Electrical stimulation-based bone fracture treatment, if it works so well why do not more surgeons use it?

Abstract

Background
Electrical stimulation (EStim) has been proven to promote bone healing in experimental settings and has been used clinically for many years and yet it has not become a mainstream clinical treatment.

Methods
To better understand this discrepancy we reviewed 72 animal and 69 clinical studies published between 1978 and 2017, and separately asked 161 orthopedic surgeons worldwide about their awareness, experience, and acceptance of EStim for treating fracture patients.

Results
Of the 72 animal studies, 77% reported positive outcomes, and the most common model, bone, fracture type, and method of administering EStim were dog, tibia, large bone defects, and DC, respectively. Of the 69 clinical studies, 73% reported positive outcomes, and the most common bone treated, fracture type, and method of administration were tibia, delayed/non-unions, and PEMF, respectively. Of the 161 survey respondents, most (73%) were aware of the positive outcomes reported in the literature, yet only 32% used EStim in their patients. The most common fracture they treated was delayed/non-unions, and the greatest problems with EStim were high costs and inconsistent results.

Conclusion
Despite their awareness of EStim’s pro-fracture healing effects few orthopedic surgeons use it in their patients. Our review of the literature and survey indicate that this is due to confusion in the literature due to the great variation in methods reported, and the inconsistent results associated with this treatment approach. In spite of this surgeons seem to be open to using this treatment if advancements in the technology were able to provide an easy to use, cost-effective method to deliver EStim in their fracture patients.

Full text

Vol.:(0123456789)
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European Journal of Trauma and Emergency Surgery
https://doi.org/10.1007/s00068-019-01127-z
REVIEW ARTICLE
Electrical stimulation‑based bone fracture treatment, ifit works
sowell why donotmore surgeons use it?
MitBalvantrayBhavsar1 · ZhihuaHan1· ThomasDeCoster2· LiudmilaLeppik1· KarlaMychellyneCostaOliveira1·
JohnHBarker1
Received: 24 November 2018 / Accepted: 29 March 2019
© Springer-Verlag GmbH Germany, part of Springer Nature 2019
Abstract
Background Electrical stimulation (EStim) has been proven to promote bone healing in experimental settings and has been
used clinically for many years and yet it has not become a mainstream clinical treatment.
Methods To better understand this discrepancy we reviewed 72 animal and 69 clinical studies published between 1978 and
2017, and separately asked 161 orthopedic surgeons worldwide about their awareness, experience, and acceptance of EStim
for treating fracture patients.
Results Of the 72 animal studies, 77% reported positive outcomes, and the most common model, bone, fracture type, and
method of administering EStim were dog, tibia, large bone defects, and DC, respectively. Of the 69 clinical studies, 73%
reported positive outcomes, and the most common bone treated, fracture type, and method of administration were tibia,
delayed/non-unions, and PEMF, respectively. Of the 161 survey respondents, most (73%) were aware of the positive outcomes
reported in the literature, yet only 32% used EStim in their patients. The most common fracture they treated was delayed/
non-unions, and the greatest problems with EStim were high costs and inconsistent results.
Conclusion Despite their awareness of EStim’s pro-fracture healing effects few orthopedic surgeons use it in their patients.
Our review of the literature and survey indicate that this is due to confusion in the literature due to the great variation in
methods reported, and the inconsistent results associated with this treatment approach. In spite of this surgeons seem to be
open to using this treatment if advancements in the technology were able to provide an easy to use, cost-effective method to
deliver EStim in their fracture patients.
Keywords Bone fracture healing· Electrical stimulation treatment· Literature review· Survey of orthopedic surgeons
Introduction
The earliest report of using EStim to treat bone fractures
in patients appeared in the mid-1800s in which Garrat [1]
described using metallic needles placed in non-healing
fractures to deliver DC EStim, that resulted in successful
healing. Today, in the clinical setting EStim is administered
using three different approaches; direct current (DC), pulsed
electromagnetic field (PEMF), and capacitive coupled (CC).
DC EStim is administered via a surgically implanted EStim
power source and electrodes, and is administered at dos-
ages between 10 and 100μA of current [2]. CC and pulsed
PEMF are both administered externally. In CC an alternat-
ing voltage is applied to cutaneous electrodes placed on
opposite sides of the fracture generating an electrical field
of 0.1–20G [3]. In PEMF alternating currents, in current-
carrying coils, on the skin over the fracture site, generate a
pulsed electromagnetic field ranging between 3 and 10V
peak-to-peak within the fracture site [4].
In most cases EStim is used as a last resort after other
treatments have failed and/or in combination with other
treatments in cases of problematic fractures that heal
slowly (delayed union) or do not heal at all (non-union) [5].
Mit Balvantray Bhavsar and Zhihua Han contributed equally to the
work.
* John H Barker
JHB121654@gmail.com
1 Frankfurt Initiative forRegenerative Medicine,
Experimental Trauma andOrthopedic Surgery, J.W. Goethe-
University, Friedrichsheim gGmbH, Haus 97 B, 1OG,
Marienburgstraße. 2, 60528FrankfurtamMain, Germany
2 Department ofOrthopedics andRehabilitation, University
ofNew Mexico, Albuquerque, NM, USA

