Download Symptomatic Multifocal Osteonecrosis

© 1999 Lippincott Williams & Wilkins, Inc.
Volume 1(369)
December 1999
pp 312-326
Symptomatic Multifocal Osteonecrosis: A Multicenter Study
[Section II: Original Articles: Miscellaneous]
Collaborative Osteonecrosis Group
(A complete list of coinvestigators is listed alphabetically at the end of the article.)
Reprint requests to Michael A. Mont, MD, Department of Orthopaedic Surgery, The Johns Hopkins
Medical Institutions, Good Samaritan Professional Building, 5601 Loch Raven Boulevard, Baltimore, MD
21239.
Received: May 26, 1998.
Revised: January 21, 1999; May 12, 1999.
Accepted: May 19, 1999.
Outline
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Abstract
PATIENTS AND METHODS
RESULTS
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DISCUSSION
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Clinical Evaluation
Radiographic Evaluation
Surgical Management
Coinvestigators
Acknowledgments
References
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Table 1
Table 2
Fig 1
Table 3
Table 4
Table 5
Table 6
Table 7
Table 8
Table. No caption av...
Abstract
Osteonecrosis of the femoral head frequently occurs in a young population (mean
age, approximately 35 years) and may lead to disabling arthritis requiring hip
arthroplasty surgery. This disease is compounded when it has concurrent involvement
of other joints. Multifocal osteonecrosis is defined as disease involving three or more
anatomic sites. The purpose of this study was to review the demographic, clinical,
radiographic staging patterns, and treatment options in patients with multifocal
osteonecrosis to facilitate earlier diagnosis and optimize treatment. Twenty-one
centers participated by submitting completed data forms on patients under their care
after review of their databases. One hundred one patients were identified. Patient
demographics, associated diseases, corticosteroids and other medications used,
presenting joints, and symptomatology were evaluated. Radiographs and magnetic
resonance imaging scans or both were used to diagnose and stage osteonecrotic
lesions. Ninety-two of the 101 (91%) patients had a history of corticosteroid therapy.
Twelve patients (of 14 tested) were found to have a coagulation disorder. All 101
patients had femoral head involvement. Osteonecrosis also was seen in the knee
(96%), shoulder (80%), ankle (44%), and seven other sites. Overall, 631 joints were
involved (6.2 lesions per patient). Bilaterality was common: hips, 98%; knees, 86%;
and shoulders, 83%. Most lesions (69%) were in a precollapse stage at the time the
patients presented for treatment. In eleven patients, the knee was the sole presenting
symptomatic joint, and the shoulder and ankle were the sole presenting symptomatic
joints in five and four patients, respectively. An improved understanding of the
epidemiology, pathogenesis, and etiology of multifocal osteonecrosis will facilitate the
diagnosis and treatment of this disease. In patients with osteonecrosis of the hip, all
symptomatic joints should be evaluated with radiographs. In patients with
osteonecrosis presumably not involving the femoral head, the patient's femoral heads
should be evaluated radiographically, regardless of whether the hips are symptomatic.
Osteonecrosis is a disease primarily affecting patients in the third through fifth
decades of life.36 It affects the hip most commonly and often leads to a disabling
arthritis, necessitating total hip arthroplasty. The disease also may affect other sites,
thus magnifying its adverse clinical effects on patients. These other sites include the
knee, shoulder, ankle, and less commonly, the elbow and wrist.
