of Osteonecrosis of the Femoral Head
David S. Hungerford and
Lynne C. Jones
Good Samaritan Hospital
In: Bone Circulation and Vascularization
in Normal and Pathological Conditions
1993, Plenum Press, New York (USA). Pages 265-274. All rights
proper diagnosis of ischemia and necrosis of bone is of primary
practical importance because of the primacy of early diagnosis
and the outcome of treatment, whatever it may be. Many authors,
supporting core decompression, electrical stimulation, bone
grafting or osteotomy have linked success to the stage at
which the diagnosis is made (Steinberg et al., 1984; Hungerford
et al., 1990). The purpose of this paper is to provide an
overview of the issues and diagnosis, some of the obstacles
and disputes, and finally to present our diagnostic algorithm
as currently practiced in trying to arrive at the proper diagnosis
for the patient presenting with a painful hip for evaluation.
Constitutes A Diagnosis of Osteonecrosis of Bone?
everyone agrees that a positive biopsy showing dead trabeculae
devoid of lacunae remains "the gold standard" for
the diagnosis of osteonecrosis, to insist that it be the "sine
qua non" for the diagnosis simply impedes progress and
condemns the physician to never making an early diagnosis.
It also ignores the possibility of sampling error if one has
anything less than the whole femoral head available for sectioning.
Moreover, such insistence ignores the marrow element of bone
as an integral part of the organ system and denies the fundamental
landmark work of Rutishauer, Rohner and Held (1960) who showed
that the bone trabecular death was the last item on a well
defined pathophysiological cascade of home ischemia and necrosis.
The initial stages of ischemia are evidenced only in morphological
changes in the marrow.
error of insisting that only the finding of dead trabeculae
in the biopsy justified the diagnosis of osteonecrosis is
demonstrated in the publication of Camp and Colwell (1986).
These authors divided their 42 cases of core decompression
into histologically positive and histologically negative cases.
Following the "sine qua non" line of reasoning,
the former were considered to have definite osteonecrosis
and the latter definitely not have osteonecrosis. This was
in spite of the fact that 6 of 15 in the biopsy negative group
had X-rays that were characteristic of osteonecrosis and during
the follow-up period an additional 3 progressed to characteristic
changes. Nonetheless, the bone scan, bone marrow pressure
tests, and venography were judged to be falsely positive in
this group of patients rather than consider that the biopsy
may have been subject to sampling error. Many other vascular
disorders of organ systems, e.g. Leriche Syndrome, cerebral
and cardiac ischemia, etc., do not demand biopsy proof of
dead muscle, brain, or heart, to establish the diagnosis and
the insistence on the part of some for this criteria for bone
is a serious impediment to early treatment and particularly
noninvasive treatment. The situation for bone ischemia and
necrosis is not dissimilar to the situation with rheumatoid
arthritis before the American Rheumatism Association adoption
of major and minor criteria, the combination of which would
be sufficient to establish diagnosis (Ropes et al., 1959).
While it is certainly not the place of this chapter or these
authors to establish such criteria, Table I suggests at least
some major and minor criteria which could be considered in
I. Diagnostic Criteria for Diagnosis of Osteonecrosis
in hot" bone scan
band on T-2 MRI scan
with joint space narrowing
cyst/sclerosis pattern in femoral head
uptake on bone scan
changes of marrow edema/fibrosis
painful range of motion with normal radiography
of alcohol abuse/steroid use
criteria could be considered sufficient to establish diagnosis
if certain other factors could be definitely excluded. For
example, marginal subchondral collapse is virtually pathognomonic
for osteonecrosis if major trauma, the only reasonable alternative
etiology, can be excluded. It would require a committee of
international experts to establish a comprehensive set of
criteria to establish diagnosis, but it would be a worthwhile
and enormously useful exercise. In the absence of such standards,
researchers will continue to argue what is and what is not
first step in the diagnostic algorithm of osteonecrosis is
good quality AP and frogleg laterals of the hip. The AP radiographs
show the principal area of interest through the anterior and
posterior margins of the acetabulum. Figure 1 shows an AP
radiograph in which the acetabular margins have been outlined
with a dotted line. Because the anterior and posterior acetabular
margins overlap the superior portion of the femoral head,
subtle abnormalities in the subchondral region may be missed.
It is imperative that good quality lateral X-rays of the femoral
head be obtained.
Figure 1. Anterior-Posterior radiograph of the hip showing
the outline of the rim of the acetabulum which covers the
area of interest for detecting early osteonecrosis.
cross-table lateral X-ray is less satisfactory than a frogleg
lateral or Lowenstein lateral to show the architectural details
of the femoral head, since the former must penetrate more
soft tissue, blurring bony outlines. The lateral is also important
for staging purposes since it is often the anterior segment
of the femoral head which first undergoes collapse or exhibits
subchondral radiolucency (Figure 2). If the X-ray is positive
and shows pathognomonic changes of avascular necrosis, no
further diagnostic tests are necessary and treatment options
can be chosen from the information available.
