Skeletal Radiol (2009) 38:425436
DOI 10.1007/s00256-008-0529-1
REVIEW ARTICLE
Bone marrow edema syndrome
Anastasios V. Korompilias & Apostolos H. Karantanas &
Marios G. Lykissas & Alexandros E. Beris
Received: 18 March 2008 / Revised: 11 May 2008 / Accepted: 18 May 2008 / Published online: 16 July 2008
# ISS 2008
Abstract Bone marrow edema syndrome (BMES) refers to
transient clinical conditions with unknown pathogenic
mechanism, such as transient osteoporosis of the hip
(TOH), regional migratory osteoporosis (RMO), and reflex
sympathetic dystrophy (RSD). BMES is primarily charac-
terized by bone marrow edema (BME) pattern. The disease
mainly affects the hip, the knee, and the ankle of middle-aged
males. Many hypotheses have been proposed to explain the
pathogenesis of the disease. Unfortunately, the etiology of
BMES remains obscure. The hallmark that separates BMES
from other conditions presented with BME pattern is its
self-limited nature. Laboratory tests usually do not
contribute to the diagnosis. Histological examination of
the lesion is unnecessary. Plain radiographs may reveal
regional osseous demineralization. Magnetic resonance
imaging is mainly used for the early diagnosis and
monitoring the progression of the disease. Early differ-
entiation from other aggressive conditions with long-term
sequelae is essential in order to avoid unnecessary
treatment. Clinical entities, such as TOH, RMO, and
RSD are spontaneously resolving, and surgical treatment
is not needed. On the other hand, early differential
diagnosis and surgical treatment in case of osteonecrosis
is of crucial importance.
A. V. Korompilias (*) : M. G. Lykissas : A. E. Beris
Department of Orthopaedic Surgery, School of Medicine,
University of Ioannina,
45110 Ioannina, Greece
e-mail: koroban@otenet.gr
A. H. Karantanas
Department of Radiology,
University of Crete School of Medicine,
Heraklion, Greece
Keywords Bone marrow edema . Regional migratory
osteoporosis . Transient osteoporosis . Reflex sympathetic
dystrophy . Osteonecrosis . MR imaging/diagnosis
Introduction
It was in 1959 when Curtiss and Kincaid described a
syndrome of transient demineralization of the hip in the
third trimester of pregnancy [1]. Since then, various terms
have been used in order to describe benign clinical entities
characterized by the common imaging finding of bone
marrow edema (BME), such as transient osteoporosis of the
hip (TOH), regional migratory osteoporosis (RMO), and
reflex sympathetic dystrophy (RSD). Hofmann et al.
proposed that such clinical conditions should be included
under the general term bone marrow edema syndrome
(BMES) [2]. It is widely accepted now that BMES
represents a distinct entity with specific clinical and imaging
features [3]. On the contrary, some authors support that this
syndrome is just an abortive form of osteonecrosis [4, 5].
When a BME pattern is present during magnetic
resonance (MR) imaging evaluation, distinction between
reversible and irreversible lesions is necessary. Clinical
entities, such as TOH, RMO, and RSD are self-limited, and
aggressive surgical treatment is not needed. On the other
hand, early diagnosis and surgical treatment in the case of
osteonecrosis is of crucial importance.
Many hypotheses have been proposed in order to explain
the pathogenesis and characteristic manifestations of the
disease, but the etiology of BMES remains unknown [6, 7].
Furthermore, the relation between each other of the clinical
entities characterized by this MR imaging abnormality is
still controversial. The BME depicted by MR imaging
could also result from other disorders such as infection,
426
inflammation, neoplasia, injury, and osteoarthritis [8]. This
article discusses the different approaches on the pathogen-
esis of the disease. The diagnostic evaluation of BMES
using clinical, radiographic, and MR imaging findings, as
well as the therapeutic concepts are also addressed.
Pathogenesis
Despite the fact that BMES is a well-described clinical
entity, its etiology and pathogenesis remain obscure. Due to
the rarity of the disease, the lack of specific symptoms on
the onset of BMES and the unpredictability of the episodes,
many patients are misdiagnosed. Moreover, there are a
limited number of extensive investigations of the pathome-
chanism of the disease. In 1959, Curtiss and Kincaid [1]
presented a neurogenic compression theory. According to
Rosen, venous obstruction and secondary localized hyper-
emia may be the cause of the transitory demineralization of