Multifocal osteonecrosis is defined as disease involving three or more separate
anatomic sites. A review of the literature revealed numerous case reports concerning
this entity,2,5-7,9,13,23,24,26,33,40,47 all of which had a limited number of patients. Some
of the case reports described this process as systemic, and one purpose of this study
was to analyze whether multifocal disease was different in patients with more limited
musculoskeletal osteonecrosis (one or a few joints). Because no one center has
sufficient numbers of patients to conduct a thorough examination of the problem, it is
necessary to conduct a metaanalysis of published results or to conduct multicenter
studies. In multiple meetings of leaders in the field of osteonecrosis (Association
Research Circulation Osseous. October 1996, Fukuoka, Japan; American Orthopaedic
Association Symposium. November, 1996, Durham, NC; The Johns Hopkins
University Center for Osteonecrosis Research and Education Symposium. August,
1995, Baltimore, MD), it was concluded that a comprehensive collaborative effort was
needed to address many of the questions concerning this entity. The purpose of this
study was to review the clinical, demographic, radiographic staging patterns, and
treatment options observed in this group of patients with multifocal osteonecrosis.
PATIENTS AND METHODS
A multicenter study of osteonecrosis was initiated by sending questionnaires to 30
investigators across the United States. A list of questions initially was compiled by six
of the coauthors and sent for review by all of the investigators. The questionnaire
included clinical and radiographic queries. The demographic data included age of the
patient at initial presentation, gender, weight, disease associations, corticosteroid use,
alcohol use, tobacco use, presenting symptom(s), and presenting joint(s). Twenty-one
centers participated by submitting completed data forms on patients under their care.
Forms were reviewed by the writing committee to verify that the patients fulfilled the
inclusion criteria and that the forms were completed. Multifocal disease was defined
as involvement of three separate anatomic sites. For example, a patient with
osteonecrosis of the hip, knee, and shoulder or the hip, knee, and ankle would meet the
inclusion criteria. A patient who had three joints involved, but not three separate
anatomic sites involved, such as two hips and one knee, would not be included.
Osteonecrosis of the knee, which could include the distal femur and the proximal tibia,
was considered one site. The centers also were asked to identify the total number of
patients seen in the same period who had any evidence of osteonecrosis in any joint as
confirmed by magnetic resonance imaging (MRI). Based on these results, an
approximation of the incidence of multifocal disease was made.
Corticosteroid use was analyzed by peak dose, duration of therapy, and by route of
administration of prednisone or its equivalent dose. The study cohort was divided into
three groups based on corticosteroid dose and treatment history (none, low
corticosteroid, high corticosteroid). Patients receiving 2 mg or less per day of
prednisone and treated for 2 years or less were included in the low corticosteroid
group. Patients with a history of corticosteroid doses greater than 20 mg per day
and/or treatment for greater than 2 years comprised the high corticosteroid group. This
system was based on groupings used by Petri et al 44 and others 10,34,35 to simplify
reporting because it is difficult to categorize corticosteroid use because of the
variability of parameters, such as time of use, peak dose, and route of administration.
Intraarticular injections and other local treatments of corticosteroid were excluded
from this analysis because they were regarded as different from systemic
administration.
Alcohol use also was quantitated to determine which patients had a history of
consuming greater than 400 mL of absolute 100% ethanol per week (the threshold
reported to be associated with osteonecrosis by the Japanese Orthopaedic
Association).29,42 Although this work has been done in a Japanese population, it
represents the best effort to date at establishing a threshold for alcohol as a relevant
associated risk factor. Cigarette consumption was evaluated to indicate which patients
had a greater than 10 pack year smoking history (equivalent to one pack per day for 10
or more years) or smoking greater than or equal to one pack per day at the time of
presentation.16,29
The temporal relationship of each patient's multiple symptomatic joints was
recorded to identify which joint(s) was affected first and afterward to characterize the
onset of symptoms. Symptomatology was categorized by presence or absence for each
affected joint.
The radiographic review included analysis by plain radiographs, MRI, or computed
tomographic (CT) scans of involved joints to determine presenting stage, size, and
location of lesions. All of the lesions were staged using one of three staging systems
(Ficat and Arlet,11 Steinberg et al,51 ARCO 36). Because most centers used the Ficat
and Arlet system, all lesions were converted to this staging system for the purpose of
reporting results (Table 1). Although the Ficat and Arlet system may be an
oversimplification, 100% of the lesions could be characterized to one of the four
stages in all patients, regardless of the system used by the responding center. The
authors acknowledge that variability may have been introduced because several
physicians from different centers reviewed the radiographs.