Figure 2. (A) The AP radiograph shows a completely
spherical head while the frog-leg lateral (B) shows subtle
flattening (arrows) indicative of early collapse.
tomography (CT) scanning is expensive, exposes the patient
to considerable radiation and is usually unnecessary for establishing
the diagnosis of osteonecrosis. However, it may be useful
in separating late precollapse stages of osteonecrosis from
the early collapse stage. Minimal collapse will only be shown
if the area of collapse is perfectly aligned tangential to
the X-ray beam, and, therefore, will often escape detection
by routine radiography but would be detected on CT scan. Therefore,
when considering more conservative treatment for pre-collapse
disease, that one would not consider for post-collapse disease,
CT scanning may be helpful in separating the two.
imaging is a useful technique for detecting osteonecrosis.
In general, the reactivity of bone around the infarcted segment
shows increased uptake on the delayed image. This represents
accumulation of the radionuclide in the area of increased
bone turnover at the junction between dead and reactive bone.
The image of increased uptake alone, however, is not restricted
to osteonecrosis but would be seen in reflex sympathetic dystrophy,
transient migratory osteoporosis, osteoarthritis, rheumatoid
arthritis, infection, and tumor to cite a few. However, rarely
one will see a "cold in hot" image which is virtually
pathognomonic for osteonecrosis. This is a very early finding
and is only seen when the area of infarction is relatively
large and the reaction to it not yet maximal. Otherwise, the
area of reaction will obscure the area of decreased uptake.
Although single photon emission computerized tomography (SPECT)
can overcome this deficiency, it is not as widely available
as other imaging forms - specifically MRI.
Figure 3. 99mTc-diphosphonate bone scan
in unilateral osteonecrosis is highly reliable. As shown here
the affected left side shows diagnostic increased uptake.
bone scanning is best in evaluation of unilateral disease,
since its highest sensitiviity is reached when asymmetry of
uptake is detected (Figure 3). If both sides are involved,
there is no reference for the detection of subtle changes
even though more dramatic changes could be detected (Figure
4). Even when the X-ray of the pelvis shows two normal hips,
bilateral preradiologic disease in the earlier stages could
be missed on bone scan because of the lack of asymmetry to
detect subtle uptake. from the diagnostic algorithm at the
end of this chapter, it will be seen that, for these reasons,
bone scanning is a diagnostic technique of secondary importance.
Figure 4. (A) bone scan; (B) AP radiograph both hips.
The right side of this patient is also affected, but the changes
are obscured by the more advanced side (arrows). The right
side was falsely interpreted as normal.
resonance imaging is opening up a whole new perspective and
a new set of questions in the diagnosis of osteonecrosis.
A full explanation of the mechanism of detection of bone necrosis
by MRI is beyond the scope for this chapter, but the interested
reader is referred to the work of Mitchell and coworkers (Mitchell
et al., 1987; Mitchell et al., 1986; Mitchell and Rao et al.,
1987). The generation of signal from the MRI is dependent
upon the tissue which is present in the femoral head. Therefore,
the initial death of any segment of the femoral head would
not be immediately detectable by MRI. MRI changes only are
detectable seven to ten days after the event. Several authors
have reported MRI to be the most accurate of all imaging modalities
(Steinberg et al., 1984; Kokubo et al., 1992), although Kulkarni
et al. (1987) reported 2 cases which were biopsy positive
but MRI negative. Also the original MRI units were not as
powerful and the programming not as sensitive as units in
use today. Assuming that a 1.2 or 1.5 tesla unit is available,
MRI detection of avascular necrosis should approach but not
equal 100%. The double line signal on T2 weighted image is
virtually pathognomonic for osteonecrosis. This double density
has been shown to represent the thickened reactive trabeculae
at the margin of the osteonecrotic lesion, representing the
area of decreased signal; and the increased water content
in the blood of the hyperemic reaction adjacent to the increased
trabecular density, representing the area of increased signal.