the femoral head [7]. Moreover, many authors have tried to
unify lesions characterized by BMES. For example, the
presence of the above-mentioned hyperemia in the initial
stage of the disease supported that RSD was the cause of
RMO. However, other investigators mentioned that these
two clinical entities although related, remain distinct [3].
Pathology of the proximal nerve roots has been proposed
as a possible pathogenic mechanism of BMES. Ischemic
events in the small vessels proximal to nerve roots may be the
cause of the disease. This scenario was based on electromyo-
graphic findings indicative of denervation related in location
and time to BMES attacks. Restoration in the blood flow in
the nerve roots and nerve regeneration may be responsible for
the clinical course of the disease, which usually lasts up to
9 months. Besides, recurrence of such ischemic events in
other vessels may explain the migratory character in cases of
RMO. These theories remain unproved, and therefore, further
studies are necessary in order to draw direct conclusions.
Apart from BME as shown on MR imaging, focal
osteopenia on radiographs is a typical finding. A BME
pattern on MR imaging is characterized by high signal
intensity compared with normal bone marrow on fat-
suppressed T2-w and short-tau inversion recovery (STIR)
images and low signal intensity on T1-w images. Although
typical in appearance on MR imaging, BME is a nonspe-
cific signal pattern that may be present in various diseases
[810]. Enhancement of the BME area after intravenous
administration of contrast agents is indicative of hyper-
vascularity and increased permeability of the capillary bed.
However, certain authors suggest that vasodilation and
increased permeability constitute a result and not a cause of
the BME disclosed with MR imaging.
Recent research emphasizes the role of the regional
accelerated phenomenon (RAP) activation. This hypothesis
Skeletal Radiol (2009) 38:425436
was supported by two observations: the coexistence of
systemic osteoporosis with BMES and the significantly
higher risk of developing transient osteoporosis in patients
suffering from osteogenesis imperfecta in comparison to
normal persons [11]. According to this theory, bone tissue
microdamage and consequent microfracture may be the
noxious stimuli that trigger RAP. RAP is an acceleration
process by which rate of bone modeling and remodeling in
local areas may be increased up to ten times in response to
noxious stimuli. Prolonged or exaggerated activation of
bone foci where normal bone repair mechanisms are most
active may be the cause of transient osteoporosis. In a
recent study of bone mass assessment in three cases of
RMO, Trevisan and Ortolani [6] suggested a wider
systemic bone loss with prevailing trabecular involvement.
These findings that also have been reported by others may
support Frosts theories in order to explain the interference
of local and systemic factors to both cause and reverse
osteoporosis [12]. It must be pointed out, however, that the
theory above is not able to explain why certain anatomic
areas are involved with the BMES.
Although many studies have tried to resolve the etiology
of BME syndromes, a common mechanism to explain the
pathogenesis of multiple clinical entities characterized by
regional osteoporosis and BME has not been found yet.
Diagnostic evaluation
Laboratory tests
Laboratory findings usually do not contribute to the
diagnosis. However, blood tests should be made in order
to distinguish BMES from other aggressive clinical entities,
such as metastatic carcinoma, multiple myeloma, leukemia,
multifocal osteomyelitis, and tuberculosis. Complete blood
count, erythrocyte sedimentation rate, C-reactive protein,
and serum cancer markers may be helpful. Histological
examination of the lesion is unnecessary.
Specific biochemical markers of bone formation includ-
ing bone-specific alkaline phosphatase, osteocalcin, pro-
collagen type I N-terminal propeptide, and C-terminal
cross-linking telopeptide were found to be elevated in
aspirates from the femoral head in patients with BMES
when compared to serum levels [13]. However, serum
concentration of all these bone markers was not different
from healthy individuals.
Conventional radiography
In an early stage, conventional radiographs may be normal.
Usually, at 36 weeks from the onset of the symptoms,
plain radiographs may reveal periarticular osseous demin-
Skeletal Radiol (2009) 38:425436 427

