Volume 4, Number 3; 141-153, June 2013

Review Article

The Effects of Aging and Electrical Stimulation Exercise
on Bone after Spinal Cord Injury
James D. Dolbow1, David R. Dolbow1,2*, Ashraf S. Gorgey1,2, Robert A. Adler1,3,
David R. Gater1,21

Hunter Holmes McGuire VA Medical Center, Spinal Cord Injury and Disorders Center, 2 Physical
Medicine and Rehabilitation Department, 3 Endocrinology and Metabolism Department, Internal
Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA[Received December 22, 2012; Revised January 31, 2013; Accepted Februray 2, 2013]

ABSTRACT: Age related bone loss predisposes adults to osteoporosis. This is especially true for individuals
with spinal cord injury (SCI). The effects of decreased bone loading with older age and paralysis significantly
contribute to decreased bone mass and increased risk for fragility fractures. Loading bone via volitional muscle
contractions or by using electrical stimulation are common methods for helping to prevent and/or decrease boneloss. However the effectiveness and safety of electrical stimulation activities remain unclear. The purpose of thisreview is to investigate the factors associated with aging and osteoporosis after SCI, the accuracy of bonemeasurement, the effects of various forms of bone loading activities with a focus on electrical stimulation
activities and the safety of physical exercise with a focus on electrical stimulation cycling. Osteoporosis remains
a disabling and costly condition for older adults and for those with paralysis. Both dual energy x-ray
absorptiometry and peripheral quantitative computed tomography are valuable techniques for measuring bonemineral density (BMD) with the latter having the ability to differentiate trabecular and cortical bone. Physicalactivities have shown to be beneficial for increasing BMD however, the extent of the benefits related to aging
and paralysis remain undetermined. Electrical stimulation activities administered appropriately are assumed safedue to thousands of documented safe FES cycling sessions. However, specific documentation is needed to verify
safety and to development formal guidelines for optimal use.

Key words: aging, osteoporosis, spinal cord injury, bone mineral density, electrical stimulation exercise

Over the past century the definition of osteoporosis
has changed significantly, from “a reduced amount ofbone that is qualitatively normal” [1] to the more current
definition: “a skeletal disorder characterized bycompromised bone strength predisposing to an increased
risk of fracture. Bone strength reflects the integration of
two main features: bone density and bone quality”. Bonequality refers to architecture, turnover, damage
accumulation (e.g. micro-fractures), and mineralization[2]. In any case, the three main factors that need to behighlighted for an accurate definition of osteoporosis are1) a decrease in bone mass, 2) a decrease in bone quality
and 3) an increased risk of bone fracture.
Typically, bone mineral density (BMD) increases
throughout childhood and early adulthood. Boneremodeling becomes the predominant means by whichbone is added or removed [3]. From the time ofattainment of peak bone mass, late twenties or early
thirties, studies show that there is a decrease in bonevolume with aging in both sexes [4,5] Although thesechanges are not at all sites and not uniform, they markthe start of age related bone loss [5,6].

*Correspondence should be addressed to: David R. Dolbow. McGuire VA Medical Center, 1201 Broad Rock Blvd,
Richmond, VA 23249, USA. Email: david.dolbow@va.gov
ISSN: 2152-5250

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J.D. Dolbow et al

The specific cause of these age related changes inindividuals is unclear. While it is known that bone masschanges according to the loading history of theindividual, there are other factors, such as heredity,
nutrition, and co-morbidities that affect bone metabolism[7]. In females, changes in bone are most evident during
and after menopause, which is associated with decreased
estrogen [7,8]. The decreased estrogen is linked withincreased activation of osteoclasts which results in an
increased imbalance between resorption and formation
causing a more rapid bone loss [5,9]. In males, thereduction in sex-hormone (androgen) production istypically more gradual but also eventually results in a net
bone loss as a consequence of increased resorption anddecreased formation [10,11]. The prevalence of low bonemass has become a major concern in the United States.
According to the National Osteoporosis Foundation an
estimated 44 million individuals aged 50 and over are
affectedbyosteoporosis
andosteopenia
http://www.nof.org/node/40 which represent 55% of thetotal U.S. population in that age range. By 2020 thenumber of individuals 50 and over with osteoporosis or
osteopenia in the U.S. is expected to increase to morethan 61 million [12]. The World Health Organization has
formulated a diagnosis protocol using T-scores tocompare the BMD of an individual over the age of 50
with the average BMD of normal bone from able-bodied
young adults. The resulting difference is shown as astandard deviation represented as T-scores. T-scores fornormal BMD, osteopenia, and osteoporosis are ≥ -1.0,
between -1.0 and -2.5, and < -2.5 respectively, as definedby the World Health Organization (Table 1). While thisscore is calculated by measuring the most frequently
fractured skeletal areas of able-bodied individuals(lumbar spine, hip, wrist), this location dependentmeasurement protocol may be less valuable whenmeasuring BMD of those with spinal cord injury (SCI)
as the most frequently fractured areas are different (distal
femur, proximal tibia) [13-18]. To date there are nostandard guidelines concerning the measurement of
BMD and the diagnosis of osteoporosis specific to the
SCI population.
As reported by the National Osteoporosis
Foundation, the cost of osteoporosis in 2005 wasapproximately 19 billion dollars. This is nearly a 38%
increase from the 13.8 billion estimated in 1997. By2025 the annual cost of osteoporosis is expected to be 25
billion [19]. Additionally, loss of wages, productivity,and other indirect costs are likely to be extensive.
A primary non-pharmacological form of treatment
for the prevention and rehabilitation of osteoporosis has
been the loading of bone through weight-bearing
activities and through exercise with bone receiving
beneficial stress via vigorous muscle contractions.

Aging and Disease • Volume 4, Number 3, June 2013

Aging and Electrical Stimulation Exercise on Bone

Typically, people become less physically active with age
resulting in less mechanical bone loading which is a key
factor in stimulating bone formation.
Becauseindividuals with complete SCI lack volitional muscle
activity below the level of injury, mechanical loading of
the bones through electrical stimulation has become apopular modality. However, questions remain
concerning the effectiveness and safety of physicalactivities using electrical stimulation to reduce or reverse
the effects of osteoporosis of those with SCI.
The purpose of this literature review is to examine
the factors associated with aging and osteoporosis after
SCI, discuss the accuracy of BMD measurement,
highlight the effects of various forms of bone loading
activities with a particular focus on electrical stimulation
activities and finally to investigate the safety of electricalstimulation activities with the focus on electricalstimulation cycling.
Table 1. World Health Organization Classifications of Bone

T-scoreClassification>-1.0

Normal-1.0 - -2.5

Low bone mass, “osteopenia”(low bone density)
Osteoporosis<-2.5<-2.5 with fragility
fracture

Severe osteoporosis

Age related osteoporotic fractures
The primary consequence of osteoporosis is theincreased risk of bone fracture. Because age related boneloss is accelerated by menopause, women are twice as
likely to experience a fracture as men after age 45[20,21]. Women over 45 years of age also have a higher
likelihood of experiencing an osteoporotic fracture than a
traumatic fracture. Osteoporotic fractures, also known as
low-trauma fractures or fragility fractures occur with low
impact that is consistent with or less than falling from astanding height. This accounts for more than 1.5 million
fractures in the U.S. each year and an estimated 9 million
worldwide http://www.nof.org/node/40.
Effects of spinal cord injury on bone mineral density
Factors that affect the likelihood of osteoporotic
symptoms include age, sex, race, diet, physical activity
and paralysis [19-23] www.consensus.nih.gov/2000/
2000Osteoporosis111html.htm. While a gradual decreasein BMD is a direct effect of aging, SCI is well
documented as rapidly accelerating the bone loss process
which helps give rise to the term accelerated aging that is142

