Managing Sarcopenia and Its Related-Fractures to Improve Quality of Life in Geriatric Populations

Abstract

Sarcopenia, an aging-induced generalized decrease in muscle mass, strength, and function, is known to affect elderly individuals by decreasing mobile function and increasing frailty and imbalance that lead to falls and fragile fractures. Sarcopenia is a known risk factor for osteoporotic fractures, infections, and early death in some specific situations. The number of patients with sarcopenia is estimated to increase to 500 million people in the year 2050. Sarcopenia is believed to be caused by multiple factors such as disuse, malnutrition, age-related cellular changes, apoptosis, and genetic predisposition; however, this remains to be determined. Various methods have been developed, but no safe or effective treatment has been found to date. This paper is a review on the association between sarcopenia and its related-fractures and their diagnoses and management methods to prevent fractures.

Full text

http://dx.doi.org/10.14336/AD
*Correspondence should be addressed to: Dr. Tetsuro Hida, Department of Orthopedic Surgery, Nagoya University
Graduate School of Medicine, 35, Tsuruma, Showa-ku, Nagoya, 466-8550, Japan. Email: hidat@med.nagoya-u.ac.jp
ISSN: 2152-5250 1
Review Article
Managing Sarcopenia and Its Related-Fractures to
Improve Quality of Life in Geriatric Populations
Tetsuro Hida1*, Atsushi Harada2, Shiro Imagama1, Naoki Ishiguro1
1Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine
2Department of Orthopedic Surgery, National Center for Geriatrics and Gerontology
[Received October 10, 2013; Revised November 19, 2013; Accepted November 24, 2013]
ABSTRACT: Sarcopenia, an aging-induced generalized decrease in muscle mass, strength, and function, is
known to affect elderly individuals by decreasing mobile function and increasing frailty and imbalance that
lead to falls and fragile fractures. Sarcopenia is a known risk factor for osteoporotic fractures, infections,
and early death in some specific situations. The number of patients with sarcopenia is estimated to increase
to 500 million people in the year 2050. Sarcopenia is believed to be caused by multiple factors such as disuse,
malnutrition, age-related cellular changes, apoptosis, and genetic predisposition; however, this remains to be
determined. Various methods have been developed, but no safe or effective treatment has been found to date.
This paper is a review on the association between sarcopenia and its related-fractures and their diagnoses
and management methods to prevent fractures.
Key words: sarcopenia, sarcopenia-related fracture, osteoporosis, diagnosis, muscle mass, treatment, pathogenesis
Sarcopenia, an aging-induced decrease in muscle mass, is
known to affect elderly individuals by decreasing
activities of daily living and increasing frailty and
vulnerability to falls and osteoporotic fractures.
In the field of orthopedics, the elements of the
musculoskeletal system have been classified as follows:
the “muscles,” the source of the power; the “tendons,”
which bind the muscles and the bones; the “bones,” which
are load-bearing structures; and the “joints,” which
connect bones with other bones. Thus far, efforts have
been made to deepen the understanding of the functions
and impairments of each of those elements. Compared
with other musculoskeletal disorders such as fractures,
osteoarthritis, and tendon or ligament ruptures, muscles
have a high capacity to regenerate and are often believed
to “heal even without treatment.” [1] Unfortunately, there
has been a delay in the understanding of the
pathophysiology of muscular regeneration and sarcopenia
as well as the awareness of treatments. In fact, the
regenerative capacity of skeletal muscles is decreased in
the elderly; in recent years, it has been found that even
when the muscles regenerate, the muscle fibers are
abnormal, fatty, and fibrosed [2-4] in aged environment.
Such a decrease in muscle mass and strength causes a
physical instability that makes the body fall easily,
resulting in reduced mobility [5]; and ultimately, the
patient experiences falls and fractures and is confined to
bed [6, 7].
Sarcopenia has been reported to affect more than 40%
of elderly individuals ≥70 years of age, approximately 50
million people worldwide. This number is estimated to
increase to 500 million people in the year 2050 [8].
Therefore, there has been major interest in developing
strategies to reduce the disadvantage of sarcopenia and
help in attenuating the age related decline and disability.
