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[ research report ]

ANTHONY G. SCHNEIDERS, PT, PhD1 • S. JOHN SULLIVAN, PhD2 • PAUL A. HENDRICK, PT, PhD3 • BENJAMIN D.G.M. HONES, PT, BPhty4
ANDREW R. MCMASTER, PT, BPhty4 • BRIDGET A. SUGDEN, PT, BPhty5 • CELIA TOMLINSON, PT, BPhty6

The Ability of Clinical Tests to Diagnose


Stress Fractures: A Systematic
Review and Meta-analysis

S
tress fractures are a bone-related overuse injury commonly seen with different sports and activities; how-
in athletes and military personnel.29,35 This condition was first ever, 80% to 95% of stress fractures oc-
cur in the lower limbs,14,25,40,43,44,46 with the
reported in the literature in 1855 by a Prussian military phys-
tibia being the most commonly injured
ician7 and first described in athletes in 1958.44 Stress fractures bone, accounting for approximately 50%
have been suggested to account for approximately 10% of all athletic of all cases.1
injuries35,41,44 and are most commonly seen in runners, with an incidence Clinically, lower-limb stress fractures
of up to 20% in this population.30 The site of the stress fracture varies can be difficult to diagnose, due to a wide
range of potential differential diagnoses16
that include compartment syndrome,
TTSTUDY DESIGN: Systematic literature review criteria. Meta-analysis was used to statistically
soft tissue injuries, infection, and other
and meta-analysis. analyze the data extracted from the ultrasound
overuse conditions such as medial tibial
TTOBJECTIVES: To evaluate the diagnostic ac- articles and demonstrated a pooled sensitivity of
64% (95% confidence interval [CI]: 55%, 73%), stress syndrome and periostitis.43,44 The
curacy of clinical tests to identify stress fractures
in the lower limb. specificity of 63% (95% CI: 54%, 71%), positive diagnosis of a stress fracture is contingent
on a detailed clinical examination14 that
TTBACKGROUND: Stress fractures are a bone-
likelihood ratio of 2.1 (95% CI: 1.1, 3.5), and
related overuse injury primarily occurring in
negative likelihood ratio of 0.3 (95% CI: 0.1, 0.9). incorporates the patient history35,41,43 and
Tuning fork test data could not be pooled; however, contributing risk factors,5,24,32,33,40 as well
the lower limb and commonly affecting running
athletes and military personnel. Physical examina- sensitivity, specificity, positive likelihood ratio, and as a thorough physical examination,35,41,43
tion procedures and clinical tests are suggested negative likelihood ratio ranged from 35% to 92%, and is most often confirmed with radio-
for diagnosing stress fractures; however, data on 19% to 83%, 0.6 to 3.0, and 0.4 to 1.6, respectively.
logical imaging.5
the diagnostic accuracy of these tests have not TTCONCLUSION: The results of this systematic Radiological imaging for stress
been investigated through a systematic review of review do not support the specific use of ultra-
the literature.
fractures has traditionally included
sound or tuning forks as standalone diagnostic
roentgenograms (plain radiographs),18
TTMETHODS: A systematic review was conducted tests for lower-limb stress fractures. As the overall
scintigraphy (bone scan), magnetic reso-
in 8 electronic databases to identify diagnostic diagnostic accuracy of the tests investigated is not
accuracy studies, published between January 1950 nance imaging (MRI), and computed
strong, based on the calculated likelihood ratios, it
and June 2011, that evaluated clinical tests against is recommended that radiological imaging should tomography. Although plain radiographs
a radiological diagnosis of lower-limb stress continue to be used for the confirmation and are commonly used as initial reference
fracture. Retrieved articles were evaluated using diagnosis of stress fractures of the lower limb. standards, they have limited useful-
the Quality Assessment of Diagnostic Accuracy
Studies tool, and a meta-analysis was performed TTLEVEL OF EVIDENCE: Diagnosis, level 1a–. ness due to their inability to detect bony
J Orthop Sports Phys Ther 2012;42(9):760-771, changes during the early development of
where appropriate.
a stress fracture,3,8,13,15,16,28,29,35,40,41,43 and
TTRESULTS: Nine articles investigating 2 clinical
Epub 19 July 2012. doi:10.2519/jospt.2012.4000
TTKEY WORDS: diagnosis, lower limb, tuning fork,
computed tomography is not frequently
procedures, therapeutic ultrasound (n = 7) and
tuning fork testing (n = 2), met the study inclusion ultrasound, validity used due to low diagnostic sensitivity.8,41
The gold standard for stress fracture

Senior Lecturer, Centre for Physiotherapy Research, School of Physiotherapy, University of Otago, Dunedin, New Zealand. 2Professor, Centre for Physiotherapy Research, School
1

of Physiotherapy, University of Otago, Dunedin, New Zealand. 3Lecturer, Division of Physiotherapy Education, University of Nottingham, Nottingham, UK. 4Physical Therapist,
School of Physiotherapy, University of Otago, Dunedin, New Zealand. 5Physical Therapist, Physio Direct, Adelaide, Australia. 6Physical Therapist, Physiotherapy Department,
Southland Hospital, Invercargill, New Zealand. Address correspondence to Dr A.G. (Tony) Schneiders, School of Physiotherapy, University of Otago, PO Box 56, Dunedin 9054,
New Zealand. E-mail: tony.schneiders@otago.ac.nz t Copyright ©2012 Journal of Orthopaedic & Sports Physical Therapy

