Efficacy of Low-Intensity Pulsed Ultrasound on Bone Mineral by cuiliqing



         Efficacy of Low-Intensity Pulsed Ultrasound on Bone Mineral Density in
                          Osteoporotic Postmenopausal Women
    Ali A. Thabet*, Anwar A. Abeed** Shamekh M. El-Shamy*** and **** Omar F. Helal
    * Department of PT for Obstetrics and Gynecology, Faculty of Physical Therapy, Cairo University.
    **Department of PT for Surgery, Faculty of Physical Therapy, Cairo University.
    ***Department of PT for Disturbance of Growth and Development in Children and its Surgery,
    Faculty of Physical Therapy, Cairo University.
    **** Department of PT for cardiopulmonary disorders and geriatrics

    --------------------------------------------- ABSTRACT-------------------------------------------

       Purpose The aim of this current study was to investigate the effect of low –intensity pulsed
ultrasound on bone mineral density (BMD) of lumbar vertebrae in osteoporotic postmenopausal
women. Methods Thirty postmenopausal women suffer from lumbar vertebrae osteoporosis were
selected from Umm El Masryeen General Hospital received ultrasound therapy three time / week for
six weeks. DXA was used for assessment of BMD before and after treatment. Results The results of
the study demonstrate highly significant increase in lumbar BMD. Conclusion It was concluded that
is effective modalities in increasing bone mineral density (BMD) of lumbar vertebrae in osteoporotic
postmenopausal women.

    Key words: Postmenopausal, Bone Mineral Density ,Low-Intensity Pulsed Ultrasound ,Osteoporosis.

                  INTRODUCTION                                   Recently postmenopausal osteoporosis has
                                                                 become an area of interest in terms of medical,

O   steoporosis is a metabolic bone disease charac-
    terized by low bone mass, which increases the
                                                                 social and economic costs35. It is a significant
                                                                 cause of women's morbidity and mortality
    bone fragility and the risk of fracture.          More       leading to fractures of the hip, spine and wrist.
    cancellous than cortical bone is lost following              Osteoporosis is a primary metabolic disease of
    the menopause due to bone trabeculae being                   bone and a major public health problem that
    more sensitive to estrogen deficiency than                   mostly occurs in the elderly23.
    cortical bone, leading to a loss of connectivity
    and an increase in its porosity4. Bones, such as             It       has     been reported that there is
    proximal femur, distal radius and the vertebrae,             disproportionate loss of trabecular bone from
    are composed of a large amount of trabeculae                 the axial skeleton about 47% throughout life
    bone. Thus, treatments to prevent or to stabilize            depending on the peak bone mass20. It was
    the osteoporosis are important35. Alternative                reported in the literature that peak bone mass in
    treatments are options for those people with an              the human skeleton is achieved in the third to
    increased risk of osteoporosis development but               fourth decade of life. However, the adult
    with restrictions for the ordinary treatments                skeleton is undergoing a continual process of
    already in existence17.                                      remodeling in which bone resorptions is

