ORIGINAL PAPER
Nagoya J. Med. Sci. 85. 275–288, 2023
doi:10.18999/nagjms.85.2.275

Interventions to improve locomotive syndrome: a systematic
review and meta-analysis of randomized controlled trials
Yoshitaka Iwamoto1,2, Takeshi Imura3, Makoto Takahashi1,2 and Ryo Tanaka4
1

Department of Neuromechanics, Graduate School of Biomedical and Health Sciences, Hiroshima University,
Hiroshima, Japan
2
Center for Advanced Practice and Research of Rehabilitation, Graduate School of Biomedical and Health
Sciences, Hiroshima University, Hiroshima, Japan3
Department of Rehabilitation, Faculty of Health Sciences, Hiroshima Cosmopolitan University, Hiroshima,Japan
4
Graduate School of Humanities and Social Sciences, Hiroshima University, Hiroshima, Japan

ABSTRACT
Locomotive syndrome is a musculoskeletal disease of individuals who are highly likely to requirenursing care. There is no systematic review that systematically evaluates and consolidates the findings of
randomized controlled trials, although the number of randomized controlled trials considering the intervention effect on locomotive syndrome has been increasing with the spread of the concept. Therefore, thissystematic review of randomized controlled trials is aimed at consolidating evidence regarding effective
interventions to improve locomotive syndrome. We searched seven databases electronically. Studies were
included in this systematic review if the following were met: (1) the articles were randomized controlled
trials written in English or Japanese in a peer-reviewed journal, and (2) the clinical evaluation of thelocomotive syndrome should include at least one of the following: the stand-up test, two-step test, and25-question Geriatric Locomotive Function Scale. This systematic review included 10 studies. Several
individual papers showed that the intervention group significantly improved the outcome measure for the
diagnosis of locomotive syndrome compared with the control group. Only oral glucosamine intake provided
sufficient information to conduct a meta-analysis, but the results were not statistically significant. Thissystematic review and meta-analysis did not provide strong evidence for specific interventions in improving
locomotive syndrome, although individual randomized controlled trials have shown that oral intake of
glucosamine, electrical stimulation, and exercise could improve locomotive syndrome. We hope that morehigh-quality randomized controlled exercise intervention trials aimed at improving locomotive syndrome,
which is a musculoskeletal dysfunction, will be carried out in the future.
Keywords: locomotive syndrome, randomize controlled trial, systematic review, meta-analysis
Abbreviations:
JOA: The Japanese Orthopaedic Association
RCT: randomized controlled trial
GLFS-25: 25-question Geriatric Locomotive Function Scale
EMS: electrical muscle stimulation
This is an Open Access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
License. To view the details of this license, please visit (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Received: February 9, 2022; accepted: June 23, 2022
Corresponding Author: Yoshitaka Iwamoto, PhD
Department of Neuromechanics, Graduate School of Biomedical and Health Sciences, Hiroshima University,
1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan
Tel: +81-82-257-5417, Fax: +81-82-257-5344, E-mail: iwamo10@hiroshima-u.ac.jp
275