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diagnosis is either triple-phase techne- is its ability to obtain a positive result Scopus, and SPORTDiscus. Key words/
tium-99m bone scan (scintigraphy)35,40,41 when the condition is actually present; terms were identified after a search for
or MRI.36,51 Scintigraphy is able to diag- inversely, specificity is the ability of that synonyms associated with the term stress
nose stress fractures by identifying areas test to obtain a negative result when the fracture. These terms were entered into
of increased uptake of the radioisotope3 condition is absent. 34 Likelihood ratios the selected databases in various combi-
and has a reported sensitivity of 100% correct the true positive rate by the false nations to identify a range of clinical tests
and specificity of 76%.8,41 MRI has been positive rate, revealing how much more employed in the examination of suspect-
shown to have comparable sensitivity3,41 likely it is that a person has the diagnosis ed stress fractures, as outlined in FIGURE
and superior specificity to scintigraphy after an index test is completed.34 Likeli- 1. The Medical Subject Heading (MeSH)
for assessment of bone pathology.41 Al- hood ratios have an advantage over sen- database search included the following
though MRI is less invasive and provides sitivity, specificity, and predictive values terms: stress fracture*, fatigue fracture*,
greater anatomic detail than scintigra- because they are independent of pathol- insufficiency fracture*, march fracture*,
phy,16,35 it is more costly.3,43 Of further ogy prevalence and therefore applicable diagnos*, investigat*, identif *, analys*,
concern is the accessibility of these pro- across settings and patients.34 The DOR physical exam*, interpret*, palpat*, pres-
cedures to many patients.43 is a statistic used to provide a summary of sure*, and ultrasound*.
Although radiological imaging can the performance of diagnostic tests and Studies were considered for inclusion
be used to confirm suspected stress augment the comparison between study if they reported on the use of clinical (in-
fractures in a primary care setting, results. It combines sensitivity, specificity, dex) tests to diagnose stress fracture and
other common clinical tests have been and +LR and –LR to convey how much were published as full reports before June
suggested to show diagnostic poten- greater the probability is that a positive 13, 2011. The inclusion criteria required
tial.13,18,26,27,29,31,36,51 The use of therapeu- test result will indicate the event of inter- that articles (1) report 1 or more index
tic ultrasound for the diagnosis of stress est, for example, the presence of a stress tests, (2) utilize at least 1 radiological
fractures has been proposed as a relative- fracture.12 reference test, (3) report or allow com-
ly accessible and effective tool for physi- Although anecdotal and selective putation of diagnostic values (sensitivity,
cal therapists.8,11,35,36,43 Numerous studies research evidence has for decades sug- specificity, +LR, and –LR), (4) not impose
suggest that the elicitation of pain as the gested the ability of nonradiological tests an age restriction for participants, (5)
ultrasound is applied over the fracture to diagnose stress fractures, it remains were published between 1950 and 2011,
site8,11,29,35,43 may be a good diagnostic in- unclear whether this actually is the case. and (6) include only lower-limb stress
dicator of an underlying stress fracture. The purpose of this study was to system- fractures. Articles specifically investigat-
Tuning forks have also been suggested atically review the literature and apply ing pathological stress fractures or stud-
as effective diagnostic clinical tools, with meta-analysis procedures to diagnostic ies not conducted on human subjects
application of the tuning fork to an iden- studies, where appropriate, to establish were excluded.
tified area of maximal tenderness overly- which clinical tests have the best accuracy Each database was searched by 2 in-
ing a suspected stress fracture suggested in musculoskeletal and orthopaedic clini- dependent reviewers (B.A.S. and C.T.) for
to provoke pain due to irritation of the cal practice to diagnose stress fractures. titles that met the inclusion criteria. The
damaged periosteum.26,41 Common clinical testing procedures and 2 reviewers then evaluated the retrieved
Systematic reviews of diagnostic accu- modalities, such as ultrasound and tun- abstracts of each article for possible in-
racy studies focus on providing validity ing forks, were considered for evaluation clusion based on the criteria specified
measures of a test and, where possible, in this review. above. References from all included ar-
pooling data through a meta-analysis to ticles were manually searched for addi-
offer clinicians a summary of evidence METHODS tional relevant articles. The full text of all
of the test’s diagnostic accuracy. To de- articles included after the manual search
termine the diagnostic accuracy and Search Strategy was examined to determine inclusion in

A
validity of a clinical test, specific Bayes- n initial systematic search of the systematic review. A third reviewer
ian probability and performance metrics the literature was conducted on (A.G.S.) was consulted if an initial con-
should be examined. These include the May 13, 2011, and the search strat- sensus could not be reached.
number of false positives and negatives egy results were monitored until June
associated with the test, together with 13, 2011. A comprehensive search with Diagnostic Accuracy Statistics
its sensitivity, specificity, positive and no language restrictions was conducted Articles investigating the diagnostic ac-
negative likelihood ratios (+LR and –LR, covering the period 1950 to 2011 in the curacy of clinical binary classification
respectively), and the diagnostic odds following databases: AMED, CINAHL, tests to diagnose radiologically con-
ratio (DOR).34 The sensitivity of a test Embase, MEDLINE, PEDro, PubMed, firmed stress fractures were required to

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[ research report ]
report, or allow calculation of, sensitiv-
ity, specificity, +LR, –LR, and the DOR Search strategy Databases
for each included test.19 We chose not to 1. stress fracture* OR fatigue • MEDLINE
report positive and negative predictive fracture* OR bone stress OR bone • CINAHL
values because they are strongly affected strain* OR insufficiency fracture* • SPORTDiscus
by the prevalence of the condition, which OR repetitive stress injur* OR • PubMed
march fracture* • Embase
we believe has not been adequately es-
2. diagnosis* OR investigat* OR • Scopus
tablished for lower-limb stress fractures. confirm* OR identif* OR clinical • AMED
A 2-by-2 contingency table was created test* OR analys* OR physical • PEDro
to identify the true positive, false posi- exam* OR interpret* OR diagnostic
tive, true negative, and false negative re- tool* OR test*
sults, as reported in the original articles. 3. tuning fork* OR vibration fork* OR Electronic database
These specific Bayesian probability and tap* OR palpat* OR squeeze* OR search, n = 9321
performance metrics were selected due tender* OR focal tender* OR
to their ability to aid in the interpre- pressure* OR ultrasound* OR
therapeutic ultrasound* OR heel Included after title
tation of clinical data extracted from
drop OR jarring test OR markle test screen, n = 739
diagnostic studies. The clinical interpre- OR drop test OR bump test OR
tations of likelihood ratios for this study percussion test OR tap* test*
are defined in TABLE 1. However, there Duplicates
4. (1 and 2)
removed, n = 210
is no current accepted taxonomy for 5. (3 and 4)
characterizing magnitudes of sensitivity
and specificity. For the purposes of this Full abstracts, n = 529
study, we have arbitrarily defined these Excluded after abstract
as low if 50% or less, low to moderate if screen, n = 514
between 51% and 64%, moderate if be-
tween 65% and 74%, moderate to high if Hand-searched reference
between 75% and 84%, and high if 85% list, abstracts Full texts, n = 15
or greater. reviewed, n = 11