TABLE 1. Ficat and Arlet Classification of Osteonecrosis
The treatment of each patient's involved joints was reviewed. Surgical treatment
was identified by joint involved and correlated with the presence of symptoms.
Outcome of treatment was not analyzed.
The data were compiled from each center and tabulated using an Access 7.0
database (Microsoft Corporation, Redmond, WA). Descriptive statistics were
calculated. Trends concerning the relationship of various demographic variables to
corticosteroid use, radiographic staging, and other variables were evaluated.
Parametric and nonparametric statistical analyses of the results were conducted using
the Computer Programs for Epidemiologic Analysis (PEPI) Software Package Version
2.03 (USD, Incorporated, Stone Mountain, GA). Frequencies were analyzed using a
chi square distribution with a Yates correction. Nonparametric data were evaluated
using the Mann Whitney two-tailed test, whereas parametric data were analyzed with
analysis of variance (ANOVA).
RESULTS
One hundred one patients with multifocal osteonecrosis were included in this
multicenter study from 21 centers throughout the United States between the years of
1980 and 1996. There were 75 female (74%) and 26 male (26%) patients, with a mean
age at presentation of 36 years (range, 15-75 years). Data were available from 12
centers concerning their total number of patients with osteonecrosis. From these
centers, 81 patients had multifocal disease of 2484 patients (3.3%) with a diagnosis of
osteonecrosis.
The most common associated factors, diseases, or comorbidities are listed in Table 2.
Twenty (20%) patients had a history of smoking at least one pack per day of tobacco
or had a greater than 10 pack year smoking history (one pack per day for 10 years).
Ten (10%) patients consumed more than 400 mL per week of alcohol, equivalent to 12
cans of beer.32 Ninety-two of the 101 (91%) patients had a history of corticosteroid
therapy. Of the nine patients with no history of corticosteroid therapy, four had
thrombophilia and hypofibrinolysis or both,14,15,17,45 one with familial Protein S
deficiency, two with high tissue plasminogen activator inhibitor, and one with
Factor V Leiden deficiency or resistance to activated Protein C. The other five patients
were not tested for a possible coagulation disorder. Twelve of 14 patients tested were
found to have a coagulation disorder. Thirty-two (32%) patients had more than one
risk factor for osteonecrosis, with the most common combination being corticosteroid
use and a smoking history (16 patients, 16%). When these patients were compared
with the 61 patients who had corticosteroid history as their only risk factor for
osteonecrosis, there was no significant difference with respect to radiographic stage at
presentation (p = 0.7).
TABLE 2. Comorbidities
Clinical Evaluation
Six hundred thirty-one bony lesions were identified (6.2 per patient) (Fig 1). All
patients had femoral head involvement. The most common other sites involved
included the distal femur (96 patients), proximal humerus (80 patients), and talus (44
patients). Other joints or bones involved included the elbow (capitellum, trochlea),
wrist (distal radius, various carpal bones), calcaneus, tarsal navicular, cuneiform,
cuboid, and metacarpal head; the distributions are shown in Figure 1. Bilaterality (as
confirmed by radiographs or MRI) was common, including 98% of the hips, 87% of
the knees, and 83% of the shoulders. The joints that were less often bilateral included
the ankles (61%) and elbows (42%), as shown in Table 3.
Fig 1. Location of 631 osteonecrotic lesions in 101 patients.
TABLE 3. Distribution of 632 Osteonecrotic Lesions in 201 Patients
Hip symptoms, with or without multiple other joint pain, was the most common
presentation (81 patients, 80%). Forty-four patients presented initially with reports of
hip pain only, whereas 37 patients presented initially with multiple symptomatic
joints. In 11 patients, the knee was the sole presenting symptomatic joint. The
shoulder and the ankle were the only presenting symptomatic joints in five and four
patients, respectively. Of the 287 joints in which symptoms initially presented, there
were 130 hips (45% of presenting joints), 70 knees (24% of presenting joints), 49
shoulders (17% of presenting joints), 29 ankles (10% of presenting joints), and nine
wrists or elbows (3% of presenting joints).
