J. Biomedical Science and Engineering, 2011, 4, 490-496
doi:10.4236/jbise.2011.47062 Published Online July 2011 (http://www.SciRP.org/journal/jbise/ JBiSE ).
Published Online July 2011 in SciRes. http://www.scirp.org/journal/JBiSE
Bone blood flow is influenced by muscle contractions
Jan Erik Näslund1, Sofie Näslund2, Erik Lundeberg1, Lars-Göran Lindberg3, Iréne Lund1
1Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden;
2Gävle Hospital, Gävle, Sweden;
3Department of Biomedical Engineering, Linköping University, Linköping, Sweden.
Received 18 April 2011; revised 11 May 2011; accepted 27 May, 2011.
ABSTRACT
Forces acting on the skeleton could be divided into
those originating from gravitational loading and those
originating from muscle loading. Flat bones in a
non-weight-baring segment of the skeleton probably
experience forces mostly generated by muscle con-
tractions. One purpose of muscle contractions is to
generate blood flow within skeletal tissues. The pre-
sent study aimed to investigate the pulsatile patellar
bone blood flow after low and high intensity leg ex-
tension exercises. Forty-two healthy individuals vol-
unteered for the study. Dynamic isotonic one leg ex-
tension/flexion exercises were performed in a leg ex-
tension machine. Randomly, the exercises were per-
formed with the left or right leg with either 10 repeti-
tion maximum (10 RM) continuously without any
resting periods (high intensity muscle work), or 20
RM with a 2 second rest between contractions (low
intensity muscle work). The work load, expressed in
kilograms totally lifted, was id entical in both leg s. The
pulsatile patellar blood flow was recorded continu-
ously using a photoplethysmographic technique.
Blood pressure was measured continuously during
muscle work by a non-invasive method (Finapress).
The patellar pulsatile bone blood flow increased sig-
nificantly more after high intensity muscle work (61%)
compared to the same work load performed using a
lower intensity (22%), p = 0.000073. Systolic blood
pressure changed equally during and after both in-
terventions. Post-exercise bone hyperaemia appears to
be correlated to the intensity of muscle contractions in
the muscle compartment attached to the bone.
Keywords: Bone; Blood Flow; Blood Pressure;
Photoplethysmography
1. INTRODUCTION
It is generally concluded that weight-baring bones grow
and are remodeled in response to mechanical loading. It
is however not totally agreed on how forces acting on
bone cells influence bone morphology (mechanotrans-
duction), but the importance of solute transport for cel-
lular mechanotransduction [1] and cellular excitation due
to interstitial fluid flow (IFF) have been implicated [2].
The contribution of strain in terms of magnitude, rate,
cycles and unusual distribution, is still a matter of debate
[3]. Also, the originating source of loading like gravita-
tional loading and muscle loading have both been proven
influencing different aspects of skeletal morphology
[4-5], while it has been discussed which type of loading
is the most important for bone health [6]. The relative
contribution of each type will most likely depend on the
specific activity, the location of the bone in question
within the skeleton, and whether the bone is weight-
baring or not [2]. In humans, gravitational loading acts
predominantly on the lower limb and on the axial skele-
ton. Non-weight bear ing bones like scapula, ribs, cranial
bones, and patella are also exposed to bone resorption,
modeling, and remodeling. A flat bone in a non-weight
baring segment of the skeleton is probably exposed to
forces mostly generated by muscle contractions. The
function of these muscle contractions may, in addition to
resisting the force of gravity and inducing locomotion,
also be to generate increase of blood flow within skeletal
tissues. It has even been speculated that a co-dependence
of muscle and bone exists, and that muscle is not only a
source of mechanical stimuli for bone but also serves as
an important endocrine organ that may indirectly regu-
late bone metabolism [7]. Dynamic muscle stimulation
has been shown to generate intramedullar pressure (ImP)
and low-level bone strain as a function of stimulation
frequency. Induced dynamic ImP may ultimately en-
hance IFF in bone [8].
The patellar bone is located in the lower limb, and by
being attached to th e quadriceps femoris muscles it takes
part in neutralizing forces during locomotion while the
gravitational reaction forces probably are of minor im-

J. E. Näslund et al. / J. Biomedical Science and Engineering 4 (2011) 490-496 491
portance since patella is not part of the axial skeleton.
Vasculature and supply of arterial blood flow are of
vital importance for most tissues. Accordingly, blood
supply is shown critical for bone metabolism, growth,
and fracture healing. The total vascular pattern in irregu-
lar and flat bones departs significantly from the vascular
organization of long bones, in that there is a considerably
periosteal blood supply which is lacking in long bones [9].
