Treatment of bone-marrow oedema of the
talus with the prostacyclin analogue iloprost
AN MRI-CONTROLLED INVESTIGATION OF A NEW METHOD
N. Aigner, G. Petje, G. Steinboeck, W. Schneider,
C. Krasny, F. Landsiedl
From the Orthopaedic Hospital Vienna-Speising, Vienna, Austria
one marrow oedema syndrome of the talus is a
B rare cause of pain in the foot, with limited options
for treatment. We reviewed six patients who had been
treated with five infusions of 50 µg of iloprost given
over six hours on five consecutive days. Full
weight-bearing was allowed as tolerated. The foot
score as described by Mazur et al was used to assess
function before and at one, three and six months after
treatment. The mean score improved from 58 to 93
points. Plain radiographs were graded according to
the Mont score and showed grade-I lesions before and
after treatment, indicating that no subchondral
fracture or collapse had occurred. MRI showed
complete resolution of the oedema within three
months.
We conclude that the parenteral administration of
iloprost may be used in the treatment of this
syndrome.
J Bone Joint Surg [Br] 2001;83-B:855-8.
Received 19 May 2000; Accepted after revision 20 February 2001
Bone marrow oedema syndrome is a well-documented
condition which occurs mainly in the head of the femur, but
also at other sites. Involvement of the talus is rare and often
overlooked. Few cases have been reported in the litera-
1-3
ture. Various options for treatment have been described,
mainly for the head of the femur and the knee. These
include symptomatic non-operative management with
reduction of weight-bearing, analgesic and anti-inflammat-
ory medication and physiotherapy, and surgical treatment
such as core decompression, alone or in combination with
N. Aigner, MD, Registrar
G. Petje, MD, Consultant Orthopaedic Surgeon
G. Steinboeck, MD, Consultant Orthopaedic Surgeon
W. Schneider, MD, Consultant Orthopaedic Surgeon
C. Krasny, MD, Registrar
F. Landsiedl, MD, Head of Department
Orthopaedic Hospital Vienna-Speising, Speisingerstrasse 109, A-1134
Vienna Austria.
Correspondence should be sent to Dr N. Aigner.
©2001 British Editorial Society of Bone and Joint Surgery
0301-620X/01/611377 $2.00
VOL. 83-B, NO. 6, AUGUST 2001
electromagnetic stimulation or bone grafting. Several
authors have reported a relationship between transient bone
4-6
marrow oedema and avascular necrosis, but the incid-
ence of progression from bone marrow oedema to early
avascular necrosis remains unclear. In cases of spontaneous
remission, the time taken for the improvement of symptoms
7,8
and changes in MRI is between six and 12 months. The
success of different options for treatment, however, is
dependent on the stage of the disease, with the best results
obtained in marrow oedema alone with a worse prognosis
for advanced bony necrosis. These methods of management
should be considered as symptomatic only since an effect
on the underlying vascular disturbance has not yet been
described. Our aim in this prospective pilot study was to
assess the efficacy of a vasoactive drug on the clinical
course, as evaluated by radiography and MRI.
Patients and Methods
We studied six patients (five female, one male) with bone
marrow oedema of the talus which was confirmed by MRI.
Their mean age was 58.4 years (25 to 73), and the duration
of symptoms was 5.4 months (1 to 12). No patient gave a
history of trauma, alcohol abuse or corticosteroid medica-
tion. Routine serology was normal in three patients, one
showed mild hypercholesterolaemia and one hypertri-
glyceridaemia. One patient played badminton regularly and
was a cigarette smoker. Previous treatment had consisted of
non-steroidal anti-inflammatory drugs and physiotherapy in
four patients without significant effect on their symptoms,
and reduction of weight-bearing in two. The foot score of
9
Mazur, Schwartz and Simon was recorded for each patient.
Plain anteroposterior and lateral radiographs and MRI were
used to confirm the diagnosis.
The treatment of all patients consisted of five infusions
with 50
g of iloprost (Ilomedin; Schering AG, Germany)
in 500 ml of sodium chloride solution given over six hours,
on five consecutive days. The treatment was interrupted for
short periods if significant side-effects occurred such as
headache, nausea or flushing. These symptoms were treated
with antiemetic or analgesic drugs, and the dosage reduced.
Clinical examination was undertaken after one, three and
six months; radiological and MRI evaluation was repeated
after three months.
855
856 N. AIGNER, G. PETJE, G. STEINBOECK, W. SCHNEIDER, C. KRASNY, F. LANDSIEDL
Results
Before treatment the mean Mazur foot score was 58 points
(26 to 69). All patients had experienced severe pain during
weight-bearing and after exercise, and four had some pain
at rest and at night for a mean of six months (2 to 12). Plain
radiographs were considered to be normal in four patients,
while in two they showed slight osteoporosis (stage-I avas-
1
cular necrosis of the ankle as described by Mont et al ).
MRI showed bone marrow oedema of the whole talus in
four patients; the other two had focal lesions, one in the
head and neck and the other in the medial aspect of the
body of the talus.
During infusion, the following side-effects were seen in
four patients: one severe and three mild cases of headache,