When the patients were divided into high and low dose corticosteroid and
noncorticosteroid groups, the data were not significantly different in terms of gender,
number of sites involved, bilaterality, and presentation (Table 4). Age in the low
corticosteroid group was significantly greater than in the other two groups (p < .005).
When the patients with systemic lupus erythematosus were analyzed separately and
compared with the remaining patients in the study group, the data were not
significantly different with respect to age (mean, 34 years; range, 15-55 years),
number of sites involved (mean, 6.1 sites; range, 4-10 sites), bilaterality, and mode of
presentation. However, there was a trend toward a greater proportion of women versus
men in the systemic lupus erythematosus group (32 women, six men) as compared
with the remaining study group (43 women, 20 men) (p = 0.076).
TABLE 4. Clinical Findings by Corticosteroid Grouping
Radiographic Evaluation
Plain radiography or MRI revealed that most (69%) joints presented in a precollapse
stage (Ficat and Arlet Stage I or II) (Table 5). Eighty-five of 200 (43%) hips had Stage
III (59 hips) or Stage IV (26 hips) disease. Only 17% of 179 knees, 38% of 146
shoulders, and 24% of 71 ankles had Stage III or IV disease. Approximately 30% of
the lesions were diagnosed solely by MRI (Stage I disease). There was a higher
incidence of these Stage I lesions in the knee (38%), shoulder (30%), and ankle (44%)
than in the the hip (18%).
TABLE 5. Ficat and Arlet Staging at Presentation
When the three corticosteroid groups were analyzed, the staging pattern and
distribution were significantly different in the low dose corticosteroid group, with a
greater incidence of presentation with postcollapse disease (Table 6) (p values ranging
from 0.001 to 0.014). When the patients with systemic lupus erythematosus were
evaluated separately and compared with the remaining patients in the study group, the
staging pattern and distribution were not significantly different (p values ranging from
0.113 to 0.956).
TABLE 6. Ficat and Arlet Staging by Corticosteroid Grouping
Surgical Management
The 180 painful hips were treated most commonly with core decompressions,
various grafting procedures, and eventually 77 total hip arthroplasties. The distribution
of procedures is listed in Table 7. The 162 symptomatic knees were managed most
commonly with core decompressions, arthroscopies, and total knee arthroplasties. The
distribution of management methods for the 138 painful shoulders and 78 painful
ankles is listed in Table 7.
TABLE 7. Methods of Treatment
DISCUSSION
Previous journal articles concerning multifocal osteonecrosis have been limited to
case reports.2,5-7,9,13,23,24,26,33,40,47 For this reason, the use of multiple centers to
garner information about this entity was used. Of 13 patients from 13 published case
reports in the English literature concerning this entity, 11 had a corticosteroid
association.2,5,7,9,23,26,33,40,47 The other two patients had the human
immunodeficiency virus and an antiphospholipid antibody syndrome.6,13 Of the
patients with a history of corticosteroid therapy, four had systemic lupus
erythematosus,5,12,26,47 one had a renal transplant,7 one had idiopathic
thrombocytopenic purpura,33 three had malignancy,7,23,40 and one had a head injury
secondary to a motor vehicle accident.2 Although these numbers are small, the
incidence of systemic lupus erythematosus (four of 13; 31%) in these reports is similar
to the incidence seen in the current study group (38 of 101; 38%).