Quality Assessment
The methodological quality of the in- Full texts, n = 4
cluded articles was assessed indepen-
dently by 2 reviewers (A.R.M. and Full texts, n = 19
B.D.H.) using the Quality Assessment of
Diagnostic Accuracy Studies (QUADAS) Excluded after full-text
screen, n = 10
tool developed by Whiting et al,50 which
is frequently used to evaluate the qual- Included in review, n = 9
ity of diagnostic studies.2 The review-
ers were blinded to the authors, date of
publication, and journals in which the Quality assessment
articles were published. The QUADAS
tool is composed of 14 items individually FIGURE 1. Search and selection strategy.
scored as either “yes,” “no,” or “unclear.”
Nine items relate to bias, 3 items to the dently scored each of the 14 criterion QUADAS Scoring
quality of the reporting, and 2 items to items as yes or no when studies either For this systematic review, the QUA-
variability. The reviewers familiarized satisfied or failed to meet the criteria. DAS scoring system proposed by the
themselves with the QUADAS tool and Items were scored as unclear when in- original developers50 was utilized to as-
discussed the quality items of the scor- sufficient information was provided to sess the quality and rate the validity of
ing system prior to the evaluation. This categorize an item. In the case of dis- the included studies. Using this system,
allowed for more uniform interpretation agreement between reviewers, a third item weightings based on and scaled
of each study and diminished quality as- reviewer (A.G.S.) adjudicated to assign for potential bias or variation were used
sessment bias. The reviewers indepen- a single score for each study. to develop the scoring for the retrieved

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is otherwise called the Woolf-Haldane
Clinical Interpretation correction (for the odds ratio). 37 Forest
TABLE 1
of Likelihood Ratios 23 plots and confidence intervals (CIs) were
generated, when appropriate (FIGURES 2
Positive Likelihood Ratio Negative Likelihood Ratio Shift in Probability Condition through 6).
>10 <0.1 Large, often conclusive
5-10 0.1-0.2 Moderate but usually important RESULTS
2-5 0.2-0.5 Small, sometimes important

T
1-2 0.5-1 Very small, rarely important he search strategy process and
result are outlined in FIGURE 1. The
initial electronic database search
Study Name n Confidence Interval
yielded a total of 9321 articles. After ex-
amining titles for context and key words,
Boam (1996) 78 0.429 (0.268, 0.605)
739 articles were subsequently selected
for possible inclusion. After title dupli-
Devereaux (1984) 18 0.533 (0.276, 0.778)
cations were removed, 529 abstracts
Giladi (1984) 106 0.745 (0.601, 0.853)
were screened based on the inclusion
and exclusion criteria, with 15 titles re-
Lowdon (1986) 32 0.900 (0.670, 0.983) tained for further analysis. A hand search
of each of these articles revealed 11 ad-
Moss (1983) 19 0.909 (0.574, 0.996) ditional studies of interest, of which 4
were deemed relevant following abstract
Nitz (1980) 54 1.000 (0.875, 0.997) review. After full-text examination, 9
articles4,13,18,26,27,29,31,36,51 met the inclu-
Romani (2000) 26 0.000 (0.014, 0.487) sion criteria and were assessed using the
QUADAS tool.50 The number of articles
Overall 333 0.642 (0.548, 0.727)
retrieved during this review was limited,
and it is recognized that rating scores
can potentially affect conclusions, based
0.0 0.2 0.4 0.6 0.8 1.0
on the quality of estimates of diagnostic
FIGURE 2. Sensitivity and 95% confidence interval data for therapeutic ultrasound to diagnose stress fractures in accuracy.49 Due to these factors, studies
the lower limb. were not partitioned relative to score or
excluded from the review or subsequent
studies. Items 1, 5, 10, 11, and 12 were were included and assumed to be accu- meta-analysis due to their QUADAS
scored 3 points for yes; items 3 and 6 rate. The data were then independently score.
were scored 2 points for yes; and all other reviewed by a second reviewer (B.D.H.).
items (2, 4, 7-9, 13, and 14) were scored Where appropriate, MetaAnalyst Ver- Study Characteristics and
1 point for yes. Items were scored zero if sion 3.13 beta, developed by Wallace et Methodological Quality
the response was no or unable to be de- al,47 was used to statistically analyze the The 9 articles retained after the system-
termined (unclear). The highest possible data extracted from included studies. atic search investigated either therapeu-
score achievable, if all criteria were met The method in which MetaAnalyst cal- tic ultrasound (n = 7) or tuning fork tests
in all categories, was 26. culates the overall test accuracy indices (n = 2) to diagnose stress fractures of
is well described in the literature.47 As the lower limb. Two different reference
Data Extraction and Quantitative previously indicated, we chose to pre- (criterion) tests (MRI and bone scintig-
Synthesis sent sensitivity, specificity, +LR, –LR, raphy) were used throughout these stud-
Data were extracted by 1 author and DOR in the meta-analysis. Where ies, with 1 study also including the use of
(A.R.M.), who was experienced in me- values of zero are identified in contin- roentgenogram51 as a comparison to the
ta-analyses, for calculation of sensitivity gency tables, MetaAnalyst adds 0.5 to all clinical test. Participants in the studies
and specificity for all clinical diagnostic cells in the contingency table to popu- reviewed ranged from 18 to 78 in num-
tools examined. If raw data were not late the cell, allowing full computation ber and from 19 to 31 years of age. The
provided, the sensitivity and specificity and synthesis of data and calculation age of participants was not specified in
values calculated by the original authors of diagnostic accuracy statistics. This 2 studies.27,31 Male participants only were

