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COPYRIGHT © 2005 BY THE JOURNAL OF BONE AND JOINT SURGERY, INCORPORATED

THE ACCURACY OF DIAGNOSTIC IMAGING

FOR THE ASSESSMENT OF CHRONIC
OSTEOMYELITIS: A SYSTEMATIC REVIEW
AND META-ANALYSIS
BY M.F. TERMAAT, MD, P.G.H.M. RAIJMAKERS, MD, PHD, H.J. SCHOLTEN, MD,
F.C. BAKKER, MD, PHD, P. PATKA, MD, PHD, AND H.J.T.M. HAARMAN, MD, PHD
Investigation performed at the Departments of Surgery and Traumatology and Nuclear Medicine,
VU University Medical Center, Amsterdam, The Netherlands

Background: A variety of diagnostic imaging techniques is available for excluding or confirming chronic
osteomyelitis. Un-til now, an evidence-based algorithmic model for choosing the most suitable imaging
technique has been lacking. The ob-jective of this study was to determine the accuracy of current imaging
modalities in the diagnosis of chronic osteomyelitis.
Methods: A systematic review and meta-analysis of the literature was conducted with a comprehensive
search of the MEDLINE, EMBASE, and Current Contents databases to identify clinical studies on chronic
osteomyelitis that evaluated di-agnostic imaging modalities. The value of each imaging technique was
studied by determining its sensitivity and specificity compared with the results of histological analysis,
findings on culture, and clinical follow-up of more than six months.
Results: A total of twenty-three clinical studies in which the accuracy was described for radiography (two
studies), magnetic resonance imaging (five), computed tomography (one), bone scintigraphy (seven),
leukocyte scintigraphy (thirteen), gallium scintigraphy (one), combined bone and leukocyte scintigraphy
(six), combined bone and gallium scintigraphy (three), and fluorodeoxyglucose positron emission
tomography (four) were included in the review. No meta-analysis was performed with respect to computed
tomography, gallium scintigraphy, and radiography. Pooled sensitivity demonstrated that
fluorodeoxyglucose positron emission tomography was the most sensitive technique, with a sensitivity of
96% (95% confidence interval, 88% to 99%) compared with 82% (95% confidence interval, 70% to 89%)
for bone scintigraphy, 61% (95% confidence interval, 43% to 76%) for leukocyte scintigraphy, 78% (95%
confi-dence interval, 72% to 83%) for combined bone and leukocyte scintigraphy, and 84% (95%
confidence interval, 69% to 92%) for magnetic resonance imaging. Pooled specificity demonstrated that
bone scintigraphy had the lowest spec-ificity, with a specificity of 25% (95% confidence interval, 16% to
36%) compared with 60% (95% confidence interval, 38% to 78%) for magnetic resonance imaging, 77%
(95% confidence interval, 63% to 87%) for leukocyte scintigraphy, 84% (95% confidence interval, 75% to
90%) for combined bone and leukocyte scintigraphy, and 91% (95% confidence interval, 81% to 95%) for
fluorodeoxyglucose positron emission tomography. The sensitivity of leukocyte scintigraphy in detecting
chronic osteomyelitis in the peripheral skeleton was 84% (95% confidence interval, 72% to 91%) com-
pared with 21% (95% confidence interval, 11% to 38%) for its detection of chronic osteomyelitis in the
axial skeleton. The specificity of leukocyte scintigraphy in the axial skeleton was 60% (95% confidence
interval, 39% to 78%) com-pared with 80% (95% confidence interval, 61% to 91%) for the peripheral
skeleton.

Conclusions: Fluorodeoxyglucose positron emission tomography has the highest diagnostic accuracy for
confirming or excluding the diagnosis of chronic osteomyelitis. Leukocyte scintigraphy has an appropriate
diagnostic accuracy in the peripheral skeleton, but fluorodeoxyglucose positron emission tomography is
superior for detecting chronic osteo-myelitis in the axial skeleton.
Level of Evidence: Diagnostic Level III. See Instructions to Authors for a complete description of levels of
evidence.