M.B.Bhavsar et al.
1 3
Examples include; spinal fusion [6], avascular necrosis [7],
internal and external fixation [8], delayed- or non-union frac-
tures [9], osteotomies [10], bone grafts [11], and femoral
osteonecrosis [12]. In these cases, EStim has been generally
reported to promote bone healing and help resolve these dif-
ficult, often chronic, costly, and debilitating fractures.
Several recently published invitro studies suggest that
EStim’s pro-healing effect is due to its influence on the
behavior and/or function of bone-forming stem cells. Along
these lines, we and others have shown that EStim causes bone
forming stem cells to migrate [13, 14], proliferate [15, 16],
differentiate [17–20], increase mineralization [21], deposit
extracellular matrix [22], attach to scaffold materials [23],
and increase the expression of several osteogenic genes [19,
20]. Importantly, all these cell behaviors/functions play key
roles in fracture healing and/or bone regeneration. In addi-
tion to these invitro findings at the cellular level, in invivo
studies in rat forelimb amputation [24] and large bone defect
models [25] we have demonstrated that EStim significantly
stimulates new bone, cartilage, and vessel formation and
promotes healing and regeneration. In spite of these posi-
tive results in preclinical and clinical studies EStim has not
become a widespread, universally used clinical treatment.
To better understand this discrepancy between the
reported positive results and the relatively low use of EStim
in fracture treatment we reviewed the literature and we asked
orthopedic surgeons worldwide (in a survey) about their
awareness, experience, and acceptance of EStim treatment
in their fracture patients. Using this combined approach,
we hoped to better understand the discrepancy between the
demonstrated success of EStim fracture treatment, and its
relatively low use clinically.
Methods
Literature review
To identify articles describing the use of EStim in bone heal-
ing, both in animal and clinical studies, we searched MED-
LINE, Google Scholar, and Web of Science databases for
articles describing invitro and invivo animal studies and clini-
cal studies published between 1977 and 2017. To maximize
the sensitivity of the search and identify the greatest number
of studies, we used different combinations of the keywords
“electrical stimulation” and “bone healing” and reviewed the
reference lists of retrieved publications to identify additional
articles we may have missed searching the three databases. We
categorized the total number of articles identified into “animal
studies”, “clinical studies”, “cell/organ invitro”, and “reviews/
meta analyses” (Table1). Since the focus of our study was to
investigate EStim’s effect on fracture healing we reviewed only
articles that described fracture healing in animal and clinical
studies, and excluded publications focused on invitro stud-
ies, electrical properties of bone, connective tissue, electri-
cal stimulation of nerves and reviews or meta-analyses. The
animal studies we identified and reviewed are listed in Table2
categorized by animal model studied, bone and fracture type,
type of EStim treatment used, outcomes, and the listing of
the published article, alongwiththe number of occurrences
in each category. The clinical studies reviewed are listed in
Table3 under the subtitles; bone and fracture type, number of
cases, EStim treatment used, outcomes, complications, and the
published article citedalongwith the total numbers for each of
these categories. The total numberfor each of these categories
issummarized in Table3. The language of the publications
reviewed was English.
Orthopedic surgeon survey
To determine the level of awareness, experience, and accept-
ance of EStim-based bone fracture treatment we asked ortho-
pedic surgeons six questions (listed in Figs.1, 2, 3, 4, 5, 6)
using a closed online automated survey method (Survey-
Monkey software, Palo Alto, USA). Survey participants were
identified from our own network of colleagues and based on
their surgical specialty, “Orthopedic Surgeons” in the online
professional networking website, LinkedIn [26]. Between May
and August 2017, a total of 620 invitations were emailed to
orthopedic surgeons worldwide, and their IP addresses were
used to record their country of origin and to prevent dupli-
cate entries. No other personal information was collected or
stored from the respondents. With this online survey method
participants were allowed to review their responses prior to
submitting their completed survey. Incomplete surveys were
not included in this analysis.
Results
Literature review
Our initial literature searches identified a total of 432 arti-
cles, published between 1977 and 2017 that focused on the
use of EStim to promote bone growth, fracture healing, and
Table 1 Total publications identified using different combinations of
the keywords “electrical stimulation” and “bone healing”
Study type Number of
publications
Animal studies 72
Clinical studies 69
Cell/organ invitro 238
Review/meta-analysis 53
Total 432

Electrical stimulation-based bone fracture treatment, ifit works sowell why donotmore surgeons…
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Table 2 Publications between 1977 and 2017 describing animal studies that use EStim to treat bone fractures
Animal model Bone affected and/or fracture type Type of EStim treatment Outcome Published article
Rabbits Femur/osteotomy Type: PEMF
Settings: 220–260G
Improved healing Aydin and Bezer [46]
Tibia/osteotomy Type: PEMF Improved healing (69%) Barak etal. [47]
Tibia/fracture Type: PEMF
Settings: pulse width 85µs
Duration: 30min/day
No effect Buzza etal. [48]
Tibia/osteotomy Type: PEMF
Settings: time-varying field 1.5Hz
Duration: 1h/day
Improved healing Fredericks etal. [49]
Lumbar spine/fusion Type: DC
Settings: 20–60µA
Improved healing France etal. [50]
Lumbar spine/fusion Type: CC Improved healing Gilotra etal. [51]
Patella–tendon junction/fracture Type: CC
Settings: 15–25mA
Improved healing Hu etal. [52]
Mandible/defect Type: DC
Settings: 20µA
Duration: 4weeks continuous
Improved healing Kim etal. [53]
Femur/defect Type: PEMF
Settings: 0.8mT
Duration: 4h/day
Improved healing Matsumoto etal. [54]
Tibia/fracture Type: PEMF
Settings: 8mT; 50Hz
Duration: 0.5h/day
Improved healing Ottani etal. [55]
Tibia/fracture Type: DC
Settings: 20µA
Duration: 0.5h/day continuous
Improved healing Rubinacci etal. [56]
Mandible/defect Type: DC
Settings: 7µA
Duration: 1–2weeks continuous
No effect Shafer etal. [57]
Tibia diaphysis/fracture Type: PEMF
Settings: 1.8G; 1.5Hz
Improved healing Shimizu etal. [58]
Femur, tibia/fracture Type: PEMF
Settings: repetitive pulse-72Hz
Duration: 12h/day continuous
No effect Smith and Nagel [59]
Tibia/osteotomy Type: PEMF
Settings: asymmetric pulse 1.5Hz
Duration: 20days continuous
No effect Taylor etal. [60]
Knee/osteochondral lesion Type: PEMF
Settings: 1.5mT; 75Hz
Duration: 4h/day for 40days
Improved healing Veronesi etal. [61]
Humerus/fracture Type: PEMF
Settings: 2G, 25µs pulses at 10Hz
Duration: 12h/day × 14days
Improved healing Yonemori etal. [62]
Tibia/fracture Type: DC
Settings: 1, 5, 20µA
Improved healing Zimmermann etal. [63]

