Download Osteonecrosis of the Hip

CLINICAL ORTHOPAEDICS AND RELATED RESEARCH
Number 465, pp. 53–62
© 2007 Lippincott Williams & Wilkins
Osteonecrosis of the Hip
Novel Approaches to Evaluation and Treatment
Frank A. Petrigliano, MD*; and Jay R. Lieberman, MD†
The treatment of osteonecrosis of the hip remains a dilemma.
Contemporary basic science research focuses on establishing
the molecular etiology of this disease with the hope of identifying targets for pharmacologic intervention. Researchers
have identified specific genetic polymorphisms that may predispose its development and these may allow early diagnosis
and treatment of at-risk patients. Refinements in magnetic
resonance imaging aid in the staging of patients with osteonecrosis and findings appear to correlate with clinical outcome. Novel nonoperative and operative modalities for the
treatment of osteonecrosis are also under investigation. The
results of new pharmacologic and biophysical treatments appear beneficial in delaying, and possibly preventing, the progression of precollapse lesions. New bone grafting strategies
may enhance the results of core decompression. Although the
results of conventional total hip arthroplasty have improved,
newer surface replacement systems provide satisfactory
short-term outcomes and may preserve bone stock in
younger patients. Further research is needed to clarify the
roles of these emerging technologies in the treatment of osteonecrosis of the hip. Until there is convincing evidence of
efficacy in randomized clinical trials, we recommend appropriate staging and core decompression with or without bone
graft for precollapse lesions and total hip arthroplasty or
surface replacement for advanced disease.
Osteonecrosis of the hip typically affects relatively young,
active patients and frequently follows an unrelenting
course resulting in considerable loss of function. There are
an estimated 20,000 to 30,000 new cases of osteonecrosis
diagnosed annually, and approximately 10% of all total
hip arthroplasties (THAs) are performed for the diagnosis.13 Because the etiology of osteonecrosis remains unknown and there is no gold standard for treating this disease, investigators continue to focus on these unanswered
problems.
The purpose of our selective review is twofold. First, it
serves to update the reader on recent progress that has been
made in defining the etiology of osteonecrosis. These include the vasoactive effects of corticosteroids and alcohol
on the femoral head,6,7 genetic polymorphisms which may
predispose certain patient cohorts to the development of
osteonecrosis,3,16 and novel radiographic indicators that
may predict future collapse of the head.3,6,7,10,16,23,27,46
Second, we review the efficacy of unique nonoperative
and operative femoral head-sparing interventions, as well
as the use of resurfacing procedures for advanced disease.
This includes the use of pharmacologic and biophysical
modalities,2,17,25,36 tantalum implants,42,45 and surface replacements.32,38,43 The potential of these novel therapies
and their present limitations will be discussed and placed
in context with respect to more standard treatments.
Level of Evidence: Level V, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.
Search Strategies
We performed a PubMed Medline literature search to
identify all English language studies on osteonecrosis of
the hip from January 1, 2000 to May 1, 2007. The terms
“osteonecrosis of the hip” OR “osteonecrosis of the femoral head” OR “avascular necrosis of the hip” OR “avascular necrosis of the femoral head” OR “aseptic necrosis
of the hip” OR “aseptic necrosis of the femoral head”
yielded 1279 citations. We (FAP, JRL) qualitatively selected those articles in which the title made reference to
etiology, imaging, and clinical treatment of osteonecrosis
of the femoral head or hip including animal studies. These
abstracts were then analyzed and full articles reviewed if
From the *Department of Orthopaedic Surgery, David Geffen School of
Medicine, University of California Los Angeles, Los Angeles, CA; and †The
New England Musculoskeletal Institute and Department of Orthopaedic Surgery, University of Connecticut School of Medicine, Farmington, CT.
Each author certifies that he or she has no commercial associations (eg,
consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the
submitted article.
Correspondence to: Frank A. Petrigliano, MD, Department of Orthopaedic
Surgery, David Geffen School of Medicine, University of California Los
Angeles, Room #16-155, 10833 Le Conte Ave, Los Angeles, CA 90095.
Phone: 310-403-0441; Fax: 310-825-1311; E-mail: fpetrigliano@mednet
.ucla.edu.
DOI: 10.1097/BLO.0b013e3181591c92
53
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
54
Petrigliano and Lieberman
we considered the approach novel and deemed it to have a
potential impact on the diagnosis, treatment, or future
study of osteonecrosis of the hip. We did not judge study
quality as this paper is intended to serve as a selected
literature review rather than a systematic review.