Yoshitaka Iwamoto et al

INTRODUCTION
Locomotive syndrome is a common concept proposed by the Japanese Orthopaedic Association(JOA). It is a musculoskeletal disease that will highly likely require nursing care.1 The intent
behind this proposed concept is to promote locomotive system (bones, muscles, joints, andperipheral nerves) health awareness for elderly people in Japan to prevent nursing care and bed
rest. Frailty and sarcopenia are similar concepts that describe a declining condition in elderly
people similar to locomotive syndrome. Locomotive syndrome is used especially to identify
physical frailty with musculoskeletal disorders without social and cognitive frailty, althoughfrailty is a state in which older adults are at high risk of death, disability, and institutionalization.2 Sarcopenia is muscle degeneration with aging and a component of locomotive syndrome.2
Therefore, we believe that this is an adaptable concept to not only older adults but also all
age groups to prevent musculoskeletal disorders and the unfavorable conditions of locomotive
syndrome in the future. In recent years, it has been used as an indicator to evaluate the decline
in motor function not only in Japan but also in other countries.3-6
There have been many intervention studies for frailty and sarcopenia, including systematic
reviews and meta-analyses of several randomized controlled trials (RCTs), which have shownthat interventions with exercise, nutrition, and drugs are effective.7-10 The guidelines for frailty or
sarcopenia have already been reported as a result and have been applied in various clinical andcommunity settings to standardize prevention, diagnosis, and treatment.11,12 JOA proposed setsof exercises for locomotive syndrome called locomotion training to strengthen lower extremity
muscle power and improve balance.13 Aoki et al investigated the effects of the exercise included
in locomotion training (single-leg standing with the eyes open and squatting) and vitamin D
supplementation on physical function and locomotor dysfunction in community-dwelling elderly
individuals.14 They found that the two-step test results of all participants in the exercise only,
vitamin D only, and exercise and vitamin D groups were improved, but it was still unclear
which was the most effective intervention because there was no significant difference between
the groups and the degree of change.
The recent publication of guidelines for locomotive syndrome edited by JOA and the JapaneseSociety for Musculoskeletal Medicine has enormous significance. It indicates recommendations
and standardized prevention, assessment, and treatment.15 Substantive evidence from high-quality
RCT is needed from the evidence-level perspective. However, there are currently a few recommendations based on high-quality RCTs. There is no review that systematically evaluates andconsolidates the findings of RCTs, although the number of RCTs considering the intervention
effect on locomotive syndrome has been increasing with the concept’s spread. Therefore, this systematic review of RCTs aims to consolidate evidence regarding effective interventions to improve
locomotive syndrome. Furthermore, we believe in its importance in maintaining musculoskeletal
health to widely promote this concept, which is not yet widely recognized internationally.

MATERIALS AND METHODS
A systematic review of the literature was performed using the Preferred Reporting Items for
Systematic Reviews and Meta-analysis Protocol (PRISMA-P).16 This review was registered in
PROSPERO (ID: CRD42021266176).
Selection criteria
Studies were included in this systematic review if the following were met: (1) the articles
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Interventions to improve LS

were RCTs written in English or Japanese in a peer-reviewed journal; (2) the clinical evaluationof the locomotive syndrome should include at least one of the following: stand-up test, two-step
test, and 25-question Geriatric Locomotive Function Scale (GLFS-25); and (3) subjects should
be to 20 years of age and older.14 Studies were excluded if the following were met: (1) the
study was a review article, and (2) insufficient information was needed to synthesize the results.
Search strategy and study selection
We searched Medline, Cochrane Central Register of Controlled Trials, Physiotherapy Evidence
Database (PEDro), Scopus, Web of Science, Ichushi Web (in Japanese), and Cumulative Index
to Nursing and Allied Health Literature (CINAHL) databases electronically. A highly sensitive
search strategy to identify RCTs was combined with the word “locomotive syndrome” and tailoredto each of the seven databases searched. There were no limits on dates. We did an electronic
database search on July 13, 2021. The full search strategies for all databases are shown insupplementary Appendix 1.
The search results from each database were aggregated into a spreadsheet using the software
Microsoft Excel 2019. The titles and abstracts were independently selected by two reviewers (YI
and TI) from studies that met the predesigned inclusion criteria after deleting duplicate papers.
The full text was obtained for the selected papers after that, and content was examined andreviewed again independently based on the inclusion criteria by the two reviewers (YI and TI).
A discussion was held, and the final decision was made by a third reviewer (RT) in case of adisagreement between the two reviewers.
Data extraction
We extracted the data of the participants, interventions, and outcome using a spreadsheet witha pre-prepared Microsoft Excel 2019. First, a reviewer (YI) extracted the data, and then, anotherreviewer (TI) cross-checked the data. Only the stand-up test, two-step test, and GLFS-25 among
the items in the outcome, which are diagnostic criteria for locomotive syndrome, were extracted.14
The meta-analysis in this review employed the stand-up test, two-step test, and GLFS-25 as
the outcome measures, which are criteria for locomotive syndrome.
Risk of bias assessment in individual studies
Two reviewers (YI and TI) independently assessed the risk of bias using the Cochrane riskof bias assessment tool, random sequence generation (selection bias), allocation concealment(selection bias), blinding of participants and personnel (performance bias), blinding of outcome
assessment (detection bias), incomplete outcome data (attrition bias), selective reporting (reporting bias), and other bias.17 The articles were evaluated based on predetermined criteria. A third
reviewer (RT) was proposed if consensus was not reached.
Certainty of evidence
The Grading of Recommendations Assessment, Development and Evaluation system was used
to assess the quality of the evidence.18 The Grading of Recommendations Assessment, Development and Evaluation system was performed when there were at least two applicable outcomes.
The quality of the evidence was classified as “very low,” “low,” “moderate,” or “high” basedon criteria. Factors that reduce quality (risk of bias, inconsistently, indirectness, impression,and publication bias) and factors that increase quality (large effect, plausible confounding, anddose-response) were evaluated.19

