Persistent synovitis with joint swelling and limited joint mobility in rheumatoid arthritis (RA) patients may result in the stretching of tendons, ligaments, and joint capsules, with subsequent joint instability and decreases in muscle mass and strength. Furthermore, joint effusions directly inhibit contraction of the surrounding muscle groups, and if a muscle contracts while the joint is malaligned, it will not be able to generate its peak contractile force. Moreover, the compromises in biomechanical integrity of the joint and its surrounding tissues result in pain, altered loading response, and patterns of motion that are often energy insufficient and further limit the patient's physical activities (1).
With regard to osseous tissues, the disease duration (2–5), physical inactivity, impaired function (5–7), and the inflammatory process itself contribute to bone loss in diseases such as RA. The concomitant use of corticosteroids further enhances the development of both muscle atrophy and decrease in bone mineral density (BMD) (1, 8, 9). The vicious circle that results in losses of muscle strength, BMD, and functional capacity in RA is finally catalyzed by the generalized fatigue that is associated with inflammation, resulting in further limitations in physical activity.
Thus, the loss of muscle strength and functional capacity (6, 10–12) as well as the accelerated bone loss (13) may develop early in the course of RA. Various clinical trials examining the effects of exercise training programs on BMD in healthy subjects have been described (14). Some studies show that exercise does not lead to maintenance or improvement in BMD (15, 16), while others report positive results (17–19). The earlier studies indicate that the important osteogenic exercise stimulus is high strain rates and high peak forces in versatile movements. Moreover, the number of loading cycles probably increases in significance if the repetitive loading magnitude is low on the loaded side (20). Exercise is reportedly an important tool for reducing pain, stiffness, and joint tenderness in RA patients (21–23). Nevertheless, although physical activity is also of central importance in maintaining or increasing muscle strength in patients with RA, long-term studies regarding the effects of strength training on muscle performance (24, 25) and BMD (23, 24) are few. There is a definite need for additional longitudinal studies to determine the adaptation of the muscles and bones to various types of exercise training in patients with RA.
Therefore, the purpose of the present study was to investigate whether the 24-month strength training program used to increase muscle strength and physical function in patients with early RA also produces positive effects on BMD in these patients.
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- PATIENTS AND METHODS
Two patients from the strength-training group and 3 from the control group dropped out of the study after the baseline measurements (2 discontinued the exercises, 1 fell ill with cancer, 1 drowned, and 1 was involved in an accident and had neurologic symptoms). One patient from the strength-training group (whose data are included for the first year) dropped out of the study after the first year because of a lack of motivation for the training. The diagnosis changed for 3 patients (spondylarthrosis, psoriatic arthritis, and longstanding RA), and their data were excluded from the analysis. At baseline, there were no significant differences in demographic, strength, or clinical variables between the patients who completed the trial and those who dropped out.
At baseline, the study groups were comparable with regard to demographic variables (Table 1). After the initial measurements, therapy with DMARDs was instituted. All patients were initially treated with sulfasalazine, except for 1 patient in each group, who received gold sodium thiomalate because of allergies to sulfonamides. During the 24-month trial, the initial DMARD was changed in 15 and 19 patients in the strength-training group and the control group, respectively, because of inefficacy and/or adverse events.
Table 1. Baseline characteristics of the rheumatoid arthritis patients, by exercise group*
|Variable||Strength-training group (n = 31)||Control group (n = 31)|
|No. of males:no. of females||13:18||11:20|
|Age, mean ± SD years||49 ± 10||49 ± 11|
|Weight, mean ± SD kg||74 ± 14||72 ± 11|
|Height, mean ± SD cm||169 ± 8||167 ± 9|
|Duration of symptoms, mean ± SD months||10 ± 10||8 ± 12|
|No. of current smokers||8||2|
|No. consuming 1–5 alcoholic drinks/week||8||10|
|No. of postmenopausal women||8||13|
|Time since menopause, mean ± SD years||8.4 ± 3.6||7.6 ± 5.6|
During the last 12 months of the study, 2 patients in the strength-training group and 10 in the control group were also treated for short periods with low-dose prednisolone (2.5–7.5 mg/day).
If the BMD measurements revealed osteopenia, treatment with alendronate (10 mg/day) was instituted. Thus, 3 patients in the strength-training group and 9 in the control group received bisphosphonate therapy for a mean ± SD of 6.2 ± 4.8 months and 8.3 ± 3.9 months, respectively.
The reported compliance with the exercise program averaged 1.5 times/week during the first 12 months and 1.4 times/week during months 13–24 in the strength-training group instead of the planned 2 times/week. The mean ± SD time used for various types of physical exercises during the first year were 240 ± 124 minutes/week for the strength-training group (including the strength-training exercise program) and 205 ± 103 minutes/week for the control group. During the second year, the corresponding values were 249 ± 121 and 187 ± 107 minutes/week. Three male patients in the strength-training group started to exercise in the gym instead of at home with the elastic bands.
