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The Role of Extracorporeal Shockwave Treatment in Musculoskeletal Disorders

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Increasing evidence suggests that extracorporeal shockwave treatment (ESWT) is safe and effective for treating several musculoskeletal disorders. Two types of technical principles are usually included in ESWT: focused ESWT (F-ESWT) and radial pressure waves (RPW). These 2 technologies differ with respect to their generation devices, physical characteristics, and mechanism of action but share several indications. Strong evidence supports the use of ESWT in calcifying tendinopathy of the shoulder and plantar fasciitis. The best evidence for the use of ESWT was obtained with low to medium energy levels for tendon disorders as well as with a high energy level for tendon calcification and bone pathologies in a comprehensive rehabilitation framework.
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Current Concepts Review
The Role of Extracorporeal Shockwave
Treatment in Musculoskeletal Disorders
Daniel Moya, MD, Silvia Ram´
on, MD, PhD, Wolfgang Schaden, MD, Ching-Jen Wang, MD,
Leonardo Guiloff, MD, and Jai-Hong Cheng, MD
äIncreasing evidence suggests that extracorporeal shockwave treatment (ESWT) is safe and effective for treating
several musculoskeletal disorders.
äTwo types of technical principles are usually included in ESWT: focused ESWT (F-ESWT) and radial pressure waves
(RPW). These 2 technologies differ with respect to their generation devices, physical characteristics, and mech-
anism of action but share several indications.
äStrong evidence supports the use of ESWT in calcifying tendinopathy of the shoulder and plantar fasciitis.
äThe best evidence for the use of ESWT was obtained with low to medium energy levels fortendon disorders as well as
with a high energy level for tendon calcication and bone pathologies in a comprehensive rehabilitation framework.
Shockwave therapy was originally developed to disintegrate
urinary stones 4 decades ago
1
. Since then, there has been re-
markable progress regarding the knowledge of its biological
and therapeutic effects. Its mechanism of action is based on
acoustic mechanical waves that act at the molecular, cellular,
and tissue levels to generate a biological response
2
.
Increasing evidence suggests that extracorporeal shock-
wave treatment (ESWT) is safe and effective for treating several
musculoskeletal disorders
3-5
. The purpose of this article was to
provide current evidence on the physical and biological prin-
ciples, mechanism of action, clinical indications, and contro-
versies of ESWT.
Physical Principles and Wave Generation
Two types of technical principles are included in ESWTfocused
ESWT (F-ESWT) and radial pressure waves (RPW), which are
often referred to in the literature as radial shockwaves. These
2 technologies differ in their generation devices, physical
characteristics, and mechanism of action, but they share several
indications.
As shown in Figure 1, the following 3 shockwave-
generation principles are used for F-ESWT
6,7
:
1. Electrohydraulic sources (Fig. 1-A) produce a plasma
bubble by high-voltage discharge between 2 electrodes in water
at the focus closest to a paraellipsoidal reector. The plasma
expansion generates a shock front, which is reected off the
reector and focused on a second focus at the target tissue.
2. Electromagnetic sources (Fig. 1-B) with at or cylin-
drical coils are also used. In the rst system, a high-voltage pulse
is sent through a coil, which is opposite a metallic membrane.
The coil produces a magnetic eld, resulting in a sudden
deection of the membrane and generating pressure waves in a
uid. The waves are focused by a lens and steepen into a
shockwave near the focus. The second electromagnetic gener-
ation source consistsof a cylindrical coil and metallic membrane
that is arranged inside a uid-lled parabolic reector. The
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Copyright Ó2018 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved. This is an open-access article
distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to
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J Bone Joint Surg Am. 2018;100:251-63 dhttp://dx.doi.org/10.2106/JBJS.17.00661
membrane is accelerated away from the coil by a magnetic eld.
An acoustic pulse emerges radially, and it is concentrated onto
the focus of the system after reection off the reector.
3. Piezoelectric sources (Fig. 1-C) produce shockwaves by
a high-voltage discharge across a pattern of piezoelectric
elements mounted on the inner surface of a spherical backing
that is placed inside a uid-lled cavity. Each element expands,
generating a pressure pulse that propagates toward the center, or
focal region, of the arrangement. Superposition of all pressure
pulses and nonlinear effects produce a shockwave at focal region.
In RPW generators (Fig. 1-D), compressed air accelerates
a projectile inside a cylindrical guiding tube. When the projectile
hits an applicator at the end of the tube, a pressure wave is
produced and radially expands into the target tissue. These de-
vices do not emit shockwaves
8
because the rise times of the
pressure pulses are too long and the pressure outputs are too low
(Fig. 2). Nevertheless, RPW may induce acoustic cavitation
9
.
The modes of action and the effects of RPW on living
tissue may differ from those of focused shockwaves because
bioeffects are related to the pressure waveform. F-ESWT and
RPW may complement each other. While RPW is suitable for
treating large areas, focused shockwaves can be concentrated
deep inside the body.
Mechanism of Action
Despite the clinical success of the treatment, the mechanism of
action of ESWT remains unknown. In 1997, Haupt proposed
the following 4 possible mechanisms of reaction phases of
ESWT on tissue
10
.
1. Physical phase: This phase indicates that the
shockwave causes a positive pressure to generate absorption,
reection, refraction, and transmission of energy to tissues
and cells
11
. Additional studies demonstrated that ESWT
produces a tensile force by the negative pressure to induce the
physical effects, such as cavitation, increasing the permea-
bility of cell membranes and ionization of biological mole-
cules. Meanwhile, many signal transduction pathways are
activated, including the mechanotransduction signaling
Fig. 1
Figs. 1-A through 1-D Illustrations of an electrohydraulic (Fig. 1-A), an electromagnetic (Fig. 1-B), and a piezoelectric shockwave source (Fig. 1-C) and a
radial pressure wave source (Fig. 1-D). The 26 dB region is dened as the volume within which the positive pressure is at least 50% of its maximum.
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pathway, the extracellular signal-regulated kinase (ERK)
signaling pathway, focal adhesion kinase (FAK) signaling
pathway, and Toll-like receptor 3 (TLR3) signaling pathway,
to regulate gene expressions
2,5,12-14
.
2. Physicochemical phase: ESWT stimulates cells to
release biomolecules, such as adenosine triphosphate (ATP), to
activate cell signal pathways
15,16
.
3. Chemical phase: In this phase, shockwaves alter the
functions of ion channels in the cell membrane and the calcium
mobilization in cells
17,18
.
4. Biological phase: Previous studies have shown that
ESWTmodulates angiogenesis (vWF [von Willebrand factor],
vascular endothelial growth factor [VEGF], endothelial nitric
oxide synthase [eNOS], and proliferating cell nuclear antigen
[PCNA]), anti-inammatory effects (soluble intercellular
adhesion molecule 1 [sICAM] and soluble vascular cell
adhesion molecule 1 [sVCAM]), wound-healing (Wnt3,
Wnt5a, and beta-catenin), and bone-healing (bone mor-
phogenetic protein [BMP]-2, osteocalcin, alkaline phospha-
tase, dickkopf-related protein 1 [DKK-1], and insulin-like
growth factor [IGF]-1)
18-22
.
The effects of ESWT are summarized in Table I,with new
functional proteins induced by ESWT promoting a chon-
droprotective effect, neovascularization, anti-inammation,
anti-apoptosis, and tissue and nerve regeneration
2,12-14,16,19,22-52
.
Furthermore, ESWT stimulates a shift in the macrophage
phenotype from M1 to M2 and increases T-cell proliferation in
the effect of immunomodulation
27,28
. ESWT activates the TLR3
signaling pathway to modulate inammation by controlling the
expression of interleukin (IL)-6 and IL-10 as well as improves
the treatment of ischemic muscle
12,13
.
Fig. 2
Illustration showing the difference in pressure waveform between
a shockwave and a radial pressure wave as used in medical applications.
