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CME Review Article

Biological Aspects and Clinical

Importance of Ultrasound
Therapy in Bone Healing

Özgür Erdogan, DDS, PhD, Emin Esen, DDS, PhD

Objectives. The purpose of this study was to review past and recent literature findings regarding the
effects of ultrasound therapy on bone healing and its clinical efficacy in medical and dental interven-
tions. Methods. A literature review was conducted on the effects of ultrasound therapy on bone heal-
ing. The studies regarding clinical applications in long bones and maxillofacial bones were evaluated
separately from each other. Results. The effects of therapeutic ultrasound on bone healing have been
studied for half a century. Numerous clinical and experimental studies have addressed this relationship,
and many of them have shown positive correlations. Although several theories have been proposed to
explain the mechanism of action, the exact mechanism has not been fully understood. Conclusions.
Therapeutic ultrasound therapy in clinical settings is a noninvasive application and has no serious com-
plications or side effects. It may be an acceptable treatment of choice in many types of clinical proce-
dures involving maxillofacial bones. Key words: bone healing; bone remodeling; fracture;
low-intensity ultrasound; maxillofacial surgery; orthopedic surgery; therapeutic ultrasound.

B
Abbreviations
BMU, basic multicellular unit; LIPU, low-intensity pulsed
ultrasound
Received November 24, 2008, from the Department
of Dental Services, Diyarbakır Military Hospital,
Diyarbakır, Turkey (Ö.E.); and Department of Oral
and Maxillofacial Surgery, Cukurova University,
Faculty of Dentistry, Adana, Turkey (E.E.). Revision
requested January 6, 2009. Revised manuscript
accepted for publication February 4, 2009.
We thank Yakup Üstün, DDS (School of Dentistry,
Cukurova University), for encouraging us to prepare
the manuscript.
Address correspondence to Özgür Erdogan, DDS,
PhD, 100 Yil Mahallesi 85337, Sokak 4-7, 01360
Seyhan-Adana, Turkey.
E-mail: ozgerdogan@yahoo.com
CME Article includes CME test
one is dynamic tissue, which is affected by many
systemic and local factors. Bone healing is associ-
ated with a variety of biochemical, biomechani-
cal, cellular, hormonal, and pathologic events.
Numerous therapeutic methods for bone healing have
been described in the literature. These applications
include systemic and local drug delivery and physical
treatments such as low-intensity lasers, electromagnetic
fields, extracorporeal shock, mechanical stimulation, and
ultrasound therapy.1 The use of ultrasound as a therapeu-
tic approach in bone healing has a history of more than
half a century. In this article, the current understanding of
the molecular mechanisms of ultrasound therapy is dis-
cussed, the findings of the literature are surveyed, and the
future of the application is evaluated. Maxillofacial bones
may differ from extremity bones by their healing mecha-
nisms.2 Therefore, research regarding maxillofacial bones
was evaluated separately from that regarding other bones
of the skeleton.

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Ultrasound Therapy in Bone Healing
Historical Perspective
The piezoelectric effect was discovered by
Jacques and Pierre Curie in 1880, when they real-
ized that some crystals produce acoustic waves if
alternating current electricity is applied to them
at their resonance frequency.2 The therapeutic
use of ultrasound in medicine was first reported
by Pohlman3 in 1939. One of the pioneers in this
area from Germany, Pohlman used ultrasound
for the treatment of back pain, neuralgia, and
myalgia. He reported improvement in symptoms
when ultrasound at a frequency of 800 kHz and
an intensity of 4 to 5 W/cm2 was applied to bio-
logical tissues for 10 days. The daily ultrasound
treatment was 10 minutes. Although this dose of
ultrasound treatment creates some increase in
heat, it did not cause any kind of thermal injury.2,3
The first official report of a diagnostic application
of ultrasound was published in 1942 by Dussik,4 a
neurologist at the University of Vienna. He used
ultrasound beams transmitted through the head
to locate brain tumors and cerebral ventricles.
Up through the 1950s, ultrasound was used as a
therapeutic tool in the treatment of many
diseases, including sciatica, neuralgia, Ménière
disease, and arthritis.5 The feasibility of generating
focused ultrasound beams was shown by
Gruetzmacher6 in 1935. Using this principle, Lynn
and Putnam7 described the equipment, which
produced high-intensity focused ultrasound
beams, in 1944. Using this equipment, they
showed irreversible thermal damage in the brains
of dogs, cats, and monkeys.7 It resulted in the
development of more sophisticated ultrasound
devices to be used as surgical cutting and abla-
tion tools in the following decades.
