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03. iwamoto

J Musculoskelet Neuronal Interact 2012; 12(3):136-143 Original Article
Whole body vibration exercise improves body balance and
walking velocity in postmenopausal osteoporotic women
treated with alendronate: Galileo and Alendronate
Intervention Trail (GAIT)
J. Iwamoto1,2, Y. Sato3, T. Takeda1, H. Matsumoto1
1Institute for Integrated Sports Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan; 2Department of Orthopaedic Surgery, Keiyu Orthopaedic Hospital, Gunma, Japan; 3Department of Neurology, Mitate Hospital, Tagawa, Fukuoka, Japan Abstract
A randomized controlled trial was conducted to determine the effect of 6 months of whole body vibration (WBV) exercise on physical function in postmenopausal osteoporotic women treated with alendronate. Fifty-two ambulatory postmenopausal womenwith osteoporosis (mean age: 74.2 years, range: 51-91 years) were randomly divided into two groups: an exercise group and acontrol group. A four-minute WBV exercise was performed two days per week only in the exercise group. No exercise was per-formed in the control group. All the women were treated with alendronate. After 6 months of the WBV exercise, the indices forflexibility, body balance, and walking velocity were significantly improved in the exercise group compared with the control group.
The exercise was safe and well tolerated. The reductions in serum alkaline phosphatase and urinary cross-linked N-terminal telopep-tides of type I collagen during the 6-month period were comparable between the two groups. The present study showed the benefitand safety of WBV exercise for improving physical function in postmenopausal osteoporotic women treated with alendronate.
Keywords: Whole Body Vibration Exercise, Flexibility, Body Balance, Walking Velocity, Osteoporosis
Introduction
clinically important and statistically significant reductions invertebral, non-vertebral, hip, and wrist fractures for secondary Osteoporosis most commonly affects postmenopausal prevention (gold-level evidence)3. RCTs in postmenopausal women, placing them at a significant risk of fractures. Alen- Japanese women with osteoporosis also revealed that short- dronate (ALN) is widely used for the treatment of post- term (1-3 years) ALN treatment suppressed bone turnover, in- menopausal osteoporosis. The Fracture Intervention Trial creased the bone mineral density (BMD), and reduced the (FIT) demonstrated the efficacy of ALN against vertebral, non- incidence of vertebral fractures4-7. ALN is regarded as a first- vertebral, hip, and wrist fractures in postmenopausal women line drug for the treatment of osteoporosis in Japan.
with osteoporosis1,2. Furthermore, a recent systematic review Because most nonvertebral osteoporotic fractures occur as analyzing 11 randomized controlled trials (RCTs) representing a result of falls, physicians must plan strategies for preventing 12,068 women confirmed that ALN treatment resulted in both falls even in patients treated with potent anti-fracture medi-cines such as ALN. Clinically, the impairment of musclestrength and muscle power of the lower extremities,balance/postural control, and walking ability have been recog- The authors have no conflict of interest.
nized as important risk factors for falls8. However, musclestrength should be distinguished from muscle power; muscle Corresponding author: Jun Iwamoto, Institute for Integrated Sports Medicine,Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo strength is defined as the maximal force that a muscle can pro- duce against a given resistance, while muscle power is defined as the product of force and speed8,9. The former is related tobone strength, whereas the latter is related to falling8-11. Thus, Edited by: J. RittwegerAccepted 5 June 2012 the improvement of muscle power, rather than muscle strength, J. Iwamoto et al.: Vibration exercise and physical function would appear to be important for the prevention of falls.
treatment for osteoporosis were a history of reflux esophagitis, Exercise is generally accepted to be effective for the pre- gastric or duodenal ulcer, gastrectomy, renal failure, or bone dis- vention of falls in the elderly. A meta-analysis study has eases including cancer-induced bone loss because of aromatase demonstrated that exercise is effective for lowering the risk of inhibitors, primary hyperparathyroidism, hyperthyroidism, falls in the elderly and that the consequent reduction in the in- Cushing syndrome, multiple myeloma, Paget’s disease of the cidence of fall-related injuries reduces health care costs12. Pre- bone, rheumatoid arthritis, or osteogenesis imperfecta. The viously, we reported that an exercise program aimed at physical activity level at baseline was considered to be compar- improving flexibility, body balance, muscle power, and walk- atively low in all the participants because none of them had been ing ability reduced the incidence of falls in the elderly13.
laborers or had been engaged in any regular or leisure-time Recently, whole-body vibration (WBV) exercise has been sporting activities. Age, height, body weight, body mass index, developed as a new modality in the field of physiotherapy and history of falls in the past 3 months, fractures after the age of 50 has been used to improve physical function in the elderly14-16.
years, and physical function were assessed at the start of the trial.