TABLE I Overview of Effects and Functional Proteins After ESWT*
Upregulation Factors Downregulation Factors
Chondroprotective effect
2,14,16,29-40
BMP-2, 3, 4, 7; IGF-1; TGFb-1; VEGF; Wnt3; RUNX2;
osteocalcin; alkaline phosphatase; osteopontin;
FAK; ERK1/2; c-Fos; c-Jun; p38 MAPK; P2X7
receptor; SOX9; PDGF; b-FGF; FGF-2; Ras; substance
P; prostaglandin E(2); Hsp70
DKK1, Wnt5a, calcitonin gene-related peptide,
miR-138
Neovascularization
25,43-45
VEGF, Flt1, Flt2, CD31, vWF, FGF, PIGF, KDR, PCNA
Anti-inammation
12,13,22,25,46
TGFb-1, TLR3, eNOS, nNOS, IL-10, IL-6, IL-8,
cyclophilin B, cyclophilin A, EGF-like domains 2,
IFN-b1
sICAM, sVCAM, iNOS, IL-18, TNFa, NF-kB
Anti-apoptosis
25,47
Bcl2, heme oxygenase (HO)-1, NAD(P)H quinone
oxidoreductase-1
Bax, cleaved caspase 3, cleaved PARP,
g-H2AX, NOX1, NOX2, TUNEL activity
Tissue and nerve regeneration
35,48-52
COL1A1, COL2A1, MMP2, MMP9,
glycosaminoglycan, collagen type III, S100b, p75,
c-Jun, GFAP, activating transcription factor 3 (ATF3),
growth-associated phosphoprotein (GAP-43)
MMP-1, MMP-13, myelin marker P0
*BMP = bone morphogenetic protein, IGF = insulin-like growth factor, TGF = transforming growth factor, VEGF = vascular endothelial growth factor,
RUNX2 = runt-related transcription factor 2, FAK = focal adhesion kinase, ERK = extracellular signal-regulated kinase, MAPK = mitogen-activated
protein kinase, PDGF = platelet-derived growth factor, FGF = broblast growth factor, Hsp = heat-shockprotein, DKK = dickkopf-related protein, miR =
microRNA, Flt = FMS-like tyrosine kinase, vWF = von Willebrand factor, PIGF = phosphatidylinositol-glycan biosynthesisclass-F protein, KDR = kinase
insert domain receptor, PCNA = proliferating cell nuclear antigen, TLR = Toll-like receptor, NOS = nitric oxide synthase, eNOS = endothelial NOS,
nNOS = neuronal NOS, IL = interleukin, EGF = epidermal growth factor, IFN = interferon, sICAM = soluble intercellular adhesion molecule, sVCAM =
soluble vascular cell adhesion molecule, iNOS = inducible NOS, TNFa= tumor necrosis factor alpha, NF-kB = nuclear factor kappa B, Bcl = B-cell
lymphoma, NAD = nicotinamide adenine dinucleotide, PARP = poly(ADP-ribose) polymerase, H2AX = H2A histone family member X, TUNEL = terminal
deoxynucleotidyl transferase-mediated dUTP nick end labeling, COL1A1 = collagen type-1 alpha 1, COL2A1 = collagen type-2 alpha 1, MMP = matrix
metalloproteinase, and GFAP = glial brillary acidic protein.
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Finally, it appears that ESWT participates in mechano-
transduction, producing biological responses through me-
chanical stimulation on tissues
2,4,7,26
.
Clinical Indications
ESWT is indicated in chronic tendinopathies in which con-
ventional conservative treatment is considered unsatisfactory
after a prolonged and comprehensive management or as an
alternative to surgery in patients with nonunion. ESWT is a
noninvasive alternative in select cases when the indication for
surgical treatment arises.
The International Society for Medical Shockwave Treat-
ment (ISMST) has developed a list of approved clinical indications
that are based on the strength of the supporting evidence
53
.The
recommendations for ESWT indications and contraindications
are summarized in Table II and Table III, respectively.
TABLE II Grades of Recommendations According to Clinical Indications for ESWT
Pathology Technology
Studies*
Grade of
Recommendation
Positive Negative
RCTs
Reviews, Systematic
Reviews, and
Meta-Analyses RCTs
Reviews, Systematic
Reviews, and
Meta-Analyses
Calcifying
tendinopathy of the
shoulder
Focused Gerdesmeyer et al.
58
,
Cosentino et al.
59
, Hsu
et al.
60
, and Rompe
et al.
69
Moya et al.
55
, Ioppolo
et al.
61
, Bannuru
et al.
62
, Huisstede
et al.
63
, Louwerens
et al.
64
, Speed
65
, and
Verstraelen et al.
66
Albert et al.
56
and Kim et al.
67
A
Calcifying
tendinopathy of the
shoulder
Radial Cacchio et al.
57
Moya et al.
55
, Bannuru
et al.
62
, Huisstede
et al.
63
, Speed
65
, and
Verstraelen et al.
66
I
Noncalcifying
tendinopathy of the
shoulder
Focused or
radial
Speed et al.
71
and
Engebretsen
et al.
72
Moya et al.
55
, Bannuru
et al.
62
, Huisstede
et al.
63
, and Speed
65
C
Lateral
epicondylopathy of
the elbow
Focused or
radial
Pettrone and McCall
85
,
Lee et al.
86
, and
Radwan et al.
87
Thiele et al.
80
and
Rompe and Maffulli
84
Speed et al.
79
Sims et al.
81
,
Buchbinder et al.
82
, and
Dingemanse et al.
83
B
Greater trochanter
pain syndrome
Radial Rompe et al.
88
and Furia
et al.
89
Mani-Babu et al.
90
B
Patellar
tendinopathy
Focused or
radial
Wang et al.
96
, Furia
et al.
97
, and Peers
et al.
99
Mani-Babu
90
, Leal
et al.
91
, Larsson et al.
94
,
and Everhart et al.
98
Zwerver
et al.
101
and
Thijs et al.
102
B
Achilles
tendinopathy
Focused or
radial
Rasmussen et al.
110
,
Furia
111
, Furia
112
,
Rompe et al.
113
, and
Rompe et al.
114
Mani-Babu et al.
90
,
Gerdesmeyer et al.
108
,
Al-Abbad and Simon
115
,
Kearney and Costa
116
,
and Roche and
Calder
117
Costa et al.
109
Scott et al.
105
B
Plantar fasciitis Focused or
radial
Chuckpaiwong et al.
121
,
Wang et al.
122
,
Gerdesmeyer et al.
123
,
Ibrahim et al.
124
,
Gollwitzer et al.
125
,
Ogden et al.
126
, Rompe
et al.
127
, Aqil et al.
128
,
Saxena et al.
133
, Weil
et al.
134
, Thomas
et al.
135
, and Wang
et al.
136
Dizon et al.
130
, Othman
and Ragab
131
, Radwan
et al.
132
, and Chen
et al.
137
Buchbinder
et al.
119
and
Haake et al.
120
A
Bone nonunion Focused Notarnicola et al.
155
,
Schaden et al.
157
, and
Lyon et al.
158
Furia et al.
154
, Kuo
et al.
156
, and Thiele
et al.
160
B
*RCT = randomized controlled trial. According to Wright
164
, grade A indicates good evidence (Level-I studies with consistent ndings) for or against recommending intervention;
grade B, fair evidence (Level-II or III studies with consistent ndings) for or against recommending intervention; grade C, poor-quality evidence (Level-IV or V studiesw ithconsistent
ndings) for or against recommending intervention; and grade I, there is insufcient or conicting evidence not allowing a recommendation for or against intervention.
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After ESWT, a comprehensive post-treatment schedule,
individualized for each pathology and each patients clinical
status, should be given to the patient including avoidance of the
use of the anatomic structure, a specic exercise program, and
instructions to avoid overload.
Shoulder Tendinopathies
Calcifying Tendinopathy of the Shoulder (CTS)
ESWT has emerged as an alternative therapy prior to invasive
procedures when conservative treatment has failed as described
for G¨
artner type-I or II rotator cuff calcications
54,55
(Fig. 3).
The rate of successful reabsorption reported by different au-
thors has a very wide range
56-66
.
Gerdesmeyer et al.
58
, in a multicenter randomized con-
trolled trial (RCT) that included 144 patients, reported sig-
nicantly better results in patients treated with F-ESWT, both
low and high energy, compared with placebo, resulting in
improvement with respect to pain, shoulder function, and
calcium resorption in 86% in the high-energy group at 1 year
compared with 37% in the low-energy group and 25% in the
placebo ESWT group. Cosentino et al.