J.D. Dolbow et aloften associated with the SCI population. Within the firstfew years of complete SCI, individuals experience a
rapid 20% -50% decrease in BMD of paralyzed
extremities with the exact rate of loss being highlyvariable among those with SCI [24-36].
In paralyzed individuals, trabecular bonedemineralizes more rapidly than cortical bone. This is
likely due to the highly metabolic characteristics oftrabecular bone. De Bruin et al reported that in the spinal
cord injured population, trabecular and cortical bone loss
in the tibia was 0.4% to 80% and 1.7% to 32.7%
respectively [13]. Cortical bone, unlike trabecular bone,demineralizes more gradually due to its less metabolic
nature and is characterized by thinning of the corticalwall.
This site-specific bone loss is similar in the upper
extremities of individuals with tetraplegia. Heretrabecular bone loss was reported to be 19% in the radius
as opposed to only 4% loss in cortical bone one year
post-injury [14,37]. Furthermore, Saltzstein et al.
determined a positive correlation between BMD anddegree of mobility in the spinal cord injured population[38].
Many studies have looked at the correlation between
SCI and fractures occurring after SCI. These studies
estimate 5% to 34% of individuals will experience afracture within the first 5 years after SCI [33,35,39,40]
and as many as 70% of all individuals with SCI willsustain a low impact fracture at some point [35]. While
there is rapid loss of bone within the first few years post
SCI the mean time from injury to the first bone fracture
has been reported to be 9 years [15,41].
Because of decreased BMD, individuals with SCI
are more likely to experience a fragility fracture thanother types of fractures [42,43]. In fact, persons with SCI
have a twofold greater risk of fracture than able-bodied
individuals with the trabecular rich areas of the distal
femur and proximal tibia being most at risk [13-18].
Although there is an acceleration of bone loss below thelevel of injury, the rate of decrease in BMD varies bybone location [14,31,36]. While the lower extremities
experience large decreases in BMD at the distal femur
and proximal and distal tibia, changes in the lumbar
spine are mixed with reports of both decreases andincreases in BMD [13,44,45].
Reflecting the high incidence of fragility fractures,studies show that a large majority of the fractures to the
distal femur and proximal tibia after SCI result from falls
from wheelchairs or during other low impact activities[42,46,48]. Fracture thresholds have been reported todescribe BMD levels at which no fractures have beenreported in an effort to provide documentation of safe
BMD levels. Eser et al determined an approximate
threshold of 70mg/cm3 and 110mg/cm3 in the distal tibia

Aging and Disease • Volume 4, Number 3, June 2013

Aging and Electrical Stimulation Exercise on Boneand distal femur respectively in a study of 99 individuals
with SCI averaging 12 years post injury [49]. However, areview of BMD by Pors-Neilsen et al reported that BMD
is a poor indicator of future fracture and many
individuals with BMD below these thresholds havesafely performed and benefited from physical activities
including functional electrical stimulation leg cycle
ergometry (FES-LCE) [50].
Due to paralysis and limited mobility of individuals
with SCI, specific therapies have been studied andimplemented in the effort to slow, and possibly reverse
the process of bone demineralization. In order toquantify the effects of SCI and therapies, themeasurement of resultant changes in bone mass isrequired. To date, there is no documented standard ofcare for the prevention of osteoporotic fractures inindividuals with SCI [46,51].
Bone measurement
The key to diagnosis and assessment of systematic bonediseases and disorders is bone densitometry [12,52].
Densitometric studies assess signs of bone instability
based on established diagnosis guidelines. The mostfundamental parameters in bone densitometry are bonemineral content (BMC), and BMD. BMC is defined as
the mass of mineral of bone per unit length of bone(g/cm). BMC however is not as widely used as BMD due
to its size-dependent parameters that have been shown tomisinterpret and thus misdiagnose individuals ofdiffering heights [53,54].
BMD is a well-known predictor of future bone
fracture [23,55-57]. Dual energy x-ray absorptiometry(DXA) is the most commonly used instrument and isconsidered the “Gold Standard” for measuring BMD[49]. While a quantitative assessment of bone can be
performed by DXA, peripheral quantitative computed
tomography (pQCT) has the added ability to provide
separate analysis of trabecular and cortical bone mineraldensity [49,55,58,59]. This is important because
trabecular bone metabolism takes place at a much fasterrate than cortical bone thus, when investigating changes
in bone mass due to SCI or a treatment protocol,
trabecular bone changes are more likely to be seen first.
When examining trabecular bone and cortical bone
together as per DXA, changes in trabecular bone may bemasked by the lack of change in cortical bone. Alongwith the ability to distinguish trabecular bone fromcortical bone, pQCT accurately measures BMD at the
distal femur and proximal femur. This is advantageous in
the SCI population due the high rate of fracture as well
as differentials in bone growth and demineralization atthese locations.

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The importance of sensitive bone measurement
Many measurement techniques i.e. (DXA, pQCT, MRI,
ultra-sound) are available to assess bone mineral atmultiple sites. The most widely validated technique isdual energy X-ray absorptiometry (DXA) scanning of
the spine, hip and forearm, http://www.who.int/
chp/topics/Osteoporosis.pdf .
An important aspect of the use of bone mineral
testing in diagnosis of osteoporosis is its relation to
fracture prediction. There are significant differences in
the performance of different techniques to predict
fractures at different skeletal sites. DXA provides
measurements of BMD and a gradient of risk for
fracture. For example there is an overall increase in
fracture risk of approximately 1.5/SD decrease in BMD.
The highest gradient of risk provided by DXA is the
femoral neck at approximately 2.6/SD [60].
The international reference standard for thedescription of osteoporosis in postmenopausal womenand in men aged 50 years or more is a femoral neck
BMD of 2.5 SD or more below the young female adultmean, using normative data from Caucasian women aged
20–29 years. Although the reference standard for thedescription of osteoporosis is BMD at the femoral neck,other central sites (e.g. lumbar spine, total hip and distal
forearm) are used for diagnosis in clinical practice. Zscores can be used to compare age and gender matched
BMD measurements [60].
While traditional DXA can provide BMD scores for
total body and regions of interest specific to diagnosis ofosteoporosis in the able-bodied population (lumbar
spine, proximal femur and wrist), this information misses
the more important details from the regions of interestfor those with SCI i.e. distal femur, proximal tibia anddistal tibia [61]. While some laboratories have developed
software that allows modification of DXA measurements
to estimate BMD of the distal femur and proximal tibia,
this practice is limited. A recent study by Eser et al.
reported that in the lower extremities, volumetricmeasurement of trabecular BMD of the epiphyses using
pQCT provided evidence that measurement of trabecularbone in the tibia can help discriminate between
individuals who have had past fractures and those whohave not [49]. Having the ability to provide detailed
analysis of bone (trabecular and cortical) may prove tobe advantageous for assessing future fractures howeverlong term studies concerning pQCT’s ability to assess
fractures are needed.
As previously mentioned, DXA does not have theability to differentiate trabecular bone from corticalbone. Moreover, BMD values when determined by DXA
have been shown to be dependent on composition anddistribution of soft tissue [50,61,62]. This may be sub-Aging and Disease • Volume 4, Number 3, June 2013

Aging and Electrical Stimulation Exercise on Boneoptimal, as studies have shown that body compositionchanges significantly after SCI [63,64]. Conversely,
measurements performed by pQCT not only distinguishtrabecular bone from cortical, but also make osteologic
judgments with less influence from the surrounding
tissue [56].
It also needs to be clearly understood that DXA
measurements of BMD are two-dimensional or areal
measurements where as pQCT measurements are threedimensional or volumetric. For this reason bone size canaffect the measurement of BMD as two vertebrae may
have identical volumetric densities but have different
areal densities. For this reason age may affect the resultsof DXA scans as the size of bones change during theaging process [12].
Modeling, remodeling, and bone loading
Through the natural process of bone modeling, bone
adapts its shape and size as a response to stress or boneloading [55]. During bone modeling, mechanical loading
alters the movement and arrangement of osteoclast cells
and osteoblast cells, which in turn results in thickeningof the cortical wall and improvements in trabecular
BMD [55,65-67]. Strain, which is the conditional resultof bone loading, has been extensively studied and shown
to change the architecture of bone as well as stimulate
growth in the process of bone healing [68-72]. Boneremodeling is the process of constant bone removal byosteoclasts and the reformation of new bone byosteoblasts. This method of continuous bone renewal
occurs throughout life [55,73].
Opposite of bone loading, bone unloading occurs in
SCI individuals due to paralysis and sedentarism. During
this time the trabecular lattice rapidly deteriorates and isgradually replaced with fatty marrow [74]. Dauty et al
conducted a study that showed that the extensive
immobility of SCI individuals was the most significant
factor in the demineralization of bone in the trochantericarea and proposed that verticulation of the body may
help slow the process of bone loss [28]. For the past half
century bone loading therapies using standing frames
and other aided-walking devices have been studied inattempts to attenuate the effects of osteoporosis in the
SCI population [75].
Studies have been mixed concerning the effects ofpassive standing. While some studies show no
significant affect in BMD of individuals that participate
in passive standing therapies others have demonstrated
that passive standing may have a positive affect during
the early stages of SCI [26,76,77]. Studies by Goemare etal and Alekna et al, reported that individuals
participating in prolonged passive standing therapies
shortly after SCI had a decreased rate of bone loss at the144