Several available systematic reviews and meta-analyses have Blood and urine samples were also obtained in the morning for discussed the effectiveness of WBV exercise17-20. Rogan et al.17 concluded that vertical sinusoidal WBV revealed only small The subjects (mean age: 74.2 years, range: 51-91 years) effects on static and dynamic balance, while side-alternating were randomly divided into two groups: an exercise group and WBV showed small to moderate improvements in the same a control group (n=26 in each group). For the exercise group, balance requirements in elderly subjects. Slatkovska et al.18 the WBV exercise was supervised and performed in the clinics clarified that WBV exercise resulted in small improvements or hospitals two days per week. Consequently, the compliance in BMD in postmenopausal women and children and adoles- with the exercises was 100%. For the control group, no exer- cents, but not in young adults. Lau et al.19 found that WBV ex- cise was undertaken. All the subjects were treated with ALN ercise was beneficial for enhancing leg muscle strength among (35 mg weekly). The doses of 5 mg daily and 35 mg weekly older adults but had no overall treatment effect on BMD in are the doses used in Japan for the treatment of post- older women. However, Conway et al.20 reported that WBV menopausal women with osteoporosis and have been recog- exercise acted to degrade the majority of goal-related activi- nized as being safe and effective4-7. The subjects did not ties, especially those with high demands on visual perception receive either elementary calcium or natural vitamin D sup- plementation, although they were instructed with the aid of Although there is a lack of long-term studies that have used brochures to achieve daily intakes of 800 mg of calcium and an adequate number of elderly subjects with robust methodolog- 800 IU of vitamin D through food consumption. The period of ical structures (e.g., inclusion of placebo and control groups), this study was 6 months. Physical function and the incidence the effects of WBV exercise seem to be modest. To our knowl- of falls and fall-related fractures were assessed 6 months after edge, the effect of WBV exercise on physical function in post- the start of the trial. At the same time, blood and urine samples menopausal osteoporotic women has rarely been investigated were also obtained in the morning for biochemical analysis.
using RCTs. Thus, an RCT was conducted to determine the ef- In particular, information regarding falls and fall-related frac- fect of 6 months of WBV exercise on physical function in post- tures was obtained every week by directly asking the partici- menopausal osteoporotic women treated with ALN.
pants. Informed consent was obtained from all the participants.
The protocol was approved by the Ethical Committee of Keiyu Subjects and Methods
Blood and urinary biochemical tests Fifty-two ambulatory postmenopausal women with osteo- Serum and urine samples were obtained from each patient porosis who visited the Department of Orthopaedic Surgery of and the following biochemical analyses were performed. The two hospitals and nine Orthopaedic Clinics in Japan during a serum calcium and phosphorus levels were measured using one-year period between October 2009 and September 2010 standard laboratory techniques. The serum alkaline phos- were recruited to our trial. The inclusion criteria were an age of phatase (ALP) level was measured using the JSCC reference more than 50 years, a fully ambulatory status, the diagnosis of method. The urinary cross-linked N-terminal telopeptides of postmenopausal osteoporosis according to the Japanese diag- type I collagen (NTX) level was measured using an enzyme- nostic criteria21,22, an osteoporosis treatment-naïve status, and the ability to measure the physical function parameters described below. The exclusion criteria for the exercise were severe gaitdisturbance requiring some form of walking aid, a severe Indices for flexibility (finger-floor distance [FFD] with the rounded back because of osteoporotic vertebral fractures, clini- body flexed in the anterior, right, and left directions), body bal- cal fractures because of osteoporosis, sciatica because of lumbar ance (tandem standing time, unipedal standing time, and 3-m spinal canal stenosis, symptomatic osteoarthritis of the knee or timed up & go [TUG]), muscle power (3-m TUG and chair- hip, rheumatoid arthritis, acute phases of other diseases, and se- rising time [5 times]), and walking ability (10-m walking time vere cardiovascular disease. The exclusion criteria for ALN and step number) were assessed. TUG reflects both dynamic J. Iwamoto et al.: Vibration exercise and physical function body balance and muscle power. Apart from muscle strength, Exercise
muscle power can be evaluated without using any machines by measuring the chair-rising time and TUG. FFD in the lateral flexions, tandem standing time, and unipedal standing time were determined by obtaining the mean values for the right Whole body vibration (WBV) exercise WBV exercise was performed using a Galileo machine (G- Data are expressed as means±SD. An unpaired t-test was used to 900; Novotec, Pforzheim, Germany). The Galileo machine is a compare anthropometry data between the two groups. The Fisher unique device for applying whole-body vibration/oscillatory exact test was used to compare the percentages of fallers in the past muscle stimulation. The subject stands with bent knees and hips 3 months and patients with prior clinical fractures between the twogroups. NS: not significant. on a rocking platform with a sagittal axle, which alternatelythrusts the right and left legs upwards and downwards, therebypromoting the lengthening of the extensor muscles of the lower Table 1. Baseline anthropometry of study subjects.
