Effects of Locomotion Training on Bone Mineral Density in Patients with Rheumatoid Arthritis
2024 年 9 巻 論文ID: 20240022
詳細
2024 年 9 巻 論文ID: 20240022
Objectives: This study aimed to evaluate the effects of locomotion training on bone mineral density (BMD) and the factors associated with increased BMD in patients with rheumatoid arthritis (RA).
Methods: We enrolled 85 patients with RA who underwent locomotion training for 6 months after receiving instructions from a physical therapist. We evaluated the BMD of the lumbar spine, total hip, and femoral neck 1 year before baseline (the start of locomotion training) and 1 year after baseline.
Results: The change in BMD from 1 year before baseline (non-exercise period) and 1 year after baseline (exercise period) were 0.1 ± 3.1% and 1.6 ± 3.7% (P=0.007) for the lumbar spine, −0.2 ± 2.4% and 1.0 ± 2.4% (P=0.005) for the total hip, and −0.6 ± 3.9% and 1.8 ± 3.5% (P<0.001) for the femoral neck, respectively. The Health Assessment Questionnaire Disability Index score at baseline was associated with increased BMD at the femoral neck. No factor was associated with increased BMD in the lumbar spine or total hip.
Conclusions: Locomotion training increased the BMD of the lumbar spine, total hip, and femoral neck during the exercise period compared with that during the non-exercise period. The current treatment for RA and osteoporosis accompanied by optional therapy with locomotion training might be effective in increasing BMD in patients with RA.
Rheumatoid arthritis (RA) is an inflammatory disease with a significant concomitant risk of osteoporosis that may be exacerbated by inflammation, receptor activator of nuclear factor kappa beta ligand, use of glucocorticoids, immobility, and low body mass index.1,2,3,4) The effectiveness of pharmacological treatments for osteoporosis in patients with RA has been reported.5,6,7,8,9)
In previous studies, resistance training, walking, and muscle exercise were reported to have positive effects on bone mineral density (BMD).10,11,12,13,14) Exercise has been recommended for postmenopausal women, patients receiving glucocorticoids, and older individuals.15,16,17) In patients with RA, a 2-year exercise program (range of motion and stretching twice a week) resulted in maintenance of BMD of the lumbar spine and femoral neck at 5 years.18) In another study of RA patients, a group that completed a 2-year program of high-intensity exercises with weight-bearing and impact-loading exercises showed a change in BMD of the total hip of −1.1%, whereas those receiving usual care showed a BMD change of −1.9%.19)
The existing evidence for the effectiveness of exercise in maintaining BMD is mostly based on the general population, whereas information on the effectiveness of low-intensity exercise in patients with RA is lacking. This study retrospectively evaluated the effects of locomotion training, a low-intensity exercise, on BMD in patients with RA.
We enrolled 103 patients with RA who underwent locomotion training for 6 months in our previous study.20) Overall, 85 patients who underwent evaluation of BMD of the lumbar spine, total hip, and femoral neck using dual-energy X-ray absorptiometry (Prodigy system; GE Healthcare, Madison, WI, USA) at the start of locomotion training (baseline), 1 year before baseline, and 1 year after baseline were included in this study. BMD of the lumbar spine was measured from L1 to L4. Of the 18 excluded patients, 15 were excluded because of a lack of BMD data, 1 was excluded because the patient switched to osteoporosis treatment during the 2-year study period, and 2 patients were excluded after switching to RA treatment following a phase change in accordance with the Japanese College of Rheumatology clinical practice guidelines.21)
This study was conducted in accordance with the principles of the Declaration of Helsinki, and written informed consent was obtained from all patients. This study was approved by the Ethics Committee for Clinical Research of Kamagaya General Hospital (approval number: TGE01619-064).
Locomotion TrainingBased on guidelines of the Japanese Orthopedic Association, the following exercises were performed at home for 6 months as locomotion training: single-leg standing with eyes open (1 min for each leg × three sets per day), squatting (five times × three sets per day), heel raises (ten times × three sets per day), and forward lunges (ten times × three sets per day).22) To prevent falls, the participants performed the exercises while holding a solid support structure. Training records were self-reported by participants in a rehabilitation notebook and were monitored regularly.