About the interaction of ultrasound with bone
tissue, the general recognition was that ultra-
sound caused damage, and its use in bones was
to be avoided. In 1949, Halsscheidt et al8 report-
ed a case of osteomyelitis in the alveolar bone in
a patient who had received ultrasound treatment
for a lesion in the lower lip. The first study regard-
ing the effects of ultrasound on bone healing was
published in 1950 by Maintz.9 That was a corner-
stone in this area because for the first time the
positive effects, but not the harmful effects, of
ultrasound on bone were shown. The author cre-
ated bilateral osteotomies in the radii of 3-
766
month-old rabbits. One limb of the rabbits
received ultrasound treatment at 0.5, 1, 1.5, or 2.5
W/cm2. According to the histologic and radiolog-
ic evaluations, it was concluded that although
ultrasound treatment at high intensities caused
thermal damage in bone, lower doses led to new
periosteal bone formation. Two years later,
Corradi and Cozzolino,10 two investigators from
Italy, showed that continuous wave ultrasound at
800 kHz and 1.5 W/cm2 stimulated new callus for-
mation along the fracture line in the radial bones
of rabbits. After this study, the authors used ultra-
sound in a clinical application, and they reported
that ultrasound treatment led to periosteal callus
formation in 8 patients.11 It was the first clinical
application of therapeutic ultrasound to stimu-
late fracture healing.
In an attempt to reduce the thermal damage to
bone and stimulate bone growth, Shiro12 advo-
cated the use of lower doses and a pulsed ultra-
sound application. The author used pulsed
ultrasound at an intensity of 0.2 W/cm2 and
reported increased osteoblastic/chondroblastic
activity in osteotomized tibias of rabbits in the
experimental group. Twenty years after Shiro’s
study, Dyson and Brookes13 used a bilateral fibu-
la osteotomy model in rabbits and applied ultra-
sound at an intensity of 0.5 W/cm2 to one side.
The study showed an increase in ossification in
the experimental group compared with the con-
trol group. The authors claimed that ultrasound
therapy was most effective in the early phase of
bone healing. In the same year, Xavier and
Dauarte14 applied lower doses of ultrasound (30
mW/cm2) to 26 patients with lower extremity
fractures and nonunions after conventional
treatments. They reported 70% healing after a
daily 20-minute ultrasound application. After
that study, Duarte15 showed an ossification
increase of 28% in osteotomized fibulas of rab-
bits that received low-intensity pulsed ultra-
sound (LIPU) compared with the control group.
In a placebo-controlled study, Pilla et al16
osteotomized the tibias of rabbits bilaterally, and
they applied LIPU (a 1.5-MHz pressure wave
administered in pulses of 200 microseconds with
an average temporal and spatial intensity of 30
mW/cm2) to rabbits in the experimental group.
The authors showed that the osteotomized legs
in the LIPU group gained the mechanical prop-
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erties of the nonosteotomized legs on the 17th
day, whereas the osteotomized legs in the control
group gained the mechanical properties of the
nonosteotomized legs on the 28th day.
The first randomized double-blind controlled
study regarding the effects of LIPU on fresh tibia
fractures in humans was published by Heckman
et al17 in 1994. In that multicenter study of 67
patients, 33 patients received LIPU treatment,
and 34 constituted the control group. The
authors reported that LIPU accelerated fracture
healing at a rate of 38%.17 Three years later,
Kristiansen et al18 reported accelerated healing
of fresh dorsal radius fractures with LIPU treat-
ment. The average healing time for the fractures
in the experimental group was 61 days, whereas
the healing time in the control group was 98
days.
Numerous studies have sought to determine
the optimal ultrasound therapy regimen for
stimulating fracture healing. For that purpose,
Yang et al19 created bilateral closed femoral frac-
tures in rats. The animals in the experimental
group received an ultrasound signal consisting
of a 200-microsecond sine wave burst of 0.5
MHz repeating at 1 kHz with an average tempo-
ral and spatial intensity of 50 or 100 mW/cm2 to
1 fracture in each limb. The fractures treated at
50 mW/cm2 had significantly higher torsional
stiffness and maximum torque when compared
with the nontreated side. However, the differ-
ences in these biomechanical parameters did
not show any statistical significance in fractures
treated at 100 mW/cm2. Tsai et al20 showed
greater mineral apposition rates in rabbit fibulas
2 and 3 weeks after fractures that had been treat-
ed with 1.5-MHz compared with 3-MHz ultra-
sound, both using an intensity of 500 mW/cm2.