I nfections involving bone continue to be a common prob-lem in
clinical practice. Despite the effectiveness of sur-gical
small percentage of infections remain refractory to therapy,
leading to chronic osteomyelitis.
management and long-term antibiotic regimens, a Several classification systems for osteomyelitis based on
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the etiology, or the physiology of the host, or on soft-tissue and
osseous defects1-4 have been published. Weiland et al. were the
first to establish the use of a period of six months to distinguish
between acute and chronic osteomyelitis 5. Schauwecker stated
that osteomyelitis requiring more than one episode of treat-ment
and/or a persistent infection lasting more than six weeks should
be considered chronic6. In our opinion, the definition used by
Schauwecker provides a clear cutoff for acute and chronic
osteomyelitis, and the essence of the six-week period is that it is
more than three times longer than the ten-day period during
which bone necrosis occurs in acute osteomyelitis. In contrast to
acute purulent osteomyelitis, chronic osteomyelitis is
characterized by a low-grade presentation, with lymphocyte and
plasma cell infiltrates with variable degrees of necrosis and
osteosclerosis. This definition of chronic osteomyelitis in-volves
patients in whom osteomyelitis is persistent despite ade-quate
therapy or in whom the diagnosis of recurrent bone infection is
being considered. The diagnosis is difficult in these patients as
chronic bone infection alters the normal anatomy and physiology
of bone. These changes and the low-grade pre-sentation require
the utmost in diagnostic accuracy. Therefore, this meta-analysis
focused on patients with chronic osteomy-elitis, as early
diagnosis is the cornerstone of management. In most patients,
additional diagnostic imaging is essential to es-tablish or rule out
an active infection7,8.
Although a variety of imaging techniques is available,
it is often difficult to choose the most appropriate technique if
bone has been altered by previous infections, or bone regen-
eration, or if there are metallic implants 7,8. The ideal imaging
technique should have a high sensitivity and specificity, and
numerous studies have been published concerning the accu-
racy of the various modalities in diagnosing chronic osteomy-
elitis. The objective of the present systematic review and
meta-analysis was to determine the accuracy of current clini-
cal imaging modalities in diagnosing chronic osteomyelitis.
Materials and Methods
Search Criteria
T he diagnostic imaging techniques that were reviewed for the
assessment of chronic osteomyelitis were radiography, computed
tomography, magnetic resonance imaging, leuko-cyte scintigraphy,
bone scintigraphy, gallium scintigraphy, fluorodeoxyglucose
positron emission tomography, and com-bined techniques, such as
combined bone and leukocyte scin-
tigraphy, and combined bone and gallium scintigraphy.
Search Strategy
A computer-aided search of the MEDLINE (from 1975), EM-
BASE (from 1980), and Current Contents databases was con-
ducted in October 2002 and was updated in July 2003 (see
Appendix). The search was restricted to primary studies that
were written in English and involved adults who were more
than nineteen years old. The search strategy of Mijnhout et al.
was used to develop a specific search strategy for each data-
base (Fig. 1)9. The reference lists of the identified studies and
relevant reviews were hand-searched for additional eligible
TH E AC C U R A C Y O F DI A G N O S T I C IM A G I N G F O R T H E AS S E S S M E N T
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studies, which were included in the final study selection.
Study Selection
Studies were eligible if they met the following inclusion crite-
ria. (1) The study was a clinical investigation that evaluated the
specified diagnostic index tests in patients with chronic osteo-
myelitis, which was defined as osteomyelitis requiring more than
one episode of treatment and/or a persistent infection that had
lasted for more than six weeks. (Studies that evaluated septic or
aseptic loosening of prostheses were not included.)
(2) The study group included ten patients or more. (3) The study
used a valid reference test (osteomyelitis was proven his-
tologically and/or bacteriologically, and/or there was a clinical
follow-up of more than six months in which no signs or symp-
toms of chronic infection were described). (4) Details provided
were sufficient to reconstruct a 2 × 2 contingency table express-
ing the results of the index tests by the disease status.
Exclusion criteria were (1) nonhuman studies and (2)
studies that included patients younger than nineteen years old
(because of the immaturity of the skeleton). If more than one
study by the same author was included, the absence of overlap
was carefully assessed by comparing the patient demograph-ics
or by contacting the author if these data were not provided.
The titles were screened for eligibility by one of the
reviewers (M.F.T.), and they were then processed for abstract
assessment. Two reviewers (M.F.T. and P.G.H.M.R.) indepen-
dently assessed the abstracts by consensus. All studies consid-
ered eligible or of dubious eligibility were retrieved, and the
final decision on inclusion was based on the full article.