The muscle pump hypothesis suggests that an arterio-
venous pressure gradient is important for muscle perfu-
sion [10]. The same process may also increase the hy-
draulic pressure in skeletal nutrient vessels and influence
the bone capillary blood flow but also the capillary fil-
tration [11]. In addition to the increased bone b lood flow
by muscle contractions different coupling factors be-
tween muscle contractions and fluid flow through bone
exists [12]. The pressure waves generated from muscle
pump contractions increase blood pressure during exer-
cise by temporarily occluding arteries and veins leading
to and from bone, and by increasing hydraulic pressure
in bone capillaries [13]. Mechanical loading and vascu-
lar pressure have been proposed to drive IFF within the
bone lacunar-canalicular system (LCS). Capillary pres-
sure in the bone Haversian system thus could drive in-
terstitial solute convection [14]. When bone is subjected
to cyclic loading interstitial fluid drains from the LCS
into and out of the vascular porosity that surrounds the
bone capillaries [2]. In vivo tracer studies have demon-
strated that vascular pressure is capable of driving IFF
even in the absence of externally applied mechanical
loading [15]. The cardiac contractions, and skeletal mus-
cular contractions, induce peak shear stresses on the os-
teocyte cell processes [16]. However, it has also been
shown that vascular pressure itself, does not enhance
acute solute transport within the LCS, and subsequently
its role in driving IFF is under debate [3].
A direct measurement of IFF or the bone capillary
pressure is currently not possible. However, thanks to
recent development we now have the possibility to
measure pulsatile bone blood flow in the patellar bone
[17]. Photoplethysmography (PPG) is a non-invasive
optical technique for the measurement of changes in
blood flow and has been used to monitor blood flow in
skin and muscles [18-20], and lately also for hemody-
namic sensing in implanted devices [21]. Furthermore, it
has also been shown that chan ges in pulsatile blood flow
within the patellar bone are possible to study continu-
ously and non-invasively using the PPG technique
[17,22]. PPG measurements might add information im-
portant for the understanding of which source of bone
strain (muscle or vascular forces) but also which type of
muscular work that predominate the adaptive stimulus in
non-wei gh t b earing flat bones.
The purpose of th e pr esent stud y was to descr ibe reac-
tive changes in pulsatile blood flow in the patellar bone
after muscle contractions with two different work load
intensities.
2. MATERIALS AND METHODS
2.1. Subjects
Forty-two healthy, regularly exercising, non-smoking,
and normotensive individuals (14 women and 28 men)
volunteered for the study, which was approved by the
local ethic committee, (2007760-31/39). All subjects
gave their written informed consent to participate in the
study.
The mean age was 29 (range 20 to 53) years for the
women and 37 (range 20 to 58) years for the men. The
mean height was 171 (range 162 to 180) cm and 181
(range 165 to 192) cm, for the women and men respec-
tively . The wei ght am ong t he wom en w as 6 4 (ra nge 55 to
73) kg and 83 (range 65 to 115) kg among the men.
The subjects were instructed to avoid exercises, other
than normal activities of daily living, during the day the
test was performed. All tests were executed in the after-
noon. After 15 minutes of rest, the bone blood flow was
recorded continuou sly from 3 minutes prior the in terven-
tion until 5 minutes after. One measurement was made on
each leg.
2.2. Muscle Contraction Exercises
Dynamic isotonic leg extension/flexion exercises were
performed in a leg extension machine (Nordic Gym
101SE, Caretaker Scand AB, Bollnäs, Sweden) with the
purpose of utili zing low or high inten sity muscle work in
one leg respectively. The order of high intensity exercise
based on 10 rep etition maximum (RM), 10 RM ~75% of
1 RM, an d l ow inte n sity exercise based on 20 RM, ~60%
of 1 RM, was randomly performed on either the left or
right leg. The high intensity work was performed con-
tinuously without any resting periods and the low inten-
sity work with a two-second rest between the contract ions.
Work volume, expressed in kilograms totally lifted, was
identical in both legs. A full isotonic leg extension and
following knee flexion was performed during two sec-
onds. The angle velocity was supervised by one of the
authors by vocally counting the time. During the 15
minute restin g period be fore exercising, t he subjects we re
sitting in the leg extension machine with their legs sup-
ported and their knee joints in a resting position (20 de-
grees of flexion). This position was also held in the
post-exercise period of 5 minutes. The time lap between
the two measurements always exceeded 25 min.
