3 +/- 3.7 kg/m2] and 12 age-sex-BMI-matched healthy controls were assessed. REE (indirect calorimetry), body composition (bioelectrical impedance), the International Physical Activity Questionnaire (IPAQ), diet, Health Assessment Questionnaire (HAQ), disease activity [disease activity score 28 (DAS28), erythrocyte sedimentation rate (ESR), C-reactive protein] and serum TNF-alpha were measured before (Baseline) as well as 2 weeks (Time-1) and 12 weeks (Time-2) after initiation of anti-TNF-alpha treatment. Controls were only assessed at Baseline. RA patients had significantly higher REE than controls at Baseline (1799.4 +/- 292.0 vs 1502.9 +/- 114.5 kcal/day, P = 0.002). Within the RA group, REE increased significantly between Time-1 and Time-2 (P = 0.001) but not between Baseline and Time-2. Sustained significant increases were observed in IPAQ (P = 0.001) and protein intake (P = 0.001). There were no significant changes in FFM or body fat. ESR (P = 0.002), DAS28 (P < 0.001), HAQ (P < 0.001) and TNF-alpha (P = 0.024) improved significantly. Physical activity (P = 0.001) and protein intake (P = 0.024) were significant between-subject factors for the elevation of REE. After 12 weeks of anti-TNF-alpha therapy, there were significant improvements in disease activity and physical function, as well as physical activity and protein intake, but no significant changes in REE or FFM. There is a need for longer-term studies in this field.

Diurnal secretion of growth hormone, cortisol, and dehydroepiandrosterone in pre- and perimenopausal women with active rheumatoid arthritis: a pilot case-control study

Rheumatoid arthritis (RA) is associated with neuroendocrine and immunologic dysfunction leading to rheumatoid cachexia. Although excess proinflammatory cytokines can decrease somatotropic axis activity, little is known about the effects of RA on growth hormone/insulin-like growth factor-1 (GH/IGF-I) axis function. We tested the hypothesis that patients with active RA exhibit decreased GH/IGF-I axis activity. To do so, we conducted a pilot case-control study at a clinical research center in 7 pre- and perimenopausal women with active RA and 10 age- and body mass index-matched healthy women. Participants underwent blood sampling every 20 minutes for 24 hours (8 a.m. to 8 a.m.), and sera were assayed for GH, cortisol, and dehydroepiandrosterone (DHEA). Sera obtained after overnight fasting were assayed for IGF-I, IGF-binding protein (IGFBP)-1, IGFBP-3, C-reactive protein (CRP), interleukin-6 (IL-6), glucose, insulin, and lipids. Body composition and bone mineral density were evaluated by DEXA (dual emission x-ray absorptiometry) scans. In patients with RA, mean disease duration was 7.6 ± 6.8 years, and erythrocyte sedimentation rate, CRP, and IL-6 were elevated. GH half-life was shorter than in control subjects (p = 0.0037), with no other significant group differences in GH deconvolution parameters or approximate entropy scores. IGF-I (p = 0.05) and IGFBP-3 (p = 0.058) were lower, whereas IGFBP-1 tended to be higher (p = 0.066), in patients with RA, with nonsignificantly increased 24-hour total GH production rates. There were no significant group differences in cortisol or DHEA secretion. Lean body mass was lower in patients with RA (p = 0.019), particularly in the legs (p = 0.01). Women with active RA exhibit a trend toward GH insensitivity and relatively diminished diurnal cortisol and DHEA secretion for their state of inflammation. Whether these changes contribute to rheumatoid cachexia remains to be determined.NCT00034060.