To determine the best timing of LIPU therapy in
a closed femoral fracture model, Azuma et al21
applied LIPU stimulation to experimental frac-
ture sides at 4 different times from the 1st day
through the 24th day. They showed that LIPU
treatment resulted in accelerated fracture heal-
ing in each group regardless of the treatment
timing. Thus, there were no differences in radio-
logic, histologic, or biomechanical parameters
among the 4 groups. The results of that study
imply that LIPU treatment accelerates all phases
of fracture healing rather than any specific stage.
J Ultrasound Med 2009; 28:765–776
Erdogan and Esen
Successful reports of LIPU therapy in the man-
agement of closed, fresh, and old fractures led to
the use of this application in other orthopedic
surgical protocols that involve bone healing.
Positive effects of LIPU have been shown in the
management of spinal fusion and distraction
osteogenesis procedures in rabbits.22–25
Currently, commercial therapeutic ultrasound
devices, which allow home application by the
patient, are available on the market. The use of
LIPU devices was initially cleared for marketing
by the US Food and Drug Administration in 1994
for treatment of fresh, closed, and posteriorly
displaced distal radius fractures and fresh,
closed, and grade 1 open tibial diaphysis frac-
tures in skeletally mature individuals when
these fractures are orthopedically managed by
closed reduction and cast immobilization.26 In
2000, the indications were expanded to include
treatment of established nonunions, excluding
the skull and vertebrae.
Bone Healing and Interaction of
Ultrasound With Bone Tissue
Bone formation may occur through transforma-
tion from cartilage tissue (endochondral ossifi-
cation), calcification surrounding the organic
matrix (intramembranous ossification), or for-
mation of new bone on existing bone (apposi-
tional ossification).27 The 3 types of ossification
occur throughout the formation of new bones,
the regeneration process of the skeleton after an
injury or surgery, and the formation of bone
tumors.28
Bone or fracture healing may be defined as the
repair of injured bone. It has 3 distinct but over-
lapping stages. These are the early inflamma-
tory stage, the repair stage, and the late
remodeling stage.29 In the inflammatory stage,
hematoma develops, and inflammatory cells
and fibroblasts infiltrate the injured area.
Granulation tissue forms; ingrowth of vascular
tissue occurs; and mesenchymal cells migrate in
this stage. In the repair stage, fibroblasts serve as
stroma for vascular ingrowth. They are responsi-
ble for synthesis of the collagen matrix and
angiogenesis. The collagen matrix ossifies, and
callus tissue consequently develops. Bone heal-
ing is completed during the remodeling stage.30
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Ultrasound Therapy in Bone Healing
Woven bone is differentiated from lamellar
bone, and the bone gains its original strength
after completion of this stage. Remodeling of
bone is regulated by a combination of resorption
and bone formation. The primary cells involved
are osteoblasts and osteoclasts. There is a close
anatomic and functional relationship between
resorptive and formative cells at remodeling
sites. These cells act within a temporary anatom-
ic structure called the basic multicellular unit
(BMU).27 A mature BMU consists of a leading
front of osteoclasts followed by osteoblasts,
blood supplies, and the associated connective
tissues. In the remodeling process, the entire
BMU moves forward, and osteoclasts resorb
bone and die by apoptosis. The resorbed bone is
replaced by newly formed bone.
Despite the complex characteristics of bone
healing and multiple effects of ultrasound on
biological tissues, much is known today about
the mechanism of action of ultrasound therapy.
Several theories have been proposed to explain
the mechanisms and effects. A combination of
physical, piezoelectric, and biological effects of
ultrasound plays a role in the interaction of
ultrasound with bone healing.
Physical Effects
Ultrasound waves generate vibrations in all tis-
sue components, including intracellular and
extracellular fluids and cell membranes, when
penetrating into tissues. They cause movements
or displacements of particles when transmitted
in tissues.31,32 Because of these motions, ultra-
sound treatment produces a micromassage
effect in tissues, which produces mechanical
stimulation.
Acoustic vibrations have thermal and non-
thermal effects in biological tissues. The energy
attenuated by tissues leads to a thermal
increase. Ultrasound signals at high intensities
create considerable heat increases. However, the
therapeutic ultrasound used for bone healing
uses low intensities, as low as 20 to 50 mW/cm2.