In this communication, we comment on the association
between sarcopenia and osteoporotic fractures, and the
management of sarcopenia to prevent osteoporotic
fractures.
Volume 5, Number 2; xxx-xx, April 2014

T. Hida et al Managing Sarcopenia and Fractures
Aging and Disease • Volume 5, Number 2, April 2014 2
Definition and Diagnosis of Sarcopenia
The term sarcopenia is a recently coined term, which
originates from the Greek words sarx, meaning muscle,
and penia, meaning loss. It was first demonstrated by
Rosenberg [9] in 1989. Recently, the European Working
Group on Sarcopenia in Older People (EWGSOP)
published a useful guideline [8] in 2010. A similar
guideline was published by the International Working
Group on Sarcopenia (IWGS)[10]. In these guidelines,
sarcopenia is defined as a progressive and generalized
loss of muscle mass and low muscle function (strength or
performance). Classification of sarcopenia by cause is
also suggested in this guideline. ‘Primary’ sarcopenia is
defined as when no other cause is evident but ageing itself.
Sarcopenia can be considered ‘secondary’ when one or
more other causes are evident. Because this classification
is preliminary one, the study comparing each type of
sarcopenia does not exist, so the evidence for specific
treatment for primary or secondary was not established
yet. Figure 1 shows the algorithm of diagnosing
sarcopenia by EWGSOP. The cutoff values for grip
strength and habitual gait speed (less than 0.8 m/s) have
been used to assess muscle strength and performance loss.
On the other hand, the IWGS guideline established a
cutoff value for gait speed (less than 1.0 m/s) only.
However, not only muscle mass loss but also muscle
strength or performance loss is mandatory to diagnose
sarcopenia.
Figure 1. Recommended algorithm for diagnosing sarcopenia from EWGSOP (ref.8, partly modified
from original)
Measuring techniques for muscle mass
In general, maximum muscle mass is observed between
the ages of 20 and 30 years in men and women, and
muscle mass gradually decreases with age [11-14]. After
the age of 45 years, 0.3% of muscle mass is lost from the
total body weight annually [15]. Three major methods are
used for evaluating muscle volume, namely (1) analysis
of cross-sectional area (CSA) by magnetic resonance
imaging or computed tomographic (CT) scanning, (2)
dual-energy X-ray absorptiometry (DXA), and (3)
bioelectrical impedance analysis (BIA).

T. Hida et al Managing Sarcopenia and Fractures
Aging and Disease • Volume 5, Number 2, April 2014 3
(1) Cross-sectional area
CSA directly reflects the muscle mass of a specific part of
the body, and is considered one of the most accurate
measuring methods. The midthigh muscle is the most
preferred part for CSA measurement; it is highly
associated with lower extremity function [2, 16-20].
Greater psoas muscle, lumbar paraspinal muscles, and
rectus abdominis muscle are also often used because they
can be evaluated simultaneously through abdominal
examination by CT scan; thus, they are mainly used for
evaluating sarcopenia in patients with gastrointestinal
disease[21-23]. However, the use of the CSA has some
limitations. For diagnosing sarcopenia, the cutoff value
from the normal young mean has not been established yet.
Other demerits for CSA are less accessibility, high cost,
and radiation exposure (CT scan). CSA is the criterion
standard for research use, but more noninvasive
alternatives such as DXA or BIA are more preferred for
clinical use.
(2) Dual-energy X-ray absorptiometry
DXA is a traditional method for determining body
composition, which is classically used for measuring bone
mineral density[24]. Two X-ray beams of different energy
levels are aimed at the patient’s body. Body compositions
such as bone mass, fat mass, and lean soft tissue mass
were determined from the absorption rate of each X-ray
beam. Whole-body DXA can independently estimate the
composition of each part of the body. Its exposure dose of
radiation is quite low compared with X-ray examination
or CT scan[25]. The lean masses of the head and trunk
contain not only muscle but also the brain and internal
organs, respectively. In contrast, the arms and legs contain
only skeletal muscle. The skin and vessels are so minimal
that they can be ignored. We can measure skeletal muscle
mass with accuracy at the arms and legs[26]. For this
reason, appendicular muscle mass (ASM) is preferred for
evaluating sarcopenia by DXA [5, 27]. DXA has adequate
precision and reproducibility compared with CSA[17].