Etiology and Pathophysiology
Although no discrete agent or pathologic mechanism has
been identified in the development of osteonecrosis of the
hip, a number of factors, including alcohol use, high-dose
corticosteroid administration, and coagulation abnormalities have been implicated in the process. Most of the theories regarding the pathophysiology of osteonecrosis point
toward alterations in intravascular blood flow, direct cellular toxicity, and most recently, impaired mesenchymal
cellular differentiation as potential mechanisms.15,18,21,44
Suh et al44 hypothesized the osteogenic and adipogenic
differentiation ability of mesenchymal stem cells may be
altered in patients with alcohol-induced osteonecrosis of
the femoral head. Bone marrow was collected from the
proximal femurs of patients having hip arthroplasty for
either alcohol-induced osteonecrosis of the femoral head
or femoral neck fractures. Cells obtained from the patients
with alcohol-induced osteonecrosis of the femoral head
demonstrated a reduced ability to differentiate toward an
osteogenic lineage compared with the cells obtained from
the patients with femoral neck fractures. Lee et al19 described the osteogenic and adipogenic capacity of bone
marrow stromal cells derived from the proximal femurs of
patients with atraumatic osteonecrosis versus those obtained from patients with osteoarthritis. The osteogenic
differentiation capacity of bone marrow stromal cells in
patients with alcohol-induced and idiopathic osteonecrosis
was considerably reduced compared with those of patients
with osteoarthritis. However, there was no difference in
the adipogenic potential of bone marrow stromal cells between groups. Cui et al4 demonstrated that in vitro alcohol
exposure resulted in reduced osteogenic gene expression
and enhanced adipogenic morphologic characteristics in a
cloned bone marrow stem cell population. The results of
these studies suggest the altered function of mesenchymal
stem cells could be responsible for the pathologic changes
noted in osteonecrosis of the femoral head. These changes
may be attributed both to decreased osteogenic differentiation and to alterations in blood flow resulting from increased adipocyte volume.4
Other authors6,7,50 have investigated the correlation between corticosteroids and the development of osteonecrosis of the hip. In an attempt to clarify this relationship,
investigators have studied the in vitro cellular response of
bone marrow stromal cells and vascular tissues to corticosteroids. Yin et al50 found bone marrow stromal cells exposed to dexamethasone demonstrated increased expres-
Clinical Orthopaedics
and Related Research
sion of the adipogenic gene 422(aP2), increased levels of
triglyceride synthesis, and a corresponding decrease in cellular proliferation as well as bone marker gene expression.
Drescher et al6 explored the effects of methylprednisolone
on vasoconstriction of femoral head epiphyseal arteries in
a porcine model. After 24 hours of methylprednisolone
treatment, the vasoconstrictive response to endothelin-1
was stronger in corticosteroid-treated vessels, whereas the
vasodilator bradykinin elicited less relaxation in the corticosteroid-treated vessels. The authors concluded methylprednisolone-enhanced contraction of femoral head arteries might decrease femoral head blood flow in this model.
In a followup study that investigated the effects of longterm (3-month) oral methylprednisolone treatment, an enhanced response to endothelin-1 was once again observed.7 Collectively, these studies suggest there may be
specific molecular pathways which are altered in some
patients that develop osteonecrosis of the femoral head. It
appears alcohol and corticosteroids have a profound effect
on bone marrow stromal cell differentiation and blood
supply, and that these alterations may impair physiologic
bone turnover and oxygenation. Nonetheless, these studies
do not explain why the vast majority of patients who abuse
alcohol or receive steroids never develop osteonecrosis of
the hip. Further studies are required to delineate the molecular pathways underlying this disease and potential targets for pharmacologic treatment and prevention.
Genetic Variants
Advances in technology have improved the accessibility of
human genotyping, intensifying efforts at describing genetic polymorphisms that may predispose patients to the
development of osteonecrosis. Liu et al23 identified a gene
mutation mapped to chromosome 12q13, which resulted in
Type II collagen abnormalities and autosomal-dominant
inheritance of osteonecrosis of the femoral head. Koo et
al16 described the association between osteonecrosis of the
femoral head and endothelial nitric oxide synthase gene
polymorphisms in Korean patients. A specific polymorphism in the endothelial nitric oxide synthase gene was
closely associated with the development of osteonecrosis
in this cohort of patients as compared with matched control subjects. The carrier state of this specific allele might
represent a genetic risk factor and nitric oxide may play a
protective role in the pathogenesis of osteonecrosis of the
femoral head.16 Baldwin et al3 examined the association of
single nucleotide polymorphisms in specific candidate
genes (cytokines, inflammation, oxidant stress, bone metabolism) in patients with sickle cell disease who developed osteonecrosis. Single nucleotide polymorphisms and
haplotypes composed of several single nucleotide polymorphisms were found in bone morphogenic protein-6,
annexin A2, and klotho. These genes are instrumental in
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Number 465
December 2007
Current Trends in Osteonecrosis of the Hip
55
bone formation, metabolic activity, and vascular development. Clearly, some patients that develop osteonecrosis of
the femoral head have a genetic predisposition to development of the disease. This would explain why only a
small percentage of transplant patients (renal, liver, and
cardiac) on steroids develop symptomatic disease. However, in order to be useful as a screening test, specific
genetic variants that are associated with the development
of osteonecrosis should be identified.