Fig. 1 A 26-year-old female

patient with a history of a
6-week left hip pain of sudden
onset and a final diagnosis of
transient osteoporosis. a The
lateral radiograph of the right
hip joint is unremarkable. b The
lateral radiograph of the left hip
joint shows marked osteopenia
of both the femoral head and
neck and the acetabulum
(arrows)

eralization (Fig. 1). Radiographic findings may be present Bone scintigraphy

weeks after the symptoms have resolved. Radiographically,
evidence of complete remineralization may delay up to
2 years.
Despite the described arthralgia and the joint effusion
that may be developed in most of the cases, the joint space
remains intact and no subchondral lesions are evident [14].
Moreover, bony margins are always preserved. Possible
complications from microdamage or stress damage are not
evident by conventional radiography.
Radiographs of patients who have transient osteoporosis
of the femoral head may reveal in later stages complete
disappearance of the osseous architecture, known as
phantom appearance of the femoral head. The trochant-
ers, the acetabula, and the iliac wings are rarely affected.
On the other hand, in patients with osteonecrosis of the
femoral head, plain radiographs show a radiolucent lesion
surrounded by a sclerotic rim. In later stages of the disease,
when subchondral bone collapse is present, a crescent
sign may develop (Fig. 2).
Bone scan using Tc99m-MDP is mainly used for the early
diagnosis of BMES because increased uptake in the
affected joint usually precedes radiological features and
can be seen within a few days after the onset of symptoms.
During the period in which clinical symptoms are present
without objective radiographic findings, bone scanning is
considered to be sensitive but not specific for the detection
of BMES. Radionuclide-increased uptake is detected in all
three phases of a three-phase bone scintigram representing
focal increase in capillary permeability and hyperemia, as
well as increased osteoblastic activity. When symptoms
subside, reduced activity on the perfusion and blood pool
phases are noted. Increased activity in the delayed bone
phase may be present for many months after the onset of
symptoms, indicating repair activity.
In addition, scintigraphy is very useful either for
monitoring the progression of the disease or for differen-
tiating BMES from other conditions that are characterized

Fig. 2 A 59-year-old man

with a history of 12-month
corticosteroid administration
due to a persistent allergic
reaction. A pain in the left hip
joint developed during the last
month. The lateral radiographs
show lysis and sclerosis in both
femoral heads (arrows in a and
b), suggesting bilateral osteo-
necrosis. The crescent sign in
the left femoral head (open
arrow) is diagnostic of advanced
osteonecrosis with subarticular
fracture but not articular
collapse
428 Skeletal Radiol (2009) 38:425436

Fig. 3 a A 54-year-old male patient with a 1-week right hip joint pain history of corticosteroid administration and a final diagnosis of
and a final diagnosis of transient osteoporosis. The bone scan (anterior avascular necrosis of the left hip. The bone scan (posterior view)
view) is showing intense uptake in the femoral head and neck, early in shows increased uptake only in the femoral head area with a cold in
the course of the disease (arrow). b A 36-year-old patient with a hot appearance (arrow)

by regional osteopenia. Clinical entities that should be abnormalities. BMES is primarily characterized by BME
distinguished from BMES by using bone scintigraphy that is not visible with radiographs or CT scan. MR
include osteonecrosis of the femoral head, stress fracture imaging is the only imaging modality that permits direct
of the femoral neck, and osteomyelitis. In transient lesions detection of BME [2]. In the presence of BME, MR
bone scintigraphy may reveal a homogenous, diffuse-
increased uptake. In the case of TOH, this involves the
entire femoral head and neck (Fig. 3a). Controversially, in
osteonecrosis of the femoral head, the radionuclide uptake
is less intense and limited to the femoral head (Fig. 3b). In
the early stages of osteonecrosis, an important element of
the radionuclide bone scan evaluation is the presence of a
cold spot resulting from decreased isotope uptake over the
anterosuperior region of the femoral head (Fig. 3b).
Abnormal findings for osteomyelitis include a positive
three-phase bone scintigraphy on all three phases with the
intensity of the uptake to be more focal at a specific area of
the femoral head. The disappointing specificity, though,
necessitates the application of additional imaging modalities.

Computed tomography

Computed tomography (CT) is unable to detect BMES

abnormalities with sufficient sensitivity. However, CT scan
may sometimes reveal demineralization in the early stages
of the disease when plain-film radiographs are reported as
normal [15]. CT may be useful in patients with contra-
indications to undergo MR imaging study. According to
Horiuchi et al. [16], CT findings such as several spotty
defects without any cortex participation may be useful for
distinguishing BMES from other clinical entities (Fig. 4).
Fig. 4 A 40-year-old man with transient osteoporosis of the left hip. a
Magnetic resonance imaging The plain AP radiograph shows osteopenia of the outer part of the left
femoral head (arrow). b The corresponding CT scan obtained on the
same day shows to better advantage the marked osteopenia of the left
During the last years, MR imaging has been the imaging femoral head with mottled or moth-eaten pattern of the trabecular
study of choice to evaluate patients with bone marrow bone (arrows)
Skeletal Radiol (2009) 38:425436 429