Technical errors in DXA for CSA by CT scan are reported
in only 2.5% of cases[25]. DXA is currently a preferred
method for research and clinical use.
(3) Bioelectrical impedance analysis
BIA also is a noninvasive and traditional method for
measuring body composition [28, 29]. Electrodes are
attached to various parts of the body, and a small electric
signal is circulated. BIA measures the impedance or
resistance of muscle and fat tissues and estimates tissue
content and composition. Modern BIA can separately
measure each part of the body. The best feature of BIA is
the portability of the equipment used, making it suitable
for epidemiological examination for community-dwelling
people [30, 31]. The validity of BIA, however, is not
ascertained for the population whose hydration status
alters with edematous disease[15], such as heart failure,
renal failure, and lymphedema. BIA is regarded as an
accurate alternative for epidemiological and clinical uses
[32-34].
Some other noninvasive methods have been
developed. In particular, ultrasonography can investigate
muscle thickness (muscle volume) [35] and muscle echo
intensity (muscle quality) [36-39] at one time.
Ultrasonography is a potentially useful method for
evaluating sarcopenia. Anthropometric measurements
such as calf circumference are traditional and convenient
methods of measuring skeletal muscle mass, although
they are easily influenced by subcutaneous fat and their
reliability is inadequate for sarcopenia screening [40].
The cutoff value for sarcopenia was established by
Baumgartner in 1998. He proposed the use ASM from
DXA examination relative to height. Individuals with
ASM/height2, which is the sum of arm and leg muscle
masses divided by the square of height, of two standard
deviations below the mean of young healthy volunteers
were considered as likely to have sarcopenia [11]. The
expression ASM/height2 is synonymous to appendicular
lean mass/height2 (often abbreviated to “aLM/h2”) [41]
and skeletal muscle mass index (often abbreviated to
“SMI”)[42, 43].The cutoff value for BIA is similar to that
for DXA[32, 33].
Sarcopenia and its related fractures
Sarcopenia-induced functional impairment and frailty
The decrease in muscle mass in the elderly has two
aspects. The first aspect is a decrease in muscle mass as
part of the musculoskeletal system. Sarcopenia should be
taken into consideration as the cause of “locomotive
syndrome”, which is defined by the Japanese Orthopedic
Association (JOA) as a condition in people with
musculoskeletal disease in high-risk groups who are
highly likely to require nursing care at some point [44-49],
as well as “musculoskeletal ambulation disability
symptom complex,” condition in which aging causes a
reduced capacity to maintain balance and a decrease in
mobility and walking ability [50]. For example, an 80
year-old female who was injured at home and developed
a hip fracture (Figure 2) had a standing height of 149 cm,
a body weight of 32 kg, and an ASM/height2 of 4.8 kg/m2,
and the fracture was diagnosed as a complication of
sarcopenia. After surgery, the patient was capable of
walking with support and was discharged from the
hospital to a nursing home [51]. It is easily imaginable that

T. Hida et al Managing Sarcopenia and Fractures
Aging and Disease • Volume 5, Number 2, April 2014 4
the risk of osteoporotic fracture is higher in elderly
individuals with sarcopenia.
Figure 2. 80 year-old woman with a hip fracture
lying on operation table. Coexisting severe sarcopenia
was pointed out.
The second aspect of the disorder is sarcopenia as a
systemic disease. Skeletal muscles are distributed
throughout the musculoskeletal system as well as in
organs throughout the body. Muscle weakness in the
pelvic floor muscle group causes urinary incontinence
[52], reduces the ability to perform activities of daily
living (ADL) [53], and may increase the risk of urinary
tract infections in the elderly. Understandably,
dysfunction of the respiratory muscles increases the risk
of aspiration and aspiration pneumonia [54, 55].