59
, in a single-blind trial
using F-ESWT, reported a signicant increase in shoulder
function, a decrease in pain compared with placebo, and cal-
cium resorption of 71% by using F-ESWT, at 6 months. Hsu
et al.
60
, in an RCT, achieved good or excellent results in 87.9%
of patients treated with high-energy F-ESWT.
Cacchio et al.
57
obtained a surprisingly high rate of re-
absorption using RPW (86.6% complete and 13.4% partial
resorption) at the 6-month follow-up; however, most studies
have considered that high-energy F-ESWT is more likely to
result in better radiographic and clinical outcomes
55,56,58-66
.
Several systematic reviews and meta-analyses have
demonstrated that high-energy F-ESWT is a safe, effective
treatment for CTS
61-66
.
Kim et al.
67
compared RPW with ultrasound-guided nee-
dling and reported that the latter treatment method was more
effective in functional restoration and pain relief in the short
term. However, Moya et al.
68
pointed out numerous methodo-
logical aws in that study. There was missing information about
the ESWT device used (focused or radial), methodological
Fig. 3
Anteroposterior radiographs of a right shoulder with a G¨artner type-II calcication of the supraspinatus before focused shockwave treatment (Fig . 3-A)and at
3 months after treatment (Fig. 3-B), showing that the calcication has disappeared.
TABLE III ESWT Contraindications
ESWT Contraindications*
High-Energy Focused
Shockwaves
Low-Energy Focused and
Radial Shockwaves
1. Lung tissue in the treatment
area
1. Malignant tumor in the
treatment area
2. Malignant tumor in the area 2. Fetus in the treatment
area
3. Epiphyseal plate in the area
4. Brain or spine in the area
5. Severe coagulopathy
6. Fetus in the treatment area
*According to the International Society for Medical Shockwave
Treatment
53
.
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explanations were short and imprecise, the point of maximum
tenderness was treated instead of focusing on topographic
anatomy or locating calcium deposits with uoroscopy or ul-
trasound, and the ESWT treatment protocol was nonstandard
68
.
Rompe et al.
69
and Rebuzzi et al.
70
compared F-ESWT
with open and arthroscopic surgery in CTS, respectively. They
concluded that the results are comparable and that high-energy
F-ESWTshould be the rst choice when conservative treatment
has failed, because of its noninvasiveness.
In summary, given its efcacy in pain reduction
55,56,58-65,69,70
and functional outcomes
55,58,61-66,69,70
,resorptionrate
55,58-61,63,64,66,69
,
safety
55,59,60,64
, noninvasiveness
55,69,70
, reduced recovery time
55
,and
cost-effectiveness
55
, we consider that high-energy F-ESWT is the
treatment of choice in CTS when conservative treatment has failed.
Noncalcifying Tendinopathy of the Shoulder
Unlike CTS, the treatment of noncalcied tendinopathies with
shockwaves is controversial
71
. Both favorable and poorly per-
forming studies in many cases present inadequate inclusion
criteria (wide age ranges, heterogeneous populations, and in-
sufcient diagnostic evaluations). It is inadmissible to consider
subacromial pain
72
or non-specic shoulder pain
73
as a
diagnosis of shoulder disease if all possible differential diag-
noses have not been ruled out. This confusion is reected in the
results of the meta-analyses and systematic reviews
62,63,65
.
Huisstede et al.
63
found no strong evidence to support the
efcacy of ESWT to treat noncalcic rotator cuff tendinosis
beyond the applied energy level. Speed
65
did not support low-
dose or high-dose F-ESWT.
We are unable to recommend the use of ESWT in non-
calcic tendinopathy of the shoulder because of the lack of
compelling evidence.
Lateral Epicondylopathy of the Elbow
There are many therapeutic options for treating lateral epi-
condylopathy. The existing evidence does not clearly support
the efcacy of any of the available treatment methods for this
clinical condition
74-79
. ESWT is not the exception
79
, although it
was approved by the U.S. Food and Drug Administration
(FDA) for treating this disease in 2002
80
.
Several systematic reviews and meta-analyses have shown
conicting evidence
81-83
. It is difcult to interpret the data be-
cause of the variety of study designs and the use of different
shockwave devices
84
.
Pettrone and McCall
85
reported a signicant improve-
ment with respect to pain and function in the active treatment
group at 6 and 12 months compared with the placebo group in
a study with Level-I evidence.
In a review study by Thiele et al.
80
, the authors stated that
several clinical trials have achieved very good results with the
use of ESWT for lateral epicondylopathy of the elbow. That
review only included Level-I studies using focused ESWT and
RPW, and the authors concluded that lateral epicondylopathy
is a primary indication for ESWT.
Lee et al.
86
found similar outcomes when comparing
steroid injections with ESWT in lateral and medial epi-
condylopathy. Radwan et al.
87
found no signicant differences
between F-ESWT and percutaneous tenotomy.
Although the strength of the supporting evidence is not
strong, no method to treat lateral epicondylopathy is backed by
studies with a high level of evidence. As the benets largely
exceed any potential harm, we recommend the use of radial or
focused ESWT technologies when conventional rehabilitation
treatment has failed.
Greater Trochanteric Pain Syndrome
There is no agreement about the optimal management for
greater trochanteric pain syndrome
88
. Numerous conservative
treatments (nonsteroidal anti-inammatory drugs, physiother-
apy, and corticosteroid injections) have been recommended
88
.
Two studies provided Level-II and III evidence for RPW
effectiveness in 74% of patients at 15 months
88
and 78.8% at 12
months
89
, respectively.
Rompe et al.
88
compared RPW with 2 other treatment
methods, steroid injection and home training exercise, in a quasi-
RCT. Although RPW was inferior to steroid injection at 1 month,
RPW demonstrated better outcomes at 4 months compared with
steroid injection and home exercise training, and it matched
home training at 15 months
88
.Furiaetal.
89
compared RPW and
nonoperative therapy in patients with greater trochanteric pain
syndrome. The RPW group had signicant improvement with
respect to pain, function, and Roles and Maudsley scales than the
standard treatment group at 12 months
89
.
Although the available evidence on ESWT in greater
trochanteric pain syndrome is limited, RPW appears more ef-
fective than a home exercise program and local corticosteroid
injection after short-term and mid-term follow-up (up to 15
months) of greater trochanteric pain syndrome
88-90
.
Patellar Tendinopathy
Patellar tendinopathy treatment represents a challenge
91
. There
is no evidence-based protocol for the appropriate management
of patellar tendinopathy
90,92-95
. Eccentric training appears to be
the rst-line treatment
92-95
.
New therapies, such as prolotherapy, dry-needling,
platelet-rich plasma (PRP), cell therapy, or hyaluronic acid,
may offer alternatives to standard treatments
93,94
.
Promising results have been shown with ESWT
90,91,96-100
.
Wang et al.
96
compared F-ESWT and conservative treatment
in an RCT and obtained good or excellent results in 90% of the
ESWT group at the 2 to 3-year follow-up evaluation com-
pared with 50% in the conservative treatment group. Furia
et al.
97
compared RPW and standard treatment in a retro-
spective study at 1 year and reported satisfactory results in
75.8% of patients receiving a single session of low-energy
radial pressure waves compared with 17.2% in other non-
operative therapies.
By contrast, in an RCT, Zwerver et al.
101
compared real and
placebo piezoelectric ESWT in athletes and did not nd signif-
icant differences between the groups in terms of pain and
function at 22 weeks. Another recent RCT on 52 athletes diag-
nosed with patellar tendinopathy evaluated the effect of ESWTor
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sham ESWT in addition to an eccentric training program and
did not nd differences at 6 months of follow-up
102
.
However, these studies describing poor results with the
use of ESWT included certain features and methodological
errors such as: no complementary studies were performed to
rule out calcication or partial rupture with a different prog-
nosis
101,102
; applying ESWT with a piezoelectric device
101,102
;
adapting the ESWT intensity to patient tolerance instead of a
specic therapeutic energy level
101
; high energy levels
101
; al-
lowing for training and competition during and after ESWT
treatment instead of removing the patient from sports
101,102
; and
ESWT as a solitary treatment not combined with exercise
101
.
Peers et al.