J.D. Dolbow et alfemoral shaft according to DXA measurements [78,79].
The attenuating effects of passive standing and walking
were studied by de Bruin et al using pQCT
measurement. Similarly, de Bruin reported a reduced rateof BMD loss overall and that trabecular bone inparticular could be preserved with early passive standing
and walking interventions [80]. New technology has
allowed for testing the advantages of body weightsupported treadmill training and mechanical orthosis, buthave resulted in limited osteogenic benefits [80-83].
However, it should be noted that few studies reporting
the effects of vertical loading on BMD in the SCI
population, measure BMD using pQCT. One such study
discovered significant benefits in the attenuative
properties of passive standing and walking [80].
While static loading therapies such as passive
standing are recommended to mitigate the damaging
effects of extended bed rest, dynamic bone loading
therapies have been recognized as more effective forbuilding BMD [84,85]. Studies involving partial orwhole body vibration have been conducted in efforts tomore accurately represent the musculoskeletal stresses
present in normal activities of daily living (ADL) [8688]. In a study by Rubin et al, sheep were exposed to
low levels of high-frequency vibrations while standing inplace for 20 minutes per day, five days a week for 1
year. A significant increase in the trabecular BMD wasreported [85]. Additionally, studies in whole body
vibration (WBV) further showed the benefits of dynamic
therapies reporting an increase in BMD in the hips ofwomen post-menopause [86-88]. Limited study has been
completed concerning body weight supported treadmill
training and its effects on bone mass, with no significant
support related to prevention of bone loss [89].
Although this literature review focuses on the effects
of decreased mechanical loading on bone after SCI, thereader should be aware that there are other components
of bone remodeling impacted by SCI including theendocrine system (blunted anabolic activity, blunted
catecholamines and decreased Vitamin D), neurologicalalterations (sensori-neural and sympathetic nervous
system blunting) and increased inflammatory processes
as demonstrated by elevated serum levels of C-reactive
protein (CRP) a sensitive marker for systemic
inflammation that is associated with obesity. However,further discussion of these factors move us beyond thescope of this review.
Electrical stimulation exercise
In the field of SCI rehabilitation, electrical stimulation
exercise has become a widely researched and practiced
therapy [90]. Due to common paralysis of the lower
extremities (LE) in both paraplegia and tetraplegia,

Aging and Disease • Volume 4, Number 3, June 2013

Aging and Electrical Stimulation Exercise on Boneseveral electrical stimulation exercise therapies involving
hybrid orthotics, neuromuscular electrical stimulation(NMES) and leg cycle ergometry have become part of
the rehabilitation treatment.
While few studies have investigated the osteogenic
benefits of hybrid orthotics to date, these studies reportminimal to no effect on BMD [91,92]. However, newhybrid orthotic devices are currently under study which
provides encouragement for more positive outcomes in
the near future. Several studies have examined theeffects of NMES knee extension (KE) on BMD [93-95].
Two of these studies tested effects after 3 months ofthrice weekly NMES-KE on individuals averaging 4-6
years post-injury and reported a decrease in the rate ofloss of tibial trabecular BMD [93,94]. Additionally, a
study by Belanger et al reported that when individuals
with an average of 10 years post-injury performed
NMES-KE 5 times per week for 6 months, 28% of lost
BMD in the distal femur and proximal tibia was regained[95]. Unlike some other electrical stimulation therapies,
NMES-KE often involves resistance against theparalyzed limb. While this limb resistance is added toincrease strain on the bone and thus intensify boneloading, the addition of resistance appeared to have little
or no impact on bone as Belanger et al reported nosignificant difference in BMD in limbs exercised withadded resistance and those exercised without [95].
Other studies have tested the effects of NMES
plantar flexion (PF) on BMD [37,96,97]. Two of thesestudies tested the effects of NMES-PF performed 5 times
per week for >2 years on individuals <4 months postinjury [37,96]. Both of these studies reported an
attenuated rate of BMD loss. When NMES-PF was
performed 5 times per week for approximately 1 year in
SCI individuals averaging 9 years post-injury, no
significant osteogenic benefits were reported.
These studies suggest that NMES may help attenuate
BMD loss early after SCI with therapy sessions 5 times
per week. Also, reports suggest that effects on BMD aresite-specific. The affect of inclusion of limb resistanceand particular guidelines for training are still to be
determined.
Functional electrical stimulation leg cycling
ergometry (FES-LCE) has been used in the SCI
population to improve glucose uptake and protein
expression [98] cardiac output [99], body composition[100], oxygen uptake [99] and increase BMD in the LE[92-94,101-103]. Like other electrical stimulation
exercises, FES-LCE produces muscle contractions that inturn apply stress to the bone. Studies on the impact of
FES-LCE in SCI individuals have reported bothsignificant increases and decreases in BMD. Because of
the wide range of variability in participants andmeasuring techniques, it is difficult to analyze the145

J.D. Dolbow et al

Aging and Electrical Stimulation Exercise on Boneefficacy and safety of this type of bone loading in the
SCI population.
In an attempt to cut through the variability, studies
with similar variables of interest were grouped together
for comparison. In the 10 FES-LCE studies analyzed
here, the variables grouped together were: mean timepost-injury, mean age of participants, intensity andfrequency of therapy, duration of therapy, andmeasurement techniques/device [94,101-109].
Results of various studies show that FES-LCE has
an attenuating effect on rapid bone loss early after SCI.
Two studies reporting on the effects of FEC-LCE
therapy in the first 2 months post injury report adecreased rate of loss. Of the studies performed at an
average of 3-6 years post-injury only one study reports

benefits. This study by Bloomfield et al reported anincrease in BMD in participants who exercised at 18
Watts or more [108]. When the studies were conducted at
an average 9-13 years post-injury, significant benefits
were reported in 4 out of 5 reviewed studies. It appears
that FES-LCE may help slow the process of bone loss inearly SCI as well as increase BMD long after SCI. These
results are concordant with a study by Eser et al thatfound that bone mass as well as total and trabecular
BMD in the femur and the tibia can take 3-8 years toreach a steady state [15]. Studies reporting increases in
BMD in individuals averaging 9-13 years post injury
indicate that osteogenic effects may be more easily seen
after plateauing takes place (Table 2).

