**3.5 Effects on bone**

294 Rheumatoid Arthritis – Treatment

after 24 weeks of PRT the number of patients in these high disability risk categories (Morley et al., 2001) were reduced to 4, 7 and 2, respectively. Given the reported links between adverse body composition and physical disability in RA patients (Giles et al., 2008) and the general elderly population (Morley et al., 2001), the positive effects of PRT on function in RA patients are anticipated. To emphasise the crucial role played by training intensity, in our RCT study (Lemmey et al., 2009) range-of-movement (ROM) exercises (i.e. the form of exercise most commonly prescribed for RA patients) were performed by the control group. Despite good compliance to the intervention, this low intensity exercise failed to have any

As mentioned earlier, the precise mechanisms underlying rheumatoid cachexia have not been clarified. However, an additional insight was provided by Lemmey et al's RCT (2009). In this study diminished muscle levels of insulin-like growth factor-I (mIGF-I) were identified in our RA patients. This finding is consistent with reports of reduced mIGF-I levels in other conditions characterised by muscle wasting: chronic heart failure (CHF) (Hambrecht et al., 2005), chronic obstructive pulmonary disease (COPD) (Vogiatzis et al., 2007), chronic renal failure (Macdonald et al., 2004, 2005), and advanced aging (Fiatarone Singh et al., 1999); and with the proposed role of mIGF-I in regulating the maintenance of adult skeletal muscle (Adams, 2002). Following 24 weeks PRT, along with muscle hypertrophy, mIGF-I levels were observed to increase 50% in our RA patients. Again, this finding of coincident increases in mIGF-I levels and muscle mass in cachectic individuals following exercise training is consistent with responses in COPD (Vogiatzis et al., 2007) and dialysis (Macdonald et al., 2005) patients, and the frail elderly (Fiatarone Singh et al., 1999); and the pivotal role put forward for mIGF-I in muscle's hypertrophic response to loading

The magnitude of effects of PRT on strength and body composition observed in RA patients are similar to those reported for healthy middle-aged or older individuals (e.g. Frontera et al., 1991; Morse et al., 2007; Nichols et al., 1993; Pedersen & Saltin, 2006). The study by Hakkinen et al. (2005) described previously provides a direct comparison of training responses. This investigation featured female RA patients and age-matched healthy women who completed the same 21 week combined resistance and aerobic exercise training program, and noted remarkably similar improvements in strength and body composition (with regard to both absolute and relative increases in quadriceps femoris cross-section and reductions in quadriceps femoris subcutaneous fat thickness) following training. This similarity in training response is consistent with recent reports that muscle quality (muscle force per size) is not compromised in RA patients (Matschke et al., 2010a, 2010b). In these studies, a range of skeletal muscle parameters (e.g. specific force, muscle architecture, coactivation of antagonist muscles, voluntary activation capacity) were observed to be the same for well controlled RA patients, including those classified as cachectic, as for matched healthy subjects. This finding that rheumatoid muscle is normal both qualitatively and in its response to resistance training is important for health professionals involved in prescribing

effect on the various measures of body composition or objective physical function.

**3.3 Impact on mechanisms of rheumatoid cachexia** 

**3.4 Responsiveness of RA patients to PRT** 

(Adams, 2002).

exercise for people with RA.

The benefit of weight-bearing and strengthening exercise in maximising and maintaining BMD, and reducing the risk of falling by improving strength and balance is well accepted in the general population (ACSM, 2010a). With specific reference to RA, a sedentary lifestyle confers a relative risk of 1.6 for low BMD in RA patients, and even moderate physical activity has been shown to reduce this risk by 50% (Tourinho et al., 2008). Additionally, de Jong et al. (2004) showed that bone loss at the hip was reduced in RA patients participating in the 2 year, high-intensity RAPIT exercise program (median -1.1% vs -1.9% for nonexercising controls, p<0.05). Further analysis revealed that these changes in BMD were significantly and independently associated with changes in strength and aerobic power, and that the high-intensity training had a benefit comparable to that of biphosphonate treatment. This finding led the investigators to conclude that intense weight-bearing exercise, including PRT, is essential for improving BMD in RA patients. Similar conclusions were made by Hakkinen et al. following their RCT (1999, 2001, 2004a). In this trial, twelve months PRT by RA patients resulted in mean BMD gains of +1.10% at the femoral head and +0.19% at the lumbar spine in contrast to losses of -0.03% and -1.14%, respectively, in the ROM controls (Hakkinen et al., 1999). Following a further 12 months PRT, the mean differences between the groups increased with the changes in BMD at the femoral head and the lumbar spine now +0.51% and +1.17% for the training group and -0.70% and -0.91%, respectively, for the controls (Hakkinen et al., 2001). These observed trends in BMD were noted again at a 3 year follow-up (Hakkinen et al., 2004a). Whilst the differences between the groups were not statistically significant, except for the femoral head at 24 months, it was suggested by the authors that such an effect would be substantial and of clinical significance if PRT was prolonged and its impact on BMD given longer to accrue.

Treatments for osteopenia or osteoporosis are judged on their ability to increase BMD, or failing that, to minimise bone loss. Thus, although the evidence from RA patients is limited, PRT appears to be as efficacious in this population as it is generally (e.g. Dornemann et al., 1997; Nelson et al., 1994; Rhodes et al., 2000).