Imaging and Evaluation
Magnetic resonance imaging (MRI) continues to be the
gold standard with 99% sensitivity and specificity in diagnosing osteonecrosis of the femoral head.21 Refinements in this imaging technique have led to improved
utility in characterizing osteonecrotic lesions. These improvements may have implications on identifying the natural history of the disease, risk for femoral head collapse,
and response to femoral head-sparing treatments. Vande
Berg et al46 prospectively followed 20 patients with newly
diagnosed rheumatic disease before the initiation of corticosteroids. Baseline femoral neck marrow status was assessed by MRI, and the presence of osteonecrosis was
further assessed at 6 and 12 months. Four patients (20%)
developed bilateral femoral head osteonecrosis at 6
months. Prior to treatment, MRI revealed these patients
had a higher mean percentage of fat marrow in the femoral
neck than those patients who did not develop osteonecrosis. These data suggest the development of corticosteroidinduced osteonecrosis may correlate with a high fat content in the proximal femur before the initiation of steroid
therapy. In another prospective investigation, Ito et al14
sought to determine the importance of MRI findings on
predicting the outcome of patients with osteonecrosis of
the femoral head. Eighty-three asymptomatic or minimally
symptomatic hips in 61 consecutive patients with MRI
evidence of osteonecrosis were followed prospectively. At
a mean followup of 60 months, 36 (43%) of the 83 hips
were symptomatic. Bone marrow edema was present in 28
hips (34%), and 27 (96%) of the 28 hips demonstrating
bone marrow edema were symptomatic. The presence of
bone marrow edema on MRI appreciably correlated with
worsening of hip pain and this was the most important risk
factor associated with progression of symptoms. Ha et al10
used MRI to predict femoral head collapse in 37 hips with
early-stage osteonecrosis of the femoral head. Using a
modified Kerboul method, a combined necrotic angle (Fig
1) was ascertained from midsagittal and midcoronal MRI
scans. Hips were classified by grades of severity and randomly assigned to a core decompression group or a nonoperative group. At a minimum 5-year followup, none of
the four hips with a combined necrotic angle of less than
or equal to 190° collapsed, whereas all 25 hips with a
Fig 1A–B. These images represent (A) midcoronal and (B)
midsagittal MRI of the left hip in a patient with osteonecrosis.
The modified Kerboul angle is obtained by adding angle A and
angle B, which represent the area of involvement. Adapted
from Ha YC, Jung WH, Kim JR, Seong NH, Kim SY, Koo KH.
Prediction of collapse in femoral head osteonecrosis: a modified Kerboul method with use of magnetic resonance images.
J Bone Joint Surg Am. 2006;88(suppl 3):35–40. Reprinted with
permission from The Journal of Bone and Joint Surgery, Inc.
combined necrotic angle greater than or equal to 240°
collapsed. Four of the eight hips with a combined necrotic
angle between 190° and 240° collapsed. No difference was
noted between untreated hips and hips undergoing core
decompression. These data suggest the modified Kerboul
combined necrotic angle, as ascertained with use of MRI,
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56
Petrigliano and Lieberman
is a useful method to predict future collapse in hips with
osteonecrosis of the femoral head and that core decompression had no effect in preventing collapse in this highrisk group of patients.
MRI continues to be the gold standard for assessing
patients with suspected or established osteonecrosis of the
hip. High fat content and bone marrow edema in the proximal femur appear to predict an increased risk of future
collapse. The association of osteonecrosis with high fat
content in the femoral neck is consistent with the aforementioned basic science studies4,19,44 that demonstrated a
relationship between adipogenesis and the development of
osteonecrosis of the femoral head.
Treatment
Nonoperative Treatment
Nonoperative treatment consisting of observation or protected weight bearing continues to have a limited role in
the treatment of osteonecrosis of the femoral head. A frequently asked question is: what is the natural history of
asymptomatic lesions in the contralateral hip? Hernigou et
al12 prospectively followed the progression of 40 hips with
small, asymptomatic Stage I lesions diagnosed by MRI
during the workup of the symptomatic opposite hip in
patients with known risk factors for osteonecrosis. At an
average followup of 11 years, 35 (88%) of the 40 hips
were symptomatic, and 29 (73%) demonstrated collapse.