In the current study, patients had a mean of 6.2 osteonecrotic lesions. The hips were
involved in all patients with disease, and there was a bilateral predominance at all
sites. In the study group, 89% of knees, 73% of shoulders, and 35% of ankles were
involved. This is a similar distribution but much higher prevalence than was seen by
Zizic et al 57 in 28 patients with systemic lupus erythematosus, who had 41 hips
(73%), 36 knees (64%), and 16 shoulders (29%) affected. In that study, some patients
had two areas involved, but none had multifocal disease defined by three separate
areas. The joint distribution in the current study group is significantly different from
that reported by McCallum and Walder 30 in patients who worked with compressed
air. Disease involvement in the patients included 34% of the knees (16 of 47 knees),
32% of the shoulders (15 of 47 shoulders), and 17% of the hips (8 of 47 hips).
However, this difference possibly could be explained by the study being performed in
1966, before the advent of MRI.
Multifocal disease was found to occur in at least 3% of patients diagnosed as having
osteonecrosis. This is likely to be an underestimation of patients with asymptomatic
multifocal disease because some patients with multifocal disease have silent lesions
that otherwise would not be identified. Patients with this disease often have
fragmented care, being seen by multiple practitioners (shoulder, hip, knee, foot
specialists), which is another reason for the potential underestimation of the disease
incidence. This is especially true because all joints do not become symptomatic at the
same time.
The current study does not answer the question of whether all hips, knees, and
shoulders should be evaluated if more than one site is involved. The authors do not
know how many patients were not identified who had two sites involved with multiple
other asymptomatic lesions. It has been suggested by various authors 51,52,58 that total
body scintigraphic bone scans may be the most cost effective means of screening for
multifocal involvement. However, not enough information is available to determine if
this is the best approach. It has been found that bone scans may miss lesions 10% to
20% of the time and may not be the best diagnostic modality in these patients.37 Thus,
a separate study is needed to determine the accuracy of this modality. In this cost
conscious climate, it is not possible to perform MRI on every patient with an
asymptomatic joint. An additional clinical research study is needed to justify the
effectiveness of these various diagnostic approaches.
The incidence might be overestimated because the participating centers have a
special interest in this disease and may be more likely to evaluate patients with this
degree of affliction. However, the type of center reporting and its patient population
are crucial because centers that specialize in treatment of patients with systemic lupus
erythematosus or patients who have had transplants may skew the prevalence of this
disease. This study may not reflect centers that have populations of various high risk
patient groups that did not contribute to this study, including patients with Gaucher
disease, sickle cell disease, and other hemoglobinopathies, those with dysbarism
(especially native diving fishermen), and patients from various leukemia and cancer
treatment centers. In addition, this study was compiled from patients from selected
centers in the United States and may not reflect the experience in other countries.
Ninety-eight percent of the hips were involved bilaterally in patients in the study
group, as were 87% of the knees and 83% of the shoulders. This finding is consistent
with a case study by Egan and Munn 6 that described a patient with antiphospholipid
syndrome and multifocal lesions affecting bilateral hips, knees, shoulders, ankles,
elbows, wrists, and feet. Similarly, Gerster et al 13 described a patient with human
immunodeficiency virus and osteonecrosis of bilateral hips, knees, and shoulders. In
contrast to the findings of the current study, Darlington 5 reported on a case of
multifocal osteonecrosis in a patient with systemic lupus erythematosus with no hip
involvement, and Murphy and Greenberg 40 described a patient with acute
lymphocytic leukemia and multifocal osteonecrosis involving only one hip.
In the general literature regarding osteonecrosis, bilaterality of hip lesions ranges
from 34% to 80%.3,4,18,31,36,46 The difference in the current study might be accounted
for by all hips in this study undergoing MRI, so asymptomatic lesions were identified.
The finding of 98% bilaterality of hip lesions in the current study emphasizes the
importance of examining the contralateral hip in a patient with multifocal
osteonecrosis, regardless of the presence or absence of symptoms. This observation is
particularly relevant in the evaluation of a patient with osteonecrosis of joints other
than the hip. It is important that such patients have their hips evaluated, regardless of
whether the joints are symptomatic. Although outcomes were not analyzed in the
current study, most authors believe such patients should have their hips evaluated,
regardless of whether these joints are symptomatic. The high incidence of bilateral hip
involvement in patients with multifocal disease may be a reflection of the severity or
intensity of risk from an undiagnosed comorbidity, such as a coagulation disorder.
