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Modern Rheumatology
ISSN: 1439-7595 (Print) 1439-7609 (Online) Journal homepage: http://www.tandfonline.com/loi/imor20
Sarcopenia and physical function are associated
with inflammation and arteriosclerosis in
community-dwelling people: The Yakumo study
Tetsuro Hida, Shiro Imagama, Kei Ando, Kazuyoshi Kobayashi, Akio
Muramoto, Kenyu Ito, Yoshimoto Ishikawa, Mikito Tsushima, Yoshihiro
Nishida, Naoki Ishiguro & Yukiharu Hasegawa
To cite this article: Tetsuro Hida, Shiro Imagama, Kei Ando, Kazuyoshi Kobayashi, Akio
Muramoto, Kenyu Ito, Yoshimoto Ishikawa, Mikito Tsushima, Yoshihiro Nishida, Naoki Ishiguro &
Yukiharu Hasegawa (2017): Sarcopenia and physical function are associated with inflammation and
arteriosclerosis in community-dwelling people: The Yakumo study, Modern Rheumatology, DOI:
10.1080/14397595.2017.1349058
To link to this article: http://dx.doi.org/10.1080/14397595.2017.1349058
Published online: 25 Jul 2017.
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ORIGINAL ARTICLE
Sarcopenia and physical function are associated with inflammation and
arteriosclerosis in community-dwelling people: The Yakumo study
Tetsuro Hida
a
, Shiro Imagama
a
, Kei Ando
a
, Kazuyoshi Kobayashi
a
, Akio Muramoto
a
, Kenyu Ito
a
,
Yoshimoto Ishikawa
a
, Mikito Tsushima
a
, Yoshihiro Nishida
a
, Naoki Ishiguro
a
and Yukiharu Hasegawa
b
a
Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan;
b
Department of Rehabilitation, Kansai
University of Welfare Sciences, Osaka, Japan
ABSTRACT
Objectives: Sarcopenia reduces physical function, while chronic inflammation causes arteriosclerosis
and decreases skeletal muscle. We conducted a cross-sectional study to elucidate the associations
among sarcopenia, physical function, arteriosclerosis, and inflammation in community-dwelling people.
Methods: We recruited 335 participants in an annual health checkup. We diagnosed sarcopenia based
on appendicular skeletal muscle mass index (aSMI) assessed by bioelectrical impedance analysis. We
measured several physical function tests, blood pressure, and serum levels of high-sensitivity C-reactive
protein (hs-CRP), total cholesterol, and low-density lipoprotein cholesterol.
Results: After controlling for age, sex, and BMI, participants in the sarcopenia group showed lower per-
formance in all measured physical tests than the normal group. Arteriosclerosis risk factors, including
blood pressure, cholesterol levels, and hs-CRP, were significantly higher in the sarcopenia group than
in the normal group. hs-CRP and total cholesterol levels were significant risk factors of sarcopenia. The
aSMI, grip strength, and maximum stride length were negatively related to hs-CRP level.
Conclusions: Community-dwelling people with sarcopenia had higher levels of hs-CRP and a higher
risk for arteriosclerosis. The serum level of hs-CRP was an independent risk factor for sarcopenia and
was associated with physical function. These findings indicate that chronic inflammation may relate
arteriosclerosis and sarcopenia simultaneously.
ARTICLE HISTORY
Received 15 February 2017
Accepted 12 June 2017
KEYWORDS
Atherosclerosis; C-reactive
protein; intima–media
complex thickness;
sarcopenia; bioelectrical
impedance analysis
Introduction
Humans lose 40%of their skeletal muscle mass by the age
of 70 years [1]. Sarcopenia, which is defined as a decrease in
skeletal muscle mass associated with aging, causes a decrease
in physical activity, and leads to falls and osteoporotic frac-
tures in the elderly [2]; it is also a potential cause of sys-
temic disorders. In recent years, sarcopenia has rapidly
emerged as an important topic in various medical specialties.
The number of patients with sarcopenia has been increasing
worldwide as a result of the aging population; there were 50
million patients in 2009, which is expected to increase to
200 million patients by 2050 [3].
Skeletal muscles are distributed not only in the loco-
motor system, where they are responsible for physical func-
tions, but also in various organs throughout the body,
which account for the majority of the body’s glucose metab-
olism. Decreased muscle mass causes deterioration of insulin
sensitivity, which is an underlying risk factor for arterio-
sclerosis [4].