coupled with bone formation20. At each                  falling and secondarily toward stabilizing bone
remodeling site (approximately 0.1mm3 of                mass17. Reversing the osteoporotic process
bone), a stereotyped sequence of events has             require therapy in the form of hormonal
been described.An initial stimulus activates the        replacement21. Calcitonin which is peptide
remodeling cycle19. Osteoclasts bone resorbing          hormone mediator for estrogen action, produce
cells that originate in the monocytemacrophage          inhibition of osteoclasts activity and therefore
cell line, resorb an apparently predetermined           decrease     the     bone       resorption21.   Also
volume of bone33. Having completed this task,           maintaining a high dietary intake of calcium,
the osteoclasts then disappear and are replaced         vitamin D, reduction of excessive consumption
by osteoblasts, which lay down osteoid refilling        of protein and phorphorous          are    indicated
the cavity24. Mineralization of osteoid completes       as therapeutic options4 . Calcium must be given
the repair process. In the aging skeleton, however,     with sodium fluoride to allow mineralization of
there is an imbalance between the resorptive and        the new osteoid. Problems with this modality,
formative process27.                                    include the questions of abnormal bone
      There are two types of osteoporosis, type I       architecture and the high incidence of side
due to a decrease in cumulating estrogens               effects18.
which affects trabecular bone (especially                     The impact of physical activity on BMD
vertebral bone) and affects females more than           was established via reducing and/or preventing
males in a ratio of 1:6. Type II, senile                the volitional bone loss in both recently
osteoporosis, which is age related and occurs in        postmenopausal and very elderly women35 .
cortical and trabecular bone, affects females and       The role of electro-therapy in the management of
males in a ratio of 2:1. 21                             menopausal osteoporosis is very limited in the
      It is evident that low bone mass is the           literature33. It was concluded that pulsed
most potent factor leading to fracture. Estrogen        electromagnetic field has an effect to slow down
deficiency is well established as a risk factor for     the bone mass loss in osteoporosis induced by
osteoporosis4. There are several risk factor            ovariectomy in rats and clinical application of
reported in the literature which accelerate the         the same current in women's osteoporosis was
development of osteopenic process includes              also reported10.
negative calcium balance, sedentary life style,           The ultrasound is a form of mechanical
immobilization,       menopause        (surgical   or   energy       which    promotes         local    bone
natural),   amenorrhea,       family     history   of   microdeformations, as the natural mechanical
osteoporosis, high alcohol intake, smoking, high        incentive, and which is crucial in stimulating
                                               4                               9.31
caffeine consumption and steroid therapy .              the bone formation            . Several studies have
Therapy should be directed primary toward               already shown that low-intensity ultrasound is
increasing physical activity, reducing the risk of      capable of accelerating the healing of fresh

fractures, delayed healing and nonunions               Further support for a beneficial skeletal effect of
         .Furthermore, recent experimental studies     low-intensity pulsed US has been provided by in
have shown the ultrasound benefits on large            vivo investigations8. In vivo, the most frequent
bone defects 26 and on spine fusion129. However,       application of low-intensity pulsed US is during
there are no studies which relate the action of        fracture repair. In animal fracture models, such
low-intensify        ultrasound     in   cases    of   US has been shown to facilitate the rate of
osteoporosis without fractures1.                       endochondral bone formation, increasing the
    Ultrasound (US), a high-frequency acoustic         return of bone mineral density (BMD) at the
energy traveling in the form of a mechanical           fracture site.This results in a 38% acceleration in
wave, represents a potential site-specific             mechanical    strength      return18.    In   humans,
intervention for osteoporosis12. Bone is a             low-intensity pulsed US has been shown to
dynamic tissue that remodels in response to            facilitate   the   return      of       BMD    during
applied mechanical stimuli14. As a form of             limb-lengthening procedures         and induce a
mechanical stimulation, US is anticipated to           30%-38% reduction in the time to union in fresh
produce a similar remodeling response. This            fractures.When applied to nonunited fractures,
theory is supported by growing in vitro and in         the same US has been shown to stimulate union
vivo evidence demonstrating an osteogenic              in >85% of cases27. pulsed-wave US at low
effect       of    pulsed-wave      US    at     low   (<100          mW/cm2)              spatial-averaged
spatial-averaged                  temporal-averaged    temporal-averaged intensities9.
intensities14. Ultrasound (US) represents a            It was found that low-intensity pulsed US to not
potential intervention for osteoporosis. US refers     only prevent femoral neck bone loss in five
to a high-frequency nonaudible acoustic energy         osteoporotic bed-ridden patients, but to increase
that travels in the form of mechanical waves3. A       BMD levels by 8.9%, on average, above
mechanical wave is one in which energy is              baseline levels. BMD on the contralateral
transmitted by the movement of particles within        nontreated side decreased by 4.0% within the
the medium through which the wave is traveling.        same period. This finding suggests an anabolic
As these waves travel as a relatively focused          effect of low-intensity pulsed US on intact
beam (typical effective radiating area = 5             bone27.
cm2)11. US can be directed onto specific regions       Ultrasound is a biophysical intervention that is
to exert a local mechanical stimulus19                 capable of generating piezo-electric effects in
Given the inherent mechanosensitivity of bone, it      bone 2, and increasing electric potentials in
has been hypothesized that US mechanical               bone 15 Using 1.27-MHz ultrasound with a very
energy may be an osteogenic stimulus18. This           low intensity of 0.00383 W cm–2 on bone,            2