The mean interval between diagnosis and the first symptoms was 80 months, and at the time of final followup the
29 hips with collapse underwent surgery. All hips were
symptomatic for at least 6 months before collapse. There
are several important messages that can be gleaned from
this study. First, when assessing the operative treatment of
patients with small lesions, a minimum 5-year followup is
necessary to truly evaluate success. Second, because small
lesions will eventually collapse, serious consideration
should be given to the prophylactic treatment of the opposite hip with a moderate to large lesion. Finally, in many
cases the hip can be observed until it becomes symptomatic before instituting operative intervention because collapse typically follows the onset of symptoms by at least 6
months.
Pharmacologic Agents
Several recent studies have explored the use of pharmaceutical agents that address one of the proposed
pathophysiological mechanisms of osteonecrosis. Accordingly, antihyperlipidemic, antihypertensive, anticoagulant,
and bisphosphonate medications have all been assessed
as potential treatment agents. A number of small series
have reported the efficacy of such medications in im-
Clinical Orthopaedics
and Related Research
proving symptoms or delaying progression of the disease.2,5,9,17,27,36,37
In a randomized, prospective study, Lai et al17 evaluated the efficacy of alendronate (70 mg orally daily for 25
weeks) in preventing femoral head collapse in patients
with Steinberg Stage II or III atraumatic osteonecrosis of
the femoral head. Thirteen patients had a history of glucocorticosteroid intake, while the remaining 27 had no
known risk factors. At a minimum followup of 24 months
(range, 24–28 months), two of 29 (7%) femoral heads in
the alendronate group collapsed, whereas 19 of 25 (76%)
femoral heads in the control group collapsed. Moreover,
one hip in the alendronate group underwent THA, whereas
16 hips in the control group underwent THA. In a nonrandomized prospective series, Nishii et al36 followed 22
patients (33 hips) with steroid-induced (26 hips), alcoholrelated (5 hips), and idiopathic (2 hips) osteonecrosis of
the hip and demonstrated a decreased frequency of femoral
head collapse (six of 13 hips in the control group versus
one of 20 hips in the treatment group) and a lower frequency of reported hip pain at a final 1-year followup in a
cohort of patients treated with alendronate (5 mg orally
daily for 12 months) for osteonecrosis of the femoral head.
Similarly, Agarwala et al2 followed 60 patients (100 hips)
with osteonecrosis for an average of 37 months (range,
3–60 months). The cause of osteonecrosis was steroids in
28 patients. Alcohol (12), idiopathic (6), trauma (5), multiple factors (alcohol, trauma, smoking) (7), postpartum
(1) and smoking (1) accounted for the rest. The authors
found a reduction in pain and disability scores and an
increase in standing and walking time in a cohort of patients with osteonecrosis of the hip treated with alendronate for 1 year. These studies suggest alendronate, which
inhibits osteoclast activity and influences bone turnover
and remodeling, can delay or prevent collapse of the femoral head in osteonecrosis of the hip. However, a large
randomized trial with longer followup is necessary to determine the efficacy of this therapy.
In a prospective investigation, Glueck et al9 compared
the efficacy of the low-molecular-weight heparin enoxaparin in 16 patients (20 hips; mean age 45 ± 8 years) who
had thrombophilic or hypofibrinolytic disorders and Ficat
Stage I or II osteonecrosis of the femoral head with 12
similar patients (15 hips; mean age 36 ± 9 years) who had
steroid-induced osteonecrosis. Nineteen of 20 hips with
primary osteonecrosis were unchanged at final followup
(108 weeks or more), whereas 12 of 15 hips with steroidinduced osteonecrosis progressed to Stage III or IV disease. This study underscores the difficulty in developing a
universal strategy to manage patients with symptomatic
disease. While osteonecrosis may be the endpoint, the etiology of the disease is variable and treatment may need to
address the underlying mechanism of disease.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Number 465
December 2007
Current Trends in Osteonecrosis of the Hip
Disch et al5 prospectively studied the effects of the
vasodilator iloprost in 16 patients with isolated bone marrow edema syndrome (Group I) and 17 patients with associated osteonecrosis of the femoral head (Group II)
(mean age, 46 years; range, 23–71 years). Patients with
bone marrow edema syndrome and early-stage osteonecrosis of the femoral head had considerable improvement
in the Harris hip score (Group I, mean 26.6-point improvement; Group II, mean 18-point improvement), range of
motion, extent of the edema on MRI, and pain on a visual
analog scale after 12 months of treatment. None of the hips
in either group demonstrated collapse nor did any hip undergo surgery during the treatment period.