Both groups had moderate disease activity at baseline, before initiation of DMARDs (Table 2). During the followup period, the parameters of disease activity improved statistically significantly in both groups. However, a significant between-group difference in favor of the strength-training group was observed.
Table 2. Parameters of disease activity and joint destruction in rheumatoid arthritis patients at baseline and after 6, 12, 18, and 24 months, by exercise group*
|Parameter||Strength-training group (n = 31)||Control group (n = 31)||Difference between groups (95% CI)|
| Baseline||24.4 ± 17.8||24.8 ± 15.7||−0.4 (−8.8 to 8.2)|
| 6 months||9.7 ± 9.5||16.7 ± 12.7||−7.0 (−12.7 to −1.3)†|
| 12 months||9.5 ± 7.5||17.3 ± 16.1||−7.8 (−14.1 to −1.4)†|
| 18 months||8.4 ± 7.2||15.5 ± 10.9||−7.1 (−11.9 to −2.3)‡|
| 24 months||10.9 ± 9.8||15.4 ± 11.5||−4.5 (−10.0 to 0.9)|
|Pain (0–100-mm VAS)|
| Baseline||41.7 ± 19.5||41.3 ± 27.1||0.4 (−11.6 to 12.4)|
| 6 months||20.0 ± 16.4||28.6 ± 23.1||−8.6 (−18.9 to 1.5)|
| 12 months||21.1 ± 20.6||24.2 ± 22.7||−3.1 (−14.3 to 8.1)|
| 18 months||14.6 ± 13.5||24.5 ± 21.3||−9.9 (−19.2 to −0.6)†|
| 24 months||13.7 ± 16.2||24.9 ± 22.8||−11.2 (−21.4 to −0.96)†|
|Morning stiffness (minutes)|
| Baseline||72.4 ± 54.5||81.5 ± 90.4||−9.1 (46.9 to 28.9)|
| 6 months||31.8 ± 41.1||62.9 ± 75.5||−31.1 (−62.0 to −25.7)†|
| 12 months||22.3 ± 31.8||42.5 ± 65.8||−20.2 (−46.9 to 6.4)|
| 18 months||18.3 ± 25.6||36.4 ± 51.3||−18.1 (−39.4 to 3.1)|
| 24 months||16.3 ± 21.3||37.7 ± 43.8||−21.4 (−39.2 to −3.5)†|
|DAS28 index (0–10 scale)|
| Baseline||4.4 ± 1.1||4.9 ± 1.1||−0.5 (−1.1 to 0.003)|
| 6 months||2.4 ± 1.0||3.4 ± 1.2||−1.0 (−1.7 to −0.5)§|
| 12 months||2.3 ± 1.0||3.0 ± 1.2||−0.7 (−1.3 to −0.2)†|
| 18 months||2.0 ± 1.0||3.0 ± 1.9||−1.0 (−1.5 to −0.4)§|
| 24 months||2.2 ± 1.2||2.7 ± 1.2||−0.5 (−1.2 to −0.004)|
|Larsen score (0–100 scale)|
| Baseline||0.9 ± 1.8||1.2 ± 2.0||−0.3 (−1.4 to 0.6)|
| 6 months||1.3 ± 2.3||1.3 ± 2.2||−0.0 (−1.6 to 0.7)|
| 12 months||1.4 ± 2.9||2.3 ± 2.7||−0.9 (−2.2 to 0.7)|
| 18 months||–||–||–|
| 24 months||1.5 ± 3.4||3.1 ± 3.5||−1.6 (−3.1 to 0.4)|
The maximum muscle strength values did not differ statistically between the groups at baseline (Figure 1). During the 24-month strength training, the mean ± SD knee extension strength per body mass increased by 59 ± 44% (P < 0.001) and 31 ± 27% (P < 0.001) in the strength-training group and the control group, respectively. The corresponding increases in trunk extension strength per body mass were 19 ± 28% (P < 0.001) versus 1 ± 19% (P not significant), trunk flexion strength 24 ± 19% (P < 0.001) versus 20 ± 43% (P = 0.007), and grip strength 50 ± 57% (P < 0.001) versus 24 ± 49% (P < 0.001) in the strength-training group and the control group, respectively. With the exception of trunk flexion strength, the muscle strength increases were significantly in favor of the strength-training group (P = 0.002–0.025).
Figure 1. Changes in mean levels of maximum knee extension (A), grip (B), trunk extension (C), and trunk flexion (D) strength at 0, 6, 12, 18, and 24 months in patients with early rheumatoid arthritis randomly assigned to strength-training exercise (EG) or range of motion exercise (controls; CG).