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[ research report ]
detail.
Study Name n Confidence Interval
The total score, item score, and per-
centage agreement between the 2 re-
Boam (1996) 78 0.488 (0.336, 0.644)
viewers who performed the quality
Devereaux (1984) 18 0.000 (0.028, 0.696)
assessment using the QUADAS tool are
presented in TABLE 3. All items had an
Giladi (1984) 106 0.673 (0.532, 0.790) initial reviewer agreement ranging from
55.6% (item 4) to 100% (items 1, 5, 7-10,
Lowdon (1986) 32 0.750 (0.430, 0.934) and 14). Items 2 and 12 had 66.7% agree-
ment, items 3 and 13 had 77.8% agree-
Moss (1983) 19 1.000 (0.601, 0.987) ment, and items 6 and 11 had 88.9%
agreement.
Nitz (1980) 54 0.800 (0.559, 0.935) Sensitivity, specificity, +LRs, and –LRs
and their associated 95% CIs were calcu-
Romani (2000) 26 1.000 (0.801, 0.995)
lated from the study data if they were
not specifically provided in the original
Overall 333 0.631 (0.542, 0.712)
articles,13,27,29,31 and all data were recal-
culated where possible for verification
0.0 0.2 0.4 0.6 0.8 1.0 purposes, even if provided in the original
articles.4,18,26,36,51
FIGURE 3. Specificity and 95% confidence interval data for therapeutic ultrasound to diagnose stress fractures in The QUADAS tool identified criteria
the lower limb. considered important to the method-
ological quality of the retrieved studies.
For instance, the study by Lowdon27 did
Study Name n Confidence Interval
not clearly define the participant charac-
Boam (1996) 78 1.074 (0.627, 1.719)
teristics, which might have given rise to
a spectrum bias, and many of the studies
Devereaux (1984) 18 1.405 (0.548, 2.805) did not clearly specify the selection crite-
ria for included subjects. The reference
Giladi (1984) 106 2.273 (1.567, 3.312) tests used also varied between studies.
Nitz and Scoville31 used plain radiogra-
Lowdon (1986) 32 2.968 (1.621, 5.563) phy, a reference test that is considered
less sensitive and specific than MRI and
Moss (1983) 19 3.670 (1.732, 8.178) scintigraphy. Lesho26 and Wilder et al51
had a significantly long time between in-
Nitz (1980) 54 3.331 (2.138, 5.065)
dex and reference testing (range, 0-432
days), which might have introduced bias
Romani (2000) 26 1.714 (0.333, 4.398)
due to a potential change in the pathology
Overall 333 2.092 (1.099, 3.517)
phase or status. However, in all cases, the
reference standard was independent of
the index tests and was always described
0.1 1.0 10.0 in sufficient detail to permit its replica-
tion. This was not always the case with
FIGURE 4. Positive likelihood ratio and 95% confidence interval data for therapeutic ultrasound to diagnose stress the index test, which was not clearly de-
fractures in the lower limb. scribed in a number of articles.4,18,31 In all
of the studies, except that by Boam et al,4
examined in 2 studies,18,31 male and fe- personnel or recreational/competitive it was unclear whether the index and/or
male participants were examined in 6 athletes, and all were suspected of having reference tests were completed without
studies,4,26,27,29,36,51 and, in the remaining stress fractures of the lower limb, the ma- the examiner’s knowledge of other test
study, Devereaux et al,13 the sex of par- jority of which were located in the tibia. results. In most studies, there were insuf-
ticipants was not specified. The majority TABLE 2 describes the study characteristics ficient or unclearly defined clinical data
of study participants were either military and participant demographics in further reported on each participant, compared

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to those that would have been available in
Study Name n Confidence Interval
a normal clinical setting. All of the stud-
ies, except those by Moss and Mowat29
Boam (1996) 78 1.043 (0.665, 1.559)
and Wilder et al,51 clearly reported un-
interpretable and/or intermediate test Devereaux (1984) 18 1.336 (0.330, 5.857)
results and withdrawals from the study,
thus negating biased assessment of the Giladi (1984) 106 0.368 (0.208, 0.570)
test characteristics and test performance
in the majority of studies. Lowdon (1986) 32 0.168 (0.036, 0.390)

Pooled Analysis Moss (1983) 19 0.155 (0.021, 0.405)