Methodological Quality Assessment
The methodological quality of the studies was graded inde-
pendently by the same two reviewers (M.F.T. and
P.G.H.M.R.), using the criteria list for evaluating the internal
and external validity of diagnostic studies recommended by
the Cochrane Methods Group on Systematic Review of
Screening and Diag-nostic Tests (www.cochrane.org).
Using the above-mentioned inclusion and exclusion cri-
teria, two independent reviewers (M.F.T. and P.G.H.M.R.) se-
lected the remaining studies. Disagreement was resolved by
consensus or, if necessary, was independently settled by a third
reviewer. The internal validity criteria (A items) were used to
determine the methodological limitations of the studies, and the
external validity criteria (B and C items) were used for de-
scriptive purposes only.
Data Extraction
The two reviewers (M.F.T. and P.G.H.M.R.) independently
ex-tracted relevant data (patient characteristics,
characteristics of the index tests that were used, and outcome
parameters) from the included studies and tabulated the data
using a standard-ized form.
Statistical Methods
Qualitative Analysis
Levels of evidence were determined with use of the framework
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Fig. 1
Flowchart for the conducted search strategy. MRI = magnetic resonance imaging, CT = computed
tomography, and PET-FDG = fluorodeoxyglucose positron emission tomography.
provided by The Journal of Bone and Joint Surgery
(www.ejbjs.org). Studies, however, were not excluded from
the systematic review on the basis of quality.
Quantitative Analysis (Meta-Analysis)
The sensitivity and specificity of the index tests were deter-
mined from the number of true-positive, false-positive, true-
negative, and false-negative results from the 2 × 2
contingency table.
The statistical diagnostic heterogeneity of the sensitivity
and specificity per index test across studies was tested by the
chi-square test for independence with k-1 degrees of freedom (k
= the number of studies). In the case of heterogeneity, the
Spearman rank correlation coefficient ρ was used in order to
measure the correlation between sensitivity and specificity. A
ρ value of less than –0.40 suggests that the variation between
studies may be explained by different cutoff points, or diag-
nostic thresholds, on a summary receiver-operating character-
istic curve10,11.
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In the absence of a cutoff point difference, heterogene-ity
was explored by subgroup analysis on the basis of the a priori
hypothesis that the accuracy of a diagnostic test is in-fluenced
by the location of chronic osteomyelitis in the skele-ton (i.e., the
axial or central skeleton compared with the peripheral skeleton),
which was assessed with univariate re-gression analyses 12.
Several authors have reported that labeled leukocytes have a
diminished sensitivity for imaging chronic osteomyelitis in the
axial skeleton6,12,13. The presence of he-matopoietic bone marrow
in the axial skeleton and alterations in the microcirculation due
to chronic infection have been suggested to explain these so-
called “cold lesions.” If the included studies described the
location in sufficient detail to allow construction of 2 × 2
contingency tables for the axial and peripheral skeleton, these
data were extracted separately on the data-extraction form. The
influence of the internal (A-criteria) and external (B-criteria)
validity on diagnostic accu-racy was assessed with univariate
meta-regression analyses.
In the case of statistical heterogeneity of one or more of
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TH E JO U R N A L O F BO N E & JO I N T SU R G E R Y · J B J S .O R G TH E AC C U R A C Y O F DI A G N O S T I C IM A G I N G F O R T H E AS S E S S M E N T
VO L U M E 87-A · NU M B E R 11 · NO V E M B E R 2005 O F CH R O N I C OS T E O M Y E L I T I S : A ME T A -AN A L Y S I S
Contents database. The total of 3384 studies, in-cluding
duplicates, formed the source population for this re-view. The
studies retrieved from MEDLINE and EMBASE showed overlap
the index tests, a random effect model was used, whereas, in the (23.1%), whereas no overlap was seen with studies retrieved
case of statistical homogeneity, a fixed effect model was used. from the Current Contents database. Of the initial 3384 studies,
3258 were excluded after review of the in-
These models calculate pooled estimates of the diag-nostic formation provided in the title and abstract.
accuracy. In addition, the models acknowledge the dif-ference in
The full articles of the remaining 126 studies (fifty-six
precision by which sensitivity and specificity were measured in
studies from MEDLINE, sixty-six from EMBASE, and four
each study (fixed effect model) and between studies (random from the Current Contents database) were reviewed for eligi-
effect model)14. Sensitivity and specificity were pooled bility. Another fifty-six articles were extracted from the refer-
independently and were weighted by the inverse of the variance,
with use of Meta-Test software (Lau J., Meta-Test version 0.6;
New England Medical Center, Boston, 1997) 15-17. Pooled
estimates are presented with 95% confidence intervals.