Although the early results with pharmacologic treatment of osteonecrosis are encouraging, appropriately powered, long-term randomized studies are mandated to further elucidate the safety and efficacy of these treatment
regimens. In addition, associated risk factors (ie, alcohol,
steroids, inflammatory disease) may influence the efficacy
of these pharmacologic agents and, again, these short-term
results should not be generalized to all patients with osteonecrosis.
Biophysical Modalities
Extracorporeal shockwave and pulsed electromagnetic
field therapy have demonstrated potential in the treatment
of femoral head osteonecrosis. In a randomized, prospective trial, the results of extracorporeal shockwave therapy
in 23 patients (29 hips) were compared with those of core
decompression and nonvascularized fibular grafting in 25
patients (28 hips) with ARCO Stage I, II, or III osteonecrosis of the femoral head.48 The etiology of osteonecrosis
was alcohol-related in 32 patients, steroid-induced in four
patients, and idiopathic in 12 patients. At an average of 25
months (range, 24–39 months) after treatment, 23 of 30
(79%) hips treated with shockwave therapy were improved
as assessed by Harris hip scores as well as evaluation of
the ability to carry out activities of daily living versus 8 of
28 hips (29%) of those treated with a nonvascularized
fibular graft. Three hips (10%) went on to THA in the
shockwave group, whereas nine hips (32%) underwent arTABLE 1.
57
throplasty after core decompression. Massari et al25 performed a retrospective analysis evaluating pulsed electromagnetic field stimulation of 76 hips with Ficat Stage I, II,
or III osteonecrosis of the femoral head. There were no
identifiable associated risk factors in fifty-one patients
(67%), whereas a predisposing risk factor could be identified in fifteen patients (20%).The authors found this modality was effective in eliminating pain in 35 of 76 patients
(46% after 60 days of therapy. Twenty hips (26%) demonstrated radiographic progression in Ficat stage at final
followup (average, 28 months). Although these short-term
results are promising, large randomized trials are necessary to clarify and substantiate the relevance of these
short-term data.
Operative Treatment
Traditional surgical treatment of osteonecrotic lesions of
the hip can be broadly categorized into either femoral
head-sparing or arthroplasty procedures. Femoral headsparing procedures are generally reserved for symptomatic
precollapse lesions or small postcollapse lesions. They include core decompression, core decompression with nonvascularized or vascularized bone grafting, and rotational
osteotomies.20,24,26,28,29,31,39,41,49,51 While a number of recent articles have focused on the outcomes of these procedures, we will review the results of novel therapies that
seem to have clinical potential. Core decompression using
a variety of techniques demonstrates effectiveness in managing small to moderate-sized lesions.20,30,40 The goal
now is to increase the success rate in patients with small
lesions and to develop more effective strategies for patients with larger lesions.
Novel Therapies
The comparatively poor results of current treatments have
prompted the investigation into a number of novel operative therapies for treatment of osteonecrosis of the femoral
head (Table 1). A pair of retrospective studies has evaluated the efficacy of bone morphogenetic protein-enhanced
bone graft in preventing disease progression in osteonecrosis of the femoral head. Mont et al28 used a modified
Results of Novel Surgical Therapies for Osteonecrosis of the Femoral Head
Authors
Mont et al30
Lieberman et al22
Veillette et al47
Shuler et al42
Gangji et al8
Hernigou and
Beaujean11
Surgical Treatment
Core
Core
Core
Core
Core
decompression
decompression
decompression
decompression
decompression
+
+
+
+
+
BMP-enriched bone graft substitute
BMP-enriched AAA cortical bone
tantalum metal implant
tantalum metal implant
MSC
Core decompression + MSC
Number of
Patients (hips)
Mean Followup
(range)
Overall
Survival
19 (21)
15 (17)
54 (60)
24 (48)
13 (18)
48 months (36–55 months)
53 months (26–94 months)
48 months (6–52 months)
39 months (27–59 months)
24 months
86%
82%
68%
86%
90%
116 (189)
7 years (5–11 months)
BMP = bone morphogenic protein; AAA = allogeneic, antigen-extracted, autolyzed; MSC = mesenchymal stromal cells
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
82%
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Petrigliano and Lieberman
trapdoor technique and bone morphogenetic proteinenriched bone graft substitute through a window at the
femoral head-neck junction in 23 patients and reported
successful clinical results (a Harris hip score of 80 points
or greater and no additional procedures) in 18 of 21 hips
(86%) at a minimum followup of 36 months (mean, 48
months; range, 36–55 months). However, this procedure
requires an extensive dissection, and it is also technically
more difficult than a standard core decompression. Lieberman et al22 reviewed the results of 15 patients treated with
core decompression in conjunction with an alloimplant
composite of allogeneic, antigen-extracted, autolyzed cortical bone perfused with human bone morphogenetic protein and noncollagenous proteins. Radiographic progression of disease was prevented in 14 of 17 hips at an average of 53 months (range, 26–94 months). Only one of 15
hips that were classified as Ficat Stage II-A developed
collapse. The other two hips that progressed already had
collapse of the femoral head before the procedure. The
data suggest core decompression may be more effective if
combined with osteoinductive and/or angiogenic factors.