TABLE 4 depicts the pooled sensitivity, spec-
ificity, +LR, –LR, and DOR values for the Nitz (1980) 54 0.055 (0.002, 0.166)

total sample of ultrasound participants (n


Romani (2000) 26 0.911 (0.545, 1.175)
= 333) included in the meta-analysis, and
FIGURES 2 through 6 depict these values in
Overall 333 0.350 (0.079, 0.861)
forest plots. Due to the 100% sensitiv-
ity of ultrasound testing reported in the
study by Nitz and Scoville,31 an accurate 0.01 0.10 1.00 10.00
DOR could not be calculated and was
therefore not included in tabulated or FIGURE 5. Negative likelihood ratio and 95% confidence interval data for therapeutic ultrasound to diagnose stress
pooled results. All other meta-analytical fractures in the lower limb.
statistics were calculated for all included
studies examining ultrasound. Our analy- Study Name n Confidence Interval
sis of the diagnostic ability of ultrasound
demonstrated low to moderate pooled Boam (1996) 78 1.078 (0.372, 2.457)
sensitivity (64%; 95% CI: 55%, 73%) and
specificity (63%; 95% CI: 54%, 71%). Devereaux (1984) 18 2.025 (0.118, 7.272)
Data pertaining to the tuning fork
test were not pooled using meta-analysis, Giladi (1984) 106 6.646 (2.741, 14.100)
due to an insufficient number of studies
meeting the inclusion criteria for this Lowdon (1986) 32 26.950 (3.609, 114.600)
review (n = 2). Lesho26 conducted the
tuning fork test using a 128-Hz tuning Moss (1983) 19 171.200 (3.794, 539.900)

fork, whereas Wilder et al51 investigated


Romani (2000) 26 3.372 (0.024, 16.420)
the diagnostic ability of forks of 3 dif-
ferent frequencies (128 Hz, 256 Hz, and
Overall 279 6.199 (0.697, 22.750)
512 Hz) against 3 radiological reference
tests. The 256-Hz tuning fork test, com-
pared to radiography, MRI, and bone 1 10 100 1000
scintigraphy, had the highest sensitivity
values (92.3%, 90.0%, and 77.7%, re- FIGURE 6. Diagnostic odds ratio and 95% confidence interval data for therapeutic ultrasound to diagnose stress
spectively), the lowest specificity values fractures in the lower limb.

(19.3%, 20.0%, and 25.0%, respectively),


and +LRs between 1.04 and 1.14. The DISCUSSION sis can lead to increased morbidity and
study by Wilder et al51 scored poorly on possible progression to complete frac-

S
the QUADAS, with a score of 12/26. The tress fractures of the lower ture. Moreover, the ability to rule out a
study by Lesho26 had a QUADAS score of limb are a common injury that can stress fracture is of significant clinical
22/26 and reported 75% sensitivity and be difficult to diagnose and trouble- benefit.
67% specificity, with a +LR of 2.3 for some to manage. Early detection is con- Although diagnosis can often be con-
the 128-Hz tuning fork used to diagnose sidered vital to provide appropriate and firmed with radiological means, it is not
tibial stress fractures. informed management, as a late diagno- always practical or accessible. Referral

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TABLE 2 Study Characteristics and Participant Demographics

Authors Index Tests and Parameters Subjects Assessors Reference Standard Definition of the Positive Index Tests
Boam et al4 Ultrasound; 2.0 W/cm2; 30-s 78 patients (87% men) who were 1 sonography technician, Scintigraphy Discomfort or pain with active
application referred for bone scintiscan to rule nuclear medicine de- ultrasound application
out tibial stress fracture (mean age, partment; 1 uninvolved
24 y) party (result tabulating)
Devereaux et al13 Ultrasound; 3-cm head; 0.75 18 patients/athletes attending the Thermogram reader; Scintigraphy Very unpleasant sensation of intense
MHz; intensity increasing sports injury clinic with signs and 1 physiotherapist; pressure or pain with ultrasound
from 0 to 2.0 W/cm2 symptoms of stress fracture of the 1 nuclear medicine application
tibia or fibula (mean age, 23 y; range, physician
18-37 y)
Giladi et al18 Ultrasound; 2.0 W/cm2 53 male soldiers with suspected stress Not specified Roentgenogram; Complaint of acute pain or a
fracture of the tibia (mean age, 19 y; scintigraphy stabbing sensation with
range, 18-23 y) ultrasound application
Lesho26 Tuning fork; 128 Hz 52 soldiers with history and physical 6 clinicians Scintigraphy Marked exacerbation or reproduction
examination suggestive of tibial of shin pain in a localized area (3
stress fracture (mean age, 24.8 y; cm in diameter) with tuning fork
range, 19-43 y) application
Lowdon27 Ultrasound; 3-cm head; 0.75 59 patients with suspected stress 1 physiotherapist Roentgenogram; Pressure, bruising, and aching are the
MHz; intensity gradually fractures; age of patients not scintigraphy precise words needed to describe
increasing from 0 to 2.0 specified; 13 control subjects a positive ultrasound response
W/cm2
Moss and Ultrasound; 3-cm head; 0.75 35 consecutive patients (29 men) at- Not clearly specified; Roentgenogram; Very unpleasant sensation of intense
Mowat29 MHz; intensity gradually tending a sports injury clinic with his- ultrasound operator scintigraphy pressure or pain with ultrasound
increasing from 0 to 2.0 tory and clinical findings suggestive application
W/cm2 of a stress fracture of the leg (mean
age, 25 y; range, 16-51 y); 3 women
with rheumatoid arthritis (ages 25,
68, and 70) and possible stress
fracture related to osteoporosis and
treatment with corticosteroids were
also included; control group of 17 fit,
physically active subjects (mean age,
26 y; range, 16-45 y)
Nitz and Ultrasound; 2.0 to 3.0 W/cm2 54 male military basic trainees present- 2 therapists Roentgenogram Report of pain at the medial tibial
Scoville31 ing with knee pain (mean age not plateau with ultrasound
specified; range, 18-33 y) application
Romani et al36 Ultrasound; 5-cm2 head; 26 patients/subjects (12 men) recruited Not clearly specified; MRI Largest pain level reported on 100-
1 MHz; 0.0, 0.5, 1.0, 1.5, from 8 university and 2 recreational 1 radiologist mm blank visual analog scale
2.0, 2.5, and 2.9 W/cm2; activities with unilateral tibia pain with ultrasound application
30-s application (less than 2 wk duration) (mean age,
20.55 y; range, 18-31 y)
Wilder et al51 Tuning fork; 128 Hz, 256 Hz, 45 consecutive runners (42.2% men) 1 clinician Roentgenogram; MRI; Pain reported with tuning fork
512 Hz; 10-s application suspected of having stress fractures scintigraphy application on a standardized
(mean  SD age, 31.2  13.1 y) pain rating scale (0-4)
Abbreviations: MRI, magnetic resonance imaging; SD, standard deviation.
*Giladi et al18 tested both tibia in 53 subjects; Lowdon27 and Moss & Mowat29 tested 32 and 19 subjects with tibial stress fractures confirmed by scintigraphy
from their respective populations of 59 and 35.