Randomized phase 2 trial of anti-tumor necrosis factor therapy for cachexia in patients with early rheumatoid arthritis

Tumor necrosis factor (TNF) is an important mediator of cachexia, and its blockade prevents catabolism in animal models. However, little evidence shows that anti-TNF therapy is effective in treating cachexia in humans. The main aim of this study was to investigate the effect of etanercept, a synthetic soluble TNF receptor, on body composition in patients with early rheumatoid arthritis (RA). Twenty-six patients were randomly assigned to 24 wk of treatment with etanercept or methotrexate; the latter is the first-line therapy for RA. Body composition, physical function, disease activity, systemic inflammation, and the circulating insulin-like growth factor (IGF) system were measured at baseline (week 0) and at follow-up (weeks 12 and 24). Twelve patients in each treatment group (9 F, 3 M) completed the study. Overall, no important changes in body composition were observed, despite a transient increase in IGF-I at week 12 (P < 0.01). However, the secondary analysis of those patients (6/treatment group) who gained weight during follow-up showed a significant effect of etanercept on the composition of the weight gained: 44% of weight gained in the etanercept group was fat-free mass, as compared with only 14% in the methotrexate group (P = 0.04). Etanercept and methotrexate were equally effective in controlling the disease and improving physical function. Anti-TNF therapy with etanercept is not superior to that with methotrexate for the treatment of rheumatoid cachexia over a period of 6 mo. However, TNF blockade seems to normalize the anabolic response to overfeeding and, if these findings are confirmed, may be useful in conditions characterized by anorexia and weight loss.

Rheumatoid Cachexia: causes, significance and possible interventions

Rheumatoid arthritis is a chronic autoimmune disease characterised by joint pain and stiffness but also systemic mutli-organ involvement. Several features are due to excessive production of inflammatory cytokines, particularly tumour necrosis factor alpha, interleukin-1 and interleukin-6. These are implicated in both local synovial inflammation, which causes joint destruction, but also systemic inflammation, which can cause loss of body cell mass, amongst other phenomena. Body cell mass breakdown in rheumatoid arthritis leads to the classical, but largely ignored, metabolic abnormality known as rheumatoid cachexia. Cachexia is a very strong predictor of adverse functional outcome and death in many disease states. In this review we highlight the mechanisms linked with rheumatoid cachexia and discuss possible interventions that may limit this in patients with rheumatoid arthritis.

Dietary treatment of rheumatoid cachexia with β-hydroxy- β-methylbutyrate, glutamine and arginine: A randomised controlled trial

Background & Aims Rheumatoid arthritis (RA) is complicated by cytokine-driven alterations in protein and energy metabolism and consequent muscle wasting (cachexia). The aim of this randomised controlled trial was to investigate the efficacy of a mixture of β-hydroxy-β-methylbutyrate, glutamine and arginine (HMB/GLN/ARG) as nutritional treatment for rheumatoid cachexia. Methods Forty RA patients supplemented their diet with either HMB/GLN/ARG or a nitrogen (7.19g/day) and calorie (180kcal/day) balanced mixture of alanine, glutamic acid, glycine, and serine (placebo) for 12 weeks. Body composition and other outcomes were assessed at baseline and follow-up, and analysed by mixed ANOVA. Results Dietary supplementation with HMB/GLN/ARG was not superior to placebo in the treatment of rheumatoid cachexia (group×time interactions P > 0.05 for all outcomes). Both amino acid mixtures significantly increased (main effect of time) fat-free mass (727±1186g, P < 0.01 ), total body protein (719±1703g, P = 0.02 ), arms (112±183g, P < 0.01 ) and legs (283±534g, P < 0.01 ) lean mass, and some measures of physical function. No significant adverse event occurred during the study, but patients in the HMB/GLN/ARG group reported fewer gastrointestinal complaints compared to placebo. Conclusions Dietary supplementation with HMB/GLN/ARG is better tolerated but not more effective in reversing cachexia in RA patients compared to the mixture of other non-essential amino acids used as placebo. Further controlled studies are necessary to confirm the beneficial anabolic and functional effects of increased nitrogen intake in this population. Rheumatoid arthritis (RA) is complicated by cytokine-driven alterations in protein and energy metabolism and consequent muscle wasting (cachexia). The aim of this randomised controlled trial was to investigate the efficacy of a mixture of β-hydroxy-β-methylbutyrate, glutamine and arginine (HMB/GLN/ARG) as nutritional treatment for rheumatoid cachexia. Forty RA patients supplemented their diet with either HMB/GLN/ARG or a nitrogen (7.19g/day) and calorie (180kcal/day) balanced mixture of alanine, glutamic acid, glycine, and serine (placebo) for 12 weeks. Body composition and other outcomes were assessed at baseline and follow-up, and analysed by mixed ANOVA. Dietary supplementation with HMB/GLN/ARG was not superior to placebo in the treatment of rheumatoid cachexia (group×time interactions P > 0.05 for all outcomes). Both amino acid mixtures significantly increased (main effect of time) fat-free mass (727±1186g, P < 0.01 ), total body protein (719±1703g, P = 0.02 ), arms (112±183g, P < 0.01 ) and legs (283±534g, P < 0.01 ) lean mass, and some measures of physical function. No significant adverse event occurred during the study, but patients in the HMB/GLN/ARG group reported fewer gastrointestinal complaints compared to placebo. Dietary supplementation with HMB/GLN/ARG is better tolerated but not more effective in reversing cachexia in RA patients compared to the mixture of other non-essential amino acids used as placebo. Further controlled studies are necessary to confirm the beneficial anabolic and functional effects of increased nitrogen intake in this population.