extremities. The reaction of the neuromuscular system is a chainof rapid muscle contractions. This type of training provides re-flex muscle stimulation with no serious adverse events. EachWBV exercise session was set at a frequency of 20 Hz and a Exercise
duration of 4 minutes. This frequency was thought to be com-fortable and safe for postmenopausal women with osteoporosis.
An intention-to-treat (ITT) analysis was performed except for the comparison of the percentage changes in parameters Data are expressed as means±SD. An unpaired t-test was used to between the two groups. The percentage changes in parameters compare biochemical markers between the two groups. Normal were calculated using only the data of participants who com- ranges of serum calcium, phosphorus, and ALP were 8.4-10.2 mg/dL, pleted the 6 months of trial and a per-protocol analysis was 2.5-4.5 mg/dL, and 100-340 IU/L. Standard range of urinary NTX adopted. Data were expressed as the means ± standard devia- was 9.3-54.3 nM BCE/mM Cr, and cut-off values of BMD loss and tion (SD). An unpaired t-test was used to compare baseline an- vertebral fracture risk were 35.3 and 54.3 nM BCE/mM Cr, respec- thropometry, biochemical markers and physical function tively.ALP: alkaline phosphatase, NTX: cross-linked N-terminal parameters at baseline and after 6 months of treatment, and telopeptides of type I collagen, BCE: bone collagen equivalent, Cr:creatinine, NS: not significant. percentage changes in assessed parameters between the twogroups. A one-way analysis of variance (ANOVA) with re-peated measurements was used to analyze the longitudinal Table 2. Baseline biochemical markers.
changes in physical function parameters within a group. TheFisher’s exact test was used to compare the percentages of fall-ers in the past 3 months and patients with prior clinical frac-tures and the incidence of falls and fall-related fractures nificant differences in any other baseline characteristics in- between the two groups. All statistical analyses were per- cluding height, body weight, or body mass index. There were formed using the Stat View J-5.0 program (SAS Institute, Cary, 6 fallers (23.1%) in the exercise group and 7 fallers (26.9%) NC, USA). The significance level was set at P<0.05 for all the in the control group in the past 3 months. There were 4 patients (15.4%) with a history of clinical fractures after 50 years ofage in the exercise group (vertebral fracture in 2 patients and distal radius fracture in 2 patients) and 5 patients (19.2%) with Baseline anthropometry, biochemical markers, and physical a history of clinical fractures after 50 years of age in the control group (vertebral fracture in 1 patient, distal radius fracture in Table 1 shows the baseline anthropometry of the study sub- 2 patients, proximal humerus fracture in 1 patient, and rib frac- jects. The mean age did not differ significantly between the ture in 1 patient). No significant difference in the percentage two groups (72.4 years in the exercise group and 76.0 years in of subjects who had experienced falls in the past 3 months and the control group). The years since menopause were ≥10 years the percentage of subjects with a history of clinical fractures for 22 women, 5-10 years for 2 women, 1-5 years for 1 woman, and unknown for 1 woman in the exercise group, and Table 2 shows the baseline biochemical markers of the study ≥10 years for 23 women, 5-10 years for 2 women, and 1-5 subjects. No significant differences in any of baseline biochemical years for one woman in the control group. There were no sig- marker levels including serum calcium, phosphorus, ALP, and J. Iwamoto et al.: Vibration exercise and physical function Exercise
Exercise
Data are expressed as means±SD. An unpaired t-test was used to com- pare physical function Paremeters between the two groups. FFD: finger floor distance, NS: not significant. A one-way ANOVA with repeated measurements was used to analyze Table 3. Baseline physical function. (Flexibility, body balance, mus-
the longitudinal changes in biochemical markers and physical func- cle power, and walking ability indices).
tion parameters within a group.ANOVA: analysis of variance, ALP:alkaline phosphatase, NTX: cross-linked N-terminal telopeptides oftype I collagen, FFD: finger floor distance, NS: not significant. urinary NTX were seen between the two groups. The mean serum Table 4. One-way ANOVA with repeated measurements.
calcium, phosphorus, and ALP levels were within the normalranges in both groups. The mean urinary NTX levels were higherthan the cut-off value for BMD loss (35.4 nM BCE/mM Cr)23,24.