for appropriate radiology also requires ical therapy practice may be able to deter- applicability of clinical tests to diagnose
that an adequate clinical examination mine whether a stress fracture is present stress fractures of the lower limb. Re-
take place to further justify these some- independent of radiology; however, to trieved studies included investigations
times expensive investigations. It has date, this has yet to be fully validated. using therapeutic ultrasound and tuning
been proposed that common and routine This systematic review and meta-analysis forks as clinical tests.
nonradiological procedures used in phys- evaluated the available evidence on the The application of ultrasound and the

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TABLE 3 QUADAS Scores for Each of the Included Studies

Item
Authors 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Total
Boam et al4 N, 0 N, 0 Y, 2 Y, 1 Y, 3 Y, 2 Y, 1 Y, 1 Y, 1 Y, 3 Y, 3 U, 0 Y, 1 Y, 1 19
Devereaux et al13 Y, 3 Y, 1 Y, 2 U, 0 Y, 3 Y, 2 Y, 1 Y, 1 Y, 1 U, 0 U, 0 Y, 3 Y, 1 Y, 1 19
Giladi et al18 Y, 3 U, 0 Y, 2 U, 0 Y, 3 Y, 2 Y, 1 U, 0 Y, 1 U, 0 U, 0 U, 0 Y, 1 Y, 1 14
Lesho26 Y, 3 Y, 1 Y, 2 N, 0 Y, 3 Y, 2 Y, 1 Y, 1 Y, 1 Y, 3 U, 0 Y, 3 Y, 1 Y, 1 22
Lowdon27 U, 0 U, 0 Y, 2 U, 0 N, 0 N, 0 Y, 1 Y, 1 Y, 1 U, 0 U, 0 U, 0 Y, 1 Y, 1 7
Moss and Mowat29 Y, 3 Y, 1 Y, 2 U, 0 N, 0 N, 0 Y, 1 Y, 1 Y, 1 Y, 3 U, 0 Y, 3 U, 0 U, 0 15
Nitz and Scoville31 Y, 3 Y, 1 N, 0 Y, 1 Y, 3 Y, 2 Y, 1 U, 0 Y, 1 Y, 3 U, 0 N, 0 Y, 1 Y, 1 17
Romani et al36 Y, 3 Y, 1 Y, 2 Y, 1 Y, 3 Y, 2 Y, 1 Y, 1 Y, 1 U, 0 Y, 3 Y, 3 Y, 1 Y, 1 23
Wilder et al51 Y, 3 Y, 1 Y, 2 N, 0 N, 0 N, 0 Y, 1 Y, 1 Y, 1 Y, 3 U, 0 U, 0 U, 0 U, 0 12
Percent agreement* 100 66.7 77.8 55.6 100 88.9 100 100 100 100 88.9 66.7 77.8 100 …
Abbreviations: N, no; U, unclear; Y, yes.
*Percent agreement between reviewers.

vibration produced by tuning forks over performance of these measures for a posi- results are therefore discussed. Lesho26
superficial stress fracture sites have been tive test to identify a stress fracture and reported moderate to high sensitivity
commonly reported to elicit pain,36,45 due a negative test to rule out a stress frac- (75%), moderate specificity (67%), and
to the accelerated osteoclastic resorption ture, it is important to note that the +LR a +LR of 2.3 for a 128-Hz tuning fork,
that occurs during the development of a (2.09) and –LR (0.35), which are consid- demonstrating a small but sometimes
stress fracture, leading to periosteal dam- ered more clinically relevant measures important ability to identify a stress frac-
age. This increased resorption results of a test’s diagnostic ability, were small ture. The high score on the QUADAS tool
in greater heat absorption at the stress (TABLE 1). The 95% CI (0.7, 22.75) associ- indicates that these results are less likely
fracture site, which corresponds to an in- ated with the pooled DOR (6.2) was very to be subject to bias.
crease in pain produced with ultrasound wide and included values considered to The study by Wilder et al51 scored
application.36 The mechanism on which be clinically useless (1.0), as well as those poorly on the QUADAS tool (12/26),
tuning fork application evokes pain at with substantial clinical utility (greater mainly due to unclear reporting of many
a stress fracture site differs from that of than 20). This indicates that these results results, suggesting a high chance of bias.
ultrasound, as it is due to the vibratory are too imprecise to draw any conclusion These authors51 investigated the diagnos-
irritation of the damaged periosteum.45 about the usefulness of ultrasound to ac- tic ability of 128-Hz, 256-Hz, and 512-Hz
An intact periosteum, or periosteum in curately diagnose a stress fracture of the tuning forks, comparing the results to 3
callus formation, is not affected by tun- lower limb in clinical practice. Addition- separate radiological reference tests.
ing fork vibrations and does not absorb ally, when studies were considered indi- The 256-Hz tuning fork had the high-
sufficient energy from ultrasound to elicit vidually, 4 of the ultrasound studies that est reported sensitivity (92.3%, 90.0%,
a painful response.36 This suggests that reported higher +LRs18,27,29,31 received rel- and 77.7%) when compared to roent-
the application of ultrasound or vibra- atively low QUADAS scores, specifically, genograms, MRI, and bone scintigraphy,
tion from a tuning fork may cause pain due to poorly described participant selec- respectively, usually indicating a high
over stress fracture sites but not over ar- tion and index testing. This suggests that probability of ruling out a stress frac-
eas without bony change or healed frac- caution should be taken when interpret- ture if the test is negative. However, the
tures.1,26 Therefore, a time delay between ing results from these studies due to po- specificity values were low for the 256-Hz
the application of the index and reference tential bias and validity issues. Moreover, tuning fork, suggesting difficulty diag-
tests, which was identified in some of the the 3 studies that scored relatively high nosing a stress fracture when the test is
articles, might have negatively affected on the QUADAS tool4,13,36 (suggesting less positive. The other tuning fork frequen-
the results. bias in the reporting of the results) had cies studied had lower sensitivities and
The results of the meta-analysis for very small +LRs. higher specificities, and the +LRs for all
the ultrasound data indicated a pooled We were unable to perform a meta- frequencies were small to very small, sug-
sensitivity of 64% and specificity of 63%. analysis on the retrieved studies that gesting a limited ability of tuning forks to
Although this suggests a low to moderate investigated tuning forks, and individual diagnose stress fractures independent of