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Yoshitaka Iwamoto et al

Statistical analyses
All statistical analysis procedures were performed using Review Manager 5.4. This review
examined the effects of various interventions on the locomotive syndrome. Therefore, for themeta-analysis, two or more RCTs with the same intervention method and evaluation conductedat the same time were employed. The value of the change from the baseline was used if actual
measurements were not given in the results section. We referred to the Cochrane Handbook for
Systematic Reviews of Interventions (Version 6.3, 2022), the random-effect model was used as
the integration method, and the mean and standard deviation were employed.20 The statisticallysignificant level was set at 0.05.

RESULTS
Search results
We found 424 papers (Figure 1) after searching the database. Approximately 222 duplicate
papers were excluded, and 202 papers were reviewed on the titles and abstracts. After that, 19
papers (1 paper added by hand search) were reviewed from the full text. Finally, 10 papers wereselected for this review because they met the inclusion criteria (Figure 1). The characteristicsof the subjects, intervention method, and results are summarized in Table 1. The subjects wereover 40 years of age. The average age of each group ranged from 51.0 to 75.6 years. There
was a proportion of women overall, and the article by Nishikawa et al only included women.21
Subjects with knee symptoms were involved in four of the papers, such as osteoarthritis, rather
than healthy subjects.22-25 No RCTs examined the main effect of exercise on locomotive syndrome
as an intervention method, and eight articles examined the effect of oral supplements.14,23-29 In
the papers examining the effects of oral intake, three papers examined glucosamine, two papers
examined SM-10, and one paper each examined vitamin D, collagen, and C. tubulosa. Simoura etal and Nishikawa et al investigated the effects of electrical stimulation on locomotive syndrome,
but their objectives were different: Simoura et al aimed to eliminate pain, whereas Nishikawa
et al aimed to increase muscle strength.21,22 Locomotive syndrome significantly improved withintervention compared to the control group, which was seen in four RCTs.21,26-28
Summary of selected papers
Nishikawa et al found that electrical muscle stimulation (EMS) of the quadriceps muscle for 8
weeks improved the two-step test and GLFS-25.21 They simultaneously measured knee extension
torque, muscle thickness, and muscle activity patterns and showed changes after 8 weeks ofintervention.21 Simoura et al found significant improvement in distance and pain in the 6-minwalk test with transcutaneous electrical nerve stimulation, but no improvement in the stand-up
test or two-step test.22
A meta-analysis of the oral glucosamine intervention was performed, and the results aredescribed as follows: Hattori et al performed an additional analysis for those with above-average
weight and the same population with a JKOM score of 30 or higher.26,28 There was no significant
difference between groups according to whether the JKOM score was 30 or higher.26 Conversely,
subjects with a JKOM score of 30 or higher and above-average weight showed significant differences in the stand-up test and two-step test, respectively, with the intervention group showing
significant improvement.28
Other oral interventions included SM-10, vitamin D, collagen, and C. tubulosa, none of whichshowed significant intervention effects between groups.14,23-25,29