The logit-transformed sensitivity, specificity, and corre-
sponding 95% confidence interval of the index tests were
compared with use of z-test statistics. A p value of <0.05 was
considered significant. All statistical analyses were performed
with the SPSS for Windows software program (version
11.0.1; SPSS, Chicago, Illinois).

Results
Studies Included

T1310he studies
search strategy identified 1784 studies from MED-LINE,
from EMBASE, and 290 studies from the Current

ence lists of these articles, and thirty of them were reviewed
for inclusion. Ultimately, twenty-three studies (eighteen stud-
ies from MEDLINE, three from the reference lists, two from
EMBASE, and none from the Current Contents database)
were included in this review 6,12,18-38. There was no
disagreement between the reviewers regarding final inclusion
of the articles. The reasons for exclusion were that the study
had fewer than ten patients (10%), an insufficient or
unspecified reference test (35%), no specified definition of
chronic osteomyelitis (33%), irreproducible 2 × 2
contingency tables (21%), or a potential overlap of the
patient population (1%). A list of the excluded studies, with
reasons for their rejection, is available on request from the
corresponding author (M.F.T.). In gen-eral, no differentiation
a priori was made for the etiology of chronic osteomyelitis,
although all included studies described a patient population
with a chronic bone infection due to trauma and/or surgery
and not to hematogenous contamina-tion of bone.
Description of Study Characteristics
The twenty-three included studies described the diagnostic
accuracy of the imaging techniques for the detection of chronic
osteomyelitis with use of radiography (two stud-ies) 31,38,
magnetic resonance imaging (five)20,21,29,31,35, computed
tomography (one)31, bone scintigraphy (seven) 22,23,28,29,31,36,38,
leukocyte scintigraphy (thirteen)12,20,24,25,28-34,37,38, gallium scin-
tigraphy (one)38, combined bone and leukocyte scintigraphy
(six)6,22,26,27,33,38, combined bone and gallium scintigraphy
(three)33,36,38, and fluorodeoxyglucose positron emission to-
mography (four) . A total of 1269 diagnostic evaluations for
chronic osteomyelitis were performed in 687 patients (54%)
with disease and 582 patients (46%) without disease. The
characteristics of the studies and the diagnostic tests per-

Fig. 2
Graphs showing the pooled estimates and corresponding confidence intervals of sensitivity
and specificity for all index tests. PET = positron emission tomography; BS = bone
scintigraphy, LS = leukocyte scintigraphy, BS-LS = bone and leukocyte scintigraphy, BS-Ga =
bone and gallium scintigraphy, and MRI = magnetic resonance imaging.
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TABLE I Diagnostic Accuracy of Radiography, Computed Tomography, and Gallium Scintigraphy for the
Detection of Chronic Osteomyelitis
No. of Patients No. of Patients
Technique with Disease without Disease
Radiography
Al-Sheikh et al.38 10 12
(1985)
Whalen et al.31 (1991) 9 2
Gallium scintigraphy
Al-Sheikh et al.38 10 12
(1985)
Computed tomography
Whalen et al.31 (1991) 6 2
formed are summarized by technique in the Appendix.
Critical Appraisal and Methodological Quality
The internal and external validity and the reproducibility of
the studies are presented in the Appendix.
Analysis
Qualitative Analysis
All studies had a level-of-evidence rating of III, which repre-
sents a nonconsecutive study or a study without consistently
applied reference standards. In nineteen of the twenty-three
studies, the reference test was not applied independently or
blindly. In four studies, an independent blind comparison was
performed, but it was done either in nonconsecutive patients
or in a narrow spectrum of patients, all of whom had under-
gone both the diagnostic test and the reference test.
Quantitative Analysis (Meta-Analysis)
Four studies (two involving radiography; one, gallium scintig-
raphy; and one, computed tomography) were excluded from the
analysis because they included too few patients (Table I).