Vibrations at these intensities generate a heat
increase of less than 1°C, which is negligible in
terms of thermal damage. However, it has been
suggested that this small increase in tempera-
ture may affect some enzymes such as matrix
768
metalloproteinase 1.33 It is known that this
enzyme is very sensitive to small variations in
temperature. The thermal and nonthermal
effects of ultrasound are not separable, and it
is assumed that nonthermal effects of ultra-
sound are usually accompanied by some heat
increase. The observed nonthermal effects of
ultrasound are stable cavitation, microstream-
ing, acoustic streaming, and direct effects to
cell membranes.
Stable cavitation defines the presence of gas
bubbles in fluids due to ultrasound energy.32
These bubbles may be in different shapes and
sizes depending on the type of ultrasound sig-
nal and may lead to local movement in the
fluid. This movement in the fluid is called
microstreaming. ter Haar et al34 showed that
ultrasound signals at a frequency of 1.5 MHz
and an intensity of 150 mW/cm2 generated
bubbles bigger than 10 mm in body fluids of
guinea pigs. Acoustic streaming is defined as
eddying of fluid near a vibrating structure such
as a stable cavitation gas bubble,35 resulting in
localized high-velocity streams of fluid created
by ultrasound signals in a liquid. These mecha-
nisms cause movement and transfer of intra-
cellular and extracellular ions. An increase
in intercellular ion transfer leads to changes in
membrane permeability, thus resulting in alter-
ations of the electrophysiologic properties of the
cells. It has been shown that ultrasound applica-
tion increases ion conductibility up to 22% and
decreases the need for adenosine triphosphate
consumption by sodium-potassium channels.36
Piezoelectric Effect
An increase in electrical potential occurs when
pressure is applied on bone tissue. This effect is
called the piezoelectric effect.37 The piezoelec-
tric effect induces bone resorption and bone
healing. Bone as dynamic living tissue remodels
itself according to environmental forces. This
remodeling action theory was explained by
Wolff’s law38 in the 19th century. Ultrasound
application generates the piezoelectric effect in
bone, thus increasing the electrical potential
within the tissue. It is suggested that an increase
in the electrical potential induces bone remod-
eling, thereby assisting fracture healing.39
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Biological Effects
As ultrasound signals travel in bone, a biological
response develops in the tissue. There are many
in vivo and in vitro studies available regarding
the biological effects of ultrasound application
on bone healing. In vitro studies on human and
animal cell cultures showed several cellular
effects of ultrasound application, which possi-
bly may be related to acceleration of bone heal-
ing or fracture repair. It has been shown that
LIPU application stimulates aggrecan messen-
ger RNA expression and proteoglycan synthe-
sis by chondrocytes, increases prostaglandin E2
synthesis by osteoblasts, and increases
platelet-derived growth factor synthesis.19,40–43
Ultrasound signals induce conformational
changes in the cell membrane and alter ionic
permeability and second messenger activity.
Changes in second messenger activity lead to
downstream alterations in gene expression,
resulting in an acceleration of the fracture repair
process by up-regulating cartilage- and bone-
specific genes.44,45 Other documented effects of
LIPU application on bone healing include
increased expression of transforming growth
factor β, increased efflux of potassium ions from
intracellular spaces, and increased calcium ion
incorporation.46,47
The rate of angiogenesis is one of the basic
elements in the bone healing process.30 It has
been shown that ultrasound application
increases synthesis of angiogenesis-related
cytokines such as interleukin 8, fibroblast
growth factor, and vascular endothelial growth
factor.48 A power Doppler ultrasound–based
study showed that low-intensity ultrasound
delivered over a 10-day period stimulated a
greater degree of vascularity at the sites of ulnar
osteotomies in dogs.45 Increased blood flow to
the fracture site promotes delivery of the key
components, such as growth factors and
cytokines, that are necessary for the normal
healing process. Capillary formation occurs in
the injured area in the inflammatory phase of
bone healing. These studies confirm that the
impact of ultrasound on angiogenesis-related
physiologic events has a major role in the
enhanced bone healing process associated with
ultrasound therapy.
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Erdogan and Esen
According to studies concerning the mecha-
nism of bone healing stimulation by ultrasound
therapy, the general consensus is that ultra-
sound application mainly affects endochondral
bone formation.21,25 These studies revealed that
ultrasound application stimulates chondrocyte
proliferation or maturation, which causes an
increase in bone healing. The number of chon-
drocytes or osteoblasts has not been shown to
be increased by ultrasound application. It may
be concluded that the fracture callus gains its
original strength with ultrasound therapy in a
shorter period by faster maturation of chondro-
cytes. Clearly, the effects of ultrasound on bone
tissue repair are not caused by a single mecha-
nism. Physiologic events related to maturation
of chondrocytes and osteoblasts, formation of
new capillaries, and an increased rate of cell
turnover activities in the repair zone are associ-
ated with physical and biological actions of
ultrasound energy, and several other mecha-
nisms of action at the cellular level will possibly
be discovered in the near future. More studies
are needed to understand these mechanisms.