Decreased masticatory muscle force and weak
swallowing function lead to malnutrition [56-60]. The
incidence of infections is known to be significantly higher
in patients diagnosed with sarcopenia and hospitalized in
geriatric wards [61]. In addition, patients with sarcopenia
have been reported to have higher HbA1c levels and be at
risk of developing diabetes [62-64]. Although sarcopenia
and diabetes are seemingly unrelated, muscles are not
only responsible for body movements but are also the
organs that account for the majority of the body's glucose
metabolism [65]. A decrease in muscle mass causes
decreased insulin sensitivity and is a risk factor for
diabetes and eventually cardiovascular diseases [13, 66].
This disorder has also recently been reported to affect the
mortality of patients with liver cirrhosis[67], cancer[21,
68-70], and other systemic disease[19, 71, 72]. Thus,
sarcopenia is also an important keyword in terms of frailty
in the elderly.
Muscle mass and bone density
Reports have shown that sarcopenia is associated with
decreased bone density. In a study conducted on 352
elderly individuals, Coin et al reported a positive
correlation between bone density and muscle mass [73].
In a survey conducted on 600 patients aged 45–80 years,
Wu et al. reported that sarcopenia was an independent risk
factor for osteoporosis [74]. In other words, it can be said
that “patients with less muscle mass have a low bone
density.” As shown in Figure 3, causes that are common
to sarcopenia and osteoporosis, such as disuse,
malnutrition, and vitamin D deficiency, lead to
simultaneous loss of bone and bone strength with a
decrease in muscle mass and a predisposition to falls [75].
These findings suggest that fractures are caused by a
combination of osteoporosis and sarcopenia.
Sarcopenia and osteoporotic fractures
Osteoporotic fractures are rapidly increasing in incidence
worldwide as the population ages [76]. According to a
report published by JOA in 2009, approximately 180,000
hip fracture cases occur per year in Japan, and
approximately 2 million vertebral fractures are reported
per year [77]. According to a report published by the
World Health Organization, hip fractures, which had an
incidence of approximately 1.5 million cases per year
worldwide in 1990, are expected to rise to 2.7 million
cases annually in 2025 (World Health Organization.
www.who.int/ageing/en/, accessed 30th, April/2009), and
the majority of this increase is predicted to be due to an
increase in the elderly population in Asian countries
including Japan and China [78]. Osteoporotic fractures
cause patients to fall into a bedridden state, severely
impacting their ADLs and leading them to require nursing
care. In other countries as well, social security costs
associated with osteoporosis are increasing steadily [79].
In world wide fragile economic condition, the prevention
of osteoporotic fractures through the early detection and
treatment of sarcopenia could be an effective prescription
for the use of limited social resources [80].
However, there have been only a limited number of
reports on the realities pertaining to sarcopenia in patients
with osteoporotic fractures [41, 81-83]. In our past study
of 327 patients with hip fracture and 2511 outpatient
controls, we found a higher prevalence of sarcopenia in
patients with hip fractures and the presence of sarcopenia
as an independent risk factor for a hip fracture [43].
Thus, sarcopenia is a potential risk factor for
osteoporosis and subsequent fracture, and its management
is the key to preventing osteoporotic fracture.

T. Hida et al Managing Sarcopenia and Fractures
Aging and Disease • Volume 5, Number 2, April 2014 5
Figure 3. Relationship between sarcopenia, osteoporosis and fracture
Etiology of sarcopenia
The etiology of sarcopenia comprises a wide variety of
causes that are involved in a complex manner, including
the aforementioned disuse secondary to comorbidities
(malnutrition[84], vitamin D deficiency [85], cerebral
infarction, heart failure, and osteoarthritis [86], disuse [6,
87]) as well as age-related hormonal changes (involving
testosterone [88-90], estrogen [91, 92], insulin-like
growth factor 1 [93], and insulin[94]), apoptosis [95],
denervation [96], and changes in inflammation and
immunity involving interleukin (IL)-1, IL-6 and tumor
necrosis factor-α[97], social causes, and mental causes
such as decline in cognitive function [98] or decrease in
social activity. It has been reported that in the histological
examination of muscle fibers, type II muscle fibers (in
other words, the so-called fast muscles) decrease with age,
while type I muscle fibers (in other words, the so-called
slow muscles) are preserved [99]. The decrease in fast
muscles causes a delay in the muscle contraction reaction
time; as a result, the righting reflex and the protective
extension reflex are too late when the body vacillates,
which may cause a fall.