The prevalence of arteriosclerosis is increasing and the
disease burden is becoming progressively more severe.
Morbidity and mortality due to arteriosclerosis has been
rapidly increasing during the last 20 years [5].
Arteriosclerosis is a disease affecting the blood vessels, which
results in the thickening, hardening, and loss of elasticity of
the arterial walls [6]; it affects arteries of the heart, brain,
and other internal organs, as well as skeletal muscles [7].
Previous studies have indicated that physical inactivity, obes-
ity, hypertension, insulin resistance, and hyperlipidemia are
causes of arteriosclerosis and subsequent cardiovascular dis-
ease [8,9]. In addition, chronic inflammation has been
shown to be a risk factor for arteriosclerosis [10,11].
Sarcopenia not only causes hyperinsulinemia due to
decreased muscle mass, but also induces obesity because of
reduced physical activity [12]. Sarcopenia considerably
affects glucose and lipid metabolism in the elderly, and was
reported to be a cause of arteriosclerotic diseases [7].
Therefore, the treatment of sarcopenia may play an import-
ant role in the prevention of arteriosclerotic diseases.
However, the association between sarcopenia and arterio-
sclerosis risk factors in community-dwelling people is
insufficiently understood. Therefore, we conducted a cross-
sectional study aiming to evaluate sarcopenia in community-
dwelling elderly people and the associations between
sarcopenia, physical function, inflammation, and
arteriosclerosis.
CONTACT Shiro Imagama imagama@med.nagoya-u.ac.jp Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya,
Japan, Address: 65, Tsurumai, Showa-ku, Nagoya 466-8550, Japan
ß2017 Japan College of Rheumatology
MODERN RHEUMATOLOGY, 2017
https://doi.org/10.1080/14397595.2017.1349058
Subjects and methods
Subjects
Our institution has performed epidemiological studies –col-
lectively called The Yakumo Study—in the Yakumo town of
Hokkaido, Japan, since 1983 through annual public health
checkups [13–16]. The current study was conducted on
community-dwelling people aged 40 years who participated
in the health checkup in 2013. Participants with inflamma-
tory diseases as rheumatoid arthritis, collagen disease, current
malignant tumor and infection were excluded. In total, 335
subjects (mean age, 64.9 years) were analyzed. All partici-
pants provided written informed consent, and the study
protocol was approved by the Institutional Review Board of
Nagoya University Graduate School of Medicine (No. 2014-
0207), and the study procedures were carried out in accord-
ance with the principles of the Declaration of Helsinki.
Muscle mass measurement and diagnosis of sarcopenia
Appendicular skeletal muscle mass was measured using bio-
electrical impedance analysis (BIA) (Inbody 720; Biospace
Co., Ltd., Seoul, Republic of Korea), which measures body
composition according to the differences in electric imped-
ance among biological tissues such as fat, muscle, and bone
[17]; the accuracy of this method is comparable to that of
the computed tomography cross-sectional area [18].
Moreover, it enables separate measurement of muscle mass
in the upper and lower extremities, and the trunk.
Therefore, the BIA is a simple, easy, and non-invasive
method for measuring muscle mass [19]. The appendicular
skeletal muscle index (aSMI) was calculated using the fol-
lowing formula: aSMI ¼arm and leg skeletal muscle mass
(kg)/height
2
(m
2
)[20]. Reference values for the diagnosis of
sarcopenia for Japanese people were reported by Tanimoto
et al., and included an aSMI of <7.0 kg/m
2
and 5.8 kg/m
2
in
men and women, respectively, as measured using BIA; these
values were determined from the mean ±2 standard devi-
ation values of 1719 Japanese volunteers aged 18–39 years
[21]. Participants were diagnosed with sarcopenia according
to these Japanese criterion values and in accordance with
the European guidelines for the diagnosis of sarcopenia [3].
Participants who did not meet the criteria of sarcopenia
were assigned to the normal group.