Clinical Applications
Currently, the clinical use of ultrasound for bone
healing mostly concerns fracture management.
Many clinical studies regarding the effects of
ultrasound treatment on bone healing have been
based on fresh fracture models. Ultrasound
treatment has been shown to reduce the healing
time of fresh fractures of tibial, distal radius, and
scaphoid bones.17,18,49 Although fresh fractures
heal mostly without complications with stan-
dard fracture care, LIPU treatment may be
considered for the management of fresh
closed fractures in patients with conditions
associated with bone metabolism such as
diabetes, steroid therapy, osteoporosis, and
smoking habits.
An open fracture is defined as one in which
there is communication with a break in the
integument, usually near the fracture site.50
A delayed union corresponds to a slower healing
process than expected. A nonunion is defined as
cessation of healing for more than 3 months, as
documented by serial radiographs including
multiple views.50 Treatment of delayed unions
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Ultrasound Therapy in Bone Healing
and nonunions may be complicated because of
systemic and local conditions such as osteo-
porosis and radiotherapy. Ultrasound treatment
has been found beneficial in the treatment of
delayed unions and nonunions. Mayr et al51 used
the application in 951 patients with delayed
unions and 366 patients with nonunions. They
reported successful healing in more than 86% of
the patients in both groups. Nolte et al52 applied
the treatment to 29 patients with nonunions
after conventional therapies. The fractures
were located in the tibia, femur, radius/ulna,
scaphoid, humerus, metatarsal, and clavicle.
Complete healing was shown in 86% of patients
in an average of 22 weeks. The efficacy of LIPU
treatment on open fractures has not been
proved by randomized clinical trials so far.
Evidence of acceleration of bone healing in
delayed unions and nonunions is weaker com-
pared with treatment for fresh closed fractures of
long bones because of the designs of the pub-
lished studies. However, this patient group con-
stitutes the major group needing ultrasound
therapy.
Another clinical procedure in which ultra-
sound therapy has been used is distraction
osteogenesis. There are few clinical studies
showing positive effects of LIPU on distraction
calluses. In a study by Tsumaki et al,53 21 patients
with osteoarthritis underwent bilateral tibial
hemicallotasis. One limb of every patient
received a 20-minute ultrasound treatment daily
for 4 weeks. The authors showed increased cal-
lus bone mineral density in the LIPU-treated
limbs. Another study by El-Mowafi and Mohsen54
showed accelerated healing of tibial distraction
calluses in LIPU-treated patients. Clinical
studies mainly favor LIPU treatment for dis-
traction osteogenesis procedures. However,
the numbers of studies and patients have been
limited, and more clinical studies are needed
in this area.
Spinal arthrodesis is another orthopedic pro-
cedure in which LIPU treatment may be advan-
tageous. Although several animal studies
showed positive effects of LIPU treatment on
spinal arthrodesis procedures, no clinical study
has been reported to date. Because of an altered
bone turnover rate, implant osseointegration is
impaired in osteoporotic patients. Management
770
of fractures is complicated in these patients for
that reason. Although it was shown that ultra-
sound treatment stimulated bone growth in tan-
talum implants in dogs, no clinical use has been
reported.55
Ultrasound Therapy and Maxillofacial
Bones
Most studies regarding the effects of ultrasound
therapy on bone healing have been conducted
on long bones; the number of studies involving
maxillofacial surgery has been limited, and the
results have been controversial. A report by
Cavaliere56 may be considered the first report of
the clinical application of ultrasound for
enhancing maxillofacial bone healing. He
applied ultrasound at relatively high intensities
(1–2 W/cm2) to 4 patients with mandibular frac-
tures and reported increased calluses and
decreased pain with the use of ultrasound thera-
py. The first in vivo study in this area was pub-
lished by Fedotov et al57 in 1986. They used
ultrasound treatment at 0.2 to 0.6 W/cm2 in rab-
bit mandibular fractures and reported a stimu-
lated reparative process at the fracture site.
Another clinical report regarding ultrasound
therapy in maxillofacial bones was published by
Harris58 in 1992. The author applied ultrasound
at 3 MHz and 1 W/cm2 for 40 days for the treat-
ment of osteoradionecrosis of the mandible.