2.3. Blood Flow Measurements
A PPG probe was attached to the skin over the patella
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using adhesive tape [17]. In the PPG technique, light
waves from a light-emitting diode is absorbed and scat-
tered in the underlying tissue. The depth by which the
light waves penetrate a tissue is primarily a function of
wavelength and the optical geometry of the probe, but
also of the optical qualities of the tissues of interest. In
the patellar probe the wavelength of 804 nm was used
with a distance between diode and the photodetector of
15 mm. Variations in the photodetector signal are related
to changes in blood flow [20].
A base-line, pre-exercise va lue was calculated from 60
seconds peak-to-peak recordings and a post-exercise
value from 60 seconds peak-to-peak recordings when the
reactive blood flow had reached a stable and steady-state
level, Figure 1. This was mostly found within one minute
after the intervention.
The PPG signal was analyzed using the software
MATLAB, R2006b.
2.4. Blood Pressure Measurements
The blood pressure was measured con tinuously in twelve
of the subjects by a non-invasive method (Finapress,
Ohmeda 2300, Englewood USA). A small cuff was
placed around the middle phalanx of the third finger on
one hand that was placed on a padded platform at the
level of the heart. A fast feedback loop including an in-
frared light source and detector, an air pump, and a mi-
croprocessor keeps the wall of the finger arteries at the
so-called unloaded size, and the cuff pressure equals the
arterial blood pressure. From the original pulse-wave
signal the systolic and diastolic values were continu-
ously determined. Mean systolic pressure was computed
(MATLAB, R2006b) from peak systolic recordings dur-
ing a 60-second, pre-exercise interval period, from a
10-second interval at the end of the exercise where the
highest systolic values could be seen, and from the
60-second post-exercise interval during which the reac-
tive bone blood flow measurements were made.
Figure 1. The PPG signal recordings of one subject from the
patellar bone at rest, during, and after high intensity muscle
work (10 RM).
2.5. Statistics
Mean values an d ranges were calculated for qu antitative,
continuous data such as age, height, weight and systolic
blood pressure. Non-normally distributed, continuous
data were given as median values with inter quartile
range (IQR) and the range from minimu m to maximum.
The dependent data of changes in measured blood flow
were expressed as the percentage change post-exercise
related to the pre-exercise level for each individual.
Wilcoxon’s paired signed rank test was used to test th e
hypothesis of no difference between the two modes of
muscle work, i.e. low and high intensity muscle work.
The level of significance was set at P < 0.05. The statis-
tical package Statistica 9.0 (StatSoft Inc., Tulsa, USA)
was used for descriptive statistics and statistical analysis.
3. RESULTS
The individual responses of the paired raw data of
measured bone blood flow in patella showed that the
bone blood flow decreased among four individuals (10%)
while it was increased among the rest 38 individuals
(90%) after the high intensity muscle work, Figure 2(a).
After the low intensity muscle work, the bone blood
flow decreased in 12 (30%), was unchanged in one (2%)
and increased in 28 (68%) of the 41 reported measures,
Figure 2(b) .
3.1. Change in Bone Blood Flow
The high intensity muscle work induced by 10 RM, in-
creased the measured bone blood flow with in median
61% (IQR 120; range, –31 to 505). The low intensity
muscle work induced by 20 RM also resulted in an in-
crease of patella bone blood flow with in median 22%
(IQR 70; range, –52 to 155). However, high intensity
muscle work induced a significantly higher blood flow
change as compared to after the low intensity muscle
work, p = 0.000073 (Wilcoxon matched pairs signed
rank sum test), Figure 3.
3.2. Blood Pressure
Mean systolic blood pressure (SBP) increased from
123.9 (range 101 to 137) before, to 158.5 (range 122 to
211) mmHg during the end of the high intensity muscle
work, n = 42, and from 121.9 (range 101 to 143) to
163.4 (range 139 to 198) mmHg during the end of the
low intensity muscle work, n = 42. During the
post-exercise periods, simultaneously with the bone
blood flow measurements, the mean SBP was 127.1
(range, 111 to 155) mmHg and 128.8 (r ange, 110 to 161)
mmHg respectively. The patterns of SBP changes were
in same range irrespective of the two levels of muscle
work intensity induced.
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0.0 0.4 0.8 1.2 1.6 2.0 2.4 2.8
Bone blood flow, mV, before high intensity muscle work
0.0
0.4
0.8
1.2
1.6
2.0
2.4
2.8
Bone blood flow, mV,after high intensity muscle work
(a)
0.0 0.4 0.8 1.2 1.6 2.0 2.4 2.8
Bone blood flow, mV, before low intensity muscle wor k
0.0
0.4
0.8
1.2
1.6
2.0
2.4
2.8
Bone blood flow, mV,after low intensity m uscle w ork
(b)
Figure. Paired raw data of measured patella bone blood flow
using PPG signal (mV) before and after high intensity, n = 42
(a), and low intensity, n = 41 (b), muscle work respectively.