theory is supported by a growing body of               measured an electric potential of 64 µV at the
evidence demonstrating the skeletal effects of         ultrasound frequency in vivo2,15.

                                                       An imaging test that measures bone density (the
    SUBJECTS, MATERIALS &                              amount of bone mineral contained in a certain
                                                       volume of bone) by passing x-rays with two
                                                       different energy levels through the bone. It is used
                                                       to diagnose osteoporosis (decrease in bone mass
      Thirty postmenopausal women were selected
                                                       and density). Also called BMD scan, bone
from Umm El Masryeen General hospital. The
                                                       mineral density scan,
criteria for inclusion were as follows: (a) DXA
diagnosis of normal BMD and osteoporosis in
                                                       (2) Ultrasonic(US) device (Enraf Nonius –
lumbar vertebrae with no evidence of vertebral
                                                       Sonoplus590): was used to deliver low –intensity
compression fractures, (b) age between 51 to 60
                                                       pulsed ultrasound therapy. The apparatus provided
years (to avoid inclusion of older patients with
                                                       the following options: 1MHz frequency with
multiple medical problems), (c) no history of
                                                       transducer having an affective radiating area of 5.0
cancer, renal disease, gastrectomy, metabolic bone
                                                       cm2. Intensity up to 1.5 W/cm2 in continuous
disease or any condition (such as a neurogenic,
                                                       mode, and up to 3W/cm2 in pulsed mode. Gel was
myopathic or connective tissue disorder) that could
                                                       used as a coupling media.
cause secondary osteoporosis, (d) no intake of any
medications associated with accelerated bone loss
(steroids) or any medications affected bone
metabolism (estrogen, calcium, vitamin D, ...etc),
(e) body mass index not exceeding 30 Kg/m2, non
smoker, parity from 1-3 times and led sedentary
life style without participation at any exercise
training during this study, and, (f) had natural
menopause at least 1 year before entry into the
study with no history of ovariectomy.

(l) Dual x-ray Absorptiometry (DXA) (Model
QDR-1000W, Hologic, Inc., Waltham, MA) was
used for     the qualitative assessment of BMD
in the vertebral bodies of the lumbar spine for both

Procedures:                                      analytical test included student t-test for
                                                 comparing of means between before and
A. Evaluation                                    after treatment. Significant level of 0.05
     Initially a screening test including        was used throughout all statistical tests
careful history taking and gynecological         within this study, P value < 0.05 indicated
examination were conducted for each              significant results. The smaller the P value
subject before entry in this study. After that   obtained the more significant was the
BMD of lumbar spine (L1.-5) was measured         result.
by DXA densitometry. Evaluation of lumbar
BMD was performed before and after the
end of six weeks of treatment.