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The study groups did not differ with regard to the extent of joint damage at baseline (Table 2). During the 24-month followup, the joint damage index increased only slightly in both study groups. Thus, the difference between the groups at the end of the study was also not significant.
As shown in Table 3, there were no significant intergroup differences in BMD at either of the measured sites at baseline. During the 24-month strength-training intervention, the femoral neck BMD was increased by 0.51 ± 1.64% (mean ± SD) in the strength-training group and decreased by 0.70 ± 2.25% in the controls. For BMD of the spine, these changes were an increase of 1.17 ± 5.34% and a decrease of 0.91 ± 4.07%, respectively. At the femoral neck, the intergroup difference was significant (P = 0.024).
Table 3. BMD in the femoral neck and lumbar spine at baseline and after 12 and 24 months in the entire rheumatoid arthritis study cohort and in patients of both groups who did and did not take prednisolone and/or alendronate*
| ||All study patients||All study patients not taking prednisolone and/or alendronate||All study patients|
|Strength-training group (n = 31)||Control group (n = 31)||Strength-training group (n = 28)||Control group (n = 18)||Taking prednisolone and/or alendronate (n = 17)||Not taking prednisolone and/or alendronate (n = 45)|
|Femoral neck BMD|
| Baseline||0.95 ± 0.12||0.95 ± 0.12||0.98 ± 0.01||0.99 ± 0.13||0.88 ± 0.12||0.98 ± 0.11†|
| 12 months||0.96 ± 0.12||0.95 ± 0.13||0.99 ± 0.10||0.99 ± 0.14||0.88 ± 0.11||0.99 ± 0.12‡|
| 24 months||0.96 ± 0.12||0.93 ± 0.13||0.98 ± 0.11||0.98 ± 0.15||0.87 ± 0.10||0.98 ± 0.12‡|
|Lumbar spine BMD|
| Baseline||1.23 ± 0.20||1.20 ± 0.20||1.25 ± 0.19||1.21 ± 0.15||1.16 ± 0.20||1.24 ± 0.17|
| 12 months||1.24 ± 0.20||1.18 ± 0.16||1.24 ± 0.18||1.22 ± 0.14||1.16 ± 0.21||1.23 ± 0.17|
| 24 months||1.24 ± 0.19||1.18 ± 0.15||1.24 ± 0.18||1.21 ± 0.15||1.16 ± 0.21||1.22 ± 0.16|
Seventeen of the 62 patients were treated for various periods with prednisolone and/or alendronate during the followup because of active disease and osteopenia, respectively. When these 17 subjects were removed from the analysis, the comparison of BMD values in the remaining patients (28 strength-training and 18 control subjects) showed no statistically significant between-group differences at either of the evaluated sites (Table 3).
However, when the group that took prednisolone and/or alendronate (n = 17) was compared with the group that did not (n = 45), there was a significant intergroup difference for BMD at the femoral neck for all 3 time points (P = 0.002–0.006). For BMD of the spine, there was a minor, but not statistically significant, difference between the groups. Both the femoral neck and spine BMD values remained unchanged in both users and nonusers during the followup. At baseline, the mean ± SD duration of RA symptoms in the users was 6.3 ± 4.2 months and the age 53 ± 7 years, compared with 12.0 ± 12.7 months (P not significant) and 48 ± 11 years (P = 0.045) in the nonusers. The users had statistically significantly lower HAQ scores (P < 0.021–0.047) during the followup compared with the nonusers. Further, their DAS28 index correlated negatively with the femoral neck BMD at month 24 (r = −0.38, P < 0.003).
The initial functional capacity, as measured by the HAQ and walking speed, was comparable between the groups at baseline (Table 4). The HAQ scores improved statistically significantly in both groups during the followup period. However, there were statistically significant between-group differences in the HAQ scores in favor of the strength-training group at months 18 and 24. The mean ± SD walking speed increased by 16 ± 17% (P < 0.001) in the strength-training group and by 9 ± 12% (P = 0.025) in the control group (Table 4).
Table 4. Parameters of functional capacity in patients with rheumatoid arthritis at baseline and after 6, 12, 18, and 24 months, by exercise group*
|Parameter||Strength-training group (n = 31)||Control group (n = 31)||Difference between groups (95% CI)|
|HAQ index (0–3 scale)|
| Baseline||0.60 ± 0.53||0.77 ± 0.55||−0.17 (−0.4 to 0.1)|
| 6 months||0.25 ± 0.36||0.47 ± 0.51||−0.22 (0.4 to 0.003)|
| 12 months||0.20 ± 0.31||0.41 ± 0.48||−0.21 (−0.4 to 0.003)|
| 18 months||0.15 ± 0.26||0.39 ± 0.45||−0.24 (−0.4 to −0.006)†|
| 24 months||0.13 ± 0.21||0.35 ± 0.45||−0.22 (−0.4 to −0.004)‡|
|Walking speed (meters/second)|
| Baseline||1.9 ± 0.5||1.9 ± 0.4||0.00 (−0.18 to 0.32)|
| 6 months||2.2 ± 0.6||2.0 ± 0.6||0.20 (−0.006 to 0.51)|
| 12 months||2.2 ± 0.5||2.0 ± 0.6||0.20 (−0.008 to 0.47)|
| 18 months||2.3 ± 0.5||2.1 ± 0.5||0.20 (−0.009 to 0.45)|
| 24 months||2.4 ± 0.5||2.1 ± 0.6||0.30 (−0.10 to 0.47)|
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- PATIENTS AND METHODS
The results of the present study show that even minimally supervised at-home strength training for 24 months led to significant increases in maximum strength and general physical function in patients with early RA, without exacerbating the disease. Despite the substantial training effects on muscle strength, the BMD values remained, as expected, relatively unchanged over the 2-year study period.