In RCT's conducted to evaluate the effect of PRT on BMD in the general population, the evidence is compelling that intensity (i.e. loading) is the key variable (see Layne and Nelson, 2001 for a review). This is consistent with Wolff's law which states that the magnitude of the stress or mechanical load applied to bone via muscles and tendons directly determines the osteogenic response (Chamay & Tschantz, 1972). The results of Kerr et al. (1996) serve to illustrate this. In this study, post-menopausal women (aged 51-62 years) were randomised to either high-intensity (HI) "strength" PRT (high load, low repetitions i.e. 3 sets of 8 repetitions) or low-intensity (LI) "endurance" PRT (low load, high repetitions i.e. 3 sets of 20 repetitions). After training 3x's/week for 12 months, the HI group had increased femoral head and distal radial BMD significantly more than the LI group; with the site-specific gains in BMD significantly correlated to the site-specific strength increases. In patients recovering from surgery, strength training has also been shown to be effective in countering glucocorticoid-induced bone loss (Braith et al., 1996). However, as for the general population, the greatest benefit of PRT in reducing osteoporotic fractures in RA patents is likely to be a consequence of lowering the incidence of falling due to improved strength and balance (Layne and Nelson, 2001; Nelson et al., 1994; Vanderhoek et al., 2000). With regards to the suitability of high-intensity PRT for individuals with low BMD; Vanderhoek et al. (2000) specifically chose osteopenic or osteoporotic elderly women (mean±sd; age = 69.0±1.3

Resistance Training for Patients with Rheumatoid Arthritis: Effects on Disability,

2004b), regular, HI PRT relative to patients receiving standard care.

**4. Fundamentals of PRT prescription for RA patients** 

or advanced programs.

**4.1 Frequency** 

volume), and type (or modality) (ACSM, 2010e).

Rheumatoid Cachexia, and Osteoporosis; and Recommendations for Prescription 297

exercise exacerbated joint damage progression in large joints with extensive pre-existing damage. Results from an 18 month follow-up study (de Jong et al., 2009), however, have seen the investigators retract this conclusion. Instead, they are now confident that longterm, intense weight-bearing exercise does not cause further damage to large joints, even those already extensively damaged. This revised interpretation thus accords with the verdict they had previously made with regard to the small joints of the hands and feet (de Jong et al., 2003). This general conclusion of training not increasing radiological progression of joint damage agrees with the findings of others (Hakkinen et al., 1994, 2001, 2004b; Nordemar et al., 1981). In the earliest of these studies, Nordemar et al. (1981) found that RA patients who had performed 4-8 years of resistance exercises for the legs had reduced joint damage in these limbs relative to non-exercising disease-matched controls. Whilst in the other studies, all by Hakkinen's group (1994, 2001, 2004b), no acceleration in joint damage was detected by x-ray in RA patients performing long-term (up to 5 years; Hakkinen et al.,

"The key factor to successful resistance training at any level of fitness or age is appropriate program design" (Kraemer & Ratamess, 2004); and this requires that specific needs and goals are addressed. For RA patients generally, the needs a PRT program should address are: counteracting rheumatoid cachexia by restoring muscle mass and reducing adiposity (especially central stores); augmenting strength and thus improving physical function and the ability to perform ADL's; and lowering osteoporotic fracture risk by stabilizing or increasing bone mass and reducing the likelihood of falling by enhancing strength and balance. In specifying these aims, the intention is not to ignore the numerous generic benefits of exercise training such as reduced CVD risk, improved insulin-sensitivity, decreased risk of specific cancers, enhanced mood and mental health etc., but to concentrate on those aspects of RA-specific health for which PRT is particularly appropriate. Additionally, individuals may also have personal goals and these should be taken into account when designing the training program. Since untrained individuals readily respond physiologically to most protocols, it is unnecessary to devise complicated

To maximise the health and performance benefits, and to best ensure safety, it is important that appropriately qualified professionals are involved in designing the PRT program and, for the initial weeks at least, in supervising training. The following training recommendations are all consistent with guidelines provided by the ACR (2022, 2006), EULAR (Combe et al., 2007), ACSM (1998, 2010a-e) and AHA (Williams et al., 2007) either for RA specifically or for the co-morbid conditions common in RA, and by the WHO (2008) "for promoting and maintaining health" in the general population. As with most exercise programs, these guidelines are based on the FITT principle: frequency, intensity, time (or

It is generally recommended that strength training is performed 2-3 days a week with at least 48 hours rest between sessions (Evans, 1999; Hass et al., 2001; Kraemer & Ratamess, 2004). Training on alternate days allows adequate time for recovery and adaptation, and this

years) for 32 weeks of HI PRT in which they performed 3 sets of 8 repetitions at 75-80% of 1 repetition maximum (1-RM, i.e. the maximum load that can be correctly lifted for a given exercise) for each exercise. As anticipated, this high intensity PRT resulted in substantial, and correlated, improvements in strength and balance. More importantly, it also proved to be well tolerated and safe with no compression fractures or other training related injuries observed.