Various types of signal transduction systems such as
the Akt/mTOR signaling system and the Notch signaling
system have recently been found to be involved in the
molecular mechanisms of muscle fiber tissue regeneration
[100-102]. Most of all, the Wnt/β-catenin signaling
system is one of the signal transduction pathways
involved in muscle regeneration.
Brack et al. reported that the serum of aged mice
contained high levels of Wnt, that the substances that
activated the Wnt signal in the serum caused abnormal
fibrosis in the regenerating muscle, and that they were
able to suppress fibrosis in aged mice by administering
Dkk1, a Wnt inhibitor [103]. Naito et al. reported
identifying the complement molecule C1q as a new Wnt
signal activator, where the administration of C1q in young
mice resulted in a decline in the regenerative capacity,
whereas the administration of neutralizing antibodies
against C1s resulted in an improvement of the age-related
decline in the regenerative capacity [104]. The findings

T. Hida et al Managing Sarcopenia and Fractures
Aging and Disease • Volume 5, Number 2, April 2014 6
showed that through Wnt signal activation, C1q caused a
decline in regenerative capacity after skeletal muscle
damage, which is one of the phenotypes of aging.
Interestingly, the Wnt/β-catenin signaling system is
also involved in osteoblast differentiation. In rats,
inhibition of the Wnt signaling system by using Dkk1 has
been found to decrease bone mineral density, while anti-
Dkk1 neutralizing antibody has been found to increase
bone mineral density [105]. In humans as well, blood
levels of DKK1 have been found in be elevated in patients
with osteoporosis, although the causality remains unclear
[106]. Activation of the Wnt signaling system through
sclerostin antibody is viewed as a target in the prevention
of osteoporotic fractures and the development of new
drugs for the treatment of osteoporosis [107]. However,
one should keep in mind that inhibiting Wnt signaling also
has some negative aspects, especially with regard to
muscle regeneration.
Much remains unknown in the molecular biological
mechanism of muscle aging, and further elucidation in
this area is desired.
Treating sarcopenia to prevent fractures
Multiple factors are involved in the pathogenesis of
sarcopenia; therefore, the development of a specific
treatment is quite difficult and evidence of effective
treatment is limited. The therapeutic methods that are
currently being attempted can be roughly classified as
follows: (1) exercise therapy, (2) nutritional therapy, and
(3) pharmacological treatment.
(1) Exercise therapy
There has been much evidence to support the fact that the
so-called elderly “muscle training” is effective. In
randomized controlled trials using high-intensity muscle
strength training in 39 postmenopausal women, Nelson et
al. reported improved muscle mass, muscle strength, and
balance [108]. In a meta-analysis of a total of 1,328
patients in 49 studies consisting of randomized controlled
trials on muscle strength training, Peterson et al.
concluded that muscle strength training effectively
increased muscle mass [109]. However, from the
perspective of preventing osteoporotic fractures,
performing exercise therapy directly may pose some
issues. Patients with osteoporotic fractures often show
various complications [110]. In addition to such a
deterioration of mental function, patients with a high risk
of fragile fracture are also affected by paralysis caused by
the original cerebrovascular disease, locomotor disorders
caused by osteoarthritis and complications of heart
disease; moreover, their locomotor functions are believed
to be lower than those of healthy subjects. When
clinicians are managing more debilitated elderly patients
with lower cognitive function and motor function, some
improvement is needed when performing efficient muscle
strength training while maintaining treatment compliance.
Of course, for highly active elderly patients who are
capable of performing exercise therapy by themselves, it
can be said that exercise therapy is safe and highly
effective for sarcopenia.
(2) Nutritional therapy
A study conducted on 403 institutionalized elderly
women in Japan showed a high rate (49.1%) of vitamin D
deficiency with serum 25(OH)D3 levels ≤16 ng/mL.
Patients with a potential vitamin D insufficiency are
believed to be numerous[111]. In addition to the role of
vitamin D in increasing the bone mass, vitamin D
receptors in striated muscles are also responsible for
increasing muscle strength and muscle mass[85, 112].