M.B.Bhavsar et al.
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Table 2 (continued)
Animal model Bone affected and/or fracture type Type of EStim treatment Outcome Published article
Dogs Ulna/fracture Type: DC
Settings: 20µA
Duration: continuous
No effect Berry etal. [64]
Tibia/fracture Type: DC
Settings: 10–20µA
Duration: continuous
Improved healing (70–80%) Bins-Ely etal. [65]
Mandible/defect Type: DC
Settings: 20µA
No effect Branham etal. [66]
Radius/fracture Type: DC
Settings: 0.1–17µA
Improved healing Chakkalakal etal. [67]
Femur/fracture Type: DC
Settings: 50µA
Duration: 6weeks continuous
Improved healing Colella etal. [68]
Radius, ulna/fracture Type: DC
Settings: 20µA
Duration: 12weeks continuous
Improved healing Connolly etal. [69]
Lumbar spine/fusion Type: DC
Settings: 0.83–10µA
Duration: 6weeks continuous
Improved healing Dejardin etal. [70]
Femur/fracture Type: CC
Settings: biphasic waveforms
Improved healing Doyle [71]
Radius/fracture Type: DC
Settings: 3–5µA
Improved healing Fuentes etal. [72]
Tibia/fracture Type: PEMF
Settings: 0–2.4G
Duration: 4h/day
Improved healing Inoue etal. [73]
Periodontal/defect Type: DC
Settings: 3–6nA
Duration: continuous
No effect Jacobs and Norton [74]
Ulna/non-union Type: DC
Settings: 20µA
Improved healing (22%) Jacobs etal. [75]
Lumbar spine/fusion Type: PEMF
Settings: 1G; 1.5Hz
Duration: 0.5–1h/day
No effect Kahanovitz etal. [76]
Femur/fracture Type: DC
Settings: 20µA
No effect Lindsey etal. [77]
Cranium/osteogenesis Type: DC
Settings: 20µA
No effect Moderessi etal. [78]
Mandible/osteogenesis Type: PEMF
Duration: 1h/day
Improved healing Ortman etal. [79]
Mandible/non-union Type: DC Improved healing Park etal. [80]
Tibia/non-union Type: DC
Settings: 20µA
Improved healing Paterson etal. [81]
Tibia/non-union Type: DC
Settings: 20µA
Improved healing Paterson etal. [82]
Tibia/defect Type: DC
Settings: 0.2–20µA
Improved healing Paterson etal. [83]

Electrical stimulation-based bone fracture treatment, ifit works sowell why donotmore surgeons…
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Table 2 (continued)
Animal model Bone affected and/or fracture type Type of EStim treatment Outcome Published article
Tibia/fracture Type: CC
Settings: 3–6.3V; 60kHz
Duration: continuous—28days
No effect Pepper etal. [84]
Hip prostheses Type: CC
Settings: 5–6V; 60kHz
No effect Schutzer etal. [85]
Mandible/defect Type: DC
Settings: 20µA
Improved healing Shayesteh etal. [86]
Femur/osteotomy Type: DC
Settings: 1.5V
Improved healing Shokry [87]
Tibia, femur/fracture Type: DC
Settings: 0–50µA
Improved healing Srivastava [88]
Rats Femur/fracture Type: PEMF
Settings: 1.5mT
Duration: 6h/day
Improved healing Atalay etal. [89]
Tibia/osteoporosis Type: CC
Settings: low voltage; 60Hz
Improved healing Brighton etal. [90]
Tibia/fracture Type: CC
Duration: 20min/day
Improved healing Giannunzio etal. [91]
Spine/fusion Type: PEMF
Duration: 18h/day
Improved healing Guizzardi etal. [92]
Tibia/osteoporosis Type: PEMF
Settings: 1G; 5ms pulse; 15Hz
Duration: 2h/day
No effect Jagt etal. [93]
Tibia/osteoporosis Type: PEMF
Settings: 30mW/cm2; 1.5MHz
Improved healing Lirani-Galvao etal. [94]
Tibia/osteoporosis Type: CC
Settings: 10V peak–peak
Duration: 2h/day
Improved healing Manjhi etal. [95]
Fibula/osteotomy Type: CC
Settings: 1590V; 60Hz
Improved healing Marino etal. [96]
Spine/injury Type: CC
Settings: 30mW/cm2
Improved healing Medalha etal. [97]
Tibia/fracture Type: DC
Settings: 20µA
Duration: 20min/day
Improved healing Nakajima etal. [98]
Femur/fracture Type: PEMF
Settings: 41Gauss
Improved healing Puricelli etal. [99]
Tibia/osteoporosis Type: PEMF
Settings: 8G; 15Hz
Duration: 2h/day
Improved healing Shen and Zhao [100]
Spine/bone growth Type: DC
Settings: 0–100µA
Improved healing Spadaro [101]
Mandible/defect Type: PEMF
Settings: 1.5–1.8G; 100Hz
Improved healing Takano-Yamamoto etal. [102]
Periodontal/defect Type: DC
Settings: 0–100µA; 9kHz
Duration: once per day
Improved healing Tomofuji etal. [103]