He found positive progress in 10 of 21 patients.58
In vitro studies conducted on mandibular
osteoblast and fibroblast cultures showed that
ultrasound signals increased proliferation of
cells, synthesis of cytokines such as interleukins
and fibroblast growth factor, and synthesis of
nitric oxide and prostaglandins, which are
important mediators in angiogenesis and bone
healing.42,59
Beginning in 2002, two different study groups
published several in vivo and human studies
regarding the effects of ultrasound on maxillofa-
cial bones. With application of LIPU, El-Bialy et
al60–64 showed enhanced bone formation at the
callus tissue of mandibular distraction osteogen-
esis in rabbits, better repair of orthodontically
induced root resorption in humans, enhanced
mandibular incisor growth and eruption in rab-
bits, enhanced mandibular growth in rabbits,
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and enhanced mandibular growth in growing
baboons when ultrasound treatment was com-
bined with functional appliances. However,
another series by Schortinghuis et al65–67 showed
contrary results. They showed no effect of LIPU
treatment on mandibular bone defects either
covered with a polytetrafluoroethylene mem-
brane, covered with a collagen membrane, or
left uncovered in rats. Similarly, 2 clinical articles
published by Schortinghuis et al68,69 reported no
notable contribution of LIPU treatment to
mandibular vertical osteogenesis procedures.
As with the management of fractures of the
long bones, the treatment of maxillofacial frac-
tures may be problematic for both the patient
and the surgeon. Most maxillofacial fractures
require intermaxillary fixation, and a long fixa-
tion duration causes many problems such as
feeding impairment, temporomandibular joint
problems, and dental/periodontal problems.
Shortening the intermaxillary fixation time may
be a main indication for LIPU applications in
the maxillofacial area. One animal study con-
ducted on rabbits showed increased fracture
healing in a mandibular fracture model.70
However, more studies are needed to determine
the optimal dosing and treatment modality
before using this procedure in clinical settings.
Some other recent studies showed positive
effects of ultrasound therapy associated with
oral surgery. Kerr et al71 evaluated the effects of
ultrasound therapy in socket preservation after
tooth extraction, which has a critical role in den-
tal implant placement. They prepared acrylic
stents for each patient and applied ultrasound
via the stents to one side after tooth extraction in
a split-mouth manner. The intensity of the ultra-
sound output was 30 mW/cm2. The pulse status
of the ultrasound transmission, however, was
not specified in the article. Although the absolute
dimension of bone volume was not affected by
the ultrasound therapy, some increase in buccal
height was found at the bone crest level and 3
mm apical to the crest level. Ikai et al72 studied
periodontal wound healing and bone repair after
LIPU treatment. They created bone defects
intraorally at the root level of premolar teeth in 4
beagles bilaterally. They applied LIPU to one side
and evaluated the bone healing using histologic
analysis and immunohistochemical studies.
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Erdogan and Esen
They reported accelerated new bone formation
on the LIPU-treated sides. There were no differ-
ences between the groups for root resorption
and gingival recession. Immunochemical analy-
sis showed expression of heat shock protein
70–positive cells in the LIPU-treated wounds.
El-Bialy et al73 investigated the effects of pulsed
and continuous ultrasound therapy on distrac-
tion osteogenesis in rabbit mandibles. They used
36 rabbits divided into 3 groups. One group
received pulsed ultrasound therapy at 30
mW/cm2, whereas the second group received
continuous ultrasound at the same intensity. The
third group received sham treatment. The data
showed increased callus healing compared with
other groups for the continuous mode in the first
2 weeks and the pulsed mode in the third and
fourth weeks.
It is mainly accepted that ultrasound treatment
enhances endochondral bone formation.21,25
The fact that maxillofacial bones have intra-
membranous ossification makes the use of ultra-
sound therapy questionable in this particular
region. The close relationship to important
anatomic structures such as the brain, parotid
gland, and eyes, in which the effects of ultra-
sound are not known, is another drawback for
use in maxillofacial bones. Another drawback is
the thicker soft tissue layer compared with tibial,
ulnar, and scaphoid bone regions. This makes
penetration of ultrasound signals weaker, thus
reducing the effectiveness of the treatment.
However, an increased interest in the therapeutic
use of ultrasound for oral and maxillofacial sur-
gical protocols is apparent in the literature. More
studies lie ahead to be conducted, and the effec-
tiveness of ultrasound therapy in this area should
be clearer in the coming years. A list of previous
animal and clinical studies involving the max-
illofacial bones is given in Table 1.
