Osteonecrosis of the Femoral Head

Introduction

Atraumatic osteonecrosis (ON) is an infarction of an area of bone secondary to a microvascular insult which leads to bone resorption and potentially structural collapse. The disease typically affects epiphyseal bone on the convex side of a joint, likely due to the lack of collateral circulation, and most commonly affects the femoral head, followed by the distal femur, proximal humerus and talus. In regards to osteonecrosis of the femoral head, the mean age at presentation is 38 years. Twenty-five percent of patients with the condition are less than 25 years of age. It may be bilateral in up to 72% of the cases. Approximately 20,000 new cases are diagnosed in the U.S. each year and about 10% of total hip arthroplasties are performed to treat degenerative disease secondary to osteonecrosis.

Anatomy

Describe the pertinent anatomy and provide links to relevant pages

Pathogenesis

The majority of osteonecrosis cases are idiopathic, related to high dose corticosteroid use or related to alcohol abuse. Additionally, there is increasing evidence for the role of clotting disorders in the development of this disease.

Up to 38% of patients with ON have a history of high dose corticosteroid use (~2 grams of prednisone within 2-3 months), however only ~5% of patients with a history of high dose corticosteroid use develop osteonecrosis ¹ ² . Similarly, up to 29% of patients with ON have a history of alcohol abuse, however only ~5% of patients with a history of alcohol abuse develop ON ¹ ³ .

ON is certainly a multifactorial process that is not clearly defined as of yet. The pathophysiology of corticosteroid and alcohol-related ON has been studied extensively and strong evidence is in support of increased adipogenesis as a major underlying mechanism. It has been reported that corticosteroids and ethanol can induce a pluripotent bone marrow cell line to preferentially differentiate into adipocytes in vitro. Increased adipogenesis causes venous sinusoidal compression, which leads to venous congestion, intraosseous hypertension, impaired arterial inflow, and ultimately, infarction ⁴ ⁵ ² .

However, as stated earlier, only 5% of patients with a history of high-dose corticosteroid use or alcohol abuse develop ON. Many groups are studying genetic traits that may predispose to the development of ON. One are of interest is clotting disorders. One series reported that 82% of patients with osteonecrosis had at least one clotting disorder vs. 30% of controls ⁶ . Some of the more common abnormalities seen included IgG anti-cardiolipin antibodies, stimulated plasminogen activator, and plasminogen activator inhibitor-1. Similar results have been reported in other studies ⁷ . Other predisposing factors may include mutations in a multidrug resistance gene, genetic variation in alcohol-metabolizing enzymes, and abnormal type II collagen.

The table below lists many of the conditions associated with osteonecrosis (Mont et al 2006).

Direct Causes	Indirect Causes	Less Common
Trauma Irradiation Hematologic disorders Cytotoxins Dysbaric Gaucher's disease Sickle cell disease/trait	Corticosteroids Alcohol abuse Idiopathic Thrombophilia Hypofibrinolysis Lupus Renal failure Organ transplant Hemophilia	Polyarteritis Thalassemia Carbontetrachloride poisoning Hyperlipidemia Cushing's disease Pregnancy

Natural History and Classification

At least 17 classification systems have been used. The majority are branches of the Ficat and Arlet System outlined below. This classification system also outlines the natural progression of the disease ⁸ :

Stage	Imaging Findings
I	Evidence seen on MRI only
II	Diffuse sclerosis, subchondral cysts. No femoral head collapse
III	Subchondral fracture ("Crescent sign") with or without collapse
IV	Collapse of the femoral head and secondary degenerative joint disease

The Kerboul Angle, also known as the "Combined Necrotic Angle" is a system used to quantify size of the lesion. To calculate, first the center of the femoral head is identified. Two lines are then drawn from this point to the borders of the lesion on both AP and Lateral radiographs. The sum of the angles on the AP and Lateral radiographs is the Kerboul angle. Lesions are classified as small, medium, or large:

Small: 160º or less

Medium: 161º - 199º

Large: 200º or more

Patient History and Physical Findings

The most common presenting complaint is groin pain. Pertinent patient history includes history of steroid use, alcohol abuse, and clotting abnormalities. Other relevant history may relate to the associated factors in the above table. Mechanical symptoms are may also be present once collapse of the femoral head has occurred. Physical exam findings include a painful, decreased range of motion, which worsen with degeneration of the joint.

Imaging and Diagnostic Studies

MRI is the modality of choice for diagnosing and monitoring Stage I disease (99% sensitivity and specificity) ⁹ . A well-demarcated, crescent-shaped lesion in the subchondral bone is typically seen. T1 images reveal a single-density line demarcating the normal-ischemic bone interface. T2 images reveal a double-density line representing an area of hypervascular granulation tissue. Bone scans are not used as frequently due to a high rate of false positives.

Once the disease has progressed to Stage II, plain films are typically the preferred imaging modality. Radiographic changes appear months after disease onset.