M.B.Bhavsar et al.
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Table 2 (continued)
Animal model Bone affected and/or fracture type Type of EStim treatment Outcome Published article
Mandible/fracture Type: DC
Settings: 9V
Duration: 24h
Improved healing Uysal etal. [104]
Cranium/defect Type: DC
Settings: 2mA; 2Hz
Duration: 15min; 3×weeks
Improved healing Yang etal. [105]
Spine/injury Type: DC (subcutaneous)
Settings: 15mA; 2Hz
Duration: 0.5h/day; 3weeks
Improved healing Yu etal. [106]
Spine/injury Type: DC (subcutaneous)
Settings: 20–150mA; 50Hz
Duration: 20min/day
Improved healing Zamarioli etal. [107]
Sheep Femur/defect Type: PEMF
Settings: 1.5mT; 75Hz
Duration: 6h/day
Improved healing Benazzo etal. [108]
Tibia/fracture Type: DC
Settings: 7.5µA
Duration: 12h/day
No effect Dergin etal. [109]
Spine/injury Type: DC
Settings: low voltage
Improved healing Flouty etal. [110]
Mandible/defect Type: DC
Settings: 10µA
Duration: 1mm/day×10days
Improved healing El-Hakim etal. [111]
Tibia/osteotomy Type: PEMF
Settings: 1.6mT
Duration: 24h/day
No effect Law etal. [112]
Tibia/fracture Type: CC
Settings: 15mA; 60kHz
Improved healing Mutthini etal. [113]
Lumbar spine/fusion Type: DC
Settings: 40–100µA
Improved healing Toth [ 114]
Horse Metacarpus/defect Type: PEMF
Settings: 28G; 75Hz
Improved healing Cane etal. [115]
Tibia/bone graft Type: PEMF
Settings: asymmetric pulse burst of 30ms duration
repeated at 1.5Hz
Improved healing Kold and Hickman [116]
Metatarsal-foot/osteotomy Type: PEMF
Settings: 20G; 15Hz
Duration: 8h/day
No effect Sanders-Shami etal. [117]
Total no.
of articles
Animal model (no.) Type of bone (no.) Type of fracture (no.) Type of EStim (%) Outcomes (%)
Dog Rat Rabbit Sheep Horse Tibia Femur Spine Mandible Other Delayed-/non-union Fusion Osteotomy Large bone defects Others PEMF DC CC Positive Negative
72 25 19 18 7 3 26 13 11 9 16 4 9 3 38 18 35 49 16 77 23

Electrical stimulation-based bone fracture treatment, ifit works sowell why donotmore surgeons…
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bone regeneration. Of these 432 publications, 72 reported
animal studies, 69 clinical studies, 238 organ or invitro
cell culture studies, and 53 were reviews or meta-analyses
(Table1). A total of 141 publications (animal + clinical stud-
ies) were selected and reviewed, the results of which are
presented herein.
Animal studies
A total of 72 animal study articles, that used EStim to treat
bone fractures were reviewed. The most commonly used
animal model was the dog (25), followed by rabbits (18),
rats (19), sheep (7) and horses (3). In these the “bone”, and
“fracture type” studied varied greatly. The bones were pri-
marily the tibia (26), femur (13), spine (11), mandible, (9)
and others (16). Some of the papers reviewed studied more
than one bone. The types of fractures/pathologies were large
bone defects (38), delayed- and non-unions (4), fusions (9),
osteotomies (3), and others (18). The most common method
used to administer electrical stimulation in the animal stud-
ies was DC EStim (49%), followed by PEMF (35%) and CC
and other types, together making up 16% of the reviewed
studies.
Clinical studies
A total of 69 articles describing clinical studies were
reviewed, in which EStim was used to promote bone healing.
The main bones treated with EStim in the clinical studies
were tibia (25), femur (15), spine (15), radius (11), humerus
(7) and others (20). As in the case with the animal study arti-
cles some of the clinical papers reported on more than one
bone. The most common types of fractures/pathologies were
delayed- and non-unions (21), spine fusions (16), arthro-
deses (5), osteotomies (4), necrosis (2), large bone defects
(2) and others (19). Most of the clinical studies reviewed
administered EStim using PEMF (60%), followed by DC
(29%), and CC and other methods (11%). The intensity of
the magnetic field used in PEMF treatment ranged between
0.3 and 6mT, while for DC the dosage was 5–40µA, and
for CC treatment the intensity ranged between 3 and 10V.
Half (50%) of the regimens used in the clinical studies con-
sisted of daily stimulation treatments ranging from 0.5 to
16h/day. Nineteen of the 69 studies (27%) reported com-
plications that included skin irritation and infections, pain
[27], dislocation of the device [28], failure of the device [29]
and poor patient compliance [30]. Fifty (72%) of the stud-
ies reviewed reported no complications. Finally, of the 69
clinical study publications 51 (73%) reported positive and
18 (27%) reported negative outcomes (Table3).
Orthopedic surgeon survey
The individual questions and the responses are displayed
in six separate graphs (Figs.1, 2, 3, 4, 5, 6). Of the 620
orthopedic surgeons who were sent emails inviting them
to participate in the survey, 161 (26%) from 34 countries
responded. Of the 161 respondents, 44% answered that they
perform more than 100, (23%) perform 51–100, (22%) per-
form 11–50, and (11%) perform 0–10 bone surgeries per
year (Fig.1). When asked if they were aware of published
clinical studies reporting successful EStim-based fracture
treatments, 85 (73%) responded “Yes” and the rest (27%)
answered “No” (Fig.2). Of the 85 respondents who said they
were aware of EStim-based fracture treatments, 27 (32%)
answered that they had used EStim in their fracture patients
while 58 (68%) had not (Fig.3). Of the 27 surgeons that
had used EStim in their patients the pathologies they treated
were mainly delayed or non-unions (61%) and large bone
defects (16%). The rest, (23%) were spinal fusion, avascu-
lar necrosis, calcaneal apophysitis, Charcot foot and ankle
reconstructions, loosened hip, knee prosthesis, or other types
of fractures (Fig.4). When asked what they considered to
be the major problems associated with using EStim in their
fracture patients, 30 (35%) identified “high cost”, 24 (28%)
answered “inconsistent results”, while 8% and 5% responded
that EStim devices were “impractical”, and “difficult” to use,
respectively. Eleven (13%) surgeons responded that they had
experienced “other” problems, and nine (11%) replied they
had not experienced problems using EStim-based treat-
ments (Fig.5). Finally, we asked, “If an easy-to-use EStim
device to treat bone fractures were available would you use
it in your patients?” and 85% answered, “Yes” and the rest
answered “No” (Fig.6).
Discussion
In his review of more than 100 studies using EStim treat-
ment, published more than 40years ago Spadaro concludes,
“About 95% are positive reports…” and goes on to qualify
this assertion saying “…despite an extraordinarily wide
selection of experimental techniques and models” [31]. In
the present literature review of 141 papers (72 animal and
69 clinical studies), published in the 40years since then, we
also found positive results, and like Spadaro also found a
great variation in bone and fracture types, treatment meth-
ods, dosages, regimens, etc., reported in the literature. The
latter made it difficult to draw well-founded conclusions
upon which to develop specific EStim treatment recommen-
dations. One of the primary contributors to this confusion
in the literature is the different types, dosages, and regimens
used to administer EStim. In the clinical studies we reviewed