imaging scans reveal low-signal intensity on T1-w images
and high signal intensity on STIR or fat-suppressed T2-
w images (Fig. 5) [17]. These changes reflect the increased
content in intra- and extracellular fluid of the bone marrow
resulting from new bone formation and repair processes.
Joint effusion may also be present.
Similar abnormal signal intensity may indicate BME
secondary to an ischemic process, such as osteonecrosis. It
has been supported but not widely accepted that MR
imaging findings in early stages of osteonecrosis may
simulate transient osteoporosis [16]. In these cases, differ-
entiation between irreversible and transient lesions should
be made based on specific imaging features. Van de Berg et
al. [18], in order to determine the MR imaging features that
most reliably distinguish these lesions, reviewed MR
images of 72 femoral head lesions with BME pattern.
According to their study, the lack of additional subchondral
changes other than BME on both T2-w and contrast-
enhanced T1-weighted images had positive predictive value
for transient lesions up to 100%. On the contrary, the
presence of a subchondral area of low signal intensity at
least 4 mm thick on either T2-w or contrast-enhanced T1-
weighted images had a strong positive predictive value for
irreversible lesions. Moreover, contour deformity and
subchondral low signal intensity areas were more frequent-
ly found in irreversible lesions. In these cases, no visible
reactive interface between necrotic and viable tissue is
observed. It must be stressed though that an irreversible
pattern is not synonymous with osteonecrosis. It could
be the end result of an insufficiency fracture of a long-
standing transient osteoporosis that was not treated with
proper weight-bearing protection. Reversibility of the
findings without persistent abnormalities suggests BME
pattern due to transient lesions.
Bone densitometry
The relationship between generalized osteoporosis and
osteopenia associated with BMES has been reported by
many authors (Fig. 6) [6, 15]. However, only few cases
using quantitative methods for bone mass assessment have
been described in the literature [6]. It is unlikely though that
the middle-aged men quite commonly affected with BMES
do indeed suffer from systemic osteopenia. One recent
study showed that, in patients with acute non traumatic
BMES in the knee, the generalized osteopenia or osteopo-
rosis is associated with a greater risk of articular collapse,
and thus, bone mineral densitometry could stand as
predictor of outcome [19]. There are indications that
systemic osteoporosis may be observed in patients with
RMO, even in young age groups [5, 20].
Differential diagnosis
Herein, the most common entities presented with a BME
pattern are briefly addressed. Differential diagnosis includes
the following.