In the strength-training group, maximum strength of the muscle groups evaluated increased by 19–59%. The corresponding change in the controls was 1–31%. In fact, the increases in muscle strength in favor of the strength-training group continued throughout the 24-month followup period. However, 1.4–1.5 weekly strength training sessions carried out in this study exceeded the normal daily tension levels of the muscles sufficiently to facilitate muscle performance (the overload principle). Although the exercise adherence in the experimental group was 70–75% of the planned rate, it was at the level achieved in other prospective interventions (24, 34). The present frequency of strength training did not inhibit the motivation of the patients for continuous training and left time and energy for other physical activities as well.
The control subjects were also able to increase their muscle strength. The improvement in muscle strength values in the controls was most probably due to an increase in the intensity of their physical activities, which was facilitated by a decrease in disease activity over time. The production of maximal voluntary muscle force is an unusual event, especially in RA patients, and for this reason, motor learning and improved coordination in strength measurements must be taken into account (35, 36). However, the increases in muscle strength in the control group were significantly inferior to those in the strength-training group, thus demonstrating the advantage of the applied dynamic strength–training regimen.
Osteoporosis is a well known extraarticular complication of RA (37). Although bone remodeling aberrations in RA have not been thoroughly defined, decreased physical activity and high levels of clinical disease activity as well as glucocorticoid treatment have been recognized as the most important contributory factors for the development of osteopenia (38–40). Most of the patients in the present study of early RA had normal BMD values at baseline. Thus, a realistic target for physical training was the maintenance of BMD and the prevention of disease-related bone loss. In addition to aerobic recreational physical activities, strength training consisted of exercises performed mostly in the supine, sitting, or standing positions using an elastic band for resistance. It seems that the “smooth” movements generally recommended for RA patients by, for example, the Arthritis Foundation (41, 42) and applied in the present study were sufficient to maintain, but insufficient to increase, BMD values. Previous studies on biking, swimming, or rowing (43–45) suggest that these typical non–weight-bearing exercises do not generate the necessary ground-reaction forces on the skeleton to increase BMD. Although our exercise modality has not been proven to be beneficial for bone density, it has many other benefits, such as increased muscle strength and walking speed, which in turn, may result in a lower risk of falling and an increase in daily activity levels.
Statistically significantly lower femoral neck BMD was found in the 17 patients who had more active disease compared with the value in the other 45 patients with less active RA. The difference between the groups was present at baseline—before the institution of glucocorticoid treatment—and persisted at months 12 and 24. A minor, not statistically significant, difference in spine BMD was also detected between these groups. On the other hand, during the 24-month followup, the contribution of glucocorticoids to inflammation and of alendronate to bone resorption apparently had a positive influence on these subjects to maintain their BMD at the baseline level by improving their capacity for physical activity. Some studies suggest that patients with clinically active disease receiving steroid therapy lose BMD significantly more rapidly than patients with inactive disease (3, 6). In the present study, the bone loss due to active disease was noted even before the initiation of glucocorticoids, which indicates that RA patients need early and effective treatment with DMARDs.
The progressive loss of function starts to develop early in RA. Inflammation disturbs bodily functions, which leads to restrictions in daily activities, tasks, and behaviors (46–48). In fact, one of the core aims of therapy for RA is the prevention or delay of disability. Dynamic strength training seems to be effective in improving muscle strength and, concomitantly, physical function, as demonstrated in this study by improvements in walking speed and self-reported physical function (HAQ). On the other hand, individually tailored dynamic muscle strength training had no negative effects on disease activity or structural joint damage.
In conclusion, the present study showed that a 24-month dynamic strength–training period results in increases in muscle strength and physical function, but it imposes only minor effects on BMD in the spine and femoral neck. High levels of disease activity, on the other hand, appear to play a central role in the loss of BMD in early RA. To improve long-term outcomes, patients with RA need to be assessed early in the disease course, and individualized therapies that include physical exercise as an integral element should be initiated in most cases.