99
retrospectively compared F-ESWT with sur-
gery in 28 patients at an average of 24 months and showed ex-
cellent or good results according to the Roles and Maudsley score
in66%oftheESWTgroup,whichwascomparablewith58%in
the surgery group. The authors concluded that F-ESWT in
chronic patellar tendinopathy is an alternative to surgery, without
resulting in incapacity, when conservative treatment fails
99
.
Review of the literature shows that ESWT is safe and
effective in the treatment of patellar tendinopathy
90,91,98
. Cur-
rent evidence supports the use of F-ESWTand RPW for patellar
tendinopathy with moderate or low-intensity protocols, espe-
cially in patients attempting to avoid an invasive intervention.
Achilles Tendinopathy
Achilles tendinopathy affects active athletes as well as the sed-
entary population
103
. According to its anatomical location, it is
classied into 2 categories, insertional and noninsertional or
midportion tendinopathy.
Conservative treatment includes pain medication, heel
lifts, eccentric exercises, physiotherapy, steroid and platelet-rich
plasma injections, low-level laser therapy, and radiofrequency,
among others
104-109
. Different shockwave sources and protocols
have been used. A Level-I study with 48 patients compared pie-
zoelectric F-ESWT and placebo ESWT and found better results
for the ESWT group
110
. Furia reported good results for inser-
tional
111
and noninsertional
112
Achilles tendinopathies with RPW.
In an RCT, Rompe et al.
113
demonstrated that RPW is
more effective than eccentric loading exercises for insertional
Achilles tendinopathy at the 15-month follow-up evaluation.
Furthermore, there is demonstrated superior efcacy of com-
bining eccentric loading and ESWT compared with eccentric
loading alone in those patients
114
.
Gerdesmeyer et al.
108
highlighted the efcacy of both F-
ESWT and RPW in chronic Achilles tendinopathy. On the other
hand
109
, Costa et al. found no signicant differences between
the F-ESWTand control groups in terms of pain, function, and
quality of life for 49 patients with Achilles tendinopathy at 3
months in a Level-I RCT
109
. Those authors concluded that there
was no support for the use of ESWT in Achilles tendinopathy.
ESWT was performed once a month for 3 months, instead of at
weekly intervals as per the standard recommendations
4,5
.Two
elderly patients had an Achilles rupture after ESWT, but, sur-
prisingly, no complementary explorations were performed
before treatment to rule out previous partial ruptures.
TABLE IV ESWT Success Rate in the Treatment of Delayed Fracture-Healing and Nonunions
Study No. of Patients Material Success Rate
Valchanou and Michailov
142
(1991) 82 Nonunions* 84%
Rompe et al.
144
(2001) 43 Tibial and femoral diaphyseal and metaphyseal
nonunions
72%
Wang et al.
145
(2001) 72 Nonunions (41 femora, 19 tibiae, 7 humeri, 1 radius,
3 cubiti, and 1 metatarsal)
80%
Schaden et al.
146
(2001) 115 72 shaft fractures in long bones and 43 fractures in
cancellous bones
75.7%
Bara and Snyder
148
(2007) 81 42 delayed unions and 39 nonunions (49 tibiae, 13
femora, 10 radial and ulnar bones, and 5 humeri)
83%
Xu et al.
149
(2009) 69 Nonunions (22 femora, 28 tibiae, 13 humeri, 5 radii,
and 1 ulna)
75.4%
Cacchio et al.
152
(2009) 126 Long-bone nonunions 71%
Elster et al.
150
(2010) 192 Tibia 80.2%
Furia et al.
154
(2010) 23 Nonunion of proximal fth metatarsal metaphyseal-
diaphyseal fractures
87%
Notarnicola et al.
155
(2010) 58 Carpal scaphoid nonunions 75.9%
Zelle et al.
151
(2010) 924 Systematic review of 10 case series and 1 RCT
including delayed union and nonunion
76%
Kuo et al.
156
(2015) 22 Atrophic nonunions of the femoral shaft 63.6%
*Patient history, concomitant treatment, and follow-up were not specied.
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Three systematic reviews
90,115,1 16
and 1 review
117
showed
satisfactory evidence of the effectiveness of low-energy ESWT in
insertional and noninsertional chronic Achilles tendinopathy
after failure of conservative treatment and before considering
surgery, especially in combination with eccentric loading.
Plantar Fasciitis
Plantar fasciitis is a degenerative musculoskeletal disorder
118
.In
2002, Buchbinder et al.
119
found no evidence to support the use
of ESWT in plantar fasciitis. In 2003, another RCT considered
electromagnetic ESWT to be ineffective in this eld
120
.
Since then, several studies with a high level of evidence
have supported both focused
121,122
and radial
123,124
technologies
for this disorder. Gollwitzer et al.
125
, in a study of the treatment
of recalcitrant plantar fasciitis with an electromagnetic device,
reported pain reduction in 69.2% of the patients in the ESWT
group compared with 34.5% in the control group. Ogden
et al.
126
, in an RCT, concluded that electrohydraulic F-ESWT is
effective and safe and that the clinical improvement lasts be-
yond 1 year. In a Level-I study, Wang et al.
122
compared
F-ESWT with conservative treatment modalities. The shock-
wave group had excellent or good results in 82.7% of the pa-
tients compared with 55% in the control group at a follow-up
of between 60 and 72 months; also, the shockwave group had a
much lower recurrence rate.
Gerdesmeyer et al.
123
, in an RCT, reported an overall
success rate of 61% with RPW compared with 42.2% in the
placebo group at 12 weeks.
Recently, a multicenter study
127
showed that the combina-
tion of a plantar fascia-specic stretching program with low-energy
RPW achieves better results than RPW alone. Three meta-analy-
ses
128-130
found that ESWT is effective for treating chronic plantar
fasciitis. Aqil et al.
128
recommended the use of shockwave treatment
in plantar fasciitis on the basis of its efcacy and safety.
Several studies have compared F-ESWT with surgery
131-134
,
supporting the use of shockwave treatment because of its effec-
tiveness
128,132,134
and because patients can quickly resume full ac-
tivities
131
and athletes have a chance to continue sports activities
133
.
Since 2010, the American College of Foot and Ankle
Surgeons has recommended ESWT as a treatment of choice for
plantar fasciitis with or without a plantar spur when nonop-
erative treatment has failed
135
.
Bone Disorders
Haupt
10
, in 1997, recognized the dynamic interaction between
ESWT and bone. It was initially hypothesized that shockwaves
Fig. 4
Figs. 4-A, 4-B, and 4-C Anteroposterior radiographs of the right femur of a 37-year-old man who had sustained a femoral fracture in a motorcycle accident;
the fracture was initially treated with an intramedullary nail, but it was revised 14 months later because of nonunion and an external xator was applied. Fig.
4-A At 6 months after the second surgery, there were no signs of bone-healing. Fig. 4-B At 4 months after F-ESWT, a successful union of the fracture was
evident. Fig. 4-C The nal result after external xator removal demonstrated complete healing.
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created microlesions in treated bone. This appreciation completely
changed when Wang et al.
19,20
demonstrated that shockwaves
generate upregulation and expression of various pro-angiogenic
and pro-osteogenic growth factors, stimulating bone-healing.
Basic research has shown that because of mechanical forces de-
livered by shockwaves to the cells and to the extracellular matrix,
messengers are liberated and activate different genes and groups of
genes in the cell nucleus
50,136-140
. This phenomenon of biological
conversion from a mechanical stimulus into electrochemical ac-
tivity is called mechanotransduction.
141
The use of ESWT for nonhealing fractures was rst re-
ported, to our knowledge, in 1991 by Valchanou and Michai-
lov
142
. Since then, several observations and trials have
supported the efcacy of ESWT for nonunion and delayed
fracture-healing
143-157
(Table IV).
Cacchio et al.
152
, in a Level-I RCT, compared different
ESWT high-energy levels (0.4 mJ/mm
2
[Group 1] and 0.7 mJ/
mm
2
[Group 2]) and surgery (Group 3) for the treatment of
hypertrophic long-bone nonunions and obtained success rates
of 70%, 71%, and 73%, respectively, at 6 months. No adverse
effects occurred in the ESWT groups compared with a 7% rate
of complications in the surgical group.
Similar results were reported by Furia et al.
154
,whoobserved
that high-energy F-ESWT was as effective as intramedullary screw
xation in the treatment of nonunion of a fracture of the fth
metatarsal; however, screw xation was more often associated
with complications that frequently resulted in additional surgery.