Fig. 5 Same patient as in

Fig. 3a. a The coronal
T1-w TSE MR image shows
low signal intensity in the right
femoral head. The transverse
fat-suppressed T2-w TSE (b)
and the coronal STIR (c) MR
images demonstrate the same
area with high signal intensity in
keeping with bone marrow
edema. A moderate joint
effusion is also evident
430
Fig. 6 A 35-year-old male patient with regional migrational osteoporosis. Both the spinal (Z score=3.3) and hip (Z score=2.6) DEXA studies
show marked osteoporosis at 16 months after the onset of symptoms
Transient osteoporosis of the hip
Transient demineralization of the hip usually involves
healthy middle-aged men and rarely women, almost
exclusively during the third trimester of pregnancy or the
immediate postpartum period [1, 7]. The syndrome is
characterized by acute disabled pain in the hip and
functional disability without a history of previous trauma.
It has been considered by many authors as an abortive form
of osteonecrosis of the femoral head or alternatively as a
variety of algodystrophy syndromes. Histological examina-
tion reveals focal areas of thin and disconnected bone
trabeculae covered by osteoid and active osteoblasts.
With few exceptions, in patients with TOH, the clinical
course is relatively short and may last up to 68 months,
with rapid aggravation of pain and functional restriction of
the hip during the first month after the onset. Radiological
findings of osteopenia of the femoral head and/or the
femoral neck may be present in 36 weeks after the onset of
the symptoms. Spontaneous clinical and radiological
recovery is the rule. Recurrence in the same joint or
migration of the disease to the contralateral femoral head
may be seen.
The imaging features of the affected femoral head are
diffuse osteopenia of both femoral head and neck on plain
radiographs, and homogenous, diffuse increased uptake on
bone scintigrams (Figs. 1 and 3a). A delay between the
onset of symptoms and conventional radiographic findings
is usually found. Characteristic BME signal on T1 and T2-
w MR images has been repeatedly demonstrated in patients
suffering from TOH (Fig. 5). The typical BME changes are
seen on MR imaging within the first 48 h after onset of
Skeletal Radiol (2009) 38:425436
symptoms. MR imaging findings in TOH are commonly
characterized by self-limited BME in the affected area,
indicating hypervascularity and repair activity [2].
Regional migratory osteoporosis
Regional migratory osteoporosis is defined as sequential
polyarticular arthralgia of the weight-bearing joints associ-
ated with severe focal osteoporosis. Although the lower
appendicular skeleton is mainly affected, there are several
reports in the recent literature describing combined axial
skeleton involvement [3]. Regional osteoporosis is a
distinctive feature of the disease.
RMO mainly affects middle-aged men with an identical
to TOH clinical presentation and course, typically without
history of trauma or injury. Although RMO was first
described by Duncan et al. [21], BME migration, its
etiology and relationship to TOH, has not been addressed
adequately in the literature [22]. It has been reported that
migration occurs in 541% of patients with hip BME [23
25]. Migration may occur in different or the same joint in
an unpredictable time interval after the onset of the first
symptoms (Fig. 7). Usually, the joint nearest the diseased
one is the next to be involved.
Diagnosis of RMO mainly depended on its benign and self-
limiting clinical and radiological behavior. Additionally, the
finding that separates RMO from other similar conditions,
such us TOH and algodystrophy, is its migratory nature [16].
The retrospective finding of BME migration to a neighboring
joint or to another site of the same joint confirms the
diagnosis of RMO. Some authors have classified TOH and
RMO under the term transient regional osteoporosis [3].
Skeletal Radiol (2009) 38:425436
Fig. 7 Same patient as in Fig. 6. a Three weeks after the onset of
symptoms, the coronal fat-suppressed proton-density (PD)TSE MR
image shows bone marrow edema in the medial femoral condyle of
the left knee. Complete resolution of symptoms and imaging findings
as shown on the corresponding MR image were seen 2 months later
(b). Fourteen months later, new onset of symptoms developed, and the
coronal fat-suppressed PDTSE MR image shows bone marrow
Reflex sympathetic dystrophy
The terms RSD, algodystrophy, chronic regional pain
syndrome, and Sudeck syndrome have been used in the
literature in order to describe the same clinical entity. RSD
is characterized by three distinct stages: acute, dystrophy,
and atrophy. The presenting symptom is a dull, burning
pain of rapid or gradual onset. The history of trauma and
the presence of secondary changes such as skin atrophy,
sensomotor alterations, and contractures may be helpful to
distinguish this condition from the other types of BMES.
However, in RMO, soft tissue involvement has also been
described. RSD has a poor prognosis lacking of the self-
limited nature of TOH or RMO. RSD usually involves the
same joint, though in chronic cases, the entire extremity
may be affected. According to Hofmann et al. [2], a
continuous transition from migratory BMES to RSD is also
possible.
The importance of differentiating RSD from other types of
BMES depends on the diverse evolution of the two
conditions. In fact, if RSD is not treated, it may determine
severe disability. Early diagnosis is difficult because clinical
431
edema in the lateral femoral condyle (c). Two months later, there
was moderate resolution of the lateral femoral condyle edema but a
new lesion was shown in the lateral tibial condyle (d) and in the left
femoral head and neck (e) (coronal STIR MR image). A small linear
