HIV/AIDS • CID 2007:44 (1 March) • 739
H I V / A I D SM A J O R A R T I C L E
The Incidence and Natural History of Osteonecrosis
in HIV-Infected Adults
Caryn G. Morse,2JoAnn M. Mican,1Elizabeth C. Jones,3Galen O. Joe,4Margaret E. Rick,5Elizabeth Formentini,2
and Joseph A. Kovacs2
1Office of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), and
Department and Departments of
2Critical Care Medicine
4Rehabilitation Medicine, and
5Laboratory Medicine, NIH Clinical Center, Bethesda, Maryland
ciency virus (HIV) infection, but the natural history has not been well described. We previously documented a
high prevalence (4.4%) of magnetic resonance imaging (MRI)–documented osteonecrosis of the hip in a cohort
of 339 asymptomatic HIV-infected patients. The present study was designed to determine the incidence of newly
diagnosed osteonecrosis in this cohort and to describe the natural history of osteonecrosis in HIV-infectedpatients.
Asymptomatic HIV-infected patients with a previous hip MRI negative for osteonecrosis underwent
follow-up MRI. Patients with asymptomatic or symptomatic osteonecrosis were enrolled in a natural history study,
which included serial MRIs and a physiotherapy follow-up.
Two hundred thirty-nine patients underwent a second MRI a median of 23 months after the initial
MRI. Osteonecrosis of the femoral head was diagnosed in 3 patients (incidence, 0.65 cases per 100 person-years).
During the period of January 1999 through April 2006, symptomatic hip osteonecrosis developed in 13 clinic
patients (incidence, 0.26 cases per 100 person-years). Among 22 patients enrolled with symptomatic hip osteo-
necrosis, 18 had bilateral involvement of the femoral heads, and 7 had osteonecrosis involving other bones. Two
(11%) of 18 asymptomatic patients and 13 (59%) of 22 symptomatic patients underwent total hip replacement.
The percentage of involvement of the weight-bearing surface of the femoral head and the rate of progression to
total hip replacement was significantly greater () in symptomatic patients than in asymptomatic patients.P ! .001
HIV-infected patients are at ∼100-fold greater risk of developing osteonecrosis than the general
population. Disease progression is slower in asymptomatic patients than in symptomatic patients. Given the high
frequency of total hip replacement in symptomatic patients, studies to assess preventive and treatment strategies
Osteonecrosis is increasingly recognized as a debilitating complication of human immunodefi-
Since 1996, the broad availability of HAART in the
United States has led to a dramatic decrease in the
incidence of opportunistic infections and malignancies
and prolonged survival for HIV-infected patients .
During this period, previously unrecognized compli-
cations of long-standing HIV infection and treatment
have had an increasing impact on the quality of life for
these patients. Osteonecrosis of the hip and of other
Received 16 August 2006; accepted 13 November 2006; electronicallypublished
23 January 2007.
Presented in part: 7th International Workshop on Adverse Drug Reactions and
Lipodystrophy in HIV, Dublin, Ireland, 13–17 November 2005 (abstract 86).
Reprints or correspondence: Dr. Caryn G. Morse, National Institutes of Health,
9000 Rockville Pike, Bldg. 10, Rm. 2C145, MSC 1662, Bethesda, MD 20892-1662
Clinical Infectious Diseases2007;44:739–48
This article is in the public domain, and no copyright is claimed.
bones is one such debilitating complication. First de-
reports and retrospectivecasestudieshavesubsequently
appeared in the medical literature . An increased
incidence of previously recognized risk factors for os-
teonecrosis, such as corticosteroid use, hypercoagulable
state, alcohol abuse, and tobacco use, has been asso-
ciated with osteonecrosis in these patients [3–13]. Ad-
ditional reported risk factors include the use of anti-
retroviral drugs (especially protease inhibitors), the
presence of lipodystrophy syndrome, and use of me-
gestrol acetate or testosterone [10, 12, 14, 15].
The annual incidence of symptomatic osteonecrosis
in the general population has been estimated to be
approximately 0.003–0.006 cases per 100 person-years
[16, 17]. Recent retrospective case studies of HIV-in-
fected patients have reported incidences ranging from
0.03 to 0.37 cases per 100 person-years [7, 8, 12, 18–
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740 • CID 2007:44 (1 March) • HIV/AIDS
of the patients in whom the diagnosis of osteonecrosis was made after the development of clinical symptoms (right). The patients indicated in blue
and red were those included in the natural history analysis for the asymptomatic and symptomatic cohorts, respectively.
Flow diagram indicating the outcome of the asymptomatic patients who underwent MRI screening for osteonecrosis (left) and the source
20], although the true incidence of symptomatic osteonecrosis
evaluation of osteonecrosis in HIV-infected patients has been
undertaken. Moreover, the natural history of osteonecrosis—
specifically, the frequency of and time to hip replacement—is
undefined in this population. Given that recent studies have
shown that treatment with bisphosphonates can reduce the
need for total hip replacement (THR) in certain populations,
it is critical to understand the natural history of osteonecro-
sis in both symptomatic and asymptomatic HIV-infected
In 2001, our research group reported an unexpectedly high
prevalence (4.4%) of MRI-documented osteonecrosisofthehip
in a cohort of 339 asymptomatic HIV-infected patients.The
identification of a cohort of HIV-infected adults with negative
results of hip MRIs, as well as a cohort of patients with MRI-
documented osteonecrosis, provided a unique opportunity to
study the incidence and naturalhistoryofosteonecrosisinHIV-
Here, we present a prospective study documenting the in-
cidence of osteonecrosis in asymptomatic HIV-infected pa-
tients. In addition, we report longitudinal follow-up data on a
cohort of prospectively identified HIV-infected patients with
asymptomatic osteonecrosis and a cohort of symptomaticHIV-
infected patients who were enrolled after receiving a diagnosis
The methods of the initial prevalencestudyhavebeendescribed
elsewhere . In brief, 339 HIV-infected adults enrolled in
studies of the treatment or natural history of HIV infection at
the National Institutes of Health Clinical Center (Bethesda,
MD) underwent MRI of both femoral heads. Because the study
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748 • CID 2007:44 (1 March) • HIV/AIDS
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Note added in proof.
of the femoral heads bilaterally, a patient with osteonecrosis of the femoral heads bilaterally received a diagnosis of osteonecrosis of
the knees bilaterally, and a patient with bilateral osteonecrosis of the femoral heads (identified initially as part of the asymptomatic
cohort) had progression to left THR. The latter patient had 25%–50% involvement of the left femoral head.
Since this manuscript was submitted for publication, an additional patient receivedadiagnosisofosteonecrosis
by guest on October 28, 2015