M.B.Bhavsar et al.
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Table 3 Publications between 1977 and 2017 describing clinical studies that use EStim to treat bone fractures
Bone affected and/or
fracture type
No. of cases Type of EStim treatment Outcome Complications Published article
Mandible/fracture 12 Type: PEMF
Duration: 2h/day×12days
Settings: pulse duration 200ns, rise time
8ns, electromagnetic segment at 50MHz
and down to Hz range
No effect Infection Abdelrahim etal. [38]
Tibia/non-union 16 Type: CC
Duration: 7–8h/day until healed or 30weeks
Settings: 6V peak-to-peak symmetrical sine
wave signal at 63kHz frequency
Improved healing (68%) None reported Abeed etal. [118]
Tibia/acute fracture 106 Type: PEMF
Duration: 10h/day×12weeks
No effect None reported Adie etal. [119]
Lumbar spine/fusion 107 Type: DC Improved healing None reported Andersen etal. [6]
Lumbar spine/fusion 107 Type: DC No effect None reported Andersen etal. [120]
Lumbar spine/fusion 98 Type: DC
Settings: 40 and 100µA
No effect None reported Andersen etal. [121]
Tibia/delayed- and non-
union
44 Type: PEMF
Duration: 3h/day, maximum 36weeks
Improved healing (77%) None reported Assiotis etal. [122]
Tibia/non-union 9 Type: PEMF
Duration: 12–16h/day, min 1h/
day×48weeks
Settings: 1–5mT peak, 5ms burst waveform
repeated at 15Hz
No effect One patient left the study prior
to end
Barker etal. [32]
Femur/arthrodesis failure 71 Type: PEMF Improved healing (85%) None reported Bassett etal. [123]
Tibia/fracture 22 Type: CC
Duration: 15h/day until healed
Settings: sinusoidal wave 3–6V at 60kHz
and 5–10mA
No effect None reported Beck etal. [124]
Metatarsal foot/fracture 25 Type: CC
Duration: 52days
Setting: amplitude of 3.0–6.3V and 60kHz
frequency
Effective current—5–10mA
Improved healing (88%) None reported Benazzo etal. [125]
Femur/intertrochanteric
osteotomy
31 Type: PEMF
Duration: 8h/day×3m
Settings: 75Hz, 1.3ms impulse width,
2.5mV amplitude, and 18Gs magnetic
field amplitude
Improved healing None reported Borsalino etal. [10]
Radius/delayed-and non-
union and osteotomy
21 Type: PEMF
Duration: 10h/day
Improved (57% non-union healed)
Improved (89% osteotomies
healed)
None reported Boyette and Herrera-Soto
[126]

Electrical stimulation-based bone fracture treatment, ifit works sowell why donotmore surgeons…
1 3
Table 3 (continued)
Bone affected and/or
fracture type
No. of cases Type of EStim treatment Outcome Complications Published article
Tibia/non-union 57 Type: DC
Settings: 10–20µA
Improved healing (70% healed) Eight patients did not receive
adequate electricity—due to
device failure
Brighton [29]
Tibia/non-union 20 Type: CC
Settings: 60kHz, 5V peak-to-peak
No effect 11 patients started with DC with-
drew prior to end of study
Brighton and Pollack [33]
Tibia/non-union 271 Type: DC and CC No effect Risk factors Brighton etal. [9]
Sesamoid-foot/delayed
union
1 Type: PEMF
Duration: 7–8h/day×52weeks
Improved healing None reported Bronner etal. [127]
Femur, Tibia, radius,
humerus/arthrodesis
24 Type: PEMF
Duration: 8h/day
Settings: 75Hz, 3.0 ± 0.5mV
No effect None reported Capanna etal. [128]
Tibia/pseudoarthroses 22 Type: PEMF
Duration: 8h/day, average 5–6ms
Settings: 75Hz, 10–20A/cm, 180–220V
Improved healing (90%) Infection (three cases), protrusion
of material (nine cases),
Screw break (three cases)
Cebrián etal. [37]
Tibia/fracture 33 Type: PEMF
Duration: 12–15/day, until healed
Settings: 0.8mT, 50Hz
Improved healing (85%) Infection Colson etal. [39]
Tibia/fracture 37 Type: DC Improved healing (100%) None reported Cundy and Paterson [81]
Tibia/non-union 17 Type: PEMF
Duration: 20h/day, 4–8weeks
Settings: 150–300Gs
No effect None reported De Haas etal. [129]
Hind foot/fusion 13 Type: DC Improved healing (92%) None reported Donley and Ward [130]
Humerus, tibia, femur/
non-union and oste-
otomy
52 Type: PEMF
Duration: 2–12m
Improved healing (82%) None reported Dunn and Rush [131]
Cervical spine/fusion 122 Type: PEMF
Duration: 4h/day×3m
Improved healing (83%) None reported Foley etal. [132]
Tibia/fracture 41 Type: DC interferential currents No effect Sepsis (six cases) Fourie and Bowerbank [133]
Tibia, hip, radius/delayed-
and non-union
12 Type: PEMF
Duration: 12h/day×3mmin
No effect None reported Freedman [134]
Knee/osteoarthritis 139 Type: CC
Duration: 6–14h/day
Improved healing None reported Garland etal. [135]
Lumbar spine/fusion 85 Type: CC
Duration: 24h/day until healed or 9m
Setting: 60kHz, current density 5µA root
mean square/cm2, 12mV root mean
square/cm
Improved healing (84%) None reported Goodwin etal. [136]
Tibia/non-union 45 Type: PEMF
Duration: 12h/day, 6–12weeks
Settings: 0.008Weber/m2
Improved healing (35% healed in
10weeks and 85% in 4ms)
Poor compliance Gupta etal. [30]