subchondral low-intensity lesion is seen on the left femoral head,
representing presumably a trabecular microfracture (open arrow).
and radiographic alterations, such as osteopenia and atrophy
of the soft tissues, are non-specific. In most cases, clinical
evaluation may suggest the diagnosis. Radiographically,
severe diffuse osteopenia is observed early, mainly in the
periarticular areas, simulating the juxta-articular osteopenia
secondary to chronic inflammatory arthropathies.
Radionuclide bone scan may reveal diffuse rather than
regional increased uptake. The three-phase bone scintigra-
phy with the Tc99m-MDP is a valuable imaging modality
for the diagnosis of RSD. An increased periarticular uptake
is a common finding, which is present in the blood pool
phase and mainly in the delayed bone phase of the three-
phase bone scintigram [2]. In 1520% of the cases, there is
a possibility of decreased uptake in the perfusion phase or
in the delayed bone phase (more often in children) [26]. In
other 1520% of the cases, mixed images may be present
[26]. The appearance of the diffuse periarticular tracer
uptake may be useful to differentiate RSD from other
conditions, such as osteonecrosis of the femoral head or
osteomyelitis. However, the information provided from the
three-phase bone scintigram is a little useful in order to
differentiate RSD from other types of BMES.
432
Although MR imaging cannot confirm the diagnosis of
RSD, it may be useful for differentiating other conditions in
the acute stage [27]. In acute RSD, MRI may reveal
edematous periarticular soft tissue, diffuse BME of the
affected joint, and joint effusion (Fig. 8) [2].However,
several investigators supported that BME is not a charac-
teristic pattern for RSD [28]. High signal intensity on T2-
w images may be restricted to the skin and superficial fascia
without any bone marrow involvement. In cases that MR
imaging demonstrates BME pattern, differential diagnosis
between RSD and transient osteoporosis is difficult.
Osteonecrosis
Osteonecrosis is not a rare disorder compared to BMES.
The incidence of the disease has been estimated to be
approximately 15,000 new cases annually in the United
States [29]. Osteonecrosis usually involves young adults in
their twenties, thirties, or forties. Men and women are
almost equally affected in most series. In 80% of patients
who have osteonecrosis, predisposing factors, such as
administration of steroids, alcohol consumption, sickle-cell
disease, lupus erythematosous, and renal transplantation
can be identified.
The pathophysiology of osteonecrosis remains obscure.
Osteonecrosis is regarded as a multifactorial disease with
both genetic predilection and exposure to certain risk
factors. BMES has been considered as a point on a
spectrum of pathology with transient BME at one end and
osteonecrosis at the other. In a study of transient osteopo-
rosis of the knee migrating from the lateral to the medial
femoral condyle, Parker et al. [14] observed that MR
imaging findings were simulating osteonecrosis. Similar
were the findings of Turner et al. in a case of hip
involvement [30].
Osteonecrosis of the knee joint may be spontaneous
(spontaneous osteonecrosis of the knee, SONK) or second-
Fig. 8 A 42-year-old male
patient with a history of
previous Achilles tear repair
and a clinical diagnosis of algo-
dystrophy 3 months postopera-
tively. The sagittal STIR (a)
and contrast-enhanced fat-
suppressed T1-w (b) MR images
show diffuse bone marrow
edema with enhancement after
gadolinium administration in the
midfoot, the hindfoot and the
distal tibia
Skeletal Radiol (2009) 38:425436
ary in younger patients who have ischemic disorders.
Demographic characteristics are different between patients
with osteonecrosis and patients with BMES [15, 16, 31].
Transient osteoporosis of the knee affects middle-age
males, while SONK is typically observed in women over
the age of 55 without classic osteonecrosis risk factors. It
has been shown that SONK represents a BMES secondary
to a subchondral insufficiency fracture rather than true
osteonecrosis and that the later the imaging diagnosis and
the lower the bone mineral mass, the higher is the risk for
articular collapse [19].
In osteonecrosis, the most frequently involved location is
the hip, followed by the knee joint. In the initial phase of
the disease, scintigraphy may reveal cold in hot image,
which is an area of increased uptake in the shape of a half-
moon (crescent) that circumscribe a cold zone of decrease
tracer uptake equivalently to the necrotic zone (Fig. 3b). In
the advanced stages of osteonecrosis, an unspecific in-
creased uptake is usually observed.
In osteonecrosis of the femoral head, MR imaging
findings were thought to be similar to those of BME
pattern. Since BME is a nonspecific finding that has been
also described in association with many transient self-
limited conditions, such as RMO, TOH, and epiphyseal
stress fractures [32], early differentiation is crucial in order
to prevent over-treatment of the benign conditions and to
reserve more aggressive therapy in cases of osteonecrosis.
Studies have shown that patients with osteonecrosis of the
femoral head do not have findings of BME typical for TOH
in the early stages of the disease [33]. In a study presenting
early findings in ON, BME was never found before the
appearance of band patterns on MRI [34]. A similar study
showed that a band pattern is the initial MR imaging
finding of early osteonecrosis without any prior diffuse
BME depicted [35]. The double-line sign is seen on T2-
w spin echo or turbospinecho (TSE) sequences and
consists of a low signal intensity outer rim and a high signal
Skeletal Radiol (2009) 38:425436 433