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Interventions to improve LS

Fig. 1

Flow diagram of the study selection process

Quality assessments
The results of the risk of bias assessment conducted using the Cochrane Risk of Bias assessment are summarized in Table 2. A low risk of bias in all items was judged in six papers.
Evidence equality was assessed using the Grading of Recommendations Assessment, Development
and Evaluation system. Owing to the small number of RCTs included, we referred to previous
studies and the Cochrane Handbook for Systematic Reviews of Interventions (Version 6.3, 2022),
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55 subjects with knee joint pain without the diagnosis of OA
Mean age (IG=51.5, CG=53.0)
Male/Female (IG=9/19, 6/23)
16 without knee OA (IG=9, CG=7)
Mean age (IG=51.0, CG=59.1)
Male/Female (IG=2/7, CG=3/4)
26 healthy participants (IG=15, CG=11)
Mean age (IG=69.2, CG=61.3)
Male/Female (IG=5/10, CG=2/9)

Nagaoka et al25
Funct Food Res
2018
Hattori et al28
Jpn Pharmacol
Ther 2019
Inada et al29
Nutrients 2021

IG: intervention group
CG: control group
GLFS-25: 25-question geriatric locomotive function scale
TENS: transcutaneous electrical nerve stimulation
OA: osteoarthritis
Ex.: exercise
VitD: Vitamin D
N.A.: not applicable

130 community-dwelling adults (G1=45, G2=42, G3=43)
Mean age (G1=71.2, G2=71.3, G3=68.8)
Male/Female (G1=11/34, G2=6/36, G3=11/32)
26 participants with knee symptoms (IG=12, CG=14)
Mean age (IG=52.9, CG=52.6)
Male/Female (IG=5/7, CG=7/7)

57 participants with knee symptoms (IG=28, CG=29)
Mean age (IG=51.5, CG=53.0)
Male/Female (IG=9/19, CG=6/23)
39 healthy participants (IG=20, CG=19)
Mean age (IG=57.0, CG=54.5)
Male/Female (IG=9/11, CG=9/10)

4, 8, 12, 16 in GLFS-25 IG showed the improvement
weeks
in 5 out of 25 items, in the two-step
test IG showed significant improvement
at 8 weeks
24 weeks
in the two-step test, all groups showed
improvement after the interventions nogroup difference
6, 12 weeks in GLFS-25 both groups showedsignificant improvement at 12 weeks,in two-step test CG showed significant
improvement at 12 weeks, no groupdifference
6, 12 weeks no group differences
6, 12 weeks N.A.

placeboplaceboplaceboplacebo

4 tablets (Yeast SM-10; 600mg) a
day for 12 weeks
3 tablets containing Glucosamine,chondroitin sulfate, and hyaluronic
acid every day for 16 weeks

4 tablets (Yeast SM-10; 600mg) a
day for 12 weeks
8 tablets containing Glucosamine,chondroitin sulfate et al every day
for 12 weeks
one stick (C.tubulosa) daily for 12
weeks

placeboplacebo

12 weeks

Δ stand-up test CG showed significant
improvement compared with IG at 4, 8,
12 weeks, in two-step test IG showedsignificant improvement compared with
CG at 8 weeks
6, 12 weeks no group differences

N.A.

4, 8, 12weeks

placebo

8 tablets containing Glucosamine,chondroitin sulfate et al every day
for 12 weeks

G1=Ex.
G1=VitD
G3=Ex.+VitD
collagen drink 125ml every day for
12 weeks8, 12 weeks in Δ two-step test and GLFS-25,
IG showed significant improvementcompared with CG at 8 weeks

N.A.

electrical muscle stimulation of thequadriceps muscle of both limbs
for 8 weeks

no intervention and group difference

no difference by intervention or between
groups in 2-step test, stand-up test

immediately
effectsham-TENS

Main findings

transcutaneous electrical nerve
stimulation (TENS)