The ingestion of a sufficient amount of vitamin D as a
supplement is known to have a preventive effect against
falls and fractures [85, 113-115]. Administration of
vitamin D in the elderly may effectively treat sarcopenia
and prevent osteoporotic fractures.
Most elderly subjects have insufficient caloric and
protein intake, and the combination of exercise and
dietary supplements containing amino acids and proteins
may have an effect on sarcopenia. A short-term increase
in muscle mass and muscle strength results, even in the
elderly [109, 116]. Bonnefoy et al. examined the
combination of dietary supplements and exercise by using
a randomized controlled trial[117]. Dietary intervention
based on nutritional supplement drinks containing
proteins and exercise therapy was conducted for 9 months
in 57 elderly women, and the effects were compared with
those of a placebo. Forty-two participants completed the
tests and showed improved muscle strength. However, it
is important to note that the effect of dietary supplements
on preventing osteoporotic fractures has not yet been
clarified and that a decrease in adherence to nutritional
therapy may occur in addition to reduced intake of regular
food.
(3) Pharmacological treatment
Testosterone is a typical and strong anabolic hormone. A
clinical trial examining testosterone replacement therapy
was discontinued after 6 months due to an increasing
number of cardiovascular events[118]. However, a
significant increase in muscle strength was found in the
testosterone-treated group.
Clenbuterol, which stimulates β2 sympathetic
receptors and is used in the treatment of bronchial asthma,
causes an increase in skeletal muscles by acting on the

T. Hida et al Managing Sarcopenia and Fractures
Aging and Disease • Volume 5, Number 2, April 2014 7
PI3K/Akt signal system [119]. Clenbuterol is known to
increase lean meat in pork, and abused by livestock
industry in some countries. β stimulant is also a target
drug in doping tests, so that athletes were warned not to
eat pork in such countries(Telegraph Sport and Agencies.
London 2012 Olympics: China bans athletes from eating
meat for fear of ingesting banned substance clenbuterol.
The Telegraph. United Kingdom: Telegraph Media Group
Limited, 2012/03/02). Clenbuterol has previously been
reported to cause an increase in muscle mass when
administered to patients with heart failure[120]; however,
a large-scale case-control study conducted in Denmark on
patients using β-stimulants and those with osteoporotic
fractures concluded that short-acting β-stimulants were a
risk factor for osteoporotic fracture and that other types of
β-stimulants had no effect on osteoporotic fractures[121].
Angiotensin-converting-enzyme (ACE) inhibitor, the
strong candidates for the treatment of sarcopenia, was
originally an anti-hypertensive medication that was used
to prevent cardiovascular disease [122] and diabetic
nephropathy [123]. ACE inhibitors have been used for a
long time and their dosage, administration, and side
effects are already known. ACE inhibiter is known to
decrease muscle fibrosis in vitro through connective
tissue growth factor (CTGF/CCN-2) [124]. Several
clinical studies have reported that ACE inhibitor
improved exercise performance in patients with heart
failure [125-128]. Of course, these studies are biased
towards improved heart function, but the direct effect on
skeletal muscle tissue cannot be denied.
Other pharmacological therapies, such as growth
hormone [129], insulin-like growth factor1 [130], and
estrogen [92, 131, 132] have also been attempted, but no
clear evidence has yet been found. The methods for
increasing muscle mass are the same for young athletes
and the elderly. Even in the elderly, muscle mass has been
shown to increase upon engaging in muscle strength
training (exercise therapy), ingesting proteins (nutritional
therapy), and doping (pharmacological treatment).
However, the fact that there is a need to continue
treatment while maintaining safety and compliance in
debilitated elderly subjects suffering from complications
makes it difficult to treat sarcopenia.
Conclusion
Awareness of sarcopenia, specifically as a risk factor for
falls and fractures in the elderly, is necessary. The
treatment of sarcopenia will be an important element in
the future prevention of fractures. However, evidence
pertaining to the treatment of sarcopenia for the purpose
of preventing fragile fractures remains insufficient. To
reduce the number of patients suffering from osteoporotic
fractures, there is an urgent need to further elucidate the
facts about and develop therapeutic methods for
sarcopenia.
Conflicts of interest
No benefits in any form have been received or will be
received from a commercial party related directly or
indirectly to the subject of this article.
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