Complications and Side Effects
Ultrasound treatment for bone healing gener-
ates low-intensity energy, which is comparable
to diagnostic ultrasound doses. Pulsed signals
and low energy minimize the thermal effects of
ultrasound on biological tissues. No serious
complications have been reported regarding the
clinical use of therapeutic ultrasound. Reported
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Ultrasound Therapy in Bone Healing

adverse effects due to ultrasound treatment been shown that ultrasound signals do not inter-
include muscle spasms on the treatment side, fere with metal objects, and its use in sites with
mild erythema, and mild swelling.47 It also has implanted metal biomaterial is safe.55 One disad-

Table 1. Clinical and Animal Studies Concerning the Effects of Ultrasound Therapy on Maxillofacial Bones
Study Indication
56
Cavaliere, 1957 Mandibular fracture
Fedotov et al,57 Mandibular fracture
1986
Harris,58 1992 Osteoradionecrosis of mandible
El-Bialy et al,60 Mandibular distraction
2002 osteogenesis
El-Bialy et al,61 Effects on mandibular incisor
2003 teeth eruption
El-Bialy et al,62 Mandibular growth modifi-
2003 cation
El-Bialy et al,63 Effects on orthodontic root
2004 resorption
Schortinghuis et al,65 Healing of mandibular defects
2004
Schortinghuis et al,66 Healing of mandibular defects
2004 covered with polytetrafluoro-
ethylene membrane
Schortinghuis et al,67 Healing of mandibular defects
2005 covered with collagen
membrane
Schortinghuis et al,68 Vertical distraction osteogenesis
2005 of the mandible
El-Bialy et al,64 2006 Mandibular growth modification Baboons (14)
Erdogan et al,70 2006 Mandibular fracture
Schortinghuis et al,69 Vertical mandibular distraction
2008 osteogenesis
Kerr et al,71 2008 Bone preservation at extraction
socket
Ikai et al,72 2008 Ossification around bony defect
created at the mesial root of
premolar tooth
El-Bialy et al,73 2008 Mandibular distraction
osteogenesis
Animal/Clinical Ultrasound Frequency,
(No. of Subjects) Intensity, Treatment Time Conclusions
2
Clinical (4) 0.7–1 MHz, 1–2 W/cm , pulsed, Increased callus tissue, less
10–15 d pain
Rabbits (36) 0.2–0.6 W/cm2, 5 min daily for 8 d Stimulated reparative
process at fracture site
Clinical (21) 3 MHz, 1 W/cm2, pulsed, 40 d Effective treatment in
48% of patients
Rabbits (21) 1.5 MHz, 30 mW/cm2, pulsed, 4 wk Enhanced bone formation
at the distraction site
Rabbits (15) 1.5 MHz, 30 mW/cm2, pulsed, 4 wk Enhanced mandibular
incisor growth and
eruption
Rabbits (8) 1.5 MHz, 30 mW/cm2, pulsed, 4 wk Enhanced mandibular
growth
Clinical (12) 1.5 MHz, 30 mW/cm2, pulsed, 4 wk Decrease in root
resorption
Rats (72) 1.5 MHz, 30 mW/cm2, pulsed, 2 or No notable benefit of
4 wk ultrasound treatment
Rats (72) 1.5 MHz, 30 mW/cm2, pulsed, 2 or No notable benefit of
4 wk ultrasound treatment
Rats (64) 1.5 MHz, 30 mW/cm2, pulsed, 2 or No notable benefit of
4 wk ultrasound treatment
Clinical (8) 1.5 MHz, 30 mW/cm2, pulsed, No stimulation of bone
total 13 h ultrasound exposure formation at the distrac-
tion gap
1.5 MHz, 30 mW/cm2, pulsed, 4 mo Enhanced mandibular
growth in growing
baboons when ultra-
sound treatment was
combined with function-
al appliances
Rabbits (30) 1.5 MHz, 30 mW/cm2 , pulsed, 3 wk Stimulated reparative
process at fracture site
Clinical (9) 1.5 MHz, 30 mW/cm2, pulsed, 46 ± No evidence of accelerat-
8.1 d ed callus healing by
ultrasound treatment
compared with control
group
Clinical (12) 30 mW/cm2 (frequency and pulse No notable effect on over-
status not specified), 10 sessions all bone volume; however,
over 4 wk increased buccal height
at the bony crest as well
as apical to the crest
Beagles (4) 1.5 MHz, 30 mW/cm2, pulsed, 4 wk Accelerated periodontal
wound healing and bone
repair, increase in level of
expression of heat shock
protein 70
Rabbits (36) 1.5 MHz, 30 mW/cm2, pulsed or Increased callus healing by
continuous, 1–4 wk continuous mode in the
first 2 wk and by pulsed
mode in 3rd and 4th wk

772 J Ultrasound Med 2009; 28:765–776

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vantage of home application of ultrasound is
patient dependency on the treatment. In such
situations, patient cooperation affects the suc-
cess of the therapy. The effects of ultrasound
therapy on growing bones and brain tissue are
not clear. Thus, its use in pediatric patients and
in skull bones should be avoided. Its use in sites
with suspected neoplasia and acute infections is
contraindicated because of possible accelerated
disease progression. Patients should be evaluat-
ed for allergic reactions to the coupling gel, and
patients with cardiac pacemakers should avoid
ultrasound treatment because of possible inter-
action with the ultrasound signals.