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[ research report ]

TABLE 4 Summary of Diagnostic Accuracy Values

QUADAS
Sensitivity Specificity Score
Authors Application Site Tests (95% CI) (95% CI) +LR (95% CI) –LR (95% CI) DOR (95% CI) (26/26)
Boam et al4 Tibia Ultrasound, scintigraphy 43 (27, 61) 48 (34, 64) 1.07 (0.63, 1.72) 1.04 (0.67, 1.56) 1.08 (0.37, 2.46) 21
Devereaux et al13 Tibia, fibula Ultrasound, radiography, 53 (28, 78) 0 (0, 70) 1.41 (0.55, 2.81) 1.34 (0.33, 5.86) 2.03 (0.12, 7.27) 19
thermography,
scintigraphy
Giladi et al18 Tibia Ultrasound, radiography, 75 (60, 85) 67 (53, 79) 2.27 (1.57, 3.31) 0.37 (0.21, 0.57) 6.65 (2.74, 14.10) 14
scintigraphy
Lesho26 Tibia Tuning fork, scintigraphy 75 67 2.3 (1.10, 4.60) 0.37 (0.10, 0.71) ... 22
Lowdon27 Unclear, leg Ultrasound, radiography, 90 (67, 98) 75 (43, 93) 2.97 (1.62, 5.56) 0.17 (0.04, 0.39) 26.95 (3.61, 7
scintigraphy 114.60)
Moss and Mowat29 Unclear, leg Ultrasound, radiography, 91 (57, 100) 100 (60, 100) 3.67 (1.73, 8.18) 0.16 (0.02, 0.41) 171.20 (3.79, 15
scintigraphy 539.90)
Nitz and Scoville31 Medial tibial plateau Ultrasound, radiography 100 (88, 100) 80 (56, 94) 3.33 (2.14, 5.07) 0.06 (0.00, 0.17) ... 17
Romani et al36 Tibia Ultrasound, MRI 0 (0, 49) 100 (80, 100) 1.71 (0.33, 4.40) 0.91 (0.55, 1.18) 3.37 (0.02, 23
16.42)
Wilder et al51 Tibia, fibula, meta- Tuning fork, roent- ... ... ... ... ... 12
tarsal, calcaneus, genogram, MRI,
navicular, talus, scintigraphy
tarsal, phalanx
128 Hz ... ... R, 83; MRI, R, 38; MRI, R, 1.33 (0.92, 1.93); R, 0.44 (0.11, 1.74); ... ...
80; S, 71 50; S, 60 MRI, 1.60 (0.68, MRI, 0.40 (0.08,
3.77); S, 1.76 (0.58, 1.92); S, 0.49 (0.18,
5.40) 1.33)
256 Hz ... ... R, 92; MRI, R, 19; MRI, 20; R, 1.14 (0.91, 1.45); R, 0.40 (0.05, 3.40); ... ...
90; S, 78 S, 25 MRI, 1.08 (0.71, MRI, 0.60 (0.02,
1.63); S, 1.04 (0.56, 19.72); S, 0.89 (0.09,
1.92) 9.17
512 Hz ... ... R, 77; MRI, 50; R, 65; MRI, 83; R, 2.17 (1.24, 3.80); R, 0.36 (0.13, 1.00); ... ...
S, 35 S, 40 MRI, 3.00 (0.45, MRI, 0.60 (0.30,
19.90); S, 0.59 1.19); S, 1.62 (0.63,
(0.22, 1.54) 4.14)
Pooled (ultrasound … … 64 (55, 73) 63 (54, 71) 2.09 (1.10, 3.52) 0.35 (0.08, 0.86) 6.20 (0.70, …
studies only) 22.75)
Abbreviations: CI, confidence interval; DOR, diagnostic odds ratio; LR, likelihood ratio; MRI, magnetic resonance imaging; QUADAS, Quality Assessment of
Diagnostic Accuracy Studies; R, radiography; S, scintigraphy.

all 3 reference standards used. Addition- may not be conclusive and, at worst, tun- pable thickening or swelling of the peri-
ally, the –LRs for all tuning fork frequen- ing forks may have limited clinical utili- osteum over the subcutaneous bone.8,15,36
cies were small to very small, with some zation in the diagnosis of stress fractures However, no studies evaluating these
tests returning a –LR greater than 1. A of the lower limb. clinical testing procedures met the inclu-
–LR greater than 1 means that a negative This systematic review only evaluated sion criteria for this review.
test is more likely to occur in people with 2 of the tests commonly proposed to di- Limitations exist in most studies,
the condition than in people without the agnose lower-limb stress fractures. Other and these are also acknowledged in this
condition.1 signs on clinical examination that have systematic review. All studies reviewed
Due to the heterogeneity of the study been suggested to identify stress frac- examined athletes and/or military per-
results reported for tuning forks, the fact tures include localized bony tenderness, sonnel, confirming that these popula-
that the authors did not report CIs for pain on palpation over superficial stress tions are at risk for the development of
sensitivity and specificity, and the poor fracture sites,3,8,11,15,30,32 pain on loading or lower-limb stress fractures. Although
LRs for both studies, at best, these results impact of the affected bone,11,15,32 and pal- this makes the results applicable to these