In one report concerning osteonecrosis of the hip, the knee and shoulder were
involved 5% to 15% of the time, with other joints less commonly involved.37 Based
on the current study, multifocal osteonecrosis will be found slightly greater than 3% of
the time in patients with osteonecrosis. However, it has been found that patients with
osteonecrosis of other joints have a much higher incidence of multifocal disease.37
From one institution with 1056 patients with osteonecrosis of the hip, 40% (n = 32) of
patients with osteonecrosis of the knee had multifocal disease. In addition, 60% (n =
28) of patients with osteonecrosis of the shoulder had multifocal involvement, and
57% (n = 8) of patients with osteonecrosis of the ankle had multifocal lesions. This
study emphasizes the possible need to screen other joints in patients with
osteonecrosis of the knee, shoulder, or ankle because such patients may have
multifocal disease approximately 50% of the time. The association between
osteonecrosis of the hip and multifocal disease is much lower (3%), so asymptomatic
joints in patients presenting only with hip disease do not need to be evaluated
routinely.
Radiographic evaluation revealed that most sites present in early stages, when
treatment methods aimed at saving the joints may be more successful. Sixty percent of
joints in this study were Ficat and Arlet Stage I or II (precollapse) at the time the
patients presented initially, when nonoperative or operative methods aimed at
preserving the joint are most effective. It is extremely important to diagnose these
lesions as early as possible to initiate treatment because the results of joint
replacement in the knee or hip have been poorer in patients with osteonecrosis than for
other diagnoses.36,39 The incidence of negative radiographic findings but positive
MRI scans (Stage I) was highest in the ankle (44%) and knee (38%) and lower for the
shoulder (30%) and hip (18%). These percentages are similar to those cited in reports
in the literature (Table 8).
TABLE 8. Literature Review of Osteonecrosis Studies
Table. No caption available.
The prevalence of corticosteroid associated osteonecrosis has been variable, being
implicated in 10% to 60% of patients with osteonecrosis in multiple large
demographic studies.1,8,20,27,32,49,53,58 For example, Jacobs,20 in a study of 269
patients, found alcoholism to be the highest association, with 104 (39%) patients, and
a corticosteroid association in 75 (28%) patients. Zizic et al,58 in a study of 169
patients, reported corticosteroid association in 88 (52%) patients and an association
with alcoholism in 19 (11%) patients. The history of corticosteroid therapy found in
11 of 13 (85%) patients in the 13 previous reports of multifocal osteonecrosis 2,57,9,12,13,23,24,26,33,40,47 is similar to that found in the current study group (91%). This
finding suggests a strong relationship between multifocal disease and corticosteroid
therapy. It is difficult to interpret the potential effect of corticosteroid use because of
the many variables, including dosage, duration of treatment, and route of
administration. In terms of dose and duration relationships, despite that this is a
collaborative study with 101 patients, the number of patients available in each group
(noncorticosteroid, low corticosteroid, and high corticosteroid) is too small to analyze
using statistical models. A finding in the current study was that low dose
corticosteroid use was associated with a greater incidence of postcollapse disease.
Although this finding remains unexplained, one possible explanation for this
observation might have been the suppression of synovitis with higher dose
corticosteroid use, leading to suppression of some symptoms that might have led to
earlier diagnosis.