Notarnicola et al.
155
found that the results of ESWT were
comparable with those of surgical stabilization and bone graft
for the treatment of carpal scaphoid pseudarthrosis.
Kuo et al.
156
reported that the success rate of ESWT was
63.6% in the treatment of atrophic nonunions of the femoral shaft
and could be as high as 100% if applied within 12 months after the
initial treatment. Poor results were associated with instability, a
gap at the nonunion site of >5 mm, and atrophic nonunion.
As some Level-I and II evidence has demonstrated that
the efcacy of ESWT is comparable with that of surgery for the
treatment of nonunions
152,154,155
, and ESWT is practically free of
adverse effects and more economic, it may progressively be
considered as the rst choice in the treatment of stable non-
unions with a gap of <5 mm in long bones (Fig. 4). For bone
treatment, the basic principles of acute fracture management
should be implemented after F-ESWT (immobilization, cast-
ing, and weight-bearing restrictions).
ESWT seems to be an effective option in adult osteo-
chondritis dissecans
158-160
, but further studies are required to
determine long-term results.
Economic and Administrative Considerations
We acknowledge that it is currently difcult to obtain reim-
bursement for ESWT in the United States. We hope that
heightened awareness as to the efcacy of ESWT, as well as
recognition of how ESWT can be a cost-saving measure, will
lead to changes in reimbursement coverage.
Shockwave treatment is indicated when standard con-
servative treatment has failed, so its cost should be compared
with the cost of surgery. Dubs
161
compared the efcacy and
costs of ESWTwith the usual treatments for CTS. In addition to
demonstrating that ESWT was more efcacious, it also allowed
for an average savings of US$2,000 per patient in comparison
with alternative therapies.
Haake et al.
162
showed that the cost of treatment for CTS
was between 2,700 and 4,300 per patient for ESWT compared
with 13,400 to 23,450 for surgery and concluded that the cost
of surgery was 5 to 7 times higher than ESWT. Ram´
on et al.
163
reported, in absolute numbers, a savings of approximately 2,000
per patient for ESWTcompared with surgery for the treatment of
calcifying tendinopathy of the shoulder.
Overview
ESWT is considered to be an alternative to surgery for several
chronic tendinopathies and nonunions because of its efcacy,
safety, and noninvasiveness. The best evidence supporting the
use of ESWT was obtained with low to medium levels of energy
for tendon disorders as well as with a high energy level for
tendon calcication and bone pathologies in a comprehensive
rehabilitation framework.
Because of the variability in the treatment protocols, the
methodological quality of many ESWT studies is limited.
Further research from well-designed, high-quality studies is
required to standardize the treatment parameters and dem-
onstrate the optimal ESWT approach for health-care decision-
making.
With adequate patient selection, appropriate indica-
tions, homogeneous ESWT therapeutic protocols, and
proper application, ESWT could make a paramount contri-
bution to noninvasive treatment of certain musculoskeletal
disorders. n
NOTE: The authors thank Dr. Achim M. Loske Mehling for his important contribution on the subject of
physical principles and wave generation, and John Furia, MD, for his kind contribution on Achilles
tendinopathy and on economic and administrative considerations.2
Daniel Moya, MD
1
Silvia Ram´
on, MD, PhD
2
Wolfgang Schaden, MD
3
Ching-Jen Wang, MD
4
Leonardo Guiloff, MD
5
Jai-Hong Cheng, MD
4
1
Buenos Aires British Hospital, Buenos Aires, Argentina
2
Hospital Quir ´
on, Barcelona, Fundaci´
on Garc´
ıa Cugat, Spain
3
AUVA-Head Ofce, Vienna, Austria
4
Chang Gung Memorial Hospital, Kaohsiung, Taiwan
5
Cl´
ınica Arauco Salud, Santiago de Chile, Chile
E-mail addresses for D. Moya: drdanielmoya@yahoo.com.ar;
drdanielmoya@gmail.com
ORCID iD for D. Moya: 0000-0003-1889-7699
259
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THE JOURNAL OF BONE &JOINT SURGERY dJBJS.ORG
VOLUME 100-A dNUMBER 3dFEBRUARY 7, 2018
THE ROLE OF EXTRACORPOREAL SHOCKWAVE TREATME NT IN
MUSCULOSKELETAL DISORDERS
... Thus, patients do not need to spend much time or money on ESWT. Because of these beneficial characteristics, ESWT has been a therapeutic option for the treatment of many musculoskeletal diseases (6,7), including plantar fasciitis (8)(9)(10), calcific shoulder tendinopathy (11), tennis elbow (12), trigger finger (13), knee ...
... Mechanotransduction is generally considered a direct physical effect because it directly acts on tissues (43). It is suggested that ESWT-induced direct mechanical perturbations might be transmitted to tissues, affecting cell membrane polarization, radical formation, cell proliferation, and growth factor production (7,44). It is also proposed that cells could sense mechanical forces and transmit mechanical stimuli into biochemical signals, which then lead to modulation of the functions of cells in turns, such as migration, proliferation, and differentiation, and even maintaining cytoskeletal structure and homeostasis, in which mechanotransduction plays an essential role (45). ...
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Neurological disorders are one of the leading causes of morbidity and mortality worldwide, and their therapeutic options remain limited. Recent animal and clinical studies have shown the potential of extracorporeal shock wave therapy (ESWT) as an innovative, safe, and cost-effective option to treat neurological disorders. Moreover, the cellular and molecular mechanism of ESWT has been proposed to better understand the regeneration and repairment of neurological disorders by ESWT. In this review, we discuss the principles of ESWT, the animal and clinical studies involving the use of ESWT to treat central and peripheral nervous system diseases, and the proposed cellular and molecular mechanism of ESWT. We also discuss the challenges encountered when applying ESWT to the human brain and spinal cord and the new potential applications of ESWT in treating neurological disorders.
... Although several studies demonstrated that ESWT is a safe and effective treatment for knee OA, further research is necessary, especially when different shockwave types are used. In general, ESWT can be classified into two groups: f-ESWT and r-ESWT, which differ in terms of physical properties and acoustic wave propagation patterns [37]. Zhao et al. performed a randomized control trial to compare r-ESWT with a placebo in 70 patients with knee OA. ...
... Therefore, the focusing mechanism can direct each shock into the bone-cartilage interface, which is the target in knee OA treatment, without any loss of energy. In addition, r-ESWT lacks the characteristic features of shockwaves, such as a short rise time, high peak pressure, and non-linearity, thus reducing its effect on knee OA [37]. ...
Article
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Both focused extracorporeal shockwave (f-ESWT) and radial extracorporeal shockwave therapy (r-ESWT) can alleviate symptoms in patients with knee osteoarthritis, but no trials have directly compared f-ESWT with r-ESWT for knee osteoarthritis. This study aimed to compare the effectiveness of f-ESWT and r-ESWT on knee osteoarthritis. Forty-two patients with bilateral knee osteoarthritis were randomly assigned to receive three sessions of either f-ESWT or r-ESWT at 1-week intervals. The patients were evaluated at baseline and at 4 and 8 weeks after the final treatment. The primary outcome was the change in pain intensity, as measured on the visual analog scale (VAS). Secondary outcomes included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), range of motion of the knee joint, and the 6-minute walk test. At the end of 4 weeks, the VAS score was substantially reduced in both groups (f-ESWT, −4.5 ± 2.5 points; r-ESWT, −2.6 ± 2.0 points), with a greater reduction in the f-ESWT group. Both groups showed significant improvement in secondary outcomes; however, the f-ESWT group yielded greater improvement in the VAS score, WOMAC score, and 6-minute walk test. Our results showed that f-ESWT was more effective than r-ESWT in improving pain and physical function in patients with knee osteoarthritis.
... 7,10,12,19,27,28 Radial shockwave, one kind of mechanical stimulation, is widely used in treating numerous musculoskeletal diseases, owing to its satisfactory therapeutic efficacy. 5,23,39 Moreover, multiple researchers have demonstrated that radial shockwave pretreatment with optimal energy is capable of priming stem cell stemness and enhancing its in vivo cartilage repair efficacy. 20,36,38,40 Our previous in vivo cartilage repair study, conducted in rabbits, indicated that the low-energy radial shockwave stimulation in MF holes after MF significantly increased the deposition of cartilaginous extracellular matrix, 35 thereby offering a novel method to enhancing cartilage repair. ...