and two severe and two mild cases of nausea. These
resolved within 15 minutes after the end of treatment. Two
patients required partial weight-bearing for one week after
treatment because of severe pain on exertion.
Four patients noticed improvement within the first few
days of treatment, and the other two within the first weeks.
In particular, rest pain disappeared within a mean of five
days (3 to 8). Pain during exercise required five weeks (3 to
6) to settle. The Mazur score improved to a mean of 91
points (81 to 100) after one month and increased to 93
points (85 to 100) after three months. At the last examina-
tion, six months after treatment, this high score had been
maintained. Patients reported no restrictions in their normal
daily activities. The very active young male patient was
able to return to the same level of sporting activities as
before the onset of symptoms.
Plain radiographs of all six patients were normal with no
sign of progression, such as sclerosis or lucencies, sub-
chondral fracture, collapse or narrowing of the joint
space.
MRI showed that the bone marrow oedema had resolved
completely within three months (Fig. 1) in all six patients,
with normal signal intensity and no signs of progression to
avascular necrosis, such as demarcation, the ‘double-line
sign’, or collapse.
Discussion
In 1959, Curtiss and Kincaid described a clinical syndrome
characterised by pain, decreased bone density on plain
radiography, followed by spontaneous regression, in the
hips of women during the last trimester of pregnancy.
Subsequent reports have referred to this syndrome as transi-
ent osteoporosis, transitory demineralisation and, as diag-
11
nosed by MRI, bone marrow oedema syndrome. The
clinical course is characterised by an abrupt or gradual
onset of pain, noted not only during activity but occasion-
ally at rest and at night, which resolves spontaneously after
six to 12 months. The term ‘migratory osteoporosis’
describes the fact that it may present subsequently in
different joints and an incidence of bilateral involvement of
12
41% has been reported. Most series describe the condi-
tion in the hip or less often, the knee, but only a few have
1,3,13-15
reported it in the foot.
Therapeutic options are limited. Some authors report
good results with core decompression. This treatment has
been recommended as a method of reducing the duration of
symptoms rapidly and completely, with a return to normal
2-5
MRI signal patterns. The theory is that pain in transient
osteoporosis and avascular necrosis is caused by raised
intramedullary pressure. Although this treatment has mini-
mal morbidity and can be performed as an outpatient
procedure, it requires partial weight-bearing for six weeks,
sometimes followed by physiotherapy. Other authors have
reported good results with a conservative regime of symp-
tomatic treatment and avoidance of weight-bearing until the
2,3,8 16
clinical and radiological findings resolve. Boos et al
reported a good clinical outcome with sympathetic nerve
blockade in three patients, but without improvement in the
17
pathological MRI signal pattern. Although Laroche et al
described reduction of pain in a small controlled study
18
using nifedipine, and Glueck et al presented preliminary
data on the use of stanozolol in the treatment of avascular
necrosis, these methods did not apply to the treatment of
12
the bone marrow oedema syndrome. Lakhanpal et al
reported no beneficial effect when using calcitonin, anti-
tuberculous drugs, prednisone or lumbar sympathectomy.
There is still controversy as to whether this syndrome is
a distinctive self-limiting disease, a type of reflex sym-
16,19
pathetic dystrophy, or a diffuse but reversible early
5,20-22
phase of avascular necrosis.
The pathogenesis of the bone marrow oedema syndrome
and avascular necrosis also remains unclear. Commonly
discussed theories include thromboemboli, arteriolar
obstruction, obstruction of venous outflow or injury to a
vessel wall caused by vasculitis, altered lipid metabolism
23-29
and decreased fibrinolysis. It was our aim to investigate
the effect of a pharmacological agent with an activity
spectrum on several parts of the terminal vascular bed and
on the aggregation of platelets.
Since 1998 we have used iloprost given parenterally in
the treatment of bone marrow oedema syndrome. This
stable prostacyclin analogue is registered for the treatment
of critical ischaemia secondary to peripheral atherosclerotic
30
obliterative disease or diabetic angiopathy. It causes dila-
tation of arterioles and venules, reduction in the permeabili-
ty of capillaries and inhibition of thrombocyte aggregation.
As well as these improvements in the viscosity within the
terminal vascular bed, it decreases oxygen radicals and
leukotrienes. Its most frequent side-effects are headache,
nausea and flushing. Treatment is contraindicated during
pregnancy and in patients who are anticoagulated or who
have gastrointestinal ulcers, cardiac failure, a recent myo-
cardial infarction or unstable angina. In this pilot study, all
patients were treated with a series of infusions of 50
g of
iloprost on five consecutive days.
With this regime, our patients showed rapid symptomatic
THE JOURNAL OF BONE AND JOINT SURGERY
 TREATMENT OF BONE-MARROW OEDEMA OF THE TALUS WITH THE PROSTACYCLIN ANALOGUE ILOPROST 857