                                                       In the present study, the response of
B. Treatment
                                                 BMD to low intensity pulsed ultrasound was
     All subjects in this study underwent
                                                 investigated. The data collected after six
20   minutes     US       application,   with
                                                 weeks     of   ultrasound   treatment   were
frequency 1MHz and intensity 0.2 w/cm2 ,
                                                 compared with the pre treatment.
for each session, three sessions per week
for six successive weeks period of               As revealed from table (1) and figure (1)
treatment. The treatment procedure was           there was a highly statistically significant
explained to all subjects. Skin was cleaned      increase (P>0.0001) in the mean value of
with alcohol to remove fat. During               lumbar T- Score between pre and post
ultrasound application, the position of the      treatment.
subjects was prone lying position with a
pillow under her abdomen. Ultrasound                   As revealed from figure (2) While
therapy was applied to the lumbar vertebrae      comparing      pre   treatment   and    post
(L1-5) using 5 cm ultrasound head.               treatment, the improvement percentage
                                                 was 14.40% and statistically difference
C. Statistical analysis                          (P>0.0001) was highly significant
     Descriptive statistics was presented
as mean, standard deviation (SD) and
percentage      for   qualitative    variable

       Table (1): The comparison between pre & post mean values of the T- score

                                                                                Imp. %
                                                 Pre-ttt   Post-ttt    MD                     t value            P value   Significance
      Mean                                       -3.0167 -2.5833                                                             Highly
                                                                      -0.4333    14.4         -6.500             0.0001
            SD                                   9.129     0.3957                                                          significant

                                                                                        Pre treatment T-score
                                                                                        Post treatment T-score
       T- Score


    Fig. (1): The mean value of T-score of pre treatment relative to those of post treatment.





                            Improvement %







                         Fig. (2): The improvement % of the mean values of T-score of post treatment.

                                                       permeability to ions and to alter cell membrane
                    Discussion                         electrophysiological properties. Ultrasound can

       The primary problem in postmenopausal with      cause an immediate decrease in intracellular

osteoporosis is thought to be enhancement of bone      potassium content in thymocytes            a reversible

resorption, with consequent net loss of bone mass      increase in the intracellular level of calcium in

as osteoblasts fail to repair the defect completely    chondrocytes), and an increase in calcium

which increase the risk to fracture. The basic         incorporation into differentiating cartilage and

problem in the remodeling of bone is directly          bone cell cultures 24.

related to the stimulation, multiplication and               Depending on the cell type, the result of

proliferation of the extraperiosteal, periosteal and   changes in intracellular calcium ions can be

medullar connective tissue that forms reparative       synthesis, secretion, or motility changes, all of

blastemas leading to the consolidation of the bone .   which could promote healing 21.

       Dual X-ray absorptiometry was used for                With respect to bone healing, there are also

assessment of bone density                             indications      that    ultrasound     influences   the

      The results of DEXA revealed a highly            adenylatecyclase cascade in the cell membranes of

significant   increase   in   lumbar    BMD       of   osteoblasts24 a finding which is similar to that

postmenopausal osteoporotic women with low             observed following an application of static

intensity pulsed ultrasound compared to pre            mechanical load27. The changes in the cell

treatment lumber BMD.                                  membrane may be the most important mechanism

      The process of bone healing or remodeling        by which the ultrasound signal influences cellular

is very similar to that of soft tissues healing. It    changes and responses24.

would therefore seem reasonable to suggest that
                                                       It is not clear if these changes are brought about by
bone healing and/or remodeling might be stimulated
                                                       a direct mechanical deformation of the cell
by ultrasound which is reported in our results. Low
                                                       membrane, deformation of cell receptors, or
intensity pulsed ultrasound can be directed onto
                                                       indirectly as a consequence of cavitation,
specific regions to exert a local mechanical stim-
                                                       microstreaming, or a combination of these or other
ulus. Given the inherent mechanosensitivity of bone,
it has been hypothesized that US mechanical energy
may be an osteogenic stimulus. This theory is                It has been argued that the beneficial effect
supported by a growing body of evidence                of ultrasound on bone healing is due to the
demonstrating the skeletal effects of pulsed-wave      piezo-electric          phenomenon19.       Bone      is
US at low (<100 mW/cm ) spatial-averaged               piezo-electric, which means that electric potentials
temporal-averaged in ten                               are produced in bone when it is subjected to
      Ultrasound is capable of producing changes       mechanical stress13. Since Wolff’s law basically
within the cell membrane. This is illustrated by       states that bone remodels according to functional
ultrasound’s capacity to alter cell membrane           demands, it is assumed that the stress-generated