Rheumatoid cachexia: metabolic abnormalities, mechanisms and interventions

We have previously identified the phrase 'rheumatoid cachexia' to describe the loss of body cell mass (BCM) that may occur among patients with rheumatoid arthritis (RA). Specifically, rheumatoid cachexia is characterized by altered energy and protein metabolism (reduced total energy expenditure, increased resting energy expenditure and increased whole-body protein catabolism) and increased inflammatory cytokine production (interleukin-1beta and tumour necrosis factor-alpha). Patients with rheumatoid cachexia consistently have a diet that appears adequate in protein and calories (based on US Dietary Reference Intakes), but with reduced physical activity. These phenomena are similar to some of the metabolic abnormalities that occur with normal ageing, but the aetiology appears to be different in RA. This review will focus on describing the metabolic abnormalities observed in rheumatoid cachexia, identifying potential mechanisms for loss of BCM and discussing strategies for intervention.

Reversal of chronic obstructive pulmonary disease-associated weight loss : are there pharmacological treatment options?

Poor nutritional status is associated with an increased incidence of morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD). While a number of factors have been shown to produce tissue catabolism, no single mechanism has been clearly identified as a primary cause for weight loss in patients with severe COPD. Without a clear understanding of the aetiology of weight loss, therapeutic strategies to reverse this process have historically been unsuccessful. A review of recent studies allows consideration of a model of mechanisms of weight loss. This model includes multiple pathways that may be activated singly or simultaneously to cause loss of weight, specifically lean body mass. These include energy imbalances, elevated levels of cytokines, tissue hypoxia and the effects of cocorticosteroid therapy. To date, interventional studies that have looked at newer pharmacotherapies such as growth hormone and anabolic steroids in patients with COPD who are losing weight have not demonstrated reversal of weight loss or improvement in nutritional status. Currently, early identification of patients at risk for weight loss and aggressive nutritional supplementation coupled with an exercise programme has demonstrated the greatest benefit. However, with increasing understanding of the mechanisms that may be implicated, new targets for therapies are being identified. Of particular research interest are molecules such as leukotrienes, hormones, tumour necrosis factor-alpha and acute-phase proteins, which are noted to be elevated in some patients with COPD-associated weight loss. Currently, inhibitors to some of these inflammatory substances are used therapeutically in other chronic illnesses such as rheumatoid arthritis and cancer cachexia. Future research may investigate their usefulness in COPD and direct new therapies that target the processes contributing to weight loss in these patients.