Article
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Background The first-line clinical strategy for small cartilage/osteochondral defects is microfracture (MF). However, its repair efficacy needs improvement. Hypothesis Appropriate energy radial shockwave stimulation in MF holes would greatly improve repair efficacy in the porcine osteochondral defect model, and it may obtain comparable performance with common tissue engineering techniques. Study Design Controlled laboratory study. Methods Osteochondral defect models (8-mm diameter, 3-mm depth) were established in the weightbearing area of Bama pigs’ medial femoral condyles. In total, 25 minipigs were randomly divided into 5 groups: control (Con; without treatment), MF, MF augmentation (MF+; treated with appropriate energy radial shockwave stimulation in MF holes after MF), tissue engineering (TE; treated with compounds of microcarrier and bone marrow mesenchymal stem cells), and sham (as the positive control). After 3 months of intervention, osteochondral specimens were harvested for macroscopic, radiological, biomechanical, and histological evaluations. The statistical data were analyzed using 1-way analysis of variance. Results Based on the macroscopic appearance, the smoothness and integration of the repaired tissue in the MF+ group were improved when compared with the Con and MF groups. The histological staining suggested more abundant cartilaginous matrix deposition in the MF+ group versus the Con and MF groups. The general scores of the macroscopic and histological appearances were comparable in the MF+ and the TE groups. The high signal areas of the osteochondral unit in the magnetic resonance images were significantly decreased in the MF+ group, with no difference with the TE group. The micro–computed tomography data demonstrated the safety of direct in situ radial shockwave performance. Biomechanical tests revealed that the repaired tissue’s Young modulus was highest in the MF+ group and not statistically different from that in the TE group. Conclusion Direct in situ radial shockwave stimulation with appropriate energy significantly improves the short-term repair efficacy of MF. More encouragingly, the MF+ group in our study obtained repair performance comparable with the TE therapy. Clinical Relevance This strategy is easy to perform and can readily be generalized with safety and higher cartilage repair efficacy. Moreover, it is expected to be accomplished under arthroscopy, indicating tremendous clinical transformative value.
... The use of shock waves for non-healing fractures in humans was first reported in 1991 by Valchanou and Michailov [2]. Since then, several studies have supported the efficacy of shock waves for the treatment of nonunions and delayed healing of long bone fractures in adults [2][3][4][5][6][7][8][9][10][11][12][13][14], however, to date, no cases have been reported in the literature on the use of this therapy in pediatric patients. The aim of this article is to report on the satisfactory results with the application of shock waves in a patient with femoral septic non-union, initially treated surgically. ...
Article
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Non-unions of the femur in children are not frequent, but when they do occur they can be very difficult to manage. Shock wave therapy has emerged as an effective option for well-chosen pseudoarthrosis cases, however there are no reports of pediatric cases. We report a 12-year-old male patient with a history of pathological fracture due to mid-diaphyseal osteomyelitis of the right femur at 8 years of age. After several surgical procedures the integrity of the femur was restored but an area of non-union persisted at mid-diaphyseal level. He was treated with 3 sessions of focused shock waves with an electrohydraulic generator. He presented a rapid healing avoiding a new endomedullary nailing surgery with bone graft. Focused shock waves may be a useful therapeutic option in children with non-unions in well-selected cases.
... Протягом останніх десятиліть у медицині став широко використовуватися метод ударно-хвильової терапії при лікуванні численних патологічних станів [3,4,5]. Також цей фізичний метод зарекомендував себе в галузі ортопедії і травматології як ефективна допомога хворим з адгезивним капсулітом плечового суглоба, ентезопатіями ліктьового суглоба, стилоідитом, трохантеритом, синдромом попереково-здухвинної зв'язки, ахілоденією, міотонічними синдромами, плантарним фасціїтом та іншою патологією [6,7,8]. ...
Article
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Relevance. Violation of bone formation processes continues to occupy a relatively high level, reaching 2.7-27.1%, so the search for new methods for their treatment and prevention remains relevant. One of these methods is extracorporeal shock wave therapy. Views on the influence of the extracorporeal shock wave therapy on the processes of bone formation significantly differ. Objective: to study the effect and mechanism of action of shock wave therapy on the processes of reparative osteogenesis in an experiment and the effect of the method on delayed union of bone fractures and pseudarthrosis in clinical conditions. Materials and Methods. In an experiment on rabbits, after a standard model of a perforated defect in the proximal tibial metadiaphysis on the days 3, 6, 9, and 12 after injury; the injury site of the animals of the main group was influenced with radial low-energy shock waves. The results of treatment were monitored with the help of clinical, radiological and histomorphological methods. The clinical section included 136 patients with union fracture disorder of long bones who had previously undergone conservative treatment or osteosynthesis. All patients underwent 1-3 sessions of extracorporeal shock wave therapy with evaluation of the results on 3, 6, and 12 months after treatment using the data of X-ray examinations and the Neer – Crantham – Shelton functional scale. Results. The studies showed that rabbits of the main group morphologically had a greater thickness and density of formed bone crossbars at the site of the proximal tibial metadiaphysis defect in a month after extracorporeal shock wave therapy, and after 45 days, a greater number of cases of restoration of its cortical layer was notified (p<0.05). Three months after treatment of patients with delayed union of bone fractures with extracorporeal shock wave therapy, consolidation was detected radiologically in 89.4% of cases; this indicator remained almost unchanged in the subsequent periods of the study. Three months after treatment of patients with pseudoarthrosis of the bones with extracorporeal shock wave therapy, radiological consolidation was detected in 46.1% of patients, after 6 months – in 75.3%, after 12 months – in 80.9%. At the end of the study, scores on the Neer – Crantham – Shelton Functional Scale also improved significantly. Conclusions. The results of the studies allow us to conclude that extracorporeal shock wave therapy is an effective non-invasive method for the treatment of delayed union of bone fractures and pseudarthrosis and is an alternative to surgical interventions.
... [7][8][9] The precise therapeutic mechanism of ESWT is yet to be elucidated, but the treatment has a positive influence on neovascularization and growth factor release. 10) ESWT has proven effective in treating calcific shoulder tendinitis, while the benefits remain controversial in non-calcific shoulder tendinitis. 11) Having reviewed the literature thoroughly, we found that few studies have compared the effects of ESWT with those of steroid injections in the treatment of patients with supraspinatus tendinitis-a subtype of non-calcific shoulder tendinitis. When designing the present study, we hypothesized that the treatment effects of ESWT would have an equivalent outcome to those of steroid injections in patients with supraspinatus tendinitis. ...
... Therapeutic effects have been attributed to effects of cavitation resulting in local analgesia and microtrauma, invigorating reparative processes in chronic disease. 20 Considering the availability of veterinary shockwave systems and their adaptability to requirements of penetration depth and patient comfort, this modality may offer advantages over conventional methods of acupuncture point stimulation (needle acupuncture with or without electrostimulation). ...
Article
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Objective The aim of this study was to compare effects with conventional (needle and electroacupuncture, NAP) and shockwave stimulation of acupuncture points (SAP) on chronic multilimb lameness in horses. Study Design Randomized crossover block design; ten mature Standardbred mares with multilimb lameness (< 4/10) underwent 3-weekly point stimulations (NAP/SAP) selected on the basis of their uniform applicability. Groups were reversed following a washout period (9 weeks). Lameness at the trot was video recorded and quantified objectively using an inertial sensor-based system during a 4-week pre- and post-treatment period. Blinded expert review of recordings resulted in subjective qualitative (better, same, or worse) and quantitative outcome measures (0–10 lameness grade). Mixed effect repeated measures analyses were performed on objective quantitative gait parameters specific to fore (Vector sum [VS Head ]) and hindlimb lameness (average differences in minimum [DIFFMIN Pelvis ] and maximum pelvic height [DIFFMAX Pelvis ]) Qualitative data were assessed in non-parametric tests. Results SAP had no effect on forelimb but improved hindlimb lameness (DIFFMIN Pelvis ; p < 0.001). NAP was associated with deterioration of forelimb lameness (VS Head , p < 0.001) and had no effect on hindlimb lameness. VS Head data differed between modalities when accounting for the time of observation (interaction effect; p = 0.002). For other quantitative gait parameters, a difference between modalities was not observed. SAP was associated with greater animal comfort post-treatment compared with pre-treatment assessments ( p = 0.036). Typically, improvement occurred by one and deterioration by two lameness grades. Conclusion SAP and NAP were not associated with the same treatment outcome. SAP slightly improved but did not alleviate all lameness. Given the non-invasive nature of SAP, this method may have potential in the management of chronic multilimb lameness.