potentials in bone serve as a signal which controls            were in agreement and supporting our finding.
bone remodeling13.
                                                               Elbialy et al.11, studied effects of ultrasound modes
          Ultrasound is a biophysical intervention that        on mandibular osteodistraction and they found that
is capable of generating piezo-electric effects in             Earlier stages of bone healing were enhanced more
bone2 and increasing electric potentials in bone               by continuous, whereas late stages were enhanced
Using 1.27-MHz ultrasound with a very low                      more by pulsed
intensity of 0.00383 W cm–2 on bone,2 measured
                                                                 Daniela and Alberto.,6 who studied the action
an electric potential of 64 µV at the ultrasound
                                                               of low-intensity pulsed ultrasound in bones of
frequency in vivo13.
                                                               osteopenic     rats    and      they found      that   the
Evidence that osteogenesis is stimulated by                    low-intensity ultrasound can interfere in a positive
ultrasound can be found in vitro studies.                      way on osteoporosis as the treated group, sites with
Osteoblasts can be stimulated to increase collagen             recent bone formation are shown, which indicates
production             and increase the production of          more active osteoblasts
prostaglandin E2, an important bone-healing                      Warden       et     al.,32     studied    Efficacy   of
mediator that exert different effects on bone cells            Low-intensity         Pulsed      Ultrasound     in    the
in the same microenvironments, such as inhibiting              Prevention of Osteoporosis Following Spinal
mature rat osteoclasts from resorbing bone and                 Cord Injury and they found that alternate doses of
stimulating osteoblasts for bone formation 17.                 US may have beneficial effects on intact bone.
                                                               These effects are likely to be restricted to the outer
In summary, ultrasound stimulation of bone healing may be
                                                               bone cortex.
mediated through cavitation, piezo-electric phenomena, and
effects on the cell membrane. This stimulation appears to be
                                                                 Sheng Sun et al.,            studied in vitro effects of
multilevel, involving different cell types in and during the   low intensity ultrasound stimulation on bone cells
healing     process.   The   particular   properties     of    and they found that low intensity ultrasound
ultrasound would create a series of environmental              treatment may have a stimulatory effect on bone
conditions that accelerate the remodeling of bone .            healing processes as the concentration of PGE2 in
It was reported that osteogenesis has been                     the culture medium significantly increased after
considered as depending directly on local                      ultrasound stimulation which stimulate bone cell
circulation . Bone develops better in a well                   metabolism.
vascularized environment therefore it would be                   Chang et al.,5 who studied cytokine release from
desirable to produce this situation through                    osteoblasts in response to ultrasound stimulation,
therapeutic means in order to achieve faster bone              they found that increase in osteoblasts growth due
consolidation. The results registered in this study            to mechanical stimulation of ultrasound and
coincide with many research studies investigating              enhance osteoblasts population together.
the effect of low intensity pulsed ultrasound on
tissue and bone repair in vivo and vitro models and