Regarding other associated factors, there was a low incidence of alcohol ingestion
(10%) and cigarette use (20%), which may reflect that lack of voluntary disclosure of
information on these habits may lead to an underestimation. Although this was
studied, there is an absence of a well documented correlation between cigarette
smoking and nontraumatic femoral head osteonecrosis in adult patients who are not
Japanese. In addition, the occurrence of thrombophilia or hypofibrinolysis or both seen
in patients in this study (12%) is falsely low because testing was performed only in 14
patients (87% positive). This rate of coagulation disorders is similar to rates reported
in the literature; between 80% and 90% of patients tested with osteonecrosis had
hypofibrinolysis and thrombophilia or both.14,15,17 Because of the high incidence of
coagulation disorders in patients with osteonecrosis, it is difficult to analyze
differences between patients with multifocal and less musculoskeletal involvement. So
far, in a review of the literature,6,14,17,35 patients with single joint involvement are just
as likely to have a coagulation disorder as are patients with more joint involvement.
The authors think epidemiologic studies are needed to evaluate specific etiologic
factors and various combinations of such factors.
A comparison of patients with multifocal disease with patients with osteonecrosis of
the hips only or osteonecrosis of a few joints was performed (Table 8). In the current
study, the high percentage of women (74%) is similar to numbers of women in other
studies, which are weighted toward patients with systemic lupus erythematosus and
other inflammatory disorders (Zizic et al,57 96% women in lupus population), but
dissimilar to incidences reported in studies where there is a preponderance of patients
who use alcohol, in which more men are seen (Jacobs,21 80% men). The current study
of patients with multifocal disease has a patient population with a higher incidence of
steroid use and bilateral hip involvement. The population of patients with multifocal
disease was similar in terms of patient age, alcohol use, and percentages of presenting
joints reported in 25 large studies.
The multitude of treatment methods aimed at preserving osteonecrotic joints used in
the United States underlie the importance of studying these methods prospectively.
These multiple methods include nonoperative (electrical stimulation, pharmacologic
agents aimed at decreasing lipid levels or altering the hypofibrinolysis and/or
thrombophilia found) and operative techniques (core decompression with or without
bone grafting, nonvascularized and vascularized bone grafting, and osteotomies).
Additional multicenter studies are needed to evaluate the outcomes of these various
treatment methods.
The authors recognize limitations of this study in that it was a retrospective, cross
sectional investigation of an uncommon condition. There were differences in
categorization, methodology, and screening methods by the different centers with no
independent evaluation. Although the authors are all experienced in using the Ficat
and Arlet staging system, there is potential variability inherent in trying to stage a
disease at multiple centers when there is not universal agreement about the staging.
However, despite these limitations, this study has enabled investigation of patients
with a condition that no one center has enough patients to evaluate. Using this type of
research design, the study: (1) determined the incidence of multifocal osteonecrosis to
be approximately 3% of the total population with osteonecrosis; (2) found the
distribution of joints with multifocal osteonecrosis to be the hip (91%), knee (87%),
shoulder (72%), and ankle (35%); (3) supports examining hips in all patients with
multifocal disease because they were found to be involved universally with
osteonecrosis; (4) emphasized the need for a high index of suspicion in patients treated
with corticosteroids (with an occurrence of 91%); and (5) described an ill defined
condition that often is confused with other disorders (infections, tumors) and
compared the similarities and differences to more limited disease.
The study also underscores the importance of establishing a collaborative national
database from multiple centers for the better design of prospective studies for the
treatment of osteonecrosis. This could be accomplished by prospective data
acquisition to assess the time course of the disease and the outcomes after
intervention, which might best be performed using randomized trials.
Coinvestigators
The data and preparation of this article required major effort on the part of all of the
following contributors: Writing team: Michael A. Mont, MD; Lynne C. Jones, PhD;
Dawn M. LaPorte, MD; Department of Orthopaedic Surgery, Johns Hopkins Medical
Institutions, Baltimore, MD; Co-authors: Roy K. Aaron, MD, Department of
Orthopaedics, Brown University, Providence, RI; Michael J. Christie, MD, Vanderbilt
Arthritis Joint Replacement Center, Nashville, TN; Charles J. Glueck, MD,
Cholesterol Center, The Jewish Hospital of Cincinnati, Cincinnati, OH; Stuart B.