Table 2. Effects of Time Post-Injury on FES-LCE Results< 2 Months

3-6 Years

9-13 Years

Lai et al [104]Decrease in rate of BMD loss in
DF (DXA)
Eser et al [105]
Small decrease in rate of BMD
loss (pQCT)

Sloan et al [106]No significant difference(DXA)
Leeds et al [107]No significant difference(DXA)
Bloomfield et al [108]No significant difference in BMD(DXA)Chen et al [102]11% and 13% increases in DF and PT
BMD respectively (DXA)
BeDell et al [109]No significant difference in hip BMD(DXA)
Frotzler et al [103]14% and 7% increases in DF BMDtrab
and BMDtot respectively (pQCT)
Hangartner et al [94]Decreased rate of BMD loss (pQCT)Mohr et al [101]
10% increase in BMD in PT (pQCT)

DF=distal femur; PT=proximal tibia; trab= trabecular; tot=total

In order from least to greatest frequency of therapy(sessions/week) results show osteogenic benefits of FESLCE may be positively correlated with frequency of
FES-LCE therapy sessions. Studies involving FES-LCE
therapy 2 times per week showed no benefits whilesessions performed 3 times per week were mixed.
Notably, only studies consisting of FES-LCE therapy
sessions 5 times per week consistently reported
substantial improvements in BMD, particularly in the
distal femur (Table 3).
Due to the slower bone metabolic processes relative
to muscle and fat, it is widely accepted that interventions
hoping to produce a measureable change in bone musttake place over several months. These studies reflect that
belief as all of the studies included interventions of 6months or greater. Of the FES-LCE studies shown here,
there appears to be no direct correlation between the
duration of therapeutic intervention and efficacy.
However it should be noted that both of the studies that

Aging and Disease • Volume 4, Number 3, June 2013provided FES-LCE for a minimum of 12 months showed
increases in BMD. Significant benefits were also foundin the study by Chen et al that only had a 6 monthintervention period 5 times per week [102]. While there
appears to be no direct correlation between duration of
FES-LCE therapies after 6 months and BMD benefits,
increases in BMD were found in therapies that last atleast 6 months (Table 3).
Concerning bone measurement after FES-LCE,
Chen at el found 11% and 13% increases in BMD at the
distal femur and proximal tibia respectively and Lai et al
found a decrease in the rate of bone loss in the distal
femur both using DXA to measure BMD [102-104]. The
remaining 4 studies using DXA found no improvements
in BMD. This is in contrast to all 4 studies using pQCT
which found either increases in BMD or decreases in therate of bone loss compared to controls. Thus, while not
all studies that reported improvements in bone used

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J.D. Dolbow et al

Aging and Electrical Stimulation Exercise on BonepQCT, all of the studies that did use pQCT showed some
improvement after training with FES-LCE (Table 3).
Tables 2 & 3 show several notable trends. Studies
showed that during periods of rapid bone loss in theearly stages after SCI, increases in bone mass wereabsent although the rate of bone loss was decreased inseveral studies. However, several years post SCI and
presumably after the rate of bone loss had slowed to nearage related bone loss, increases in BMD after FES-LCE
was possible. Additionally, FES-LCE therapy regimens
with higher frequency and duration resulted in greater
improvements. Finally, the amount of therapeutic
benefit reported from FES-LCE appears to be positively
correlated with the ability to examine bone
microarchitecture thus it appears that being able toanalyze trabecular and cortical bone separately provides
valuable information concerning bone alterations withtraining.
Effects of reduced training and detraining on FESLCE efficacy
Of the FES-LCE studies examined, 4 incorporated
follow up testing concerning the effects of detraining or
reduced training on FES-LCE [100-103]. In those that
tested detraining, Chen et al and Lai et al reported thatthe rate of BMD loss resumed to pre-training levels after
cessation of FES-LCE at 6 months and 3 months
respectably [102,104]. However, in a follow up study by
Frotzler et al where FES-LCE was discontinued after 1
year of cycling 5 times per week, trabecular BMD andtotal BMD were preserved by 73% and 64% respectively
at the distal femur after 6 months [110].
Of the studies testing the effects of reduced training,
Mohr et al reduced FES-LCE regimen from 3 sessions
per week to 1 session per week for 6 months and foundthat BMD returned to pre-training levels [101]. However,when the FES-LCE sessions were reduced from 5 times
per week to 2-3 times per week for 6 months, Frotzler etal found that gained BMD was preserved at 95%
trabecular BMD and 96% total BMD in the distal femur[110]. While these studies report mixed results, it may beinteresting to note that the only study utilizing ameasuring
deviceable
toexaminebone
microarchitecture reported preservation of bone withbone reduced training and detraining. In addition to
NMES-KE, NMES-PF, and FES-LCE, new technology
has allowed the testing of FES rowing therapies. While
FES rowing has shown to be beneficial to peak oxygen
consumption and peak heart rate in SCI individuals, nofound studies report benefits to bone [111,112].

Table 3. Effects of Frequency and Intensity on FES Therapy Results
2 sessions/week

3 sessions/week

5 sessions/week

BeDell et al [109]No significant difference in hip BMD(~9 months)

Lai et al [104]Decrease rate of BMD loss in DF(3 months)

Bloomfield et al [108]No significant difference in BMD(~9 months)

Eser et al [105]
Small decrease in rate of BMD loss
(6 months)

Chen et al [102]11% and 13% increases in DF and PT
BMD respectively(6 months)
Frotzler et al [103]14% and 7% increases in DF BMDtrab
and BMDtot respectively(12 months)

Leeds et al [107]No significant difference in BMD(6 months)
Sloan et al[106]No significant difference in BMD(3 months)
Mohr et al [101]
10% increase in BMD in PT(12 months)
Hangartner et al [94]Decreased rate of BMD loss
(3 months)
DF=distal femur; PT=proximal tibia; trab= trabecular; tot=total

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J.D. Dolbow et al

Functional electrical stimulation cycling for older
adultsThere is a lack of research concerning the effects ofelectrical stimulation activities on older adults as moststudies have focused on younger adults. However, in two
published case reports of thrice weekly FES-LCE on
older adults with chronic SCI, physiological andpsychological benefits were shown (increased lean mass,decreased % body fat, and increased scores on quality oflife questionnaires) but there were no changes in BMD[113,114]. It must be noted that one study duration was
only 8 weeks which is typically considered too soon tosee changes in BMD and both studies measured total
BMD via DXA which does not have the ability toseparate trabecular and cortical bone values. Long term
studies using pQCT to measure BMD in older adults
with chronic SCI are needed to determine the effects oflonger term FES-LCE. In addition the lack of data
concerning electrical stimulation activities on older
adults with SCI and osteoporosis gives rise to thequestion of the safety.
Safety: functional electrical stimulation
Safety has become an increased consideration in FESLCE therapies. This concern was sparked by a study
performed in 1984 during which a SCI patient
experienced a lateral femoral condyle fracture during themeasuring of maximal isometric muscle testing [115].
Even though isometric maximal muscle strength testingis vastly different than FES-LCE, the fact that they bothuse electricity as the external stimulus creates the needfor a closer examination. One major factor that theinvestigators theorized contributed to the fracture was aspontaneous spasm that took place in the quadriceps andthe hip flexors just before the fracture occurred. A
review of this case was conducted by Hartkopp andcolleagues in which the circumstances surrounding thecase were analyzed and further discussed [116].
The subject who experienced the fracture was a 50
year old male 4 years post motor complete SCI at level
T6. Within the year before the fracture the subject safely
trained using FES-LCE for 6 months (twice a week for
30 minutes per day) in addition to beginning recreational
walking therapy. Furthermore, a short time before thestudy resulting in the fracture, the subject had
participated in a tibialis anterior training study lasting for
2 months. The subject also owned a standing frame
which he used at home a minimum of 1 hour several
times per week. Preliminary measurements found thesubject had a BMD that was 40% lower thancorresponding age- and sex- matched individuals in theable-bodied population.