4. DISCUSSION
To our knowledge, the present stud y is the first to quan-
tify blood flow changes in human bone tissue in response
to muscle contractions. We used a type of exercise often
performed in muscle research, namely leg extension/
flexion exercises in a sitting position [23]. Our study
indicates that pulsatile blood flow in the patellar bone is
under the influence of contractions in the quadriceps
femoris muscles, and exercise-induced bone hyperemia
appears to be associated with the intensity of muscle
contractions performed in muscles attached to the bone.
The patellar bone comprises a thin layer of cortical
bone that surrounds a centre composed of trabecular b one
but lacks a bone marrow cavity [24]. The intraosseous
vessels in the patellar bone are encased in a rigid and
High intensityLow intensity
-100
0
100
200
300
400
500
600
Percentage, %, change in bone blood flow after
muscle work
Median
Raw Data
Figure 3. Percentage change in patella bone blood flow after
high, n = 42, and low intensity muscle work, n = 41, respectively.
unyielding bony cylinder making the patellar bone suit-
able for PPG measurements. The pulse pressure could be
transmitted directly to the sinusoids and venules across
the extravascular fluid. It has been shown that the sinu-
soids, even in diaphyseal marrow, dilate and contract
rhythmically, probably as a passive response to a pulsatile
flow of blood in medullary arteries [25].
The question what source of bone strain predominates
the adaptive stimulus is not easy to answer since the rate
at which bone is exposed to strain can influence the
adaptive response even to a greater extent than the abso-
lute magnitude of the strain [3]. Despite the available
data showing that bone responds to a variety of me-
chanical loads, many factors limit how to translate the
evidence into effective practice. Obvious confounders
include age- and sex-specific responses, along with nu-
trition, hormonal status, medications, and location of the
bone within the skeleton. Also, we have to accurately
define bone metabolism and take different aspects of
skeletal adaptation into consideration; i.e. increased or
reduced bone resorption and bone formation, periosteal
or endosteal changes, but also whether bone mineral
density (BMD) or bone mineral content (BMC) have
been measured. Studies have shown, at least in men, that
high-impact training and strength training produce
site-specific increases in BMD due to bone formation
[26]. While aerobic training (in this case most likely
comparative to our low intensity muscle work) leads to
changes indicating reduced bone resorption activity, an-
aerobic training (comparative to our high intensity mus-
cle work) seems to result in an accelerated bone turn
over. The impact of physical activity on bone turnover
therefore may depend on the kind of exercised per-
formed [27]. Notable, measurements of BMD are rarely
performed in non-weight baring bones.
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It has been reported that muscle exercise hyperaemia is
larger if the muscle work continues for a longer time at a
level where aerobic metabolism is the prime source for
energy demand [28]. The results of our study indicate a
reversed reaction in bone tissue, i.e. the more intensive
muscle work, the larger bone hyperaemia. There are two
possibilities for the changes in bone blood flow seen in
our study. First ly, the proposed muscle p ump mec han ism
is of different magnitudes in the two interventions used
by us [11]. Leg extensions with a resistance of 10 RM
create a higher pressure in the muscle compartment than
if the muscles contract against 20 RM and this higher
pressure might cause exercise hyperaemia in bone. Also,
Recek [29] emphasized the importance of muscles as
blood pumps. Theoretically, the pulsatile bone blood flow
might be influenced by the SBP during the ex ercises since
it is well-known that SBP rises during muscle activity.
However, we found that the SBP was similarly changed,
measured both at the end of the exercise periods and in
the post-exercise periods, irrespectively of the type of
muscle work performed. This indicates that at least the
reactive pulsatile patellar bone blood flow is not primarily
dependent on the SBP.
Secondly, in muscle tissue local hypoxia is known to
be of great importance for peripheral blood flow even
though most details of this process are still unknown. The
metaboreflex, i.e. activated chemically sensitive nerves
located in muscle parenchyma evoke increases in sym-
pathetic activity, has been shown to regulate cardiac
output, blood pressure and regional blood flow regula-
tions [30]. Hypoxia is a possible regulator of microcir-
culation also in bone tissue. This has however not yet
been studie d in humans. S him and Peterso n [31] observe d
that the metabolic control mechanism was the most potent
one regulating bone blood flow in rabbits. The blood flow
appeared to be closely related to the oxygen and carbon
dioxide tension, the pH, and the acid metabolites in blood.