    Monici et al.,19 who studied the effect of low                   formation and enhance fracture healing by initiating
intensity ultrasound stimulation on model of osteoclastic            enhanced angioneogenesis.
precursor,   they found            that    ultrasound    inducing    Carvalho and Cliquet,3 who studied the action of
enhancement      of        the    osteoclastic     function   and    low-intensity pulsed ultrasound in bones of osteopenic
impairment of osteoclastic one at the same time makes                rats and found that the low-intensity ultrasound can
ultrasound a potential tool to counteract osteoporosis.              interfere in a positive way on osteoporosis.
    Ramas et al.,23 who studied stimulating bone growth
using piezoelectric ultrasound transducers on the                                            Conclusion
edentulous jaw and they found that ultrasound activating
                                                                           Although osteoporosis is a primary metabolic
bone growth through the mechanical stress induced by
                                                                     disease of bone and a major public health problem that
the propagation of ultrasound into the bone.
                                                                     mostly occurs in postmenopausal period, there is no cure
                                                                     of it. Therapy should be directed primarily toward
Tsumaki et al.,30 who studied low-intensity pulsed
                                                                     increasing physical activity, reducing the risk of falling
ultrasound accelerates maturation of callus in patients
                                                                     and secondarily toward stabilizing bone mass. The
treated with opening-wedge high tibial osteotomy by
                                                                     results of this study demonstrated the superiority of low
hemicallotasis and they found that low-intensity pulsed
                                                                     intensity pulsed ultrasound to increase BMD of lumbar
ultrasound applied during the consolidation phase of
                                                                     vertebrae in postmenopausal women with osteoporosis.
distraction osteogenesis accelerates callus maturation
                                                                            Although the findings of this study are highly
after    opening-wedge           high     tibial   osteotomy by
                                                                     significant, but treatment of low bone mass might not be
hemicallotasis in elderly patients.
                                                                     effective enough to guarantee that any gains in mass will
Eung et al.,12 studied           the effects of low intensity        be of sufficient magnitude to reduce fracture risk
ultrasound stimulation on the proliferation of alveolar              significantly, so further research is required to examine
bone marrow stem cells and they found that the alveolar              long term effectiveness of this treatment and combine it
bone marrow stem cell counts were significantly                      with physical activity that reported its effectiveness on
increased    that     indicate      low-intensity       ultrasound   bone repair in literatures.
stimulation enhanced bone regeneration.

Rutten et al.,26 who studied low-intensity pulsed
ultrasound increases bone volume, osteoid thickness and                 1- Aynaci, O.; Onder, C.; Piskin A. and
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                         ‫لدى السيدات بؼد إنقطاع الطمث مغ وجود هشاشة في الؼظام‬

   ‫*ػلي ػبد المنصف ثابث و **أنور ػبد الجيد ػبيد و ***شامخ محمد الشامي و ****ػمر فاروق هالل‬
                   ‫*قسى ع.ط اليشاض انُساء وانتىنيذ- كهيت انؼالد انطبيؼً- رايؼت انقاهشة‬
                          ‫** قسى ع.ط نهزشاحت- كهيت انؼالد انطبيؼً- رايؼت انقاهشة‬
 ‫*** قسى ع.ط الضطشاباث يشاحم انًُى وانتطىس ورشاحتها نذي االطفال- كهيت انؼالد انطبيؼً- رايؼت انقاهشة‬
                ‫**** قسى ع.ط اليشاض انباطُت وانًسُيٍ- كهيت انؼالد انطبيؼً- رايؼت انقاهشة‬

  ‫انهذف يٍ هزا انبحج دساست كفاءة انؼالد بانًىراث انصىتيه يُخفضت انشذة ػهً كخافت انؼظاو نذي انسيذاث بؼذ‬
‫إَقطاع انطًج يغ ورىد هشاشه فً ػظاو انًُطقت انقطُيت. اشتشك فً هزة انذساسه حالحىٌ سيذة تؼاَيٍ يٍ هشاشه فً‬
‫ػظاو انًُطقت انقطُيت اختيشٌ يٍ يستشفً أو انًصشييٍ انؼاو وتى ػالرهٍ بانًىراث انصىتيه يُخفضت انشذة حالث‬
‫يشاث اسبىػيا نًذة ستت اسابيغ .تى تقييى انحالث قبم وبؼذ انؼالد ػٍ طشيق االشؼت انسيُيه انًىردورت (ديكسا). وقذ‬
 ‫اكذث َتائذ هزة انذساست ػهً كفاءة انؼالد بانًىراث انصىتيه يُخفضت انشذة ػهً صيادة كخافت انؼظاو فً انًُطقت‬
                       ‫انقطُيت نذي انسيذاث بؼذ إَقطاع انطًج يغ ورىد هشاشه فً انؼظاو‬

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