Fig. 1a Fig. 1b Fig. 1c

A 69-year-old woman with bone marrow

oedema of the talus. Figures 1a to 1c –
Anteroposterior and lateral T1- and
T2-weighted MR images of the hindfoot
before treatment. Figures 1d and 1e – Lat-
eral T1- and T2-weighted MR images five
weeks after therapy showing reduction of
the bone marrow oedema. Figures 1f to 1h –
Anteroposterior and lateral T1- and
T2-weighted MR images 14 weeks after
treatment. The oedema in the talus has re-
solved.

Fig. 1d Fig. 1e

Fig. 1f Fig. 1g Fig. 1h

improvement which was maintained over six months.
These results were achieved with or without a short (one
week) period of protected weight-bearing. MRI was per-
formed 12 weeks after treatment as proposed by Boos et
16
al. We found a complete return to normal signal patterns.
Although the clinical outcome was good, the possibility of
side-effects, such as nausea, vomiting and headache, should
be noted.
To date, this treatment has been given to more than 350
patients with bone marrow oedema at different sites includ-
ing the femoral head, the condyles of the femur and tibia,
and the hand (unpublished data). All patients with bone
marrow oedema syndrome, without demarcation of avas-
cular bone, had the same excellent results with an accel-
erated resolution of the condition. This treatment is
relatively inexpensive and as there is no need for reduced
weight-bearing it allows an early return to normal life.
This pilot study has its limitations since the number of
patients was very small, due to the rarity of the condition. A
multicentre, randomised study will be necessary to compare
this infusion therapy with core decompression or con-
servative treatment.
No benefits in any form have been received or will be received from a
commercial party related directly or indirectly to the subject of this
article.

VOL. 83-B, NO. 6, AUGUST 2001

858 N. AIGNER, G. PETJE, G. STEINBOECK, W. SCHNEIDER, C. KRASNY, F. LANDSIEDL
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