Follow-up

ControlIntervention

Table 1 Summary of included studies

Aoki et al14
J Orthop Sci
2018
Yamamoto et al24
Jpn Pharmacol
Ther 2018

Tomonaga et al23
Jpn Pharmacol
Ther 2017
Najima et al27
Jpn Pharmacol
Ther 2017

Study
Participants
Electrical stimulation
Shimoura et al22 50 participants with knee pain (IG=25, CG=25)
Arch Phys Med Mean age (IG=59.1, CG=57.9)
Male/Female (IG=6/19, CG=9/16)
Rehab 2019
Nishikawa et al21 19 participants (IG=10, CG=9)
J Electromyogr Mean age (IG=75.6, CG=77.3)
Male/Female (IG=0/10, CG=0/9)
Kinesiol 2019
Dietary supplement intake
Hattori et al26
57 without knee OA (IG=28, CG=29)
Jpn Pharmacol Mean age (IG=54.4, CG=53.4)
Male/Female (IG=12/16, CG=12/17)
Ther 2016

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Interventions to improve LS

Table 2Study
Shimoura et al,22
2019
Nishikawa et al,21
2019
Hattori et al,26
2016
Tomonaga et al,23
2017
Najima et al,27
2017
Aoki et al,14
2018
Yamamoto et al,24
2018
Nagaoka et al,25
2018
Hattori et al,28
2019
Inada et al,29
2021

Results of Cochrane Risk of Bias assessment

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1: Random sequence generation (selection bias)
2: Allocation concealment (selection bias)
3: Blinding of participants and personnel (performance bias)
4: Blinding of outcome assessment (detection bias)
5: Incomplete outcome data (attrition bias)
6: Selective reporting (reporting bias)
7: Other bias＋: Low risk of bias－: High risk of bias？: Unclear risk of bias

and we did not examine publication bias by funnel plot asymmetry or other statistical methods.20,30
All parameters were judged to be low to moderate, with inconsistency and impression being thefactors that reduced quality (Table 3).
Meta-analysis results
Two studies including 96 participants were used in a meta-analysis to examine the effect oforal glucosamine intake on GLFS-25, with no statistically significant differences at 4 weeks (MD:1.01; 95%CI: −0.74 to 2.76; Figure 2a), 8 weeks (MD: 0.40; 95%CI: −1.63 to 2.44; Figure 2b),or 12 weeks (MD: 0.72; 95%CI: −0.99 to 2.44; Figure 2c).
Two studies including 96 participants were used in a meta-analysis to examine the effect oforal glucosamine intake on the two-step test, with no statistically significant differences at 8
weeks (MD: −0.00; 95%CI: −0.17 to 0.17; Figure 2d).
We attempted to determine the effect of oral yeast SM-10 intake on each outcome measureused as diagnostic criteria for locomotive syndrome by meta-analysis, but Nagaoka et al did not
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2

12 weeks22

8 weeks

8 weeks2

4 weeks

No. ofstudies

RCT

RCT

RCT

RCT

Study
designNot serious

Not serious

Not serious

Not serious

Risk ofbias

GLFS-25: 25-question geriatric locomotive function scale
RCT: randomized controlled trial
a: wide 95% confidence interval

2-step test

GLFS-25

OutcomeIndirectness
Not serious
Not serious
Not serious
Not serious

Inconsistency(estimates)
Not serious(I2 = 0%)Not serious(I2 = 0%)Not serious(I2 = 0%)
Serious(I2 = 89%)
Seriousa