Statistical AnalysisComparison of percentage changes (Δ) in BMD of the lumbar spine, total hip, and femoral neck from 1 year before baseline (non-exercise period) and 1 year after baseline (exercise period) were assessed using the paired t-test. Increased BMD was defined as a greater increase in ΔBMD during the exercise period than during the non-exercise period. Factors associated with increased BMD were evaluated between patients with and without increased BMD using univariate and multivariate logistic regression analysis. Multivariate logistic regression analysis was performed using the variables identified in the univariate analysis with P<0.1. Statistical significance was set at P<0.05. All analyses were performed using the R Statistical Package, version 3.3.2 (http://www.r-project.org/).
A total of 85 patients were enrolled in this study. The rate of patient compliance was 78.4% for a training adherence rate >80%. The demographic and clinical characteristics of the patients are summarized in Table 1. In patients receiving osteoporosis treatment, active vitamin D was used alone in 2 patients and in combination with other drugs in 20 patients.
| Variable | n=85 |
| Age, years | 68.5 (±11.6) |
| Sex, female | 78 (91.8%) |
| Disease duration, years | 13.8 (±9.6) |
| Body mass index, kg/m2 | 22.7 (±3.3) |
| Anti-CCP Ab positive | 64 (75.3%) |
| Current osteoporosis treatment | 34 (40.0%) |
| Denosumab | 18 (21.2%) |
| Bisphosphonate | 12 (14.1%) |
| SERM | 2 (2.4%) |
| Active vitamin D (alone) | 2 (2.4%) |
| bDMARD or tsDMARD use | 46 (54.1%) |
| Methotrexate use | 58 (68.2%) |
| Glucocorticoid use | 16 (18.8%) |
| CDAI | 4.5 (±3.8) |
| HAQ-DI | 0.2 (±0.4) |
| BMD T-score | |
| Lumbar spine | −0.6 (±1.4) |
| Total hip | −1.3 (±0.9) |
| Femoral neck | −1.8 (±1.0) |
Data shown as mean ± standard deviation or number (percentage).
Anti-CCP Ab, anti-cyclic citrullinated peptide antibody; SERM, selective estrogen receptor modulator; bDMARD, biological disease-modifying antirheumatic drug; tsDMARD, targeted synthetic disease-modifying antirheumatic drug; CDAI, Clinical Disease Activity Index.
The ΔBMD values for the non-exercise period and the exercise period were 0.1 ± 3.1% and 1.6 ± 3.7% (P=0.007) for the lumbar spine, −0.2 ± 2.4% and 1.0± 2.4% (P=0.005) for the total hip, and −0.6 ± 3.9% and 1.8 ± 3.5% (P<0.001) for the femoral neck, respectively (Fig. 1). The proportions of patients who showed increased BMD at the lumbar spine, total hip, and femoral neck were 55.3%, 60.0%, and 60.0%, respectively. The factor most associated with increased BMD at the femoral neck was the Health Assessment Questionnaire Disability Index (HAQ-DI) score at baseline (odds ratio, 0.304; 95% confidence interval, 0.073–0.927) (Table 2). No factor was associated with increased BMD in the lumbar spine or total hip.
Percentage changes in the bone mineral densities of the lumbar spine, total hip, and femoral neck for the non-exercise period (the year before baseline) and the exercise period (the year after baseline). Non-exercise period vs. exercise period: **P<0.01.
| Variable | Increased BMD (+) (n=51) | Increased BMD (−) (n=34) | P value (univariate) | P value (multivariate) |
| Age, years | 71 [62.5, 77.5] | 70.5 (61.3, 74.8) | 0.608 | |
| Female | 46 (90.2%) | 32 (94.1) | 0.697 | |
| Body mass index, kg/m2 | 21.9 [19.9, 23.9] | 23.7 (22.1, 25.3) | 0.041 | 0.074 |
| Duration of RA, years | 12 [7, 18.5] | 12 (7, 17) | 0.469 | |
| Anti-CCP Ab (+) | 38 (74.5%) | 26 (76.4) | 1.000 | |
| Glucocorticoid use | 10 (19.6%) | 6 (17.6) | 1.000 | |
| Osteoporosis treatment | 20 (39.2%) | 14 (41.8) | 1.000 | |
| CDAI at baseline | 2.8 [1.4, 6.5] | 4.7 (1.8, 8.3) | 0.190 | |
| HAQ-DI at baseline | 0 [0, 0.125] | 0.125 (0, 0.5) | 0.028 | 0.013 |
Data given as median [interquartile range] or number (percentage).