M.B.Bhavsar et al.
1 3
Table 3 (continued)
Bone affected and/or
fracture type
No. of cases Type of EStim treatment Outcome Complications Published article
Foot joint/arthropathy 11 Type: PEMF (combined)
Duration: 0.5h/day
Improved healing None reported Hanft etal. [137]
Hand/acute fracture 53 Type: PEMF
Duration: continuous for 52weeks
Settings: pulse amplitude 50mV
Pulse width 5μs; burst width 5ms
Burst refractory period 62ms
Repeat repetition rate 15Hz
No effect None reported Hannemann etal. [138]
Hand/acute fracture 102 Type: PEMF
Duration: continuous max 52weeks
Settings: pulse amplitude 50mV
Pulse width 5μs; burst width 5ms
Burst refractory period 62ms
Repeat repetition rate 15Hz
No effect None reported Hannemann etal. [139]
Metatarsal-foot/delayed-
and non-union
9 Type: PEMF
Duration: 8–10h/day×3m
Settings: 0–20Gs, 4.5ms pulse bursts dura-
tion repeated at 15Hz
Improved healing (100%) None reported Holmes [140]
Tibia/non-union 30 Type: PEMF
Duration: 8h/day
Settings: 1–15mV, 5ms bursts of asym-
metrical 15Hz pulses
Improved healing (83%) None reported Ito and Shirai [141]
Radius/fracture 18 Type: DC (pulsed)
Settings: 2Hz, 30µA
Improved healing None reported Itoh etal. [142]
Lumbar spine/fusion 17 Type: DC and PEMF No effect Infection Jenis etal. [143]
Tibia/fracture 24 Type: pulsed DC
Duration: 6m
Settings: 1Hz, 40µA
Improved healing (30%) Skin reaction and infection Jorgensen [144]
Tibia/fracture 3 Type: DC
Duration: 30–60min 3–4×day
Settings: pulse width 300µs,
1–2Hz < 20mA
Improved healing (66%) None reported Kahn [145]
Lumbar spine/fusion 31 Type: DC Improved healing (78%) None reported Kane [146]
Spine/fusion 65 Type: DC Improved healing (96%) None reported Kucharzyk [147]
Radius/colles’ fracture 30 Type: PEMF
Duration: 30m/day, 5days/week×2weeks
Settings: 6mT, 25Hz
Improved healing None reported Lazovic [148]
Lumbar spine/fusion 104 Type: PEMF (combined)
Duration: 30m/day×9m
Improved healing (64%) None reported Linovitz [149]

Electrical stimulation-based bone fracture treatment, ifit works sowell why donotmore surgeons…
1 3
Table 3 (continued)
Bone affected and/or
fracture type
No. of cases Type of EStim treatment Outcome Complications Published article
Humerus neck/fracture 21 Type: PEMF
Duration: 30m/day×10days
Settings: 35Hz, max pulse 300W
No effect None reported Livesley [150]
Radius/non-union 10 Type: PEMF
Duration: 104days
Settings: 2.5Gs
Improved healing (66%) None reported Madronero etal. [151]
Tibia/osteotomy 18 Type: PEMF
Duration: 8h/day×57days
Settings: pulse duration 1.3ms, 75Hz,
3.0 ± 0.5mV
Improved healing Thrombophlebitis (three cases) Mammi etal. [152]
Lumbar spine/fusion 42 Type: PEMF
Duration: 4h/day
Improved healing (97%) None reported Marks [153]
Femur/fracture 32 Type: PEMF
Duration: 1h/day×8weeks
Settings: 5–105Hz, 0.5–2.0mT
Improved healing (94%) None reported Martinez-Rondanelli etal.
[154]
Femur head/osteonecrosis 66 Type: PEMF
Duration: 8h/day×3–7m
Settings: 75Hz, 1.3ms pulse, 2 ± 0.5mV
Improved healing (94%) None reported Massari etal. [155]
Mandible/fracture 40 Type: DC
Duration: 10–14days
Settings: 10–20µA
Improved healing None reported Masureik and Eriksson [156]
Lumbar spine/fusion 122 Type: DC
Duration: 24weeks min
Settings: 20µA
Improved healing (76%) Infection (four cases) Meril [40]
Tibia/delayed- and non-
union
57 Type: PEMF Improved healing (75%) None reported Meskens [157]
Tibia/congenital pseudar-
throsis
27 Type: DC
Duration: 6m
Settings: 20µA
Improved healing (74%) Infection (two cases) Paterson and Simonis [158]
Humerus, ulna, radius,
femur, tibia/non-union
93 Type: PEMF
Duration: 13weeks
Settings: pulse amplitude 50mV
Pulse width 5s at 15Hz
Improved healing (74%) None reported Punt etal. [159]
Ankle/cystic osteochon-
dral defect
68 Type: PEMF
Duration: 4h/day×60days
Settings: 1.5mT at 75Hz
No effect Temporary foot paresthesia×2
Wound drainage×2
Reilingh etal. [160]
Lumbosacral spine/fusion 53 Type: DC
Duration: 20.5m
Settings: 10µA/cathode
Improved healing (96%) None reported Rogozinski and Rogozinski
[161]
Foot, ankle arthrodesis/
delayed union
19 Type: PEMF
Duration: 5–27m
Improved healing (77%) None reported Saltzman etal. [162]