Seriousa

Seriousa

Seriousa

Imprecision

None

None

None

None

Other
considerations

Table 3 Grade summary of findings
Certainty assessment

49

49

49

49

Intervention
group

47

47

47

47

Control
group

No. of patients

Important
Important
Important
Important+++○Moderate+++○
Moderate++○○
Low

Importance+++○Moderate

Certainty

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Interventions to improve LS

Fig. 2 Forrest plot displaying the mean differences between the intervention and control groups
Fig. 2a: 25-question Geriatric Locomotive Function Scale (GLFS-25) at 4 weeks
Fig. 2b: GLFS-25 at 8 weeks
Fig. 2c: GLFS-25 at 12 weeks
Fig. 2d: two-step test at 8 weeks

provide figures for the results, so we could not perform the analysis.25

DISCUSSION
The purpose of this systematic review is to consolidate evidence on effective interventions
that improve locomotive syndrome. Several individual papers showed that the intervention group
had significantly improved the outcome measure for the diagnosis of locomotive syndrome
compared with the control group. However, only the oral intake of glucosamine provided sufficient information to conduct a meta-analysis, and the results were not statistically significant.
Therefore, the overall, evidence for locomotive syndrome improvement by intervention is stillinsufficient. Conversely, this systematic review and meta-analysis is the first paper that examinedinterventions that improve locomotive syndrome, which is a novel approach to identify the levelof evidence of each intervention effect.
Each paper showed the effect of oral glucosamine intake compared to the placebo group,26-28
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Yoshitaka Iwamoto et albut the meta-analysis did not show a significant difference between the groups. Hattori et alsuggested that the reason that the oral intake of glucosamine improves locomotive syndrome isthat glucosamine protects knee joint cartilage by inhibiting the degradation of type 2 cartilage
collagen, and has anti-inflammatory and chondrogenic effects.26,28,31-33 These effects of glucosamine
on knee cartilage protection and inflammation are thought to have increased knee range of motion and have improved bending and stretching of the knee, thereby improving the locomotive
syndrome. Hattori et al conducted a subgroup analysis of those with a JKOM score of 30 orhigher,26 as well as those with a score of 30 or higher, weight that was above the mean formen and women of their age group,28 and showed greater improvement. The dietary supplement
also contained small amounts of chondroitin in all studies, which has been shown to have antiinflammatory effects.34 On the basis of these findings, the choice of oral glucosamine may be
more beneficial for subjects with knee joint discomfort.
Nishikawa et al showed that an 8-week EMS intervention on the quadriceps muscle improved
locomotive syndrome.21 They showed that isokinetic muscle strength and muscle thickness
increased at the same time.21 It was reported that EMS improves muscle performance such asmuscle strength and thickness,35,36 but it has also been shown to increase the amount of activity
in daily life. In their RCT, EMS was implemented only in the intervention group and none in
the control group. They additionary suggested that the effects of EMS on muscles other than thequadriceps should be examined because various muscles in the lower extremities work together
to perform activities of daily living such as walking.
Other oral interventions were considered, but these did not significantly improve locomotive syndrome compared to the placebo group; these include the yeast SM-10,23,25 collagen,24
C.tubulosa,29 and vitamin D.14 Aoki et al’s RCT was the only one to use exercise as an intervention method.14 There was no control group to consider the effect of the exercise-only intervention
in that report, and although all intervention groups showed improvement in locomotive syndrome,
there was no significant difference between the groups. They performed one-legged stance andsquatting movements as exercises with the guidance of a physical therapist for the first time intheir RCT. There is a possibility that adherence and effectiveness may be reduced in the caseof unsupervised self-exercise. We expect that a physiotherapist-supervised exercise, follow-up byvideophone, and group exercise will have a greater effect on locomotive syndrome improvement.
This systematic review and meta-analysis is the first report to examine effective interventions
based on the findings from RCTs for improving locomotive syndrome. It would also provide
useful information for board members when developing or updating guidelines, as well as forclinicians when making choices and decisions regarding locomotive syndrome prevention ortreatment. Interventions were orally consumed foods that could be obtained without a physician’sprescription in more than half of the RCTs. The locomotive syndrome is a concept proposed by
JOA and is a musculoskeletal system problem. The effects of combined nutrition and exercise
and the effects of medications have been investigated in systematic reviews of frailty andsarcopenia, which have similar locomotive syndrome concepts.7-10 Locomotive syndrome is aproblematic condition caused by locomotive system problems,1 and exercise therapy is importantfor improvement. It is hoped that further RCTs will be widely conducted to investigate the effects
of interventions with physician-prescribed drugs and exercise.
There are some limitations to this review. First, there may be a conflict of interest fromthe viewpoint of scientific objectivity concerning company-sponsored research. The possibilityof conflict of interest is explicitly stated in the individual studies and we did not treat it as
a risk-reducing factor because the experiments are conducted by a third-party organization. As
such, these study results may need to be interpreted conservatively. Second, we did not assess
publication bias, which means that effect estimates may be optimistic because of unpublished
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negative data. Third, we only included papers that evaluated locomotive syndrome. Previous
systematic reviews of RCTs on frailty and sarcopenia might include subjects with locomotive
syndrome who have not been specifically evaluated. The results of those studies might apply tothose with locomotive syndrome. However, because locomotive syndrome indicates a decline inmobility and it has been reported that the decline in physical function begins with a decline inmobility,37 we believe that the results of this study will provide findings independent of previous
systematic reviews. Fourth, the small number of RCTs and participants included in the study may
lead to biased interventions and subject characteristics. This may prevent results generalization.
We determined that the number of RCTs was small because the locomotive syndrome is a concept
proposed by JOA, but it is not widespread worldwide unlike frailty and sarcopenia. However,
we believe that it is an important concept for all generations in maintaining locomotive system
health, and we hope that it will be further promoted.
Electrical stimulation and exercise could improve locomotive syndrome, although individual
RCTs have shown that oral intake of glucosamine in this systematic review and meta-analysis
did not provide strong evidence for specific intervention to improve locomotive syndrome. RCT
findings suggest that the current interventions for locomotive syndrome are limited to oral
supplements, and we hope to carry out more high-quality RCTs of exercise interventions aimed
at improving the locomotive syndrome, which is a musculoskeletal dysfunction. In addition, we
hope that this concept will be widely recognized as beneficial for locomotive system health.