Table 3 shows the baseline physical function of the study subjects. No significant differences in any of the baseline phys- Exercise
ical function indices for flexibility (FFD in the anterior and lateral flexions), body balance (unipedal standing time, tandem standing time, and TUG), muscle power (TUG and chair rising time), or walking ability (10-m walking time and step length) Data are expressed as means±SD. The unpaired t-test was used to comparepercentage changes in biochemical markers between the two groups. ALP: Number of subjects who completed the 6 months of trial alkaline phosphatase, NTX: cross-linked N-terminal telopeptides of type I All the participants in the exercise group completed the 6 months of trial. In the control group, however, 3 participantsdropped out of the trial because of non-compliance, 1 participant Table 5. Percentage changes in biochemical markers.
withdrew because of canker sores caused by ALN treatment, 1participant withdrew because of the need for a extraction of atooth (fear of osteonecrosis of the jaw), and 1 participant with-drew because of the occurrence of a non-traumatic clinical ver-tebral fracture during the 6-month study period.
Exercise
The serum calcium and phosphorus levels did not change significantly, but the serum ALP and urinary NTX levels de- creased significantly in both groups (Tables 4 and 5). Table 5 shows the percentage changes in the biochemical markers. No significant differences in the percentage changes in the serum calcium, phosphorus, ALP, and urinary NTX levels were ob- Data are expressed as means±SD. An unpaired t-test was used to com- served between the two groups. The mean reduction in the pare percentage changesin physical function parameters between the serum ALP level was 21.7% in the exercise group and 17.5% two groups. FFD: finger floor distance, NS: not significant. in the control group, while the mean reductions in the urinaryNTX level were 41.8% and 40.0%, respectively.
Table 6. Percentage changes in physical function parameters.
Changes in physical function parameters The FFD for the lateral flexions, the 10-m walking time, and the chair rising time decreased significantly and the tan- J. Iwamoto et al.: Vibration exercise and physical function dem standing time increased significantly in the exercise exercise group and 17.5% in the control group, and the urinary group, whereas none of the indices for flexibility, walking abil- NTX levels were decreased by 40.0% and 41.8%, respectively.
ity, body balance, or muscle power walking ability improved Our clinical practice-based studies showed that the reduction significantly in the control group (Tables 4 and 6). Table 6 rates in urinary NTX and the serum ALP levels after ALN shows the percentage changes in the physical function param- treatment were 40.2-43.6% at 3 months and 17.1-19.0% at 6 eters. The percentage changes in the FFD for the lateral flex- months, respectively25,26. The discrepancy between our present ions, the unipedal standing time, the tandem standing time, and and previous studies and strictly conducted RCTs regarding the 10-m walking time were significantly greater in the exer- the reduction in the serum total ALP levels, which are affected cise group than in the control group, but no significant differ- by bone, intestine, and liver diseases, may be attributable to ences in the percentage changes in the FFD for the anterior the characteristics of the study subjects. The exclusion criteria flexion, the TUG, the chair-rising time, or the 10-m walking in the present study were not as strict as those used for strictly step number were observed between the two groups. In par- conducted RCTs; therefore, more frail patients might have ticular, the unipedal standing time and the tandem standing time were dramatically increased in the exercise group (mean The similar reductions in the serum ALP and urinary NTX increase rates: 159.9% and 150.0%, respectively). levels after 6 months of ALN treatment in the exercise andcontrol groups suggest no significant effect of WBV exercise Incidence of falls and fall-related fractures on bone turnover. Our previous study showed that WBV exer- Three participants in the control group and one participant cise and ALN did not have any additive effects on the lumbar in the exercise group experienced one fall each during the 6- spine BMD and the urinary NTX and serum ALP levels in month intervention period. The incidence of falls during the postmenopausal women with osteoporosis27. Chilibeck et al.28 study period did not differ significantly between the two reported that etidronate increased the lumbar spine BMD and groups (11.5% in the control group vs. 3.8% in the exercise strength training resulted in greater increases in the muscular group). The four above-mentioned falls resulted in bruises or strength and lean tissue mass and greater loss of fat mass in sprains of the upper extremities, requiring no intensive treat- postmenopausal women, but that there was no interaction be- ments and healing within several days. There were no fall-re- tween exercise and etidronate. Experimental studies using lated fractures reported in either group.