M.B.Bhavsar et al.
1 3
Table 3 (continued)
Bone affected and/or
fracture type
No. of cases Type of EStim treatment Outcome Complications Published article
Tibia, femur/non-union 10 Type: CC
Duration: 6m
Setting: 5–10V peak-to-peak sine, 60kHz
Improved healing (60%) Electrode allergic skin reaction
(two cases)
Scott and King [163]
Tibia/delayed union 20 Type: PEMF
Duration: 12h/day×12weeks
Settings: 200µs with 25µs interval, 5T/s
Improved healing None reported Sharrad [28]
Humerus, ulna, radius,
femur, tibia/non-union
53 Type: PEMF
Duration: 12–16h/day×3m
Settings: 5ms bursts, 15Hz, 11.5mV
Improved healing (71%) Plate/screw loosening (eight
cases)
Sharrad etal. [8]
Humerus, ulna, radius,
femur, tibia/non-union
31 Type: PEMF
Duration: 8h/day×5m
Improved healing (77%) None reported Shi etal. [164]
Lumbar spine/fusion 13 Type: PEMF
Duration: 8–10h/day×4m
Settings: 0–0.0003T, 50ms pulse repetition
rate
Improved healing (76%) None reported Simmons [165]
Lumbar spine/fusion 100 Type: PEMF
Duration: 2h/day×90daymin
Improved healing (67%) None reported Simmons etal. [166]
Metatarsal-foot/non-union 5 Type: PEMF
Duration: 10h/day×24weeks max
Improved healing None reported Streit etal. [167]
Femur head/avascular
necrosis
20 Type: CC
Duration: 24h/day×6m
No effect None reported Steinberg etal. [168]
Lumbar spine/fusion 143 Type: DC
Duration: 24weeks
Settings: 20µA
Improved healing (91.5%) Pain Tejano etal. [27]
Ankle/cystic osteochon-
dral defect
68 Type: PEMF
Duration: 4h/day×60days
Settings: 1.5mT at 75Hz
Improved healing None reported van Bergen etal. [169]
Radius/fracture 15 Type: PEMF
Duration: 8weeks
Settings: 0.00004T at 1–1000Hz
Improved healing None reported Wahlstrom and Knutsson
[170]
Cervical spine/arthrodesis 16 Type: DC
Duration: 26weeks min; settings: 12µA
Improved healing (93%) Infection (one case)
Local discomfort (four cases)
Welch etal. [171]
Total no. of
articles
Type of bone (no.) Type of fracture (no.) Type of EStim
(%)
Compli-
cations
(%)
Outcomes (%)
Tibia Femur Spine Radius Humerus Others Delayed-/
non-union
Fusion Arthrode-
sis
Osteotomy Necrosis Bone
defect
Others PEMF DC CC Yes No Positive Negative
69 25 15 15 11 7 20 21 16 5 4 2 2 19 60 29 11 27 73 73 27

Electrical stimulation-based bone fracture treatment, ifit works sowell why donotmore surgeons…
1 3
Fig. 1 How many bone surgeries do you perform per year?
Fig. 2 Did you know that electrical stimulation has been proven to
accelerate bone healing in many clinical studies?
Fig. 3 Have you ever used an electrical stimulation device to treat
bone fractures in your patients?
Fig. 4 In what type of bone fractures have you used an electrical
stimulation device?
Fig. 5 What problem(s) do you see in current devices?
Fig. 6 If an easy-to-use electrical stimulation device to treat bone
fractures were available, would you use it in your patients?

M.B.Bhavsar et al.
1 3
that the most commonly used method of administering
EStim was PEMF while in the animal studies DC was the
predominant treatment method. This preference in patients
is most likely due to the fact that PEMF is administered
using an external noninvasive device, whereas DC treat-
ment requires that the EStim device be surgically implanted.
While being noninvasive is a major benefit of PEMF for
clinical use, patient non-compliance, associated with its use,
is a major problem and is cited as one of the primary reasons
for inconsistent results when using PEMF [28–30].
Another source of confusion is the dosages and regimens
used. The most commonly used dosage for administering
PEMF ranged between 0.3 and 6mT, while for DC the inten-
sity was 5–40µA, and for CC treatment the intensity ranged
between 3 and 10V. Half of the regimens used in the clinical
studies consisted of daily EStim treatments ranging from 0.5
to 16h/day, delivered either continuously or in interrupted
intervals, the latter being for periods of 1–6h/day. The dos-
ages, regimens, and exposure times in the animal studies
also varied widely. This great variation makes it difficult to
combine the results of these studies into one or a few treat-
ment recommendations. Another reason why it is difficult
to combine the results of the different studies is because
of the many different bones and fracture types studied. Of
all the different bones and fracture types reported in the
clinical articles by far the most common bone was the tibia
and the most studied fracture types were delayed- and non-
unions. In fact, this was confirmed in our survey in which
orthopedic surgeons that use EStim mostly used it to treat
delayed- and non-unions in their patients (Fig.4). Again,
this variation in bone and fracture types described in the
literature would make it difficult to compare healing rates
between, say a mandible and a tibia, or between non-unions
and osteotomies, which makes it difficult to draw meaning-
ful conclusions.
Poor fracture healing is often associated with both a lack
of healing and mal-position of bone fragments. In these
cases, surgeons prefer operative intervention to EStim
because of the ability to restore alignment as well as facili-
tate fracture healing. Revision fixation and osteotomies, to
correct alignment, are fraught with high rates of delayed
bone healing and persistent non-unions. While EStim does
not improve the position of bone fragments, it still can play
an adjunctive role in the treatment of non-unions [34].
When EStim is used as an adjunct to other treatment
attempts, as a last resort it can require prolonged and costly
interventions. While the clinical studies we reviewed did
not provide information about costs associated with EStim
treatments, information available online from companies
who sell clinical EStim devices indicate that the current
unit cost of most EStim devices, regardless of the company
(OL1000 Bone Growth Stimulator, Orthopak, EBI Bone
Healing System, Physio-Stim Lite, or Exogen), is about US
$3000. Additional coststo treat delayed unions is approxi-
mately$24,892, that includes $20,575 for surgery and recov-
ery + $4317 outpatient costs. These figures are quoted from
a report published by EXOGEN [35].
Added to this, failure rates in these treatments is relatively
high (17–64%) and when present can lead to additional costs
[36]. Finally, the costs associated with using EStim devices
are usually not reimbursed, thus further reducing the incen-
tive to use this treatment option. While comparing the costs
of EStim to other treatments used in problematic fractures
is beyond the scope of this paper, from the responses we
received in our survey it is clear that high costs is an impor-
tant factor for surgeons in their decision whether or not to
use EStim. Of the drawbacks associated with using EStim,
the greatest number of surgeons surveyed cited high costs as
being the main problem with using EStim in their fracture
patients (Fig.5).
The second most cited problem with EStim was incon-
sistent results. While the questions in our survey did not ask
about the specific cause of the inconsistent results associated
with using EStim, from our literature review we were able
to identify some possible causes. In the clinical papers a
few different device-related problems were cited that could
cause “inconsistent results”. These included “damaged”
or “disconnected” implanted stimulators, misplacement of
hardware, and migration of the EStim device’s electrode
leads that can occur due to muscle movement or insufficient
flexibility of the muscles [9, 28, 37]. Eight and five percent-
age of surgeons surveyed indicated that the problems they
encounter using EStim were associated to the devices used
to administer the treatment, choosing “impractical”, and
“difficult to use”, respectively, to describe their experience.
In a white paper generated by industry that compares costs
associated with the use of five different EStim bone stimula-
tors the authors write that using these devices the “probabil-
ity of failure” ranges between 17 and 64% [36]. While the
exact causes of failure are not specified in this paper these
high failure rates could certainly cause inconsistent results.
Of the 69 clinical studies we reviewed, 19 reported com-
plications experienced during treatment with EStim. In
these 19 studies, the most common type of complication
experienced was skin irritation and infections, when using
the externally applied PEMF device, and infections at the
fracture line when using the implanted DC device [24–27].
Other types of complications experienced with EStim treat-
ment were pain [27], dislocation of the device [28], failure
of the device [29] and poor patient compliance [30]. The
above-mentioned complications and particularly patient non-
compliance could be other causes of the inconsistent results
surgeons cited in our survey. Existing external PEMF units
are cumbersome and require manyhours of treatment per
day over months, which interferes with activities of daily
living, causing decrease compliance. If a patient does not (or