Article
Joint immobilization, which ensures rest and accelerates tissue recovery in musculoskeletal disorders, often causes joint contracture, for which there is still no effective prevention. To address this, we investigated the effects of extracorporeal shockwave therapy (ESWT) in preventing joint contracture, in a unilaterally immobilized knee rat model. Under general anesthesia, ESWT (0.25 mJ/mm2, 3000 shot, 4 Hz, 3 d/week) was administered from one day after immobilization up to 2, 4, and 6 weeks. The immobilized control group received general anesthesia without ESWT. We evaluated joint angle, tissue elasticity, and gene and protein expression related to fibrosis, inflammation, and angiogenesis in the joint capsule. Relative to the control, the ESWT group had greater joint angle at 4 and 6 weeks, and lower posterior‐capsule elasticity at 6 weeks. In the ESWT group, at 6 weeks, gene expression of collagen type I (col1α1), connective tissue growth factor (CTGF), and α‐smooth muscle actin (α‐SMA) was significantly downregulated, whereas interleukin‐6 (IL‐6) and hypoxia inducible factor‐1α (HIF‐1α) gene expression was upregulated, relative to that in the control. Compared with that in the control, at 4 and 6 weeks, the ratio of CTGF+ cells were significantly lower in the ESWT group; at 4 weeks, the ESWT group had significantly fewer CD68+ cells in the adhesion area, and at 6 weeks, significantly more blood vessels. This article is protected by copyright. All rights reserved.
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During the last three decades, biomedical applications of shock waves have developed enormously. Extracorporeal shock wave lithotripsy revolutionized the treatment of urolithiasis, and basic research generated new applications of shock waves in diverse areas of medicine and biotechnology. Today, extracorporeal shock wave therapy and radial pressure wave therapy are helpful in an increasing variety of indications in orthopedics and traumatology. The bactericidal effects of shock waves may have uses in medicine as well as in the industry, and shock wave-induced noninvasive drug and gene delivery has attracted significant interest. Moreover, shock wave-mediated genetic transformation of microorganisms could revolutionize many areas in biotechnology. As the understanding of the detailed phenomena involved in the interaction of shock waves with living organisms progresses, novel research areas will arise; however, the need for team work has increased the necessity for researchers to understand concepts belonging to areas that are different from their field of expertise. This book was written with the aim of widening the reader’s spectrum of knowledge regarding the uses of shock waves in medicine and biology, as well as to contribute to safer and more efficient treatments and encourage scientific research. Because the biomedical applications of shock waves encompass an extensive field, most readers will be experienced in certain areas and inexperienced in others.
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Background Platelet-rich plasma (PRP) has emerged as a popular biologic treatment for musculoskeletal injuries and conditions. Despite numerous investigations on the efficacy of PRP therapy, current utilization of this treatment within the United States is not widely known. Purpose To investigate the national utilization of PRP, including the incidence and conditions for which it is used in the clinical setting, and to determine the current charges associated with this treatment. Study Design Descriptive epidemiology study. Methods Using a national database (PearlDiver) of private insurance billing records, we conducted a comprehensive search using Current Procedural Terminology (CPT) codes to identify patients who received PRP injections over a 2-year period (2010-2011). Associated International Classification of Diseases, 9th Revision (ICD-9) codes were identified to determine the specific conditions the injection was used to treat. The aggregate patient data were analyzed by yearly quarter, practice setting, geographic region, and demographics. PRP therapy charges were calculated and reported as per-patient average charges (PPACs). Results A total of 2571 patients who received PRP injections were identified; 51% were male and 75% were older than 35 years. The overall incidence ranged from 5.9 to 7.9 per 1000 patients over the study period. PRP was most commonly administered in hospitals (39%) and ambulatory surgical centers (37%) compared with in private offices (26%). The most common conditions treated were knee meniscus/plica disorders, followed by unspecified shoulder conditions, rotator cuff injuries, epicondylitis, and plantar fasciitis. Further evaluation revealed that 25% of all patients received injections for cartilage-related conditions, 25% meniscus, 25% unspecified, 12% tendon, 8% glenoid labrum, and 5% ligament. The PPAC for PRP treatment was US$1755 per injection. Conclusion Despite a lack of consensus regarding PRP indications and efficacy, we observed widespread application of this treatment for a myriad of musculoskeletal injuries. Most treated patients were older than 35 years, and the most commonly treated conditions included cartilage and meniscus disorders. Given the current controversy surrounding this treatment, further studies are necessary to guide clinicians on the value of this therapy for each clinical diagnosis.
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Purpose: To compare the efficacy of common invasive and noninvasive patellar tendinopathy (PT) treatment strategies. Methods: A systematic search was performed in PubMed, Google Scholar, CINAHL, UptoDate, Cochrane Reviews, and SPORTDiscus. Fifteen studies met the following inclusion criteria: (1) therapeutic outcome trial for PT, and (2) Victorian Institute of Sports Assessment was used to assess symptom severity at follow-up. Methodological quality and reporting bias were evaluated with a modified Coleman score and Begg's and Egger's tests of bias, respectively. Results: A total of 15 studies were included. Reporting quality was high (mean Coleman score 86.0, standard deviation 9.7), and there was no systematic evidence of reporting bias. Increased duration of symptoms resulted in poorer outcomes regardless of treatment (0.9% decrease in improvement per additional month of symptoms; P = .004). Eccentric training with or without core stabilization or stretching improved symptoms (61% improvement in the Victorian Institute of Sports Assessment score, 95% confidence interval [CI] 53% to 69%). Surgery in patients refractory to nonoperative treatment also improved symptoms (57%, 95% CI 52% to 62%) with similar outcomes among arthroscopic and open approaches. Results from shockwave (54%, 95% CI 22% to 87%) and platelet-rich plasma (PRP) studies (55%, 95% CI 5% to 105%) varied widely though PRP may accelerate early recovery. Finally, steroid injection provided no benefit (20%, 95% CI -20% to 60%). Conclusions: Initial treatment of PT can consist of eccentric squat-based therapy, shockwave, or PRP as monotherapy or an adjunct to accelerate recovery. Surgery or shockwave can be considered for patients who fail to improve after 6 months of conservative treatment. Corticosteroid therapy should not be used in the treatment of PT. Level of evidence: Level IV, systematic review of Level II-IV studies.
Article
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Patellar tendinopathy is a common cause of pain in athletes' knees. Historically, it has been related to jumping sports, such as volleyball and basketball. Repetitive jumping generates a considerable load of energy in the extensor mechanism, leading to symptoms. The main pathophysiologic phenomenon in patellar tendinopathy is tendinosis, which is a degenerative disorder rather than an inflammatory disorder; therefore, the other popular term for this disease, tendinitis, is not appropriate. The nonsurgical treatment of patellar tendinopathy is focused on eccentric exercises and often has good results. Other experimental options, with variable levels of evidence, are available for recalcitrant cases. Surgical treatment is indicated for cases that are refractory to nonsurgical treatment. Open or arthroscopic surgery can be performed; the two methods are comparable, but arthroscopic surgery results in a faster recovery time.