Assessment of physical function
We determined back muscle strength as the maximal iso-
metric strength of the trunk muscles in a standing posture
with 30lumbar flexion using a digital back muscle strength
meter (T.K.K.5002; Takei Co., Niigata, Japan) [22]. The test
was performed once on 334 participants (124 men and 210
women). Grip strength was measured bilaterally in the
standing position using a handgrip dynamometer (Toei
Light handgrip dynamometer; Toei Light Co., Ltd., Saitama,
Japan). Both hands were tested once, and the average value
was used to characterize the grip strength of the subject
[23]. We evaluated the 10-m fastest walking speed as a
reflection of the mobility of participants [2]. Participants
walked the 10-m straight course once at their fastest pace,
and the walking speed was calculated. The 3-m timed up
and go (3mTUG) test measured the time it took a subject to
rise from a standard chair (46-cm seat height from the
ground), walk a distance of 3 m, turn around, walk back to
the chair, and sit down [24]. Each subject performed the test
twice, and the quickest score was recorded. The maximum
stride was measured as follows: a participant in the standing
position was instructed to put his/her right foot forward as
far as he/she could, then to bring the left foot up to the
right foot without touching the hands on the floor or the
knees. This was repeated with the left foot forward. The best
value was used to characterize the maximum stride of the
subject [25].
Assessment of risk factors for arteriosclerosis
Blood pressure in the right arm was measured while the
individual was in a seated position after at least 5 min of
rest. Chronic inflammation was assessed by measuring
serum levels of high-sensitivity C-reactive protein (hs-CRP)
in blood samples using immunoagglutination assay with
latex beads (N-Assay LA CRP-T, Nittobo Medical Co., Ltd,
Tokyo, Japan). The lowest detectable concentration was
0.02 mg/dL, and the intra-assay coefficient of variation was
less than 5%.
We also measured other risk factors of arteriosclerosis,
including total cholesterol, and low-density lipoprotein
(LDL) cholesterol from the same blood samples.
Biochemical analyses of the blood samples were performed
using an autoanalyzer (JCA-RX20; Nihon Denshi, Tokyo,
Japan) on the day of the health checkup.
Statistical analysis
The prevalence of sarcopenia in men and women was ana-
lyzed using the v
2
test. The subjects were divided into the
sarcopenia and normal groups. The measurements of vari-
ous arteriosclerosis risk factors were compared by perform-
ing an analysis of covariance using the Student’st-test and
the generalized linear model (GLM). The analysis was
adjusted for the sex, age, and body mass index (BMI), which
are known factors related to sarcopenia [26]. To determine
the risk factors associated with sarcopenia among the
parameters that exhibited significant differences in the anal-
yses conducted after GLM adjustment, logistic regression
analysis with the step-wise method was performed using the
aforementioned significant values as covariates, in addition
to age, sex, and BMI. To examine the relationships between
the level of hs-CRP and the aSMI and physical function
measurements (grip strength, back strength, fastest walking
speed, 3mTUG, and maximum stride length) were set as the
dependent variable in each separate multiple linear regres-
sion models. The hs-CRP level, age, male sex, and BMI were
set as covariates in all models. Statistical analyses were per-
formed using SPSS, version 22 (IBM SPSS Inc., Armonk,
NY), and p<.05 was considered significant.
2 T. HIDA ET AL.
Results
The baseline data of the participants are shown in Table 1.
A total of 146 men (mean ages of 66.8 years) and 189
women (mean ages of 63.4 years) were included in this
study. Table 2 shows the muscle mass measurements of all
subjects as well as the prevalence of sarcopenia diagnosed
based on the aSMI. All muscle measurements, including arm
muscle mass, leg muscle mass, aSMI, arm SMI, and leg SMI,
were higher in male participants than in female participants
(all p<.001) The prevalence of sarcopenia in men and
women was 21.2%(31 of 146) and 30.7%(58 of 189),
respectively (p¼.052).
Physical functions measured in the sarcopenia and normal
groups after controlling for age, sex, and BMI are shown in
Table 3. All of the measured functions, including grip
strength, back muscle strength, walking speed, and maximum
stride length, showed a significant deterioration in the sarco-
penia group as compared with the normal group.
Various arteriosclerosis risk factors controlled for sex,
age, and BMI are shown in Table 4. The mean systolic and
diastolic blood pressures, and levels of total cholesterol, LDL
cholesterol, and hs-CRP, were significantly higher in the sar-
copenia group than in the normal group.