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Aging and Electrical Stimulation Exercise on Bone

After reviewing the case, Hartkopp, et al proposedseveral key experimental factors that they report likely
placed extraneous stress on the bone [116]. One major
conditional factor that may have precipitated the fracture
was the fixed 90 degree flexion of the knee. At thisangle, a maximal isometric contraction can have acontact force at the patellofemoral joint of up to 3.4
times the individual’s body weight [117]. Studies suggestthat testing with the knee flexed approximately 30
degrees can reduce this compression force at thepatellofemoral joint by 40% [117,118]. The dangers of
ES on a fixed limb are non-existent in FES-LCE as FESLCE limbs are constantly moving and never fixed.
Additionally, in the case of the fracture, electricalintensities were reported to be up to 800 mA and theintensity together with the muscle spasm was estimatedto produce a force of 92.5 Nm on the fixed limb. This
extreme intensity is far above conditions in FES-LCE
that typically have a maximum electrical current of
140mA. This removes any unnecessary stress on thelimb during exercise.
Another safety recommendation proposed by
Hartkopp et al was to reduce electrical stimulation
frequency to 50 Hz or less to reduce the likelihood ofspasm. This recommendation is well respected in FESLCE as exercise default settings for electrical frequency
are typically 33 Hz [116]. Furthermore, modern FESLCE equipment such as the RT300 cycle has spasm
control features that immediately stop the activity whena spasm is detected. FES-LCE cycles also have safetyaccommodations that account for resistance speed. Thesefeatures automatically reduce the amount of resistance if
cycle speed drops below a pre-set control speed. This is asafety precaution preventing excessive fatigue.
Lastly, the strength of the bone in relation to theimproved strength in LE muscle during FES-LCE was aconsidered possible safety risk. As has been wellestablished, FES-LCE stimulates improvements instrength in the lower extremities [66,68,95]. This being
the case, the fragility of the bone should be taken into
consideration. In 2008 Frotzler et al published a study
establishing similar BMD safety thresholds (114mg/cm3
and 72mg/cm3 for the distal femur and distal tibia).
However after muscle conditioning and 12 months of
FEC-LCE, participants who initially had BMD below
this threshold were above it after the FEC-LCE therapy[103]. Comparable studies using FES-LCE have also
reported results showing an increase in BMD at the distal
femur and proximal tibia [101-104,108].
The argument can be made that some FES-LCE
studies have reported a decrease in BMD [85,95,96].
This being the case, it is also well known that the rate ofbone loss in the first couple years of SCI is rapid[13,26,32-36]. Studies that resulted in a decrease in148

J.D. Dolbow et al

BMD were conducted within this initial 2 year period.
Each also reported a significant attenuation in the rate ofloss compared to individuals not receiving FES-LCE
therapies. We could find no cases that report anacceleration of bone loss during FES-LCE training.
We were unable to find consistent documentation inmost studies concerning the BMD T-scores ofparticipants in order to document the safety records ofthose with -2.5 or less T-scores (osteoporosis) while
participating in FES-LCE. This information is needed toconfirm the safety of FES-LCE activities for individuals
with chronic SCI and significant bone loss. The absenceof reported bone fractures in the literature during FESLCE, an activity that has been utilized for several
decades, indicates the probable lack of bone fracturesduring this activity and a level of low risk of fracture isassumed. However, documented data is needed forverification.
Concerning the development of osteoporosis after
SCI and the effects of physical activity on thedevelopment of osteoporosis, in a poster presentation at
the “International Society for Clinical Densitometry” in
2009, Sadowski et al reported on the Prevalence andRisk Factors for Osteoporosis in Individuals with
Paralysis. BMD was determined by DXA of the lumbar
spine and bilateral hips. Thirty-three percent (51/154) ofindividuals with paralysis were found to haveosteoporosis, defined as one or more regions with a Tscore equal to or less than -2.5. There was no significant
difference in the prevalence of osteoporosis with regards
to gender (male 33.3 %, female 32.7 %) (p = 0.94), or
level of injury (tetraplegia 34.8 %, paraplegia 30.8 %) (p=0.60). Osteoporosis was more prevalent in individuals
whose injury was over 1 year old (under 1 year injury,
13.3 %, 1-5 years 41.4 %, over 5 years 33.3 %)(p=0.024) [119]. A later poster presentation with thesame title presented by Whiting et al at the Kennedy
Krieger Institute Research Symposium: Contemporary
Trends in Spinal Cord Injury Management, 2012
reported on a total of 290 adults with paralysis using
DXA of the lumbar spine and bilateral hips and similarly
found that 105 or 36% of the participants had T-scores of-2.5 or less. Using multivariate logistic regression
analysis, the researchers estimated that osteoporosis was
61% fewer among SCI participants that were ambulatoryand 48% fewer for those that participated in FES-LCE 2
or more times per week [120].

Aging and Electrical Stimulation Exercise on Boneability to differentiate trabecular and cortical bone which
is valuable when determining fracture risk andeffectiveness of treatments involving bone mass of thosewith SCI.
There is ample evidence showing thatphysical activities that provide adequate stress to bone
can play a role in the improvement in BMD. Whether
these improvements are enough to prevent or reduce
osteoporosis and decrease fractures still remains
undetermined. Because of the lack of documentation
concerning BMD T-scores and osteoporotic identifiers inmost of the studies using FES-LCE, it is not possible toquantify the numbers of persons with SCI andosteoporosis that have safely used FES-LCE.
However, we can confidently state that hundreds ofindividuals with SCI have performed thousands of FESLCE sessions and due to the lack of documentation
concerning bone fractures resulting from FES-LCE, we
can state that FES-LCE has been shown to be a safe
activity.
However,
descriptive
researchdata
demonstrating safe use of FES-LCE by older individuals
with SCI and osteoporosis is needed to verify theassumption that this activity is safe for older adults withSCI and osteoporosis. This data is also needed to provide
information for the development of guidelines for
optimal and safe exercise parameters.
Declaration of Interest
The authors of this paper have no conflict of interest to
declare financially, personally or otherwise.
References
[1]
[2]

[3]

[4]
[5]

[6]

Conclusion
Osteoporosis remains a disabling and costly condition
for older adults and for persons with paralysis. While
DXA and pQCT are both valuable forms of
measurement concerning BMD, pQCT has the unique

Aging and Disease • Volume 4, Number 3, June 2013[7]

Albright F (1947). Osteoporosis. Ann Intern Med, 27:
861-882.
NIH Consensus Development Panel on Osteoporosis
Prevention, Diagnosis, and Therapy. Osteoporosis
prevention, diagnosis, and therapy (2001). JAMA,
285:785-795.
Heaney RP, Abrams S, Dawson-Hughes B, Looker A,
Marcus R, Matkovic V (2000). Peak bone mass.
Osteoporos Int, 11:985–1009.
Mazess RB (1982). On aging bone loss. Clin Orthop
Relat Res, 165:239–252.
Parkinson IH, Fazzalari NL (2013). Characterisation ofTrabecular Bone Structure. Silva MJ, editor. Skeletal
Aging and
Osteoporosis: Biomechanics
andMechanobiology. Springer. 31-46.
Birkenhager-Frenkel DH, Courpron P, Hupscher EA,
Clermonts E, Coutinho PI, Schmitz PL, et al. (1988).
Age-related changes in cancellous bone structure. A
two-dimensional study in the transiliac and iliac crest
biopsy sites. Bone Miner, 4:197–216.
Kanis JA, Borgstrom F, De Laet C, Johansson H,
Johnell O, Jonsson B, et al. (2005). Assessment of
fracture risk. Osteoporos Int, 16: 581–589.

