Resistance training (done right) can safely reverse cachexia in RA patients

Expert opinion in rheumatoid arthritis (RA) has largely shifted away from resting joints to “protect” them toward incorporating exercise into the RA management program. This shift hit a snag when Rall et al reported no improvements in skeletal muscle mass or fat-free mass (FFM) in RA patients after 12 weeks of “high-intensity” exercise, despite an increase in strength. Dr Samuele M Marcora (University of Wales-Bangor) reports in the June 2005 issue of the Journal of Rheumatology that progressive resistance training (PRT) can reverse RA-related cachexia, increase FFM, and improve functional ability, but only when done at more intense levels than those used in the Rall study.

“As a consequence of the increases in muscle mass and the subsequent gains in strength, patients reported an improvement in their ability to perform advanced activities of daily living (p=0.008 by ANCOVA). We interpret this as a reduction in disability. With specific regard to the 30-second sit-to-stand test (SST-30), 12 wks of PRT increased mean reps from 11.3 to 15.7. This postintervention mean was equivalent to the level of performance we have observed in healthy age- and sex-matched controls. Thus, for this test, PRT was able to restore normal physical function in established RA patients,” coauthor Dr Andrew Lemmey (University of Wales-Bangor) tells rheumawire.Muscle wasting second only to disease activity in causing disability According to Lemmey, the most important “new” concept for clinicians is that muscle loss occurs in RA patients despite pharmacological “control” of disease. “This loss of muscle is crucial in terms of the patient’s function, level of disability, quality of life, and viability,” Lemmey says.The investigators have also completed a study investigating the contribution of muscle wasting to disability in RA patients, and Lemmey tells rheumawire they found that, second only to RA-disease activity, muscle mass was the best predictor of disability in RA (and superior to deformed joint score, psychological score, and physical function). “Given that disability is such a common, severe, and costly consequence of RA and that muscle wasting contributes in a major way to this disability, it is essential that clinicians recognize the need to maintain and/or restore muscle mass in their patients. High-intensity exercise is clearly a means of doing this. Anabolic hormones may also prove successful. We are currently investigating the efficacy of nandrolone decanoate (Deca-Durabolin) for improving muscle mass and function in RA patients,” Lemmey says. Nandrolone has long been a favorite of some bodybuilders and professional athletes and has been used off label to treat AIDS-related wasting.Eight exercises, eight reps, repeat three times The Welsh researchers conducted a nonrandomized, phase 2, parallel-group controlled trial that included 10 mildly disabled patients with well-controlled RA in the exercise group and 10 similar, age- and sex-matched RA patients in the control group. Control patients were willing to take part in the exercise program but unable to, mostly due to logistical problems.”It should be noted that the patients used in our study were ‘typical’ RA patients in terms of age, sex, disease duration and severity, medication, etc. Consequently, while our sample was small and not randomly chosen, we are confident that PRT will be beneficial and suitable for most RA patients,” Lemmey says.All patients fulfilled American Rheumatism Association 1987 revised criteria for the diagnosis of RA, were functional class 1 or 2, and had been on stable drug therapy during the previous three months.Baseline and 12-week follow-up outcome measures included body mass, body composition assessed by DEXA, bone-mineral content, fat mass, lean mass, fat-free mass (the sum of total bone-mineral content and total lean mass), percent body fat, intracellular and extracellular water, total body water, handgrip strength, strength of knee extensors and elbow flexors, SST-30, the Health Assessment Questionnaire (HAQ), the advanced activities of daily living scale, the RA Disease Activity Index (RADAI), fatigue, and body mass index (BMI).The exercise program included three sets of eight repetitions of each of the following: leg press, chest press, leg extension, seated row, leg curl, triceps pushdown, standing calf raise, and biceps curl. Subjects trained three times per week for 12 weeks. Intensity was increased by assessment of one-repetition maximum every two weeks. The baseline condition of study subjects clearly illustrated the problem of cachexia, which affects more than half of RA patients. The syndrome is characterized by cytokine-driven alterations in protein and energy metabolism and accelerated loss of skeletal mass, although only a minority of RA patients appear wasted, since the loss of muscle mass is masked by an increase in fat mass. Despite an “overweight” category BMI, adequate protein-energy intake, and normal physical activity, all but one of the subjects in this study presented with muscle atrophy, down to only 79% to 74% of normal muscle mass. The researchers report that, compared with the control subjects (who continued their normal activities without additional exercise), the PRT subjects had large and significant increases in total lean mass (+1242 g) and in FFM (+1253 g). “This increase in FFM mostly reflects a significant and moderate increase in estimated total body protein (+1063 g), as PRT did not have a significant effect on total body water and total bone-mineral content,” they write. The investigators note that the increase in FFM suggests that PRT can correct the negative nitrogen balance characteristic of RA.The increase in lean mass was mostly in the arms and legs, “suggesting a very large effect on total body skeletal muscle mass.” This finding largely lays to rest concerns in the wake of the study by Rall et al that RA patients might be resistant to anabolic stimuli. These changes resulted in a moderate increase in handgrip strength, a large increase in elbow flexor strength (+54 N) and a very large increase in SST-30 performance (+3.6 repetitions). PRT did not affect modified HAQ scores, but at follow-up, the exercise subjects reported a large and clinically relevant improvement in advanced activities of daily living score (-0.25).Despite its high intensity and volume, the proposed PRT program did not significantly affect RADAI, fatigue, or erythrocyte sedimentation rate. One reason Rall et al did not use a more intensive exercise regimen was fear that it would exacerbate disease activity.Lemmey attributes the difference between their results and those of Rall et al to “the combination of a higher number of resistance exercises per training session and higher training frequency.” The total number of weight lifts per week was 576 in this study vs 240 in the Rall study.A similar PRT program should be included in the management of RA as adjunct treatment for cachexia. “We believe the most likely reason [for the different outcomes] is volume of training. Our patients performed eight resistance exercises per session and trained three times per week, whereas [subjects in the Rall study] only performed five exercises per session and trained twice a week,” Lemmey says. The researchers also observed that the exercise patients had a trend toward loss of fat mass in the trunk, a marker associated with increased risk of cardiovascular disease. “Intense PRT with adequate volume seems to be an effective and safe intervention for stimulating muscle growth in patients with RA. Pending confirmation of these results in a larger randomized controlled trial that includes patients with more active and severe disease, a similar PRT program should be included in the management of RA as adjunct treatment for cachexia,” Marcora writes.As a follow-up to this study, the researchers are currently conducting a larger (n=40), randomized, double-blind, placebo-controlled phase 3 trial (supported by the Arthritis Research Campaign), in which RA patients are performing high-intensity PRT twice a week for 24 weeks or range-of-movement, home-based exercises twice a week for 24 weeks. In addition to confirming the benefits of the pilot study, this phase 3 study aims to determine the roles of the insulinlike-growth-factor and tumor-necrosis-factor systems at both the systemic and local (muscle) levels with regard to skeletal muscle catabolism and anabolism in RA.(Source: Rall LC, Meydani SN, Kehayias JJ, et al. The effect of progressive resistance training in rheumatoid arthritis. Increased strength without changes in energy balance or body composition. Arthritis Rheum 1996; 39:415-426: Rheumawire: Joint and Bone: July 2005.)