Perhaps larger lesions could be successfully treated if the
strut graft was coated with growth factor as well. However, the durability and long-term physiologic effects of
bone morphogenetic protein utilized in this capacity is
unknown. Further studies are required to determine the
superiority of this procedure to core decompression alone
and other femoral head-sparing procedures.
Mesenchymal stem cells have also demonstrated clinical utility as an adjunct to core decompression in the treatment of osteonecrosis of the hip. In a small pilot study,
Gangji et al8 studied 13 patients (18 hips) with ARCO
Stage I or II disease. Fourteen patients had corticosteroidinduced osteonecrosis, two had alcohol-related disease,
and two cases were idiopathic. Patients were randomized
to be treated with either a 3-mm core decompression or a
core decompression with implantation of autologous bone
marrow mononuclear cells (Fig 2). After 24 months, the
group treated with the bone marrow graft had a considerable reduction in subjective symptoms as compared with
the group treated without bone marrow. Five of the eight
hips treated with core decompression alone had radiographic evidence of deterioration, whereas only one of the
10 hips treated with the bone marrow graft demonstrated
progression of disease. Furthermore, survival analysis
demonstrated a considerable increase in the time to collapse for the group treated with autologous marrow. Hernigou et al11 prospectively followed 189 hips in 116 patients
treated with core decompression and injection of concentrated autologous bone marrow mononuclear cells for a
minimum of 5 years (mean, 7 years; range, 5–11 years).
The etiology of osteonecrosis was corticosteroid-induced
in 31 hips (16%), alcohol-related in 56 hips (30%), sickle-
Clinical Orthopaedics
and Related Research
Fig 2A–B. (A) An osteonecrotic lesion of the femoral head is
injected with concentrated bone marrow aspirate. (B) This intraoperative fluoroscopic image demonstrates the correct position of the trocar in an osteonecrotic lesion. Adapted from
Hernigou P, Mathieu G, Poignard A, Manicom O, Beaujean F,
Rouard H. Percutaneous autologous bone-marrow grafting for
nonunions. Surgical technique. J Bone Joint Surg Am.
2006;88(suppl 1):322–327. Reprinted with permission from
The Journal of Bone and Joint Surgery, Inc.
cell disease in 64 hips (34%), idiopathic in 10 hips (5%),
and related to other causes in 28 hips (15%).When patients
were operated on before collapse (Stage I and Stage II),
arthroplasty was only performed in nine of the 145 hips
(6%). However, THA was necessary in 25 hips among the
44 hips (57%) operated on after collapse (Stage III and
Stage IV). The number of progenitor cells harvested from
each patient varied according to etiologic factor, and the
final concentration of progenitor cells had an influence on
the outcome of the hips. Patients who had a greater num-
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Number 465
December 2007
ber of progenitor cells transplanted in their hips demonstrated better survival. Patients with steroid- or alcoholrelated osteonecrosis received a low number of transplanted cells and had a greater risk of failure at the latest
followup than patients with other diagnoses who received
a higher number of transplanted cells (ie, sickle cell, idiopathic); however, no threshold dose was identified. This
may explain in part the influence of the etiologic factors on
the outcome of the hips, which was also observed in this
study. Those patients with alcohol- or steroid-related osteonecrosis often have marrow aspirates that yield fewer
progenitor cells and this may affect the results of therapy.
Conversely, the inferior results noted in these patients may
not only reflect the dose-response relationship between
progenitor cells and survival but the poor bone quality and
overall reparative potential of these subjects. Although
cell-based therapies for osteonecrosis have demonstrated
encouraging early data, further corroborating evidence of
its superiority to standard core decompression is necessary.