Electrical stimulation-based bone fracture treatment, ifit works sowell why donotmore surgeons…
1 3
is not able to) utilize the PEMF EStim device in the manner
prescribed then the beneficial effects are diminished. Smaller
units are available and only require 30-min treatments,
however, they require very precise fitting to encompass the
fracture site within the small field which also decreases the
effectively applied dose and clinical efficacy. Although 73%
of clinical studies demonstrate a benefit to EStim, the mag-
nitude and consistency of the effect are less than reported in
animal studies. Patient compliance is much lower in clinical
studies thanin animal studies. We believe that problems with
compliance account for the large gap in the results reported
in the clinical versus animal studies.
In a study we reviewed, Simmons etal. compared PEMF
(where patient compliance is required) to DC EStim (where
compliance is not an issue since the device is implanted),
and found that spinal fusion rates in the former were lower
than in the latter [41], attributing this difference to patient
non-compliance. In another study non-compliance was cited
as a possible reason for EStim-treated patients having the
same spinal fusion rates as non-treated controls [42]. The
above problems, “high cost”, “inconsistent results”, and
“impractical/difficult to use” go a long way toward answer-
ing our original question, why EStim-based fracture treat-
ments have not gained more acceptance in the orthopedic
community.
When comparing EStim to other adjunct treatments
used to treat delayed healing or non-unions, Ebrahim etal.
compared EStim with low intensity-pulsed ultrasound and
found no significant difference [43]. Kertzman etal. used
radial extracorporeal shock wave therapy to treat fracture
non-unions of superficial bones and found that 70% of tibia
non-unions healed within 6months suggesting that this
approach is on par with EStim [44]. Similarly, in a recent
study by Putnam etal. non-unions in 26 patients using surgi-
cal volar plate fixation and cancellous grafting, they found
82% healed by 12weeks [45]. With this, one can reasonably
assume that rates of success with these different procedures
are similar to those reported with EStim.
The present study had several drawbacks, the greatest
being difficulty making sense of the large variation in the
methods reported in the different studies we reviewed. In
both the animal and clinical studies, the bones and frac-
ture types studied, the EStim method/dosages/regimens,
and the methods used to report outcomes differed greatly.
This made it difficult to combine these various parameters
into well-founded treatment recommendations. Another
weakness in this study was positive publication bias. All
the articles we reviewed were published, and since stud-
ies that found EStim to be effective are more likely to be
written up, submitted, and accepted for publication, our
review did not include unpublished studies with negative
results. Another shortfall is related to the questions we
used in our survey. We did not test these questions for
validity or reproducibility prior to sending them out. Had
this been done perhaps we could have improved the quality
of the answers we received. Finally, in the survey we could
have included more specific questions that might have pro-
vided answers to other important questions such as the
specific causes of the problem’s respondents encountered
with EStim treatment. While it would have been nice to
get more information with more detailed questions, we
decided to have few and simple questions thinking that this
would help maximize the response rate in this first study.
Conclusion
Most of the orthopedic surgeons we surveyed were aware
of EStim and its positive outcomes in fracture treatment.
These positive outcomes were confirmed in the litera-
ture we reviewed, in which both preclinical animal and
clinical studies reported positive overall outcomes using
EStim to treat bone fractures. Despite the awareness and
positive impression our respondents had about EStim only
a fraction actually useit in their fracture patients. The
reason for this discrepancy could be problems such as,
confusion in the literature, due to the great variation in
methods reported, and the inconsistent results associated
with this treatment approach. On the positive side, when
asked “If an easy-to-use electrical stimulation device to
treat bone fractures were available, would you use it in
your patients?”, 85% of the surgeons surveyed responded
“Yes”. This suggests that despite the problems, given an
easy-to-use method for administering EStim, surgeons
are open to using this treatment approach. An improved
delivery system for EStim could overcome the compliance
problem, markedly increase the clinical efficacy and make
EStim an accepted form of treatment of non-unions and
acute fractures associated with poor healing.
Funding This study was supported in part by the Friedrichsheim Foun-
dation (Stiftung Friedrichsheim) based in Frankfurt/Main, Germany,
and the Chinese Scholarship Council (CSC).
Compliance with ethical standards
Conflict of interest The authors have no conflicts of interest to declare.
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