This study showed that locomotion training in patients with RA significantly increased the BMD of the lumbar spine, total hip, and femoral neck during the exercise period when compared with the trends of declining BMD data observed during the non-exercise period.23,24) In patients with RA, the reductions in total hip BMD for those aged 40–49, 50–59, and 60–70 years were 3.7%, 6.0%, and 8.5%, respectively, whereas the reductions in the femoral neck BMD for those aged 50–59 and 60–70 years were 4.2% and 5.0%, respectively.23) Our results showed that BMD at all sites did not decrease as much as that observed before locomotion training.
The effect of exercise on BMD is influenced by exercise intensity. In a study of patients with osteoporosis, the intervention group (high-intensity resistance exercise, maintaining intensity of 80%–85%, one-repetition maximum) showed significantly increased BMD in the lumbar spine (+2.9%) compared to that of the control group (−1.2%) and significantly increased BMD in the femoral neck (+0.3% vs. −1.9%).17) In another study of healthy volunteers, the BMD of the femoral neck increased more in the intervention group (high-intensity exercise with aerobic threshold; +1.6%) than in the control group (+0.6%).25) In studies on low-intensity exercise, walking more than 8000 steps per day for more than 4 days a week for 12 months was significantly associated with an increased BMD in the lumbar spine relative to the control group (+1.7% vs. −1.9%).14) A 6-week exercise program that included squats, front lunges, side lunges, calf raises, and toe raises improved pelvic BMD and knee extensor strength compared to the control group BMD, although the BMD of the spine was not increased in postmenopausal women.26) In the present study, low-intensity exercise, such as locomotion training for over 6 months, may have contributed to increased BMD of the lumbar spine, total hip, and femoral neck.
In this study, the HAQ-DI score at baseline was associated with increased BMD of the femoral neck. Similarly, in previous reports, the HAQ-DI score was associated with the lumbar spine and trochanter in the hips of patients with early RA.27) In patients with RA, BMD at the femoral neck but not at the lumbar spine was associated with quadriceps strength.28) Locomotion training primarily involves lower extremity exercises. We believe that patients with low HAQ-DI scores had physical functions conducive to exercise, which led to increased BMD at the femoral neck.
This study has some limitations. First, the effects of osteoporosis and RA treatments 1 year before and 1 year after baseline were not fully elucidated. We believe that any effects of these altered treatments on the study results were minimal, because the same treatments for osteoporosis and RA were consistently maintained in the patients. Second, the period of locomotion training in this study was only 6 months, and the subsequent 6 months was not subject to any specific guidance on exercise continuity. Third, although the same patients were evaluated for BMD before and after locomotion training, a control group was not included. Despite these limitations, we believe that the results of this study are meaningful. In the future, a prospective study of patients with the same background of osteoporosis and RA treatments will be necessary to confirm the effects of locomotion training.
This study is the first to demonstrate that locomotion training increased the BMD of the lumbar spine, total hip, and femoral neck when compared with BMD data for the non-exercise period. The current treatment for RA and osteoporosis accompanied by optional locomotion training might be effective in increasing BMD in patients with RA who cannot perform high-intensity training.
The authors thank the medical staff of the clinical research center in our institutions for their assistance.
T. Mochizuki received honoraria for lectures from AbbVie, Astellas, Bristol-Myers, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, Janssen, Mochida, and Pfizer. K. Yano received honoraria for lectures from AbbVie, Astellas, Ayumi, Bristol-Meyers, Eisai, Hisamitsu, Mochida, and Takeda. K. Ikari received honoraria for lectures from AbbVie, Astellas, Bristol-Myers, Chugai, Eisai, Eli Lilly, Janssen, Takeda, Tanabe-Mitsubishi, and UCB. The remaining author declares no conflict of interest. The sponsors were not involved in the study design; collection, analysis, and interpretation of data; writing of the article; and/or the decision to submit the results for publication.