Article
Background: Autologous whole blood or platelet-rich plasma (PRP) injections are commonly used to treat lateral elbow pain (also known as tennis elbow or lateral epicondylitis or epicondylalgia). Based on animal models and observational studies, these injections may modulate tendon injury healing, but randomised controlled trials have reported inconsistent results regarding benefit for people with lateral elbow pain. Objectives: To review current evidence on the benefit and safety of autologous whole blood or platelet-rich plasma (PRP) injection for treatment of people with lateral elbow pain. Search methods: We searched CENTRAL, MEDLINE, and Embase for published trials, and Clinicaltrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) search portal for ongoing trials, on 18 September 2020. Selection criteria: We included all randomised controlled trials (RCTs) and quasi-RCTs comparing autologous whole blood or PRP injection therapy to another therapy (placebo or active treatment, including non-pharmacological therapies, and comparison between PRP and autologous blood) for lateral elbow pain. The primary comparison was PRP versus placebo. Major outcomes were pain relief (≥ 30% or ≥ 50%), mean pain, mean function, treatment success, quality of life, withdrawal due to adverse events, and adverse events; the primary time point was three months. Data collection and analysis: We used standard methodological procedures expected by Cochrane. Main results: We included 32 studies with 2337 participants; 56% of participants were female, mean age varied between 36 and 53 years, and mean duration of symptoms ranged from 1 to 22 months. Seven trials had three intervention arms. Ten trials compared autologous blood or PRP injection to placebo injection (primary comparison). Fifteen trials compared autologous blood or PRP injection to glucocorticoid injection. Four studies compared autologous blood to PRP. Two trials compared autologous blood or PRP injection plus tennis elbow strap and exercise versus tennis elbow strap and exercise alone. Two trials compared PRP injection to surgery, and one trial compared PRP injection and dry needling to dry needling alone. Other comparisons include autologous blood versus extracorporeal shock wave therapy; PRP versus arthroscopic surgery; PRP versus laser; and autologous blood versus polidocanol. Most studies were at risk of selection, performance, and detection biases, mainly due to inadequate allocation concealment and lack of participant blinding. We found moderate-certainty evidence (downgraded for bias) to show that autologous blood or PRP injection probably does not provide clinically significant improvement in pain or function compared with placebo injection at three months. Further, low-certainty evidence (downgraded for bias and imprecision) suggests that PRP may not increase risk for adverse events. We are uncertain whether autologous blood or PRP injection improves treatment success (downgraded for bias, imprecision, and indirectness) or withdrawals due to adverse events (downgraded for bias and twice for imprecision). No studies measured health-related quality of life, and no studies reported pain relief (> 30% or 50%) at three months. At three months, mean pain was 3.7 points (0 to 10; 0 is best) with placebo and 0.16 points better (95% confidence interval (CI) 0.60 better to 0.29 worse; 8 studies, 523 participants) with autologous blood or PRP injection, for absolute improvement of 1.6% better (6% better to 3% worse). At three months, mean function was 27.5 points (0 to 100; 0 is best) with placebo and 1.86 points better (95% CI 4.9 better to 1.25 worse; 8 studies, 502 participants) with autologous blood or PRP injection, for absolute benefit of 1.9% (5% better to 1% worse), and treatment success was 121 out of 185 (65%) with placebo versus 125 out of 187 (67%) with autologous blood or PRP injection (risk ratio (RR) 1.00; 95% CI 0.83 to 1.19; 4 studies, 372 participants), for absolute improvement of 0% (11.1% lower to 12.4% higher). Regarding harm, we found very low-certainty evidence to suggest that we are uncertain whether withdrawal rates due to adverse events differed. Low-certainty evidence suggests that autologous blood or PRP injection may not increase adverse events compared with placebo injection. Withdrawal due to adverse events occurred in 3 out of 39 (8%) participants treated with placebo versus 1 out of 41 (2%) treated with autologous blood or PRP injection (RR 0.32, 95% CI 0.03 to 2.92; 1 study), for an absolute difference of 5.2% fewer (7.5% fewer to 14.8% more). Adverse event rates were 35 out of 208 (17%) with placebo versus 41 out of 217 (19%) with autologous blood or PRP injection (RR 1.14, 95% CI 0.76 to 1.72; 5 studies; 425 participants), for an absolute difference of 2.4% more (4% fewer to 12% more). At six and twelve months, no clinically important benefit for mean pain or function was observed with autologous blood or PRP injection compared with placebo injection. Authors' conclusions: Data in this review do not support the use of autologous blood or PRP injection for treatment of lateral elbow pain. These injections probably provide little or no clinically important benefit for pain or function (moderate-certainty evidence), and it is uncertain (very low-certainty evidence) whether they improve treatment success and pain relief > 50%, or increase withdrawal due to adverse events. Although risk for harm may not be increased compared with placebo injection (low-certainty evidence), injection therapies cause pain and carry a small risk of infection. With no evidence of benefit, the costs and risks are not justified.
Article
Extracorporeal Shock Wave Therapy (ESWT), after its first medical application in the urological field for lithotripsy, nowadays represents a valid therapeutical tool also for many musculoskeletal diseases, as well as for regenerative medicine applications. This is possible thanks to its mechanisms of action, which in the non-urological field are not related to mechanical disruption (as for renal stones), but rather to the capacity, by mechanotransduction, to induce neoangiogenesis, osteogenesis and to improve local tissue trophism, regeneration and remodeling, through stem cell stimulation. On the basis of these biological assumptions, it becomes clear that ESWT can represent a valid therapeutic tool also for all those pathological conditions that derive from musculoskeletal trauma, and are characterized by tissue loss and/or delayed healing and regeneration (mainly bone and skin, but not only). As a safe, repeatable and non–invasive therapy, in many cases it can represent a first–line therapeutic option, as an alternative to surgery (for example, in bone and skin healing disorders), or in combination with some other treatment options. It is hoped that with its use in daily practice also the muscle–skeletal field will grow, not only for standard indications, but also in post–traumatic sequelae, in order to improve recovery and shorten healing time, with undoubted advantages for the patients and lower health service expenses.
Article
Objective: To evaluate the effectiveness of a combined treatment of focused shockwave therapy (ESWT) and eccentric training compared with sham-shockwave therapy (placebo) and eccentric training in participants with patellar tendinopathy (PT) after 24 weeks. Design: Randomized controlled trial. Setting: Sports medicine departments of a university hospital and a general hospital in the Netherlands. Participants: Fifty-two physically active male and female participants with a clinical diagnosis of PT (mean age: 28.6 years; range, 18-45) were randomly allocated to the ESWT (n = 22) or sham shockwave (n = 30). Interventions: Extracorporeal shockwave therapy and sham shockwave were applied in 3 sessions at 1-week intervals with a piezoelectric device. All participants were instructed to perform eccentric exercises (3 sets of 15 repetitions twice a day) for 3 months on a decline board at home. Main outcome measures: The Victorian Institute of Sport Assessment-Patella (VISA-P) scores (primary), pain scores during functional knee loading tests, and Likert score (secondary) were registered at baseline and at 6, 12, and 24 weeks after the start with the ESWT or sham-shockwave treatment. Results: No significant differences for the primary and secondary outcome measures were found between the groups. In the ESWT/eccentric group, the VISA-P increased from 54.5 ± 15.4 to 70.9 ± 17.8, whereas the VISA-P in the sham-shockwave/eccentric group increased from 58.9 ± 14.6 to 78.2 ± 15.8 (between-group change in VISA-P at 24 weeks -4.8; 95% confidence interval, -12.7 to 3.0, P = 0.150). Conclusions: This study showed no additional effect of 3 sessions ESWT in participants with PT treated with eccentric exercises. The results should be interpreted with caution because of small sample size and considerable loss to follow-up, particularly in the ESWT group.
Article
Background aims: As new approaches for peripheral nerve regeneration are sought, there is an increasing demand for native Schwann cells for in vitro testing and/or reimplantation. Extracorporeal shockwave treatment (ESWT) is an emergent technology in the field of regenerative medicine that has also recently been shown to improve peripheral nerve regeneration. Methods: In this study, we elucidate the effects of ESWT on Schwann cell isolation and culture. Rat sciatic nerves were dissected and treated with ESWT, and Schwann cells were isolated and cultured for 15 passages. Results: Single treatment of the whole nerve ex vivo led to significantly increased extracellular adenosinetriphosphate as an immediate consequence, and subsequently a number of effects on the culture were observed, starting with a significantly increased Schwann cell yield after isolation. In the ESWT group, the quality of culture, reflected in consistently higher purity (S100b, morphology), proliferation rate (5-bromo-2-deoxyuridine, population doublings per passage) and expression of regenerative phenotype-associated markers (P75, glial fibrillary acidic protein, c-Jun), was significantly improved. In contrast, the control group exhibited progressively senescent behavior, reflected in a decrease of proliferation, loss of specific markers and increase in P16(INK4A) expression. Conclusions: ESWT has beneficial effects on Schwann cell isolation and culture.