Meta-analysis was performed for fluorodeoxyglucose
positron emission tomography, bone scintigraphy, leukocyte
scintigraphy, combined bone and leukocyte scintigraphy,
combined bone and gallium scintigraphy, and magnetic reso-
nance imaging. The sensitivity and specificity of the studies
according to the index test and the pooled estimates by ran-
dom effects analysis are described in the Appendix. The
pooled estimates of the diagnostic accuracy of all index tests
are given in Figure 2. Although included in the meta-analysis
of sensitivity, five studies were excluded from the analysis of
specificity because they did not provide information about
the proportion of patients without disease.
Fluorodeoxyglucose Positron Emission Tomography
The sensitivity and specificity of fluorodeoxyglucose positron
emission tomography were homogeneous (Q sens = 0.23, Qspec =
0.51: three degrees of freedom). The pooled sensitivity of
fluorodeoxyglucose positron emission tomography was sig-
nificantly higher than that of the other tests (p < 0.05). The
specificity of fluorodeoxyglucose positron emission tomogra-
phy was significantly higher than that of leukocyte scintig-
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Sensitivity Specificity
(95% Confidence Interval) (95% Confidence Interval)
0.60 (0.28-0.86) 0.67 (0.36-0.89)
0.78 (0.40-0.96) 1.00 (0.16-1.00)
0.80 (0.44-0.96) 0.42 (0.17-0.71)
0.67 (0.24-0.94) 0.50 (0.03-0.97)
raphy (p = 0.033), bone scintigraphy (p = 0.0001), and
magnetic resonance imaging (p = 0.0011), but it was not
found to be significantly different from that of combined
bone and leukocyte scintigraphy (p = 0.17) and combined
bone and gallium scintigraphy (p = 0.10).
Bone Scintigraphy
The sensitivity and specificity of bone scintigraphy were ho-
mogeneous (Qsens = 9.34: seven degrees of freedom, Q spec =
6.86: six degrees of freedom). The sensitivity of bone scintig-
raphy was significantly higher than that of leukocyte
scintigra-phy (p = 0.027), but it was not different from that of
the combined techniques or magnetic resonance imaging.
Leukocyte Scintigraphy
The sensitivity and specificity of leukocyte scintigraphy were
heterogeneous (Qsens = 54.46: twelve degrees of freedom, Qspec =
20.39: ten degrees of freedom). The Spearman correlation fac-tor
was –0.032, indicating that the heterogeneity could not be
explained by different cutoff points. The meta-regression re-
vealed a significant association between the variance in the ac-
curacy of leukocyte scintigraphy with the location of chronic
osteomyelitis in the skeleton (axial versus peripheral skeleton) (p
< 0.05), but not with any of the other covariates.
The sensitivity of leukocyte scintigraphy was not
signifi-cantly different from that of combined bone and
gallium scin-tigraphy (p = 0.78) and was significantly lower
than that of the other tests (p < 0.05). No significant
difference in specificity was detected between leukocyte
scintigraphy and combined bone and leukocyte scintigraphy
(p = 0.32), combined bone and gallium scintigraphy (p =
0.16), or magnetic resonance imaging (p = 0.94).
Subgroup Analysis of Leukocyte Scintigraphy
The sensitivity and specificity of leukocyte scintigraphy were
homogeneous for the axial skeleton (Qsens, axial = 7.65: five de-
grees of freedom, Qspec, axial = 7.96: four degrees of freedom). In
contrast, the sensitivity was homogeneous but the specificity
was heterogeneous for detecting chronic osteomyelitis in the
peripheral skeleton (Qsens, peripheral = 10.99, Qspec, peripheral = 15.39: six
degrees of freedom). The sensitivity of leukocyte scintigraphy
in the axial skeleton was significantly lower than that in the
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peripheral skeleton (p = 0.0010), whereas the difference in
specificity was not significant. The sensitivity of leukocyte
scintigraphy in the axial skeleton was significantly lower than
that of the other techniques, whereas the sensitivity in the pe-
ripheral skeleton was not significantly different from that of
the other techniques except for fluorodeoxyglucose positron
emission tomography.
Combined Bone and Leukocyte Scintigraphy
The sensitivity of combined bone and leukocyte scintigraphy
was homogeneous (Qsens = 8.90: five degrees of freedom),
whereas its specificity was heterogeneous (Q spec = 15.26: five
degrees of freedom). Combined bone and leukocyte scintigra-
phy had a significantly higher sensitivity than leukocyte scin-
tigraphy (p = 0.04) and a significantly higher specificity than
bone scintigraphy (p = 0.001). The differences in specificity
for leukocyte scintigraphy and sensitivity for bone scintigra-
phy were not significant.