Future of Ultrasound Therapy for Bone
Healing
Minimal complication rates and adverse effects
of ultrasound therapy for acceleration of bone
healing made it possible to use this therapy in
clinical settings. Although there are many clinical
and animal studies available showing positive
effects of ultrasound, controversial results exist as
well. Most fresh fractures and surgical approach-
es associated with bone tissue heal uneventfully
with conventional treatments. However, in cases
in which faster healing is desired by the patient
or the physician, ultrasound therapy may be
considered as an alternative treatment.
There is evidence of successful treatment of
nonunions and delayed unions with LIPU thera-
py.51,52 One main indication for ultrasound treat-
ment may be this group of patients in the future.
Osteoporosis is a major disease affecting bone
tissue, especially in developed countries with
large elderly populations. Integration of bioma-
terials may be impaired in osteoporotic patients.
Tanzer et al55 showed increased bone growth in
porous intramedullary tantalum implants in the
ulnas of dogs. One potential use of ultrasound
treatment is to accelerate osseointegration of
implants (fracture management and dental
implants) in osteoporotic patients. More animal
and clinical studies are needed in this area. It has
been shown that ultrasound treatment positive-
ly affects soft tissue wound healing as well.74
Complicated fractures that involve soft tissue
and bone injury combined may benefit from
ultrasound therapy.
J Ultrasound Med 2009; 28:765–776
Erdogan and Esen
Osteoradionecrosis is avascular necrosis of
bone, which develops as a consequence of
radiotherapy. It is characterized by hypoxia and
hypovascularity. The conventional treatment
approach is surgical debridement with addi-
tional antibiotic and hyperbaric oxygen therapy.
It has been shown that ultrasound treatment
increases vascularity by inducing synthesis of
angiogenesis-related cytokines.45,48 One study
showed that supportive ultrasound application
helped considerably for the treatment of
osteonecrosis of jaws.58 Ultrasound therapy may
be considered a supportive treatment option for
osteonecrosis. Hypovascularity and hypoxia due
to radiotherapy impair the success of recon-
structive procedures in oncologic surgery. One
potential use of ultrasound is as a supportive
therapeutic procedure after reconstructive
surgery at sites that receive radiotherapy.
Experimental and clinical studies are being
conducted continuously to elucidate the mecha-
nisms of action and effectiveness of ultrasound
therapy in clinical settings. Although current
indications for use in clinical settings may be
limited to a small group of patients, ultrasound
therapy may be an important treatment option
in the management of the bone injuries and dis-
eases mentioned above.
Conclusions
The use of ultrasound in medicine was initially
developed for therapeutic rather than diagnostic
purposes. Therapeutic ultrasound in clinical set-
tings is a noninvasive application and has no
known serious complications or side effects. It is
an acceptable treatment of choice in fractures
with delayed unions and nonunions. Although it
does not seem possible to treat osteoporosis
itself because of application difficulties and a low
penetration rate, its use for acceleration of
osseointegration of metal biomaterials in osteo-
porotic patients has a promising future in ortho-
pedic surgery and oral-maxillofacial surgery. Its
use in the treatment of fresh fractures and surgi-
cal interventions associated with bone tissue,
such as spinal arthrodesis and distraction osteo-
genesis, in healthy patients may not be worth-
while because bone healing usually occurs in
these situations. Although much is known about
773
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Ultrasound Therapy in Bone Healing
the molecular effects of ultrasound treatment on
bone healing, more studies are needed to fully
understand the mechanisms.
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