149

J.D. Dolbow et al[8]Compston JE, Mellish RWE, Croucher P, Newcombe
R, Garrahan NJ (1989). Structural mechanisms oftrabecular bone loss in man. Bone Miner, 6:339–350.
[9]
Riggs BL, Melton LJ (1986).
Involutional
osteoporosis. New England J Med, 314:1676–1686.
[10] Kaufman JM, Goemaere S (2008). Osteoporosis inmen. Best Pract Res Clin Endocrinol Metab, 22:787–812.
[11] Szulc P, Kaufman JM, Delmas PD (2007). Biochemicalassessment of bone turnover in men. Osteoporos Int,
18:1451–1461.
[12] Bonnick SL, Lewis LA (2006). Bone Densitometry forTechnologists. 2nd Ed. Totawa, NJ: Humana Press Inc.
[13] de Bruin ED, Dietz V, Dambacher MA, Stussi E(2000). Longitudinal changes in bone in men withspinal cord injury. Clin Rehabil,14(s2):145-152.
[14] Frey-Rindova P, de Bruin ED, Stussi B, Dambacker
MA, Dietz V (2000). Bone mineral density in upper andlower extremities during 12 months after spinal cord
injury measured by peripheral quantitative computed
tomography. Spinal Cord, 38(s1):26-32.
[15] Eser P, Frotzler A, Zehnder Y, Wick L, Knecht H,
Denoth J, Schiessl H (2004). Relationship between the
duration of paralysis and bone structure: a pQCT studyof Spinal cord injured individuals. Bone, 34(5):869880.
[16] Garland DE, Adkins RH (2001). Bone loss at the kneein spinal cord injury. Top Spinal Cord Inj Rehabil,
6(3):37-46.
[17] Frisbie JH (1997). Fractures after myelopathy: The risk
quantified. J Spinal Cord Med, 20:66-69.
[18] Ingram RR, Suman RK, Freeman PA (1989). Lower
limb fractures in the chronic spinal cord injured patient.
Paraplegia, 27:133-139.
[19] Burge R, Dawson-Hughes B, Solomon DH, Wong JB,
King A, Tosteson A (2007). Incidence and economic
burden of osteoporosis-related fracture in the Unitedstates, 2005-2025. J Bone Miner Res, 22:465-475.
[20] Cummings S, Black D (1993). Bone density at various
sites for prediction of hip fracture. Lancet, 341: 72-75.
[21] Borer KT (2005). Physical Activity in the Prevention
and Amelioration of Osteoporosis in Women:
Interaction of Mechanical, Hormonal and Dietary
Factors . Sports Med, 35:779-830.
[22] Hannan MT, Felson DT, Dawson-Hughes B, Tucker
KL, Cupples CA, Wilson PW, et al. (2000). Risk
Factors for Longitudinal Bone Loss in Elderly Men and
Women: The Framingham Osteoporosis Study. J Bone
Miner Res, 15:710–720.
[23] Russo CR, Lauretani F, Bandinelli S, Bartali B, Di Iorio
A, Volpato S, et al. (2003). Aging bone in men andwomen: beyond changes in bone mineral density.
Osteoporosis Int, 14:531-538.
[24] Johnell O, Kanis JA (2006). An estimate of theworldwide prevalence and disability associated withosteoporotic fractures Osteoporosis Int, 17:1726-1733.
[25] Biering-Sorensen F, Bohr HH, Schaadt OP (1990).
Longitudinal study of bone mineral content in the
lumbar spine, the forearm and the lower extremities
after spinal cord injury. Eur J Clin Invest, 20:330-335.

Aging and Disease • Volume 4, Number 3, June 2013

Aging and Electrical Stimulation Exercise on Bone
[26]

[27]

[28]

[29]

[30]

[31]

[32]

[33]

[34]

[35]

[36]

[37]

[38]

[39]
[40]
[41]

[42]

Biering-Sorensen F, BohrH, Schaadt O (1988). Bonemineral content of the lumber and lower extremities
years after spinal cord lesion. Paraplegia, 26:293-301.
Chantraine A, Nusgens B, Lapiere CM (1986). Boneremodeling during the development of osteoporosis inparaplegia. Calcif Tissue Int, 38:323-327.
Dauty M, Perrouin Verbe B, Maugars Y, Dubois C,
Mathe JF (2000). Supralesional and sublesional bonemineral density in spinal cord-injured patients. Bone,
27:305-309.
Del Puent A, Pappone N, Mandes MG, Mantova D,
Scarpa R, Oriente P (1996). Determinants of bonemineral density in immobilization: A study onhemiplegic patients. Osteoporosis Int, 6:50-54.
Dolbow DR, Gorgey AS, Daniels JA, Adler RA, Moore
JR, Gater DR Jr. (2011). The effects of spinal cord
injury and exercise on bone mass: A literature review.
NeuroRehabilitation, 29:261–269.
Garland DE, Stewart CA, Adkins RH, Hu SS, Rosen C,
Liotta FJ, Weinstein DA (1992). Osteoporosis after
spinal cord injury. J Orthop Res, 10:3871-78.
Garland DE, Adkins RH, Kushwah V, Stewart C.
(2004) Risk factors for osteoporosis at the knee in the
spinal cord injury population. J. Spinal Cord Med,
27(3):202-206.
Lazo MG, Shirazi P, Sam M, Giobbie-Hurder A,
Blacconiere MJ, Muppidi M (2001). Osteoporosis andrisk of fracture in men with spinal cord injury. Spinal
Cord, 39:208-214.
Sheild RK (2002). Muscular, skeletal, and neural
adaptations following spinal cord injury. J Orthop
Sports Phys Ther, 32:65-74.
Szollar SM, MartinEM, Sartoris DJ, Parthenmore JG,
Deftos LJ (1998). Bone mineral density and indexes ofbone metabolism in spinal cord injury. Am J Phys Med
Rehabil, 77:28-35.
Uebelhart D, Demeaux-Domenech B, Roth M,
Chantraine A (1995). Bone metabolism in spinal cord
injured individuals and in others who have prolonged
immobilization. A review. Paraplegia. 33:669-73.
Shields RK, Dudley-Javoroski S, Frey Law LA. (2006)
Electrically induced muscle contractions influence bonedensity decline after spinal cord injury. Spine,
31(5):548-553.
Saltzstein RJ, Hardin S, Hastings J (1992).
Osteoporosis in spinal cord injury: using an index ofmobility and its relationship to bone density. J Am
Paraplegia Soc, 15(s 4):232-234.
Heaney RP (1998). Pathophysiology of osteoporosis.
Endocrinol Metab Clin North AM, 27:255-65.
Jiang SD, Dai LY, Jiang LS (2006). Osteoporosis after
spinal cord injury. Osteoporos Int, 17:180–192.
Ragnarsson KT, Sell GH (1981). Lowers extremities
fracture after spinal cord injury: a retrospective study.
Arch Phys Med Rehabil, 62:418-423.
Zehnder Y, Lüthi M, Michel D, Knecht H, Perrelet R,
Neto I, et al. (2004). Long-term changes in bonemetabolism, bone mineral density, quantitative
ultrasound parameters, and fracture incidence after
spinal cord injury: a cross-sectional observational study

150

J.D. Dolbow et al

[43]

[44]

[45]

[46]

[47]

[48]

[49]

[50]

[51]
[52]

[53]

[54]

[55]
[56]

[57]

in 100 paraplegic men Osteoporosis International,
15:180-189.
Keating JF, Ker M, Delargy M (1992). Minimal trauma
causing fractures in patients with spinal cord injury.
Disablil Rehabil, 14:108-109.
Qin W, Bauman WA, Cardozo C (2010). Bone andmuscle loss after spinal cord injury: organ interactions.
Ann NY Acad Sci, 1211:66-84.
Sabo D, Blaich S, Wenz W, Hohmann M, Loew M,
Gerner HJ (2001). Osteoporosis in patients withparalysis after spinal cord injury A cross sectional studyin 46 male patients with dual-energy X-ray
absorptiometry. Archives of Orthopaedic and Trauma
Surgery, 121:75-78
Morse LR, Lazzari AA, Battagino R, Stolzmann KL,
Matthess KR, Gagnon DR, et al. (2009). Dual Energy
X-Ray Absorptiometry of the Distal Femur May Be
More Reliable than the Proximal Tibia in Spinal Cord
Injury. Arch Phys Med Rehabil, 90:827-831.
Kirby RL, Ackroyd-Stolarz SA, Brown MG, Kirkland
SA, MacLeod DA (1994). Wheelchair-related accidents
caused by tips and falls among noninstitutionalized
users of manually propelled wheelchairs in Nova
Scotia. Am J Phys Med Rehabil, 73:319-330.
Vestergaard P, Krogh K, Rejnmark L, Mosekilde L(1998). Fracture rates and factors for fractures inpatients with spinal cord injury. Spinal Cord, 36:790796.
Eser P, Frotzler A, Zehnder Y, Denoth J (2005).
Fracture threshold in the femur and tibia of people withspinal cord injury as determined by peripheral
quantitative computed tomography. Arch Phy Med
Rehabil, 86:498-504.
Pors-Nielsen S (2000). The fallacy of BMD: a criticalreview of the diagnostic use of x-ray obsorptiometry.
Clin Rheumatol, 19:174-183.
Cummings SR, Bates D, Black DM (2002). ClinicalUse of Bone Densitometry. JAMA,288:1889-1897.
Genant HK, Engelke K, Fuerst T, Harris ST, Gluer CC,
Grampp S, et al. (1996). Noninvasive assessment ofbone mineral structure: state of the art. J Bone Mineral
Res, 11:707-730.
Gilsanz V (1998). Bone density in children: a review of
the available techniques and indications. Eur J Radiol,
26:177-182.
Rauch F, Schoenau E (2001). Changes in bone density
during childhood and adolescence: an approach basedon biological organization. J Bone Miner Res, 16:597604.
Brandi ML (2009). Microarchitecture, the key to bonequality. Rheumatology, 48(S4):iv3-iv8.
Melton LJ III, Atkinson EJ, O'Fallon WM, Wahner
HW, Riggs BL (1993). Long-term fracture prediction
by bone mineral assessed at different skeletal sites. J
Bone Miner Res, 8:1227–1233.
Black DM, Cummings SR, Genant HK, Nevitt MC,
Palermo L, Browner W (1992). Axial and appendicularbone density predict fracture in older women. J Bone
Miner Res, 7:633–638.