Goodman, MD, Division of Orthopaedic Surgery, Stanford University Medical Center,
Stanford, CA; Steven Haas, MD, Hospital for Special Surgery, New York, NY;
William L. Healy, MD, Department of Orthopaedic Surgery, Lahey Hitchcock
Medical Center, Burlington, MA; David A. Heck, MD, Indiana University,
Indianapolis, IN; Peter A. Holt, MD, The Good Samaritan Hospital, Baltimore, MD;
David S. Hungerford, MD, Department of Orthopaedic Surgery, The Johns Hopkins
Medical Institutions, Baltimore, MD; Richard Iorio, MD, Department of Orthopaedic
Surgery, Lahey Hitchcock Medical Center, Burlington, MA; John Paul Jones, MD,
Diagnostic Osteonecrosis Center and Research Foundation, Kelseyville, CA; John
Klibanoff, MD, Department of Orthopaedics, Strong Memorial Hospital, Rochester,
NY; Carlos J. Lavernia, MD, Department of Orthopaedics and Rehabilitation,
University of Miami School of Medicine, Coral Gables, FL; Tung Le, Department
of Orthopaedic Surgery, The Johns Hopkins Medical Institutions, Baltimore, MD;
Dennis W. Lennox, MD, Department of Orthopaedic Surgery, The Johns Hopkins
Medical Institutions, Baltimore, MD; Roger N. Levy, MD, Department of
Orthopaedics, Mount Sinai Medical Center, New York, NY; Michelle Petri, MD,
Department of Rheumatology, The Johns Hopkins Medical Institutions, Baltimore,
MD; Aiman Rifai, DO, Department of Orthopaedics, The Johns Hopkins Medical
Institutions, Baltimore, MD; Aaron G. Rosenberg, MD, Midwest Orthopaedics,
Chicago, IL; Melvin P. Rosenwasser, MD, Columbia University Medical Center, New
York, NY; Richard N. Stauffer, MD, Department of Orthopaedic Surgery, The Johns
Hopkins Medical Institutions, Baltimore, MD; Marvin E. Steinberg, MD, Department
of Orthopaedic Surgery, University of Pennsylvania Medical Center, Philadelphia,
PA; Bernard N. Stulberg, MD, Cleveland Center for Joint Reconstruction, Cleveland,
OH; Audrey Tsao, MD, Department of Orthopaedic Surgery, Jackson, MS; James
Urbaniak, MD, Division of Orthopaedic Surgery, Duke University Medical Center,
Durham, NC; Thomas Parker Vail, MD, Division of Orthopaedic Surgery, Duke
University Medical Center, Durham, NC; Gwo-Jaw Wang, MD, Department of
Orthopaedics, University of Virginia Medical Center, Charlottesville, VA; Steven B.
Zelicof, MD, PhD, Joint Reconstructive Service, Westchester County Medical Center,
Valhalla, NY; and Thomas M. Zizic, MD, The Good Samaritan Hospital, Baltimore,
MD.
Acknowledgments
The authors thank Regina M. Barden, RN, BSN, Midwest Orthopaedics, Chicago,
IL; Enrique Barrientos, PAC, Joint Reconstruction Service, New York Medical
College, Valhalla, NY; Gail Bunce, RN, Providence, RI; Melanie J. Capps, RN,
Vanderbilt Arthritis Joint Replacement Center, Nashville, TN; Eunice Gunneson,
PAC, Division of Orthopaedic Surgery, Duke University Medical Center, Durham,
NC; Karen M. Hartman, CRC, Department of Orthopaedic Surgery, University of
Pennsylvania Medical Center, Philadelphia, PA; Clara Maye-Lewis, Arthritis
Division, Good Samaritan Hospital, Baltimore, MD; Cindy Partridge, BS, Indiana
University, IN; and Rose Sampson, Arthritis Division, Good Samaritan Hospital,
Baltimore, MD.
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