A summary of the logistic regression analysis for risk fac-
tors of sarcopenia is shown in Table 5. Covariates included
age, sex, BMI, and factors associated with arteriosclerosis
that were significantly different between the two groups in
the GLM analysis. This analysis showed that serum levels of
hs-CRP (odds ratio [OR] ¼277.5; p<.001) and total choles-
terol (OR ¼1.02, p<.001) were significant risk factors for
sarcopenia. The results of the multiple linear regression
analysis revealed that the aSMI, grip strength, and maximum
stride length were negatively related to the levels of hs-CRP
(Table 6).
Discussion
This study is the first to examine the associations between
sarcopenia, physical function, and arteriosclerosis risk fac-
tors, including chronic inflammation, in Japanese commu-
nity-dwelling subjects. We found that the majority of
Table 2. Muscle mass measurements.
Total Male Female pvalue
Arm muscle mass (kg) 4.32 ± 0.64 5.50 ± 0.46 3.42 ± 0.30 <.001
Leg muscle mass (kg) 12.65 ± 1.45 15.13 ± 1.13 10.74 ± 0.82 <.001
aSMI (kg/m
2
) 6.77 ± 1.05 7.62 ± 0.83 6.13 ± 0.67 <.001
arm SMI (kg/m
2
) 1.72 ± 0.38 2.03 ± 0.29 1.48 ± 0.23 <.001
leg SMI (kg/m
2
) 5.05 ± 0.70 5.59 ± 0.58 4.65 ± 0.48 <.001
Prevalence of sarcopenia 26.6% 21.2% 30.7% .052
Values are expressed as mean ± standard deviation.
aSMI: appendicular skeletal muscle mass index; SMI: skeletal muscle mass
index.
Table 1. Demographic data of the participants.
Total Male Female
Number of participants 335 146 189
Age (years) 64.9 ± 9.3 66.8 ± 8.8 63.4 ± 9.5
Height (cm) 157.1 ± 8.6 164.1 ± 6.0 151.6 ± 5.9
Weight (kg) 59.0 ± 11.3 65.7 ± 10.9 53.9 ± 8.5
BMI (kg/m
2
) 24.0 ± 3.6 24.5 ± 3.7 23.1 ± 3.5
Waist circumference (cm) 83.3 ± 9.5 84.1 ± 9.3 82.6 ± 9.6
Hip circumference (cm) 92.1 ± 7.0 93.4 ± 6.7 91.1 ± 7.1
% body fat (%) 26.5 ± 7.0 21.8 ± 5.5 29.2 ± 6.4
Systolic blood pressure (mm/Hg) 128 ± 19 129 ± 18 127 ± 19
Diastolic blood pressure (mm/Hg) 71 ± 12 74 ± 13 69 ± 11
Total cholesterol (mg/dl) 213 ± 34 204 ± 30 220 ± 36
LDL-cholesterol (mg/dl) 123 ± 31 119 ± 28 127 ± 33
Triglyceride (mg/dl) 99 ± 61 111 ± 78 89 ± 40
hs-CRP (mg/dl) 0.09 ± 0.13 0.11 ± 0.15 0.08 ± 0.10
Values are expressed as mean ± standard deviation.
BMI: body mass index; LDL: low-density lipoprotein; hs-CRP: high-sensitive
C-reactive protein.
Table 3. Physical function measurements.
Normal Sarcopenia pvalue
Number of participants 246 89
Grip strength (kg) 33.5 ± 0.2 25.2 ± 0.4 <.0001
Back strength (kg) 75.6 ± 1.4 55.1 ± 2.4 <.001
FFD (cm) 2.30 ± 0.68 1.38± 1.14 .518
Fastest walking speed (m/s) 1.99 ± 0.02 1.86± 0.03 .018
3mTUG (s) 8.19 ± 0.05 7.10 ± 0.08 <.0001
Maximum stride length (cm) 117.8 ± 0.6 110.5 ± 1.0 <.005
Values were controlled for age, sex, and body mass index with general linear
model, and expressed as mean ± standard error.
FFD: floor-finger distance; 3mTUG: 3-m timed up and go.
Table 4. Risk factors for atherosclerosis.