Following a period of ischemia, the outflow venous
volume increased two to three times in their study.
Brookes & Revell [9] suggested that local acidosis pro-
vides a stimulus for bone accumulation, and Gross et al.
[32] hypothesized that hypoxia was responsible for the
bone vasoregulation found in their study. These state-
ments are in accordance with our results showing that
high intensity muscle work increased the post exercise
patellar blood flow 61%. Gross et al. [32] showed that,
during low and moderate levels of exercise (treadmill
running) in dogs, the vascular resistance in axial bone
increased two to fourfold, wh ile an increased vasodilata-
tion in adjacent muscles was found. Our study indicates a
reversed reaction in the patellar bone. In contrast to us,
Gross et al. [32] studied blood flow regulation during
steady-state treadmill running and not post exercise hy-
peraemia after resistant exercises.
The large bone hyperaemia seen in our study could
serve other aspects of bone homeostasis than nutrition
delivery. It has been proposed that an adaptive response
to alternating venous pressure by the muscular pump
mechanism could accelerate the IFF and thus impact bo ne
metabolism. Exercise hyperaemia might indu ce reactions
of vital importance for bone tissue such as increasing the
IFF [12]. Interestingly, gravitational loaded bone models
have shown that removing muscle loads will increase
internal bone stresses during movement [12]. The fact
that muscles both impart and neutralize forces on long
bones during gait must be recognized when discussing
muscle load on bone tissue. In cranial bones this situation
is hardly present, but the patellar bone might resemble
long bones in this aspect.
4.1. Limitations and Strengths of the Study
This is the first report of non-invasive bone blood flow
measurement after muscle exercise in humans, and as
such many limitations must be discussed. The most ob-
vious limitation of the present PPG techn ique is the lack
of a gold standard technique to compare it against. The
patellar probe has been shown to discriminate between
blood flow in the skin over the patella, and the patellar
blood flow [17]. In a review by Allen [20], the validity
and reliability of PPG measurements were discussed. For
basal perfusion of the microcirculation the amplitude of
the PPG pulse often correlated with laser Doppler blood
flow (LDF). Recently, Hagblad et al. [33] showed that,
combining PPG and LDF blood flow at different depth
could be measured. Ultrasound measurements were used
to differentiate the tissues beneath the probe and thus
validate the capillary beds measured. A similar PPG
probe as in o ur study wa s used to m easure blood flow at a
depth of 23 mm, a distance well within the range of the
patellar trabecular bone.
There are a limited number of studies quantifying the
repeatability or reproducibility of PPG measurements.
Jago and Murray [34] addressed the uncertainty in PPG
measurements for a group of healthy adult subjects. An
averaging period covering at least 60 heartbeats has been
suggested to improve confidence in the single timing
amplitude measurements extracted from the PPG pulse
[20], and this time period was used in our study. Also, the
PPG signal is calibrated before every new measurement
and this will have impact on the magnitude of the PPG
signal (voltage levels). Thus, results can only be ana-
lyzed as changes from one point in time to another. The
same limitation is, however, present in studies using LDF
[35] or NIRS [36].
Using a non-invasive technique to study blood flow has,
however, many advantages. It is suitable for human
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studies and involves neither invasive manipulation of
tissues nor their innervations, both which affect blood
flow heterogeneity. The PPG technique also makes it
possible to study blood flow continuously.
Since we do not know if the blood flow increase found
is physically important, we cannot provide a power cal-
culation. Are 42 subjects enough or does the variability
seen in the measurem ents indicate that blood flow in bone
tissue must be studied using larger cohorts? However, in
studies on blood flow using other optical techniques,
often less than 20 subjects has been included [35].
It has been suggested that 10 - 15 minutes of rest is
enough to down-regulate bone blood flow to base-line
values [37]. We used the proposed resting time but, since
this has not been extensively studied in humans, there
might be a need for a much longer resting period, maybe
hours. Also, it is possible that base-line levels of bone
blood flow is influenced by auto-regulation and might
therefore continually be changing during rest. The
activity during the day before the measurement, loco-
motion, and posture maintenance could have a greater
impact on resting bone blood flow than what has been
reported. In the future, we eventually must control the
pre-exercising circumstances more properly.
5. CONCLUSIONS
Resistance exercise induced patellar bone hyperaemia
appears to be dependent of the intensity of muscle
contractions in the quadriceps femoris muscle.
6. CONFLICT OF INTEREST
The authors declare no conflict of interest.
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