Aging and Disease • Volume 4, Number 3, June 2013

Aging and Electrical Stimulation Exercise on Bone
[58]

[59]

[60]

[61]

[62]

[63]

[64]

[65]

[66]
[67]

[68]

[69]

[70]
[71]
[72]

Black DM, Greenspan SL, Ensrud KE, Palermo L,
McGowan JA, Lang TF, et al. (2003). The effects ofparathyroid hormone and alendronate alone or in
combination in postmenopausal osteoporosis. N Engl J
Med, 349:1207-1215.
Black DM, Bilezikian JP, Ensrud KE, Greenspan SL,
Palermo L, Hue T, et al. (2005). One year ofalendronate after one year of parathyroid (1-84) for
osteoporosis. N Engl J Med, 353:555-565.
Shields RK, Schlechte J, Dudley-Javoroski S, Zwart
BD, Clark SD, Grant SA, et al. (2005). Bone Mineraldensity after spinal cord injury: a reliable method ofknee measurement. Arch or phys med and rehabil,
86:1969-1973.
Tothill P, Laskey MA, Orphanidou CI, van Wijk M(1999). Anomalies in dual energy X-ray absorbtiometry
measurements of total-body bone mineral during weightchange using Lunar, Hologic and Norland instruments.
Dr J Radiol, 72:661-669.
Farrell T, Webber C (1989). The error due to fat
inhomogeneity in lumbar spine bone mineralmeasurements. Clin Phys Physiol Meas, 10:57-64.
Spungen AM, Adkins RH, Stewart CA, Wang J,
Pierson RN Jr, Waters RL (2003). Factors influencing
body composition in persons with spinal cord injury: across sectional study. Journal of Applied Physiology,
95:2398-2407.
Kocina P (1997). Body composition of spinal cord
injured adults. Sports Medicine. (Auckland, N.Z.),
23:48-60.
Hangartner TN, Gilsanz V (1996). Evaluation ofcortical bone by computed tomography. J Bone Miner
Res, 11:1518-25.
Frost HM (1987). Bone “mass” and the “mechanostat”:
A proposal. Anat Rec, 219:1–9.
Heinonen A, Sievanen H, Kyrolainen H, Perttunen J,
Kannus P (2001). Mineral mass, size, and estimatedmechanical strength of triple jumpers’ lower limb.
Bone, 29:279–85.
Kontulainen S, Sievanen H, Kannus P, Pasanen M,
Vuori I (2003). Effect of long-term impact-loading on
mass, size, and estimated strength of humerus andradius of female racquet-sports players: A peripheral
quantitative computed tomography study between
young and old starters and controls. J Bone Miner Res,
18:352–59.
Haapasalo H, Kontulainen S, Sievanen H, Kannus P,
Jarvinen M, Vuori I (2000). Exercise-induced bone gain
to enlargement in bone size without change involumetric bone density: a peripheral quantitative
computed tomography study of the upper arms of maletennis players. Bone, 27:351-357.
Thompson D’AW (1917). On Growth and Form.
Cambridge: Cambridge Press.
Wolff J. Das Gesetz der (1892). Transformation derKnochen. Berlin: Hirschwald.
Schultheis L (1991). The mechanical control system ofbone in weightless spaceflight and in aging. Exp
Gerontol, 26:203-14.

151

J.D. Dolbow et al
[73]

[74]

[75]

[76]

[77]

[78]

[79]

[80]

[81]

[82]

[83]

[84]

[85]

[86]

[87]

Manolagas SC (2000). Birth and death of bone cells:
basic regulatory mechanisms and implications for thepathogenesis and treatment of osteoporosis. Endocr
Rev, 21:115-137.
Shields RK, Dudley-Javoroski S, Boaldin KM (2006).
Peripheral
quantitative
computed
tomography:
Measurement sensitivity in persons with and without
spinal cord injury. Arch Phys Med Rehabil, 87:13761381.
Abramson AS, Delagi EF (1961). Influence of weightbearing and muscle contraction on disuse osteoporosis.
Arch Phys Med Rehab, 42:147–151.
Ben M, Harvey L, Denis S, Glinsky J, Goehl G, Chee S,
et al. (2005). Does 12 weeks of regular standing provent
loss of ankle mobility and bone mineral density inpeople with recent spinal cord injuries? Australian
Journal of Physiotherapy, 51:250-256.
Kunkel CF, Scremin E, Eisenberg B, Garcia JF, Roberts
S, Martinez S (1993). Effect of 'standing' on spasticity,
contracture, and osteoporosis in paralysed males. Arch
Phys Med Rehab, 74: 73–78.
Goemare S, Van Laere M, De Neve P, Kaufman JM(1994). Bone mineral status in paraplegic patients who
do or do not perform standing. Osteoporosis Int, 4:138–
143.
Alekna V, Tamulaitiene M, SineviciusT, Juozulynas A(2008). Effect of weight-bearing activities on bonemineral density in spinal cord injured patients during
the period of the first two years. Spinal Cord, 46:727732.
de Bruin ED, Frey-Rindova P, Herzog RE, Dietz V,
Dambacher MA, Stussi E (1999). Changes of tibia boneproperties after spinal cord injury: effects of earlyintervention. Arch Phys Med Rehab, 80:214–220.
Giangregorio LM, Hicks AL, Webber CE, Phillips SM,
Craven BC, Bugaresti JM, et al. (2005). Body weightsupported treadmill training in acute spinal cord injury:
impact on muscle and bone. Spinal Cord, 43:649–657.
Giangregorio LM, Webber CE, Phillips SM, Hicks AL,
Craven BC, Bugaresti JM, et al. (2006). Can bodyweight supported treadmill training increase bone mass
and reverse muscle atrophy in individuals with chronic
incomplete spinal cord injury? Applied Physiology,
Nutrition, and Metabolism, 31:283-291.
Ogilvie C, Bowker P, Rowley DI (1993). The
physiological benefits of paraplegic orthotically aided
walking. Paraplegia, 31:111-115.
Dudley-Javoroski S., Shields RK (2008). Muscle andbone plasticity after spinal cord injury: Review ofadaptations to disuse and to electrical muscle
stimulation. J Rehabil Res Dev, 5:283-296.
Rubin CT, Lanyon LE (1984). Regulation of boneformation by applied dynamic loads. J Bone Joint Surg,
66A:397–402.
Gusi N, Raimundo A, Leal A (2006). Low-frequency
vibratory exercise reduces the risk of bone fracture
more than walking: A randomized controlled trial.
BMC Musculoskelet Disord, 7:92.
Rubin C, Turner S, Muller R, Mittra E, McLeod K, LinW, et al. (2002). Quantity and quality of trabecularAging and Disease • Volume 4, Number 3, June 2013

Aging and Electrical Stimulation Exercise on Bone

[88]

[89]

[90]

[91]

[92]

[93]

[94]

[95]

[96]

[97]

[98]