Fig. 9 Same patient as in Fig.

2. Typical findings of osteonec-
rosis findings with serpentine
band-like sign and the double-
line sign are shown on the
coronal T1-w (a) and the axial
T2-w (b) TSE MR images
(arrows). c The oblique axial
fat-suppressed contrast
enhanced T1-w MR image of
the right hip shows only the
osteonecrotic lesions (arrows)
with no marrow edema. d The
sagittal T2-gradient-recalled
echo MR image of the left hip
shows subarticular collapse with
contour deformity (white
arrows). There is also anterior
labrum degeneration (open
arrow). e The oblique axial fat-
suppressed contrast-enhanced
T1-w MR image of the left hip
shows diffuse enhancement
secondary to the articular
collapse

intensity inner rim (Fig. 9). This sign was introduced by and repair tissue at the necrotic-viable osseous interface.
Mitchell et al. [36] and was considered pathognomonic for Recently, it was suggested that the double line sign has
osteonecrosis of the femoral head since the outer rim the characteristics of a chemical shift artifact, but this does
represents the reactive bone and the inner rim the vascular not reduce its diagnostic value for diagnosing hip osteonec-

Fig. 10 A 17-year-old male patient with a history of left hip pain not bone marrow edema in the femoral neck and intertrochanteric area
responding to analgesics. The oblique axial (a) and axial (b) contrast- (arrows), as well as synovitis (open arrows). The reformatted coronal
enhanced fat-suppressed T1-w MR images show diffuse enhancing CT image (c) depicts a small osteoid osteoma (arrow)
434 Skeletal Radiol (2009) 38:425436

Fig. 11 a A 29-year-old
male patient with ankylosing
spondylitis since 3 years. The
coronal fat-suppressed
T2-w TSE MR images show
bone marrow edema in the pubic
bones (arrows). b A 40-year-old
female patient with inflammato-
ry bowel disease. The sagittal
STIR MR image show bone
marrow edema in the os calcis
(arrows)

rosis for those who use non-fat-suppressed T2-w SE or Neoplasia

turbo (fast) SE MR sequences [37]. A circumscribed
subchondral band-like lesion with low signal intensity
on T1-w images is pathognomonic for hip osteonecrosis
(Fig. 9) [36]. BME has been shown to appear after the onset
of hip pain and to correlate significantly with the
subsequent collapse of the femoral head, suggesting
progression to advanced osteonecrosis and therefore repre-
senting a poor prognostic [38, 39]. Newer techniques, such
as diffusion-weighted imaging, do not seem to provide
useful data for differentiating osteonecrosis-associated
BME and transient BME [40]. In the absence of subchon-
dral low-signal-intensity areas, lesions on T2-w images or
contrast-enhanced T1-w images seem to have a positive
predictive value for a transient pattern of the disease [18].
Therefore, concomitant subchondral changes with the
typical BME pattern may help to differentiate transient
from irreversible lesions. According to a recent study, a
delayed enhancement in contrast-enhanced images is
another MR imaging finding highly suggestive of a
transient lesion [25].
Metastatic carcinoma, multiple myeloma, leukemia, and
lymphoma, either by directly infiltrating the bone marrow
or with their associated marrow edema, may resemble
BMES. Usually, physical examination and laboratory tests
may help to distinguish these aggressive conditions from
BMES. Radiography reveals characteristic bone destruction
of the metaphyses and diaphyses of long bones in cases
of neoplastic processes. Any BME located in the femoral
neck and intertrochanteric zone in an adolescent or
young adult patient should further be examined with
CT since an occult osteoid osteoma might be the cause
(Fig. 10). On the contrary, BMES usually involves
epiphyses where diffuse osteoporosis with preservation of
the articular cartilage is the rule [15]. However, in multiple
myeloma, diffuse rather than regional demineralization may
be present.
CT is also of great value in order to further analyze the
lesion matrix and the cortex integrity. Bone scintigraphy
may reveal the presence of multifocal tracer uptake,