ovariectomized rats (a model of postmenopausal osteoporosis)examined the effects of bisphosphonates and running exercise on bone mass and strength. Lespessailles et al.29 reported thatzoledronic acid and running exercise did not produce any ad- During the study period, no serious adverse events, such as ditive effects on bone mass and strength, whereas Fuchs et al.30 severe fall-related injuries or adverse cardiovascular effects, showed that combination of running exercise and ALN was were observed in the exercise group.
more beneficial in preventing declines in bone mass andstrength than either intervention alone. Thus, it is certain that Discussion
bisphosphonates increase bone mass or strength while exer-cises improve physical function and body composition. How- Muscle power of the lower extremities, balance/postural con- ever, it remains uncertain whether simultaneous application of trol, and walking ability are key physical function parameters bisphosphonates and exercises produces synergetic or additive for the prevention of falls. An RCT was conducted to determine effects on bone parameters. The effect of WBV exercise on the effect of 6 months of WBV exercise on the physical function BMD and bone turnover markers could possibly be masked parameters in postmenopausal osteoporotic women treated with by the strong influence of bisphosphonates.
ALN. The focus of discussion was: 1) whether ALN would suc- We administered WBV exercise to the subjects two days per cessfully reduce bone turnover markers in postmenopausal week at a frequency of 20 Hz and for a duration of 4 minutes.
women with osteoporosis; 2) whether 6 months of WBV exer- The intensity and frequency of the exercise program were con- cise (4 minutes per day, 2 days per week) would be safe and sidered to be reasonable for postmenopausal osteoporotic would improve physical function parameters in postmenopausal women (mean age, 74.2 years), enabling the exercise to be osteoporotic women treated with ALN; and 3) whether the im- continued without any fatigue or difficulty for 6 months. WBV provement in the physical function parameters, if any, would be exercise was not only effective for improving physical func- useful for preventing falls and fractures.
tion, i.e., the indices for flexibility, body balance, and walking An RCT (Phase III study) showed that ALN (5 mg daily or velocity, but also was well tolerated. No serious adverse 35 mg weekly) similarly reduced urinary NTX levels (approx- events, such as fall-related injuries or adverse cardiovascular imately -45% at 6 months) in Japanese patients with involu- effects, were observed in any of the subjects during the exer- tional osteoporosis6. Another RCT (Phase III study) showed cise program, suggesting the safety of WBV exercise.
that ALN (5 mg daily) reduced serum ALP levels (about -30% WBV exercise significantly improved the FFD for the lat- at 6 months) in Japanese patients with osteoporosis7. In the eral flexions in terms of lateral flexibility. This outcome may present study, after 6 months of treatment with ALN (35 mg have contributed to the prevention of falls resulting from stag- weekly), the serum ALP levels were reduced by 21.7% in the gers. Our previous study showed that WBV exercise was use- J. Iwamoto et al.: Vibration exercise and physical function ful for reducing chronic back pain, probably by relaxing the The limitations of the present study should also be dis- back muscles in postmenopausal osteoporotic women treated cussed. First, the study period was short and the sample size with ALN27. The relaxation of the back muscles caused by the was small, as discussed above. Second, we did not evaluate WBV exercise, in which the right and left legs are thrust up- vitamin D insufficiency/deficiency by measuring the serum wards and downwards, might have partly contributed to the 25(OH)D levels and we did not provide calcium/vitamin D improvement in lateral flexibility. However, the WBV exercise supplements to the subjects. In Japan, vitamin D supplemen- did not significantly improve the FFD for anterior flexion. An- tation is uncommon and the measurement of serum 25(OH)D terior flexibility is affected by the tightness of the hamstrings.
levels is not covered by health insurance. Because low serum Because the WBV exercise promotes lengthening predomi- levels of 25(OH)D are correlated with an increased risk of falls nantly of the extensor muscles of the lower extremities, tight- and vitamin D supplementation reduces the incidence of falls ness of the hamstrings might have been less relaxed by the in the elderly33-35, evaluating the vitamin D status is important.
exercise, resulting in no improvement in anterior flexibility.