Also, the single density line which is so often seen outlining
the necrotic lesion on the T1 weighted image is thought to
be highly specific for osteonecrosis (Figure 5). MRI also
has two additional values. Firstly, the MRI effectively outlines
the area of involvement. Steinberg and his colleagues (1992)
have shown a closer correlation to the outcome of core decompression
to the size of the area involved than to the stage of the
disease. Confirmation of this work is required, but it would
be enormously useful even in the preradiologic stages of the
disease to be able to delineate the subgroup that will or
will not benefit from core decompression to the size of the
area involved than to the stage of the disease. Confirmation
of this work is required but it would be enormously useful
even in the preradiologic stages of the disease to be able
to delineate the subgroup that will or will not benefit from
core decompression. MRI will also allow the sequential evaluation
of asymptomatic lesions that are being followed and cannot
be done by conventional radiography and can also show the
revascularization front and give evidence of tissue changes
in response to treatment. Thickman et al. (1986) demonstrated
that success in core decompression was characterized by either
normalization of the MRI image or at least stabilzation of
the MRI image whereas failed cases showed evidence of disease
progression on the MRI.
Figure 5. The single line of decreased signal intensity
on this T-1 weighted image is outlining the area of necrosis.
many instances the MRI shows extensive marrow changes involving
the whole proximal end of the femur. Again, Mitchell and coworkers
have shown high incidence of marrow abnormalities in the contralateral
side in patients with unilateral disease (Mitchell et al.,
1986). The relationship of these marrow changes to the eventual
detection of full fledged necrotic lesions is not yet well
understood, but there is some supporting evidence that bone
infarction may be preceded by a period of bone ischemia. A
great deal of additional follow-up work on the evolution of
MRI changes in susceptible populations and in the asymptomatic
side of patients presenting with unilateral disease should
be helpful in elucidating these issues. Furthermore, much
more work is urgently needed to correlate the histologic changes
with the MRI findings.
resonance imaging is a rapidly evolving discipline. Advances
in the hardware, software, and signal capabilities are being
exploited to enhance the capability of this diagnostic tool.
New MRI angiographic techniques which enable noninvasive visualization
of the vascular bed in combination with faster imaging methods
may offer the capability of measurement of blood flow to assess
osteonecrosis status (Cova et al., 1991; Tsukamoto et al.,
Marrow Pressure and Venography
marrow pressure (BMP) and venography were the mainstay of
the preradiologic diagnosis of osteonecrosis prior to the
advent of MRI. Unpublished data from our unit on 101 cases
of biopsy-proven avascular necrosis seen between 1974, when
we started to do the functional investigation of bone, and
1980 showed that bone marrow pressure was elevated as a baseline
measurment in 90 of the cases. The stress test was positive
in 88 of the cases; the venogram was abnormal in 90 of the
cases. In fact, there was only 1 case in which all three diagnostic
procedures were normal, but because of a high index of suspicion,
core bopsy was obtained which showed histologic evidence of
osteonecrosis. There were two cases of suspected osteonecrosis
in which all three parameters were normal and the biopsy was
also normal. Subsequently, other sources were found to account
for their symptoms and no further evidence of osteonecrosis
has surfaced. Therefore, bone marrow pressure, stress test,
and venography taken as a composite diagnostic test have a
high degree of sensitivity and specificity, if one considers
any of the tests being abnormal as being indicative of osteonecrosis.
Because BMP and venography are invasive and painful under
local anesthesia, with the advent and widespread availability
of MRI, bone morrow pressures have been reserved for a secondary
diagnostic measure when the MRI and X-rays are both normal
and a patient in whom one has a high degree of suspicion of
osteonecrosis. Nonetheless, bone marrow pressure measurements
showing a high percentage of abnormality in the intertrochanteric
region suggests that the vascular abnormality of osteonecrosis
affects a more widespread area than that which is delineated
by the area of absoulute necrosis and it may well be that
the bone marrow pressure itself, plays an important role in
the pathogenesis of osteonecrosis. This consideration is further
strengthened by our experience in measuring bone marrow pressures
on the asymptomatic radiologically negative contralateral
side in patients presenting with unilateral osteonecrosis.
Between 1980 and 1985 we measured the bone marrow pressure
and carried out venography in 48 bones in 42 patients (Zizic
et al., 1989). Thirty-six cases had abnormality of baseline
bone marrow pressure and/or positive stress test. In twelve
joints, the bone marrow pressure and stress tests were normal.
All patients were followed a minimum of four years. Fifteen
out of the 36 cases (42%) with abnormal diagnostic tests developed
signs and symptoms of avascular necrosis. All had eventual
histologic proof of dead bone marrow and trabeculae. None
of the patients with complete normalcy of the bone marrow
pressure tests (n = 12) subsequently developed avascular necrosis
or radiologic changes (p <0.005). Moreover, those patients
who eventually developed avascular necrosis did so within
two years and no patient who remained asymptomatic for two
years subsequently developed signs and symptoms of avascular
necrosis within the followup period (maximum 8 years). This
allowed us to separate unilateral patients into a subgroup
which was at a 42% risk for developing disease and another
subset which, apparently, had no risk for developing the disease.