The use of adjuncts such as porous tantalum implants in
combination with core decompression has the potential to
provide the structural advantages of bone graft without the
associated risk of autograft harvest or the infectious complications associated with allograft bone.42,45,47 Veillette
et al47 prospectively evaluated 54 consecutive patients (60
hips) in whom osteonecrosis of the femoral head was
treated with core decompression and insertion of a porous
tantalum implant (Fig 3). The associated risk factors included corticosteroid use in 22 patients (26 hips), excessive alcohol consumption in two patients (two hips), none
known in 13 patients (15 hips), trauma in six patients (six
hips), and other factors in nine patients (nine hips). Nine
hips (15.5%) were converted to THA, including six with
Stage II disease and three with Stage III disease. KaplanMeier analysis revealed an overall survival rate of 68.1%
at 48 months. However, in the absence of chronic systemic
disease, a survival rate of 92% was observed at final followup. In another prospective study evaluating tantalum
implants for the treatment of early osteonecrosis of
the femoral head (Stage I or II), 86% of patients demonstrated femoral head survival at a minimum of 2 years
followup and an average followup of 39 months (range,
27–59 months). Three of 22 had progressive pain and collapse and subsequent conversion to THA. Patients who did
not require arthroplasty demonstrated good-to-excellent
functional results as characterized by the Harris hip
score.42 Although these data appear promising, long-term
followup is necessary. In addition, there are concerns
about the difficulty of conversion to a THA and the generation of metal debris in the joint if arthroplasty becomes
necessary.
Current Trends in Osteonecrosis of the Hip
59
Fig 3A–B. (A) A porous tantalum implant is designed to buttress the osteonecrotic lesion and allow for osseous ingrowth.
(B) A postoperative radiograph demonstrates the placement of
the implant in the femoral head. Adapted from Tsao AK, Roberson JR, Christie MJ, Dore DD, Heck DA, Robertson DD,
Poggie RA. Biomechanical and clinical evaluations of a porous
tantalum implant for the treatment of early-stage osteonecrosis. J Bone Joint Surg Am. 2005;87(suppl 2):22–27. Reprinted
with permission from The Journal of Bone and Joint Surgery,
Inc.
Resurfacing Procedures
Although femoral head-sparing procedures may provide
reasonable clinical results for patients with small precollapse lesions, these interventions are less predictable for
hips with very large lesions or a collapsed femoral head.
Accordingly, patients with advanced disease are often candidates for arthroplasty procedures. Total hip arthroplasty
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60
Clinical Orthopaedics
and Related Research
Petrigliano and Lieberman
is an effective procedure for treating patients with osteonecrosis of the femoral head.33–35 The advent of cementless fixation has allowed for reproducible results. Studies
of the outcomes of osteonecrosis of THA in patients need
to focus on specific patient populations with osteonecrosis
(ie steroid-induced, alcohol-induced, posttraumatic) to determine which patients may not do as well with THA. In
addition, because patients with osteonecrosis tend to be
less than 50 years old, bearing surface selection is often a
critical element when performing these procedures. Further study is necessary to determine the optimal bearing
surface for these patients.
Because THA is demonstrably effective, we will focus
our review on recent data regarding resurfacing arthroplasty. Although resurfacing arthroplasty is not a new
technique, it has received a great deal of attention in the
lay press because it has recently been FDA approved for
use in the United States, and it is being extensively used in
Europe, Canada, and Australia. Joint resurfacing is an appealing treatment option for young patients with osteonecrosis of the femoral head, because it preserves bone and
may provide easier conversion to a secondary procedure.
Improvements in design and encouraging early clinical
outcomes have resulted in renewed enthusiasm for the use
of metal-on-metal articulations in total joint resurfacing.
Mont et al32 reported on the outcomes of 42 osteonecrotic
hips that were treated with a hybrid metal-on-metal surface
replacement prosthesis. These patients were matched to a
cohort of patients undergoing the same procedure for osteoarthritis of the hip. All patients were followed for a
minimum of two years, with a mean duration of followup
of 41 months (range, 24–61 months). Good or excellent
outcomes (Harris hip score 80 or greater) were noted in 39
hips (93%) in the osteonecrosis group and 41 hips (98%)
in the osteoarthritis group. In a consecutive single-surgeon
series of 60 hips in 73 patients undergoing metal-on-metal
resurfacing for osteonecrosis, Revell et al38 reported an
overall survival rate of 93.2% at a mean of 6.1 years
(range, 2–12 years). In general, the results of hip resurfacing have been best in men with excellent bone stock. This
procedure may not be as successful in patients with osteonecrosis who are on steroids or in females with narrow
femoral necks. The outcome of a resurfacing arthroplasty
is also dependent upon interdigitation between the cement
and the bone in the femoral head. Thus, fixation may be
compromised in patients with extensive femoral head involvement. In addition, patients with a history of renal
impairment or potential for renal impairment are not candidates for metal-on-metal bearing surfaces. Finally, the
outcomes of total hip resurfacing need to be compared
with THA to better define its role in the treatment of
osteonecrosis.
DISCUSSION
Osteonecrosis is a disease that typically affects a younger
population in which THA may not be an attractive option.