[99]

bone in the femur are enhanced by a strongly anabolic,non-invasive mechanical intervention. J Bone Miner
Res, 17:349–357.
Verschueren S, Roelants M, Delecluse C, Swinnen S,
Vanderschueren D, Boonen S (2004). Effect of 6-monthwhole body vibration on hip density, muscle strength,
and postural control in postmenopausal women: arandomized controlled pilot study. J Bone Miner Res,
19:352–359.
Hicks AL, Martin-Ginis KA (2008). Treadmill training
after spinal cord injury: It’s not just about walking. J
Rehabil Res Dev, 45:241-248.
Gater DR, Dolbow DR, Tsui B, Gorgey AS (2011).
Functional electrical stimulation therapies after spinal
cord injury. NeuroRehabilitation, 28:231–248.
Needham-Shropshire BM, Broton JG, Klose KJ,
Lebwohl N, Guest RS, Jacobs PL (1997). Evaluation ofa training program for persons with SCI paraplegia
using the Parastep® 1 ambulation system: Part 3. Lackof effect on bone mineral density. Arch Phys Med
Rehab, 78:799–803.
Thoumie P, Le Claire G, Beillot J, Dassonville J,
Chevalier T, Perrouvin-Verbe B, et al. (1995).
Restoration of functional gait in paraplegic patientswith the RGO-II hybrid orthosis. A multicenter
controlled study. II: Physiological evaluation.
Paraplegia, 33:654–659.
Rodgers MM, Glasser RM, Figoni SF, Hooker SP,
Ezenwa BN, Collins SR, et al. (1991). Musculoskeletal
responses of spinal cord injured individuals tofunctional neuromuscular stimulation-induced knee
extension exercise training, J Rehabil ResDev, 28:1926.
Hangartner TN, Rodgers MM, Glaser RM, Barre PS(1994). Tibial bone density loss in spinal cord injured
patients. Effects of FES exercise, J. Rehabil. Res Dev,
31:50-61.
Belanger M, Stein RB, Wheeler GD, et al. (2000).
Electrical stimulation: can it increase muscle strengthand reverse osteopenia in spinal cord injured
individuals? Arch Phys Med Rehabil, 81:1090-1098.
Shields
RK,
Dudley-Javoroski
S(2006).
Musculoskeletal Plasticity After Acute Spinal Cord
Injury: Effects of Long-Term Neuromuscular Electrical
Stimulation Training. J Neurophysiol, 95:2380-2390.
Shields
RK,
Dudley-JavoroskiS(2007).
Musculoskeletal adaptations in chronic spinal cord
injury: Effects of low term soleus electrical stimulation
training. Neural Rehab Neural Repair, 21:168-179.
Hjeltnes N, Galuska D, Bjornholm M, Aksnes AK,
Lannem A, Zierath JR (1998). Exercise-induced
overexpression of key regulatory proteins involved inglucose uptake and metabolism in tetraplegic persons:molecular mechanism for improved glucose
homeostasis, FASEB J, 2:1701-1712.
Hooker SP, Figoni SF, Rodgers MM, Glaser RM,
Mathews J, Suryaprasad AG, et al. (1992). Physiologic
effects of electrical stimulation leg cycle exercise
training
inspinalcord
injuredpersons,
ArchPhysMedRehabil, 3:470-476.

152

J.D. Dolbow et al[100] Bauman WA, Alexander LR, Zhong YG, Spungen AM(1994). Stimulated leg ergometry training improves
body composition and HDL-cholesterol values, Journalof the American Paraplegia Society, 17: 201.
[101] Mohr T, Podenphant J, Bioring-Sorensen F, Galbo H,
Thamsborg G, Kjaer M (1997). Increased bone mineraldensity after prolonged electrically induced cycle
training of paralyzed limbs in spinal cord injured man.
Calcif Tissue Int, 61:22-25.
[102] Chen SC, Lai CH, Chan WP, Huang MH, Tsai HW,
Chen JJ (2005). Increases in bone mineral density after
functional exercises in spinal cord injured patients.
Disabil Rehabil, 27:1337-1341.
[103] Frotzler A, Coupaud S, Perret C, Kakebeeke TH, Hunt
KJ, Donaldson Nde N, et al. (2008). High-volume FEScycling partially reversed bone loss in people withchronic spinal cord injury. Bone, 43:169-176.
[104] Lai CH, Chang WH, Chan WP, Peng CW, Shen LK,
Chen JJ, et al. (2010). Effects of functional electricalstimulation cycling exercise on bone mineral density
loss in the early stages of spinal cord injury. J. Rehabil.
Med, 42:150-154.
[105] Eser P, de Bruin ED, Telley I, Lechner HE, Knecht H,
Stussi E (2003). Effect of electrical stimulation-induced
cycling on bone mineral density in spinal cord-injured
patients. Eur J Clin Invest, 33:412-419.
[106] Sloan KE, Bremner LA, Byrne J, Day RE, Scull ER(1994). Muskuloskeletal effects of an electricalstimulation-induced cycling programme in spinal
injured. Paraplegia, 32:407-415.
[107] Leeds EM, Klose KJ, Ganz W, Serafini A, Green BA(1990). Bone mineral density after bicycle ergometry
training. Arch. Phys. Med. Rehabil, 71:207-209.
[108] Bloomfield SA, Mysiw WJ, Jackson RD (1996). Bonemass and endocrine adaptations to training in spinal
cord injured individuals. Bone, 19:61-68.
[109] BeDell KK, Scremin AM, Perell KL, Kunkel CF(1996). Effects of functional electrical stimulationinduced lower extremity cycling on bone density ofspinal cord- injured patients. Am J Phys Med Rehabil,
75:29-34.
[110] Frotzler A, Coupaud S, Perret C, Kakebeeke TH, Hunt
KJ, Eser P (2009). Effects of detraining on bone andmuscle tissue in subjects with chronic spinal cord injury
after a period of electronically-stimulated cycling: asmall cohort study. J Rehabil Med, 41:282-285.
[111] Wheeler GD, Andrews B, Lederer R, Davoodi R, Natho
K, Weiss C, et al. (2002). Functional electrical

Aging and Disease • Volume 4, Number 3, June 2013

Aging and Electrical Stimulation Exercise on Bonestimulation-assisted rowing: Increasing cardiovascular
fitness through functional electrical stimulation rowing
training in persons with spinal cord injury. Arch Phys
Med Rehabil, 83:1093-1099.
[112] Laskin JJ, Ashley EA, Olenik LM, Burnham R,
Cumming DC, Steadward RD, et al. (1993). Electricalstimulation-assisted rowing exercise in spinal cord
injured people. A pilot study. Paraplegia, 31:534-541.
[113] Dolbow DR, Gorgey AS, Cifu DX, Moore JR, Gater
DR (2012). Feasibility of home-based functional
electrical stimulation cycling: a case report. Spinal
Cord, 50:170-171.
[114] Dolbow DR, Gorgey AS, Moore JR, Gater DR (2012).
A Report of Practicability of a Six Month Home Based
Functional Electrical Stimulation Cycling Program foran Individual with Tetraplegia. Journal of Spinal Cord
Medicine, 35:182-186.
[115] Fournier A, Goldberg M, Green B, Brucker B,
Petrofsky J, EismontF, et al. (1984). Medical
evaluation of the effects of computer assisted muscle
stimulation in paraplegic patients. Orthopedics, 7:11291133.
[116] Hartkopp A, Murphy R, Mohr T, Konradsen H, Heron
I, Mordhorst CH, et al. (1998). Bone fracture during
electrical stimulation of the quadriceps in a spinal cord
injured subject. Arch Phys Med Rehabil, 79:1133-1136.
[117] Smidt GL (1973). Biomechanical analysis of knee
flexion and extension. J Biomech, 6:79-92.
[118] Buff HU, Jones LC, Hungerford DS (1988).
Experimental determination of forces transmitted
through the patello-femoral joint. J Biomech, 21:17-23.
[119] Sadowsky CL, Whiting HM, Pai S, Becker D,
Houndayer TP, Al-Adawi S, et al. (2009). Prevalenceand Risk Factors for Osteoporsis in Individuals with
Paralysis. Poster Presentation at 2009 International
Society for Clinical Densitometrist. Orlando, FLA.
[120] Whiting HM, Pai S, Houdayer TP, Sadowsky CL, ALAdawi S, McDonald JW (2012). Prevalence and Risk
Factors for Osteoporsis in Individuals with Paralysis.
Poster Presentation at 2012 Research Symposium:
Contemporary Trends in Spinal Cord Injury
Management. Kennedy Krieger Institute, Baltimore,
Md.

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