Combined Bone and Gallium Scintigraphy
The sensitivity of combined bone and gallium scintigraphy
was heterogeneous (Qsens = 8.04: two degrees of freedom),
and its specificity was homogeneous (Qspec = 3.27: two
degrees of freedom). Combined bone and gallium
scintigraphy had a significantly higher specificity (p =
0.0006), but not sensitivity (p = 0.07), than bone scintigraphy
alone. The sensitivity and specificity of combined bone and
gallium scintigraphy did not significantly differ from that of
combined bone and leukocyte scintigraphy.
Magnetic Resonance Imaging
The sensitivity and specificity of magnetic resonance imag-
ing were homogeneous (Qsens = 4.62: four degrees of free-dom,
Qspec = 0.02: two degrees of freedom). The sensitivity of
magnetic resonance imaging for chronic osteomyelitis in the
peripheral skeleton was not different from that of leukocyte
scintigraphy or combined bone and gallium scintigraphy.
Discussion
This meta-analysis showed that fluorodeoxyglucose posi-tron emission
tomography is the most sensitive technique for detecting chronic
osteomyelitis and that it has a greater
specificity than leukocyte scintigraphy, bone scintigraphy, or
magnetic resonance imaging. Fluorodeoxyglucose positron
emission tomography was better than leukocyte scintigraphy
for imaging chronic osteomyelitis in the axial skeleton.
Several authors have reported a loss of sensitivity of
leukocyte scintigraphy when imaging chronic osteomyelitis
in the axial skeleton6,12,13. The nonspecific uptake of labeled
leukocytes has been suggested to be due to the presence of
hematopoietic bone marrow in the axial skeleton. The de-
creased uptake of labeled cells in infections of the axial skel-
eton, so-called “cold lesions,” is poorly understood, but
microthrombotic occlusion and inflammatory compression of
the blood vessels may prevent labeled cells from reaching the
site of infection. Indeed, the observed variance in diag-
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nostic accuracy of leukocyte scintigraphy in this meta-
analysis could be explained by the location of the chronic
osteomyeli-tis. Subgroup analyses demonstrated that the
pooled sensitiv-ity of leukocyte scintigraphy decreased
significantly (from 84% to 21%) for chronic osteomyelitis of
the peripheral and axial skeleton, respectively. Indeed,
leukocyte scintigraphy for chronic osteomyelitis in the axial
skeleton was the least sensitive of the imaging techniques.
Thus, while leukocyte scintigraphy is an accurate technique
for the detection of chronic osteomyelitis in the peripheral
skeleton, it is an inap-propriate technique for diagnosing
chronic osteomyelitis in the axial skeleton. In the studies
analyzed, white blood cells were labeled with technetium99m
or indium111, but there was no evidence that the labeling
technique affected the diag-nostic accuracy of the method.
Bone scintigraphy has been suggested to be a sensitive
technique to screen for bone alterations caused by chronic os-
teomyelitis. However, in this analysis, the sensitivity of bone
scintigraphy for chronic osteomyelitis was not significantly
different from that of leukocyte scintigraphy, and it was the least
specific of the techniques investigated. This low specific-ity has
led to the suggestion that bone scintigraphy should be combined
with other techniques, such as leukocyte scintigra-phy or
gallium scintigraphy. Although the specificity of the combined
techniques was significantly higher, it was still not significantly
different from that of leukocyte scintigraphy as a single
technique. Hence, leukocyte scintigraphy seems more
appropriate for evaluating chronic osteomyelitis, at least in the
peripheral skeleton.
Some radiographic techniques available for diagnosing
chronic osteomyelitis, such as radiography, computed tomog-
raphy, and magnetic resonance imaging, were poorly repre-
sented in this meta-analysis. Although there were several studies
of magnetic resonance imaging, there were few that described
the accuracy of radiography and computed tomography. Mag-
netic resonance imaging is very sensitive for detecting bone al-
terations, such as those that occur in chronic osteomyelitis. In
general, magnetic resonance imaging can show sites with tissue
edema and increased regional perfusion. These observations can
also be observed for a long time after bone surgery. There-fore,
magnetic resonance imaging lacks specificity unless clear
morphological signs for osteomyelitis are observed, and it is of
limited value if there are metal implants. Thus, other diag-nostic
procedures are often needed21. The sensitivity of mag-netic
resonance imaging was comparable with that of leukocyte
scintigraphy in the peripheral skeleton, although the specificity
was lower. For chronic osteomyelitis located in the axial skele-
ton, the diagnostic accuracy of fluorodeoxyglucose positron
emission tomography was significantly higher than that of
magnetic resonance imaging.