The success of interventions that forestall or prevent femoral head collapse and maintain hip function would represent a substantial achievement in the treatment of this
disease. Pharmacologic,2,9,17,36 biophysical,1,48 and novel
surgical modalities8,11,22,28,42,47 have been proposed as potentially effective treatments for early-stage disease.
Pharmacologic intervention is an appealing option for
patients with osteonecrosis of the hip. These treatments are
noninvasive, require infrequent outpatient visits, and theoretically could be given as prophylaxis in patients who are
receiving high-dose steroids or may have other associated
risk factors. The preliminary results of studies evaluating
these agents have been promising, demonstrating improvement of symptoms and delay or prevention of disease progression in patients with early-stage disease. However, a
review of the most recent literature regarding bisphosphonate, anticoagulant, and vasodilatory agents reveals insufficient evidence to support their routine use in the treatment or prevention of osteonecrosis of the hip. Long-term
randomized controlled trials are needed to more accurately
characterize the role of these agents. Furthermore, study
patients should be stratified by diagnosis and lesions size
(as quantified via MRI) to increase the relevance of the
findings, as these variables appear to have a substantial
impact on outcome.
Biophysical modalities have also demonstrated efficacy
in reducing pain and delaying disease progression in earlystage osteonecrosis. Again, these therapies should be assessed in randomized trials that stratify patients by diagnosis and lesion size.
The most recent surgical innovations currently under
investigation represent modifications of standard core decompression. There is substantial interest in the development of biologically based therapies that can enhance core
decompression with either osteoinductive (bone morphogenic protein) or osteogenic (mesenchymal cells) agents
that have the clinical potential to provide better results for
larger lesions. The preliminary results with the use of bisphosphonates, bone morphogenic protein, and bone marrow stem cells suggest perhaps a combination therapy consisting of a short-acting osteoclast inhibitor in conjunction
with an osteoinductive or osteogenic agent may provide
the best opportunity to enhance the results of core decompression. Appropriately powered head-to-head randomized trials comparing these approaches with standard core
decompression may help corroborate the theoretical advantage of biologically enhanced grafts in this setting.
In general, patients with collapse of the head will require an arthroplasty procedure. Total hip arthroplasty is
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Number 465
December 2007
Current Trends in Osteonecrosis of the Hip
61
TABLE 2. Contemporary and Potential Future Treatment Algorithm for Osteonecrosis of the
Femoral Head
Radiographic Stage
Symptoms
I and II
Asymptomatic
IA, IB, IC, IIA, IIB, and IIC
Symptomatic
IC, IIC, IIIA, IIIB, IIIC, and IVA
Symptomatic
IVB and IVC
Symptomatic
V and VI
Symptomatic
Contemporary Treatment
Potential Future Treatment
Observation, possible core
decompression ± bone grafting
Core decompression ± bone
grafting (vascularized or
nonvascularized)
Pharmacologic or biophysical treatment
Core decompression ± bone
grafting (vascularized or
nonvascularized), osteotomy,
resurfacing arthroplasty, total hip
arthroplasty
Resurfacing arthroplasty, total hip
arthroplasty
Total hip arthroplasty
Pharmacologic or biophysical
treatment ± core decompression and
biologic adjuvant (growth factor, MSC) or
tantalum implant
Pharmacologic or biophysical treatment +
core decompression and biologic
adjuvant (growth factor, MSC) or tantalum
implant, resurfacing arthroplasty, total hip
arthroplasty
Resurfacing arthroplasty, total hip arthroplasty
Resurfacing arthroplasty, total hip arthroplasty
MSC = mesenchymal stromal cells
effective for treating these patients, but surface arthroplasty has captured the attention of both patients and surgeons because of the opportunity to preserve femoral bone
stock in this young patient population. The limited studies
that have evaluated resurfacing for osteonecrosis of the
hip32,38 have demonstrated mid-term prosthesis survival
rates (> 93%) and subjective outcomes (good or excellent
in 93%) that are only slightly inferior to results for osteoarthritis. However, the results of these procedures were not
stratified by the etiology of osteonecrosis. The long-term
results of these cohorts must be evaluated to determine if
these patients fair better than those treated with THA with
regard to patient satisfaction, functional outcome, and revision rates.
At the present time, we recommend MRI staging and
continued utilization of core decompression with or without bone grafting for patients with precollapse lesions
(Table 2). In general, patients with collapse of the femoral
head will require an arthroplasty procedure. The selection
of THA versus resurfacing arthroplasty will depend on
surgeon and patient preference, overall quality of bone
stock of the femoral head, and the durability and safety of
metal-on-metal weight-bearing surfaces. Randomized
trails comparing THA to resurfacing arthroplasty are necessary to delineate the indications for resurfacing arthroplasty.
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