ACKNOWLEDGEMENT
We thank Yuta Ogata (Kurume University Medical Center) for his assistance with the literaturecollection. This work was supported by MHLW FA Program Grant Number 22FA1003.

CONFLICT OF INTEREST
The authors have no conflicts of interest to disclose.

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Appendix 1
Search strategy【Medline】#1 locomotive syndrome[Title/Abstract]#2 (((((randomized[Title/Abstract]) OR (placebo[Title/Abstract])) OR (drug therapy[Title/
Abstract])) OR (randomly[Title/Abstract])) OR (trial[Title/Abstract])) OR (groups[Title/Abstract])#3 #1 AND #2【Cochrane Central Register of Controlled Trial】#1 (locomotive syndrome):ti,ab,kw#2 (randomized):ti,ab,kw OR (placebo):ti,ab,kw OR (drug therapy):ti,ab,kw OR (randomly):ti,ab,kw
OR (trial):ti,ab,kw OR (groups):ti,ab,kw#3 #1 AND #2【Physiotherapy Evidence Database (PEDro)】“locomotive syndrome”【Scopus】
TITLE-ABS-KEY ( “locomotive syndrome” ) AND ( TITLE-ABS-KEY ( randomized ) OR
TITLE-ABS-KEY ( placebo ) OR TITLE-ABS-KEY ( “drug therapy” ) OR TITLE-ABS-KEY( randomly ) OR TITLE-ABS-KEY ( trial ) OR TITLE-ABS-KEY ( groups ) )【Web of Science】#1 ALL=(“locomotive syndrome”)#2 (((((ALL=(randomized)) OR ALL=(placebo)) OR ALL=(“drug therapy”)) OR ALL=(randomly))
OR ALL=(trial)) OR ALL=(groups)#3 (#1) AND (#2)
【Ichushi Web [in Japanese]】(ロコモティブシンドローム/TH or ロコモティブシンドローム/AL) and (RD=ランダム化比較試験)【Cumulative Index to Nursing and Allied Health Literature】“locomotive syndrome” AND (randomized OR placebo OR “drug therapy” OR randomly OR
trial OR groups)
References End

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