Normal Sarcopenia pvalue
Number of participants 246 89
hs-CRP (mg/dl) 0.073 ± 0.008 0.135 ± 0.014 <.0005
Systolic blood pressure (mm/Hg) 126 ± 1 133 ± 2 .003
Diastolic blood pressure (mm/Hg) 70 ± 1 74 ± 1 .005
HbA1c (%) 5.86 ± 0.04 5.84 ± 0.07 .836
Total cholesterol (mg/dl) 209 ± 2 223 ± 4 .005
Triglyceride (mg/dl) 98 ± 4 101 ± 7 .705
LDL-cholesterol (mg/dl) 120.1 ± 2 131.2 ± 3.6 .011
Values were controlled for age, sex, and body mass index with general linear
model, and expressed as mean ± standard error.
hs-CRP: high-sensitive C-reactive protein; HbA1c: hemoglobin A1c; LDL: low-
density lipoprotein.
Table 5. Summary of logistic regression analysis for risk factors of sarcopenia.
B
Odds
ratio
95% Confidential
interval pvalue
hs-CRP (mg/dl) 5.63 277.5 23.6–3261.1 <.00001
Total cholesterol (mg/dl) 0.016 1.02 1.01–1.03 <.001
Age (years) 0.11 1.12 1.07–1.17 <.00001
BMI (kg/m
2
)0.67 0.51 0.43–0.61 <.00001
The dependent variable was the presence of sarcopenia. Covariates were age,
male sex, BMI, systolic blood pressure, diastolic blood pressure, and levels of
total cholesterol, low-density lipoprotein cholesterol, and hs-CRP.
BMI: body mass index; hs-CRP: high-sensitive C-reactive protein.
Table 6. Summary of multiple linear regression analysis.
hs-CRP
Bpvalue
Dependent variables
aSMI (kg/m
2
)0.132 <.001
Grip strength (kg) 0.118 <.001
Back strength (kg) 0.067 .102
Fastest walk speed (m/s) 0.034 .526
3mTUG (s) 0.017 .78
Maximum stride length (cm) 0.097 .039
Analysis was performed on each dependent-variable model. The covariates
were hs-CRP, age, male sex and BMI.
hs-CRP: high-sensitive C-reactive protein; aSMI: appendicular skeletal muscle
mass index; BMI: body mass index; 3mTUG: 3-m timed up and go.
MODERN RHEUMATOLOGY 3
physical functions were poorer and risk factors of arterio-
sclerosis (including blood pressure and the levels of hs-CRP,
total cholesterol, and LDL cholesterol) were worse in the
sarcopenia group than in the normal group after controlling
for age, sex, and BMI. We also found that the hs-CRP and
total cholesterol levels, as well as age and BMI, were signifi-
cant risk factors for sarcopenia. In multiple linear regression
models, chronic inflammation was associated with low
muscle mass and poor physical function (grip strength and
stride length).
The prevalence of sarcopenia, as diagnosed by the aSMI
value, was 26.6%among all subjects in this study, whose
mean age was 65 years. This value is consistent with those
previously reported by other researchers in Japan and other
countries (22.7–35.7%for women in their 70s and 80s) [26],
as well as with the findings of our former survey conducted
on outpatients (22.7%in women in their 70s) [27].
Regarding the relationship between physical functions
and sarcopenia, the results from most parameters in the
physical function tests (grip strength, back strength, walking
speed, 3mTUG, and maximum stride) were worse in sub-
jects with sarcopenia than in those without sarcopenia. This
finding is consistent with those in previous reports [28,29].
Loss of physical function due to decreased muscle mass
leads to reduced mobility; this can cause falls and fractures
[30], which are potential risk factors for being bedridden in
the elderly [31]. Therefore, the prevention and treatment of
sarcopenia could be critical for improving the physical func-
tion of the elderly.
The systolic and diastolic blood pressures were higher in
subjects with sarcopenia than in those without sarcopenia.
In addition, the serum levels of total cholesterol and LDL-
cholesterol, also known as ‘bad cholesterol’[32], were sig-
nificantly higher in subjects with sarcopenia than in those
without sarcopenia. These findings suggested that patients
with sarcopenia are at risk for developing arteriosclerosis.
We found that participants with sarcopenia had signifi-
cantly higher levels of hs-CRP than those without sarcope-
nia. In addition, multivariate analyses revealed that the level
of hs-CRP was an independent risk factor for sarcopenia.