Third, it is important to evaluate muscle mass as well as mus- The WBV exercise resulted in a significant and dramatic cle function in elderly people because sarcopenia is an increas- improvement in the unipedal standing time and the tandem ing problem in the aging society36,37. Sarcopenia is an standing time in terms of static body balance. This outcome age-related condition defined by the combined presence of re- may have contributed to the prevention of falls, since the duced muscle mass, that is, a T score of muscle mass (cor- unipedal standing balance exercise performed with open eyes rected for height, body weight, or fat mass) of 2SDs or less, reportedly reduced the cumulative number of falls among and reduced muscle function measured as gait speed less than Japanese elderly individuals (mean age: 81.6 years)31.
0.8 or 1 m/sec38. Fjeldstad et al.39 reported that resistance train- Although the WBV exercise significantly improved the 10- ing alone and with WBV exercise resulted in positive body meter walking time in terms of walking velocity, it did not sig- composition changes by increasing lean mass in older women, nificantly improve the chair-rising time or the TUG in terms but that only the combination of resistance training and WBV of muscle power and dynamic body balance. Chair-rising/sit- exercise was effective for decreasing percent body fat. von ting and the walking velocity may be affected by type II mus- Stengel et al.40 reported that WBV exercise embedded in a cle fiber function, in terms of the speed of muscle contraction.
multipurpose exercise program showed minor additive effects A chain of rapid muscle contractions during WBV exercise on body composition and neuromuscular performance in older may be sufficient to influence the type II muscle fiber function, women. Thus, it would be of importance to examine the effect resulting in the improvement of walking velocity. However, of WBV exercise on body composition as well as muscle and the length of each muscle contraction during the WBV exer- fat mass in postmenopausal osteoporotic women. Further stud- cise is substantially smaller than that observed during chair- ies are needed to resolve these limitations.
rising/sitting. Thus, squatting on the rocking platform of the In conclusion, an RCT was conducted to determine the ef- Galileo machine during the WBV exercise would be required fect of 6 months of WBV exercise on physical function in post- to improve the chair-rising time and the TUG.
menopausal osteoporotic women treated with ALN. The 6 Despite a favorable improvement in physical function, in- months of WBV exercise (4 minutes per day, 2 days per week) cluding gait and balance32, the incidence of falls was not sig- was well tolerated and improved the indices for flexibility and nificantly reduced by the WBV exercise (11.5% in the control body balance as well as the walking velocity. The present study group vs. 3.8% in the exercise group), probably because of an showed the benefit and safety of WBV exercise for improving inadequate statistical power. The study period was 6 months, physical function in postmenopausal osteoporotic women and the sample size was 52 (n=26 in each group). Furthermore, the SDs of some physical function parameters were high be-cause the groups are heterogeneous, especially in age which Doctors who participated in the study certainly influences muscle mass. Long-term exercise is The following doctors participated in the study; Hiroyuki Suzuki (De- needed to reduce the life-time risk of falls and fall-related in- partment of Orthopeadic Surgery, Kawakita General Hospital, Tokyo), juries in postmenopausal women with osteoporosis. However, Hisashi Hirabayashi (Department of Orthopeadic Surgery, Tokyo Adventist because our exercise program proved easy for our subjects Hospital, Tokyo), Takami Kumakubo (Kumakubo Orthopaedic Clinic, (mean age: 74.2 years) to continue without any difficulty, we Tokyo), Yoshito Kikuchi (Kikuchi Orthopeadic Clinic, Tokyo), Yu Miyazaki believe that it could be continued under the instruction of gen- (Miyazaki Orthopeadic Clinic, Tokyo), Kazunori Hayashi (Nakasugidori Orthopaedic Clinic, Tokyo), Akira Kawashima (Kawashima Orthopeadic The present study had several strengths. First, the RCT was Clinic, Chiba), Michimasa Ui (Ui Orthopeadic Clinic, Chiba), Iwao Ibata strictly performed not by exercise-related experts, but mainly by (Ibata Orthopaedic Clinic, Chiba), Hiroyuki Okada (Fujinoki Or- general practitioners (compliance with the exercises: 100%) thopaedics and Internal Medicine Clinic, Gunma), and Tadahiko Aibara without the need for any special machines to evaluate physical (Aibara Orthopeadic Clinic, Ehime). function. Second, the exercise program was safe and well toler- ated. These strengths suggest the clinical usefulness and conven-ience of the exercise program for improving physical function in We would like to thank Mr. Toshihiro Yamaguchi (Tokyo Branch of MSD postmenopausal osteoporotic women treated with ALN.
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