Unfortunately, this was before the era of MRI and comparable
information is not available in a patient population that
has had an MRI evaluation.
biopsy, as a diagnostic procedure, will be indicated in those
patients in whom there remains a high index of suspicion for
osteonecrosis, but for whom pathognomonic changes are not
evident on the X-ray, MRI, or bone scan. The indication for
core biopsy, as a diagnostic procedure, is separate from core
biopsy as a therapeutic procedure and, in the authors' opinion,
is only necessary for the establishment of diagnosis if the
image modalities have not established the diagnosis with overwhelming
but probably not absolute certainty. Nonetheless, as intimated
earlier in this chapter, the biopsy is subject to several
errors which are reviewed in detail in the chapter in this
book by Bauer and Stulberg. To summarize, the biopsy is subject
to sampling error in which the biopsy tract does not actually
enter the area of necrosis, but passes tangential to it and
to heat artifact due to thermal changes induced by the insertion
of the biopsy trocar. This would be most likely to occur with
small biopsy and power inserted biopsy devices and to processing
error to overdecalcification which can cause loss of trabecular
osteocytes. For this reason, a biopsy which fails to show
osteonecrotic trabeculae in the face of pathognomonic MRI
bone scan, SPECT scan, or X-ray changes should not constitute
the absence of the diagnosis, but should be interpreted as
a sampling error. Morover, the bone marrow in the biopsy specimen
must be as carefully evaluated as the traveculae, and evidence
of bone marrow necrosis should be reported as such and considered
as the earliest stage of osteonecrosis. It may be reversible
spontaneously or under treatment but to consider that it is
not part of the disease process is to ignore perhaps the most
treatable phase of the disease.
our experience, the majority of patients in whom the diagnosis
of osteonecrosis of the hip is eventually established have
some medical condition with which an increased incidence is
associated. In fact, only a small percentage of patients who
develop avascular necrosis are otherwise completely healthy,
with both normal history and laboratory findings. This has
not been a universal finding with some authors reporting an
incidence of idiopathic osteonecrosis of the femoral head
as high as 30 or 40%. However, Matsuo and coworkers (1988)
in a careful epidemiologic study have identified an increased
risk of avascular necrosis with as little as 400 ml. of ethanol
consumption in some parts of Germany and France. Therefore,
with closer questioning, it is felt that many of the cases
reported as idiopathic could actually be considered alcohol-associated.
Table 2 shows the etiologic associations of the first 90 patients
that we treated for avascular necrosis. The most important
information from this figure is that only 6% had no detectable
etiologic association. Therefore, a high index of suspicion
of osteonecrosis of the femoral head must be entertained for
anyone presenting with hip pain, negative X-ray, and particularly
with a predisposing etiology.
2. Clinical conditions associated with ON
the report of Merle D'Aubigne et al. (1965) only 13% of patients
had evidence of disease at the time of first visit, increasing
to 50% bilaterality during the period of follow-up. Incidence
of bilaterally as reported in the literature varied from 50
to 80% (D'Aubigne et al., 1965; Jacobs, 1978; Kerboul et al.,
1974). Therefore, particular attention must be paid to the
asymptomatic side and the patient should be alerted to report
for immediate evaluation should symptoms develop on that side
while they are under treatment for the index joint.
A Proposed Diagnosed Algorithm
6 shows the diagnostic algorithm that we are currently practicing
for all patients who present with hip complaint. In addition
to the obvious clinical history and physical exam, all patients
receive AP and frogleg pelvis X-rays, so that both hips can
be evaluated radiographically simultaneously. If the hip is
positive for avascular necrosis, then treatment choices can
be based upon the findings. If it is negative, then the patient
is referred for MRI of both hips. If the MRI is positive,
treatment choices can be based upon that finding and those
treatment choices are beyond the scope of this article. If
the MRI is negative, the patient is referred for a technetium
99 m bone scan. If the bone scan is positive the patient is
scheduled for a core biopsy to establish diagnosis. If the
bone scan is negative, the patient is schedule for bone marrow
pressure study and venogram and, if any of the three tests
- bone marrow stress test, bone marrow pressure stress test,
or venogram - are positive a core biopsy is carried out.
Figure 6. Diagnostic Algorithms
biopsy is for diagnostic purposes, although we also believe
that it has therapeutic effect if the patient is suffering
from early osteonecrosis of the femoral head. If the bone
marrow pressure stress test and venogram are all negative,
the patient is observed for change in symptoms, physical findings,
and imaging findings. Under normal circumstances, if the symptoms
persisted in equal or greater intensity, X-ray and MRI would
be repeated at three months. We believe that it is important
not to miss the early diagnosis of osteonecrosis and that
the outlined algorithm is a responsible way to establish a
diagnosis while keeping down medical expenses.
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