We assessed the methodological quality of the primary
studies because it affects the interpretation of results 14,39. Rather
than excluding studies of poor quality, we chose to an-alyze
each component of the study validity in a statistical re-gression
model to determine the effect of design flaws on the estimates of
diagnostic accuracy. However, differences in accu-
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racy could not be explained by regression analysis of the
methodological criteria.
In general, the methodological quality of a diagnostic
test is judged against a valid reference test with an indepen-
dent selection of subjects for the index and reference tests,
and by whether these are assessed independently of each
other. In this meta-analysis, a valid reference test was an
inclusion crite-rion, but one-third of the studies did not meet
this criterion. While most studies described the independent
selection of pa-tients for the reference test and an
independent comparison of the index test, 13% and 17% of
the studies, respectively, did not. Furthermore, few of the
primary studies described the re-producibility (interobserver
variance) of the imaging tech-nique investigated, which is a
major study limitation because diagnostic results may be
hampered by large interobserver variability.
Systematic reviews are hampered by publication bias, i.e.,
the preferential publication of studies with significant positive
results rather than those with negative results 14. How-ever, Olson
et al. found that, among submitted manuscripts, no significant
difference was detected with respect to the pub-lication rates of
those with positive results compared with those with negative
results40. Advantages of systematic reviews and meta-analyses
are an increase in statistical power and in the ability to assess
sources of heterogeneity when there is no consistency in the
reported accuracy across studies and to provide overall estimates
of diagnostic accuracy. With this approach, a ratio for clinical
decision-making on how to inter-pret and generalize these results
can be made on the aggregate of pertinent knowledge rather than
on the basis of the results of a single study or of personal
experience.
This meta-analysis demonstrated that fluorodeoxyglu-cose
positron emission tomography has the highest accuracy for
confirming or excluding the diagnosis of chronic osteomy-elitis.
Hence, on the basis of the current evidence, fluorodeox-yglucose
positron emission tomography might be used as the first choice
in a patient with a suspected chronic bone infec-tion. Because of
the limited availability of positron emission tomography
systems, leukocyte scintigraphy can be used with satisfactory
diagnostic accuracy for detecting chronic osteo-
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Appendix
The search string used to identify articles, the character-istics
of the included articles, the methodological quality
assessment criteria, and figures showing the diagnostic accu-
racy of each of the specific modalities are available with the
electronic versions of this article, on our web site at jbjs.org
(go to the article citation and click on “Supplementary Mate-
rial”) and on our quarterly CD-ROM (call our subscription
department, at 781-449-9780, to order the CD-ROM).
M.F. Termaat, MD
P.G.H.M. Raijmakers, MD, PhD
H.J. Scholten, MD
F.C. Bakker, MD, PhD
P. Patka, MD, PhD
H.J.T.M. Haarman, MD, PhD
Departments of Surgery and Traumatology (M.F.T., H.J.S., F.C.B., P.P., and
H.J.T.M.H.) and Nuclear Medicine (P.G.H.M.R.), VU University Medical
Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands. E-mail
address for M.F. Termaat: mf.termaat@vumc.nl. E-mail address for
P.G.H.M. Raijmakers: p.raijmakers@vumc.nl. E-mail address for H.J.
Scholten: h_scholten@hotmail.com. E-mail address for F.C. Bakker:
fc.bakker@vumc.nl. E-mail address for P. Patka: p.patka@vumc.nl. E-mail
address for H.J.T.M. Haarman: hjtm.haarman@vumc.nl
In support of their research or preparation of this manuscript, one or
more of the authors received grants or outside funding from The Associ-
ation of University Hospitals (VAZ) and Health Care Research Board
(CVZ). None of the authors received payments or other benefits or a
commitment or agreement to provide such benefits from a commercial
entity. No commercial entity paid or directed, or agreed to pay or direct,
any benefits to any research fund, foundation, educational institution, or
other charitable or nonprofit organization with which the authors are af-
filiated or associated.
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