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specific populations, the results cannot be homogeneity within the literature. An change in the stage of stress fracture pa-
generalized to other populations that also additional limitation is due to the time thology. Additionally, methods reported
have a high incidence of stress fractures, frame of the reviewed studies, as recent in the literature of obtaining patient re-
including those with underlying patholo- advances in the technical capacity of ra- sponses to the application of ultrasound
gies such as osteoporosis,17,39,48 rheuma- diological imaging have likely contribut- or tuning forks vary, as these rely on the
toid arthritis,10,11,39 and cancer.22 ed to the heterogeneity of the reference patient’s reported response, which is not
The insertion of dummy values into data available for this review. dependable and is based on the individ-
unpopulated cells to allow computation Inconsistencies also exist between ual’s interpretation of the rating method
of data in the meta-analysis might also definitions of a stress reaction and stress used,18 the individual’s cooperation, and
be considered a limitation of this review. fracture in the literature, making compar- other nonspecific factors such as pain tol-
Although the use of diminutive values in ison of study results sometimes difficult. erance and motivation. A common pain
contingency tables is common practice in An accepted definition for the 2 terms or sensation rating scale should be uti-
logistic regression models,42 meta-analy- would allow for more agreement be- lized in future studies to monitor patient
sis of diagnostic studies is rare, and this tween results and comparability between responses and to allow for more accurate
approach has not yet been fully validated, studies, as it would be clear what patho- testing in the clinical setting.27,36
despite the meta-analysis computer soft- logical stage of stress fracture was being
ware that does this by default. An inher- investigated. The use of 1 consistent gold CONCLUSION
ent limitation in any meta-analysis is that standard reference test would also allow

T
it requires the elimination of publication for more comparability between stud- o our knowledge, this is the
bias to obtain valid estimates21,38; howev- ies. There has been previous contention first review to systematically evalu-
er, this bias is suggested to be problem- within the literature as to whether MRI ate studies investigating the clinical
atic in all studies, whether randomized or scintigraphy is the most appropriate diagnosis of lower-limb stress fractures.
trials, observational studies, or diagnostic form of radiological imaging to identify The strengths of this study are in its sys-
studies. a stress fracture.5,18,26 However, it has re- tematic search of the literature, the use
Two types of heterogeneity also con- cently been suggested that single-photon of meta-analytical methods to pool di-
tribute to the limitations of this review.20 emission computed tomography may be agnostic data, and the use of a quality-
Clinical heterogeneity may exist due to more effective than MRI and scintigra- assurance tool (QUADAS) to evaluate all
the mixed nature of the populations in phy in the identification of lower-limb included articles. The results of this study
the contributing studies, whereas statisti- stress fractures.9 Single-photon emission do not support the specific use of ultra-
cal heterogeneity may exist due to the in- computed tomography has been shown to sound as a standalone diagnostic test for
consistent results reported across studies, have higher sensitivity and accuracy than lower-limb stress fractures. Additionally,
which was clearly the case in this review. scintigraphy alone in the evaluation and the literature supporting the use of tun-
Although MetaAnalyst is one of the few grading of femoral neck stress fractures. 9 ing forks needs to be interpreted with
programs that allow meta-analysis of di- The use of single-photon emission com- caution, considering the limited number
agnostic studies, it does not compute the puted tomography should be investigated of studies investigating this modality, the
I2 statistic. Quantification of the degree of in future studies to determine its ability differing results between different tun-
heterogeneity of the studies in this meta- to be used as a gold standard measure ing fork frequencies, and the reference
analysis could not be done. Furthermore, when diagnosing stress fractures.9 standard used. As the overall diagnostic
the extended time frame (1980-2009) of Recommendations for future research accuracy of the tests investigated is not
the reviewed studies resulted in the use can be proposed from the findings of this strong, based on the calculated LRs, it is
of different statistics and methodologies systematic review. First, the test param- recommended that radiological imaging
for the diagnostic studies. Therefore, the eters utilized when applying ultrasound36 should continue to be used for the confir-
results of this meta-analysis need to be and tuning forks need to be fully stan- mation and diagnosis of stress fractures
interpreted with caution. It is recom- dardized and reported6 to allow for test of the lower limb. t
mended that future studies use the Stan- reproducibility and conformity through-
dards for the Reporting of Diagnostic out the literature. Second, it is suggested KEY POINTS
Accuracy checklist to improve the accu- that well-defined methods and larger FINDINGS: This review does not support
racy and completeness of diagnostic ac- sample sizes be incorporated into future the use of therapeutic ultrasound or
curacy studies and their reporting.6 The research. Third, reference testing and in- tuning forks as a standalone test for the
use of the Standards for the Reporting dex testing need to be undertaken within diagnosis of lower-limb stress fractures.
of Diagnostic Accuracy checklist would an appropriate time frame to ensure IMPLICATIONS: Evaluation of the validity
allow for improved reproducibility and that both tests are completed without a of diagnostic tests provides clinicians

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[ research report ]
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@ MORE INFORMATION
Orthop (Belle Mead NJ). 2001;30:848-860. org/10.1186/1471-2288-5-19
47. Wallace BC, Schmid CH, Lau J, Trikalinos TA. 50. Whiting P, Rutjes AW, Reitsma JB, Bossuyt PM,
Meta-Analyst: software for meta-analysis of Kleijnen J. The development of QUADAS: a tool WWW.JOSPT.ORG

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