Fig. 12 Two cases

(a 70-year-old man;
b 35-year-old woman) with
septic arthritis, osteomyelitis,
and soft tissue infection follow-
ing arthroscopy performed
2 weeks before imaging. The
contrast-enhanced fat-
suppressed T1-w MR images
show the abnormal signal
fintensity in the bone marrow
(arrows)
Skeletal Radiol (2009) 38:425436
whereas MR imaging determines bone involvement and
involvement of the surrounding soft tissues. BME may be
present in various tumors or tumor-like conditions [41]. In
such cases, intravenous contrast administration distin-
guishes tumor tissue from concomitant BME.
Inflammatory and infectious arthritis
Infectious arthritis, rheumatoid arthritis, gout, multifocal
osteomyelitis, and tuberculosis should be distinguished
from BMES. A thorough history and physical examination
may reveal predisposing conditions and associated systemic
symptoms. Asymmetrical polyarthritis that usually involves
the upper extremities, periarticular soft tissue swelling, and
marked joint effusion are some of the clinical findings that
differentiate inflammatory arthritis from BMES. Routine
laboratory examinations are also helpful.
In most cases, an accurate diagnosis can be made by
radiographs and MR imaging evaluation. However, MR
imaging is indicated only in cases in which diagnosis
remains questionable. Juxta-articular demineralization due
to disuse or hyperemia may be found at both sides of the
affected joint [15]. In patients with inflammatory or reactive
arthritis, BME pattern may be present (Fig. 11). This MR
imaging feature represents only a concomitant component
without any influence on the therapeutic algorithm [14]. In
contrast to BMES, in patients with inflammatory arthritis,
periarticular rather than regional BME is usually found.
Similar findings are obtained with bone scintigraphy at the
symptomatic sites. Other potential MR imaging findings are
hyaline cartilage abnormalities, bony erosions, joint effu-
sion, synovial, and periarticular soft tissue involvement. In
septic arthritis, the associated osteomyelitis and infectious
myositis are better seen with MR imaging due to its high
tissue contrast demonstration (Fig. 12).
Treatment
BMES is a self-limiting disease with unknown etiology.
Therefore, symptomatic approach is often followed. Today,
therapeutic strategies include partial weight-bearing, mild
analgesics, and nonsteroidal anti-inflammatory drug admin-
istration. Although glucocorticoids were thought to alter the
process of the disease, many authors supported that
remineralization was not achieved with the use of gluco-
corticoids. Moreover, sympathetic blockade had insufficient
results in the treatment of BMES [3].
Several authors described the beneficial effect of various
agents. Intravenous administration of pamidronate, a potent
bisphosphonate, was efficacious for the treatment for both
RSD and TOH [42]. Considering the close relationship of
these two conditions with RMO, Horiuchi et al. [16]
435
speculated that this drug may have promising results in
patients with RMO. In order to minimize the extensive
bone loss during the acute episodes, calcitonin has also
been used [43]. Furthermore, a prostacyclin analogue,
Iloprost (Ilomedin, Schering, Berlin, Germany), has been
administered with clinical success in patients with painful
BME of the knee [44]. Pain relief and rapid regression of
the BME was attributed to prostacyclin properties to dilate
vessels and reduce the permeability of capillaries.
Although non-weight bearing has beneficial effect on the
affected joint, it may lead to severe demineralization if
disuse is prolonged. Trevisan and Ortolani [6] proposed
densitometric assessment during the clinical management of
the disease. According to their study, quantitative evaluation
of bone mineral content and density during the acute attacks
may be useful on an individual basis for the weight-bearing
restriction management [6].
Conclusions
Since 1959, when Curtiss and Kincaid described three cases
of transient demineralization of the hip joint, a large
number of BMES cases have been reported in the literature.
Despite the new imaging modalities, diagnosis of BMES
remains a challenge. In an initial stage clinical and
radiographic findings are nonspecific. Local regional
osteoporosis and BME pattern are common features that
may be present in all types of BMES, such as TOH,
regional migratory osteoporosis, and RSD. Moreover, a
clinical overlap between these conditions is usually found.
As a consequence, in the recent literature, there is still
conflict concerning common or distinct pathophysiology of
these diseases.
Spontaneous recovery distinguishes the disease from
other aggressive conditions. However, unpredictable recur-
rence of symptoms in a different joint and rarely to the
same joint makes its treatment difficult to assess. The
possibility of such lesions should always be considered in
patients with regional demineralization in plain radiographs
and BME pattern in MR imaging. Early differentiation from
other aggressive conditions with long-term sequelae and
poor prognosis is essential in order to avoid unnecessary
treatment.
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