The hs-CRP level was also negatively associated with phys-
ical function in multiple linear regression models. Physical
inactivity, diabetes, and obesity result in the development of
chronic inflammation [33]. Inflammatory cytokines, includ-
ing tumor necrosis factor-aand interleukin-6, which are
produced by inflammatory cells and adipose tissue, activate
nuclear factor-jB via receptors present in skeletal muscles
[33]. Furthermore, these cytokines accelerate muscle degrad-
ation by increasing the levels of ubiquitin kinases (i.e.
muscle RING-finger protein 1 and F-box protein 32) in the
ubiquitin-proteasome system, which is the main protein deg-
radation system in skeletal muscles [34,35]. The present
findings suggest chronic inflammation may directly relate to
sarcopenia.
Screening for chronic inflammation according to hs-CRP
levels has recently attracted attention as a method for the
assessment of arteriosclerotic diseases [36]. Chronic inflam-
mation is closely related to arteriosclerosis, and the serum
levels of inflammatory cytokines are often elevated in
patients with arteriosclerotic diseases [37]. Risk factors, such
as hypertension, diabetes, and hyperlipidemia, damage the
vascular endothelium, which consequently produces various
inflammatory cytokines [38]. These inflammatory cytokines
cause hematocytes, such as circulating monocytes, to adhere
to the endothelium, infiltrate the subendothelium, and con-
vert macrophages into foam cells [39]. This inflammatory
process is believed to be involved in the formation of
arteriosclerotic lesions (also called plaques) [11]. The present
findings suggest that chronic inflammation might be the
cause of both arteriosclerosis and sarcopenia. A vicious cir-
cle around sarcopenia, arteriosclerosis, and inflammation
may exit. Cutting out this negative circulation can be a key
for future sarcopenia and arteriosclerosis treatment. The
treatment of chronic inflammation through medicine and
exercise might be useful not only for the treatment of
arteriosclerosis, but also for sarcopenia.
The current study has some limitations. We diagnosed
sarcopenia based on anthropometric analyses via BIA.
Although we conducted several physical performance tests,
including the fastest walking speed test, we did not measure
normal walking speed. However, the current criteria for
diagnosing sarcopenia include a combination of muscle vol-
ume measurements and the assessment of grip strength and
normal walking speed [3,40]. Therefore, in future studies,
we will measure normal walking speed to evaluate sarcope-
nia. Furthermore, we did not analyze the confounders of
sarcopenia and inflammation such as osteoporosis, nutrition
status, insulin resistance, vitamin D level, and daily activities
[3]. These confounders possibly affect the analysis. Relation
between inflammatory and degenerative osteoarthritis is
becoming clear recently [41]. Status of osteoarthritis is a
potential bias to the systemic inflammation. Additionally, we
did not directly analyze arterial stiffness or plaque of vessels
with ultrasound or pulse wave velocity test. Although, we
performed blood test including levels of hs-CRP and choles-
terol and measured blood pressure for evaluation of risk fac-
tors of arteriosclerosis. We should take into account to
assess arteriosclerosis in detail for further study.
In conclusion, we revealed that community-dwelling peo-
ple with sarcopenia had elevated blood pressure and
increased serum levels of total cholesterol, LDL-cholesterol,
and hs-CRP. Multivariate analyses showed that the serum
level of hs-CRP was an independent risk factor for sarcope-
nia and was associated with physical function. These find-
ings indicate that chronic inflammation relates to
arteriosclerosis and sarcopenia simultaneously. In addition,
the measurement of serum hs-CRP level may be useful not
only for the assessment of arteriosclerosis, but also for the
screening of sarcopenia.
Acknowledgements
The authors wish to thank Ms Makiko Noda, Ms Marie Miyazaki, and
Ms Erika Takano for their assistance in data collection.
Conflict of interest
None.
4 T. HIDA ET AL.
Funding
This study was funded by research grants from the Foundation for
Total Health Promotion in 2012, the Tateisi Science and Technology
Foundation in 2013 (No. 2031014), the Japan Osteoporosis Foundation
in 2013 and 2014, the Japan Orthopaedics and Traumatology Research
Foundation, Inc. (No. 307) in 2014, the Research Foundation for the
Electrotechnology of Chubu in 2015(R-27213), and the Chukyo
Longevity Foundation in 2015. The sponsors had no role in the study
design, data collection, data analysis, data interpretation, or writing of
the report. No benefits in any form have been or will be received from
a commercial party related directly or indirectly to the subject of this
article.
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