Differential Diagnosis

Transient osteoporosis of the hip

Femoroacetabular impingement

Tumor

Treatment

Nonoperative therapy

Observation

When a patient develops ON for the first time they will usually present with pain in just one hip. As these patients are being worked up or treated, ON is often incidentally found in the contralateral hip on x-ray or MRI. The question is: should these asymptomatic lesions be treated?

There is conflicting data available on this topic. Min et al published a study in 2008 that examined the natural history of asymptomatic hips. At an average follow-up of 8 years, only 23% of all asymptomatic hips had collapsed. The size of the lesion was highly predictive of outcome. Survival was 100% for lesions occupying less than 15% of the femoral head, 79% for medium-size lesions (15-30% of the femoral head), and 9% for lesions larger than 30% of the femoral head ¹⁰ . This study suggests that small lesions could potentially be observed. However, a similar study published in 2004 examined only the fate of very small lesions and found that 73% went on to collapse within 12 years. This group concluded that detecting collapse in very small Stage I lesions was difficult and that the patients should be followed very closely for many years ¹¹ .

In summary, observation of small, asymptomatic lesions is controversial. Collapse rates of 23% - 73% have been reported. Medium-sized, asymptomatic lesions should be treated. Large lesions have a worse prognosis and treatment is largely directed by age and overall health.

Medical

Encouraging results have been reported for numerous medical and biophysical therapies, including statins, bisphosphonates, low molecular weight heparin, stanozolol, iloprost, extracorporeal shock-wave therapy, hyperbaric oxygen, puerarin (herbal), and electromagnetic therapy.

Statins

Pritchett et al published a retrospective review in 2001 that reported the incidence of osteonecrosis in 284 patients who had received high dose corticosteroids while concurrently on a statin. At 7.5 years follow-up MRI's were performed on all patients who complained of hip pain. Only 3 patients (1%) developed osteonecrosis which is significantly lower than the historical value of 5% for patients receiving high-dose steroids ¹² . A similar effect has been demonstrated in a rabbit study ¹³ .

Bisphosphonates

A prospective, randomized, controlled trial has reported the results of 54 patients with large pre-collapse or early post-collapse lesions randomized either into a group that received observation only or a group treated medically with alendronate for 25 weeks. Seven percent (2/29) of the lesions treated with alendronate had progressed at a minimum 2-year follow-up versus 76% (19/25) of the controls ¹⁴ .

Low Molecular Weight Heparin

Enoxaparin has been reported to decrease disease progression in patients with an underlying thrombophilia and/or hypofibrinolysis and Stage I or II disease ¹⁵ .

Operative Treatment - Femoral Head-Sparing Techniques

Core Decompression

Ficat and Arlet first described core decompression in 1964 while investigating painful hips in patients who had normal radiographic findings. The rationale behind the procedure is to reduce intraosseous pressure in the femoral head, thereby improving arterial inflow and potentially decreasing pain. The technique entails directing a k-wire into the necrotic area under fluoroscopic guidance, which is then over-drilled with a drill and trephine. Typically the patient is kept on protective weight bearing for approximately six weeks to reduce the incidence of proximal femoral fracture, which is the main complication of this technique. In general, core decompression is indicated for precollapse lesions with less than 30% involvement of the femoral head. A success rate of 84% for Stage I lesions and 65% for Stage II lesions has been reported {ref: 8595753}.Efficacy of the procedure drops significantly once the femoral head develops a subchondral fracture.

A modification of this technique has been described and entails involves multiple percutaneous small drillings rather than one larger core ¹⁶ . Lower morbidity and the fact that it can be done on an outpatient bases are among the rationale for the variation. Similar results to core decompression and zero complications have been reported ¹⁶ .

Another variation includes placement of a tantalum rod in the core tract. This technique theoretically provides subchondral support and decreases the risk of proximal femoral fracture. Accurate placement of the device is key. The one or two studies published on this technique have shown comparable or slightly better results than those of standard core decompressions {ref: 17079367}. Indications for this technique remain the same as for standard core decompression. One issue to keep in mind is that if these patients eventually require a total hip arthroplasty, the tantalum rod will require removal.

Nonvascularized bone grafting

Cortical Strut Grafting (typically with a fibular allograft) is not commonly used today. Long-term success rates have been poor (as low as 30%) and future conversion to total hip arthroplasty is complicated. However, some studies have reported promising results using cortical strut grafting combined with bioactive materials such as autogenous bone marrow cells, demineralized bone matrix, and bone morphogenic protein ¹⁷ .

Two other nonvascularized bone grafting procedures termed the "Lightbulb" and "Trapdoor" procedures may be used for post-collapse disease. These procedures essentially entail an open surgery in which a window is cut in the femoral neck or femoral head and the subchondral void is packed with various types of bone graft ¹⁸ ¹⁹ . One study had reported a 83% success rate for patients with Stage III disease and 33% for those with Stage IV disease at a 4-5 year follow-up using the trapdoor procedure ¹⁸ .

Vascularized bone grafting

In general, free vascularized fibular grafting is considered for patients <35 years-old with pre-collapse lesions or those with collapse of <2mm.The procedure typically employs two teams, one prepared the proximal femur and dissects the vessels while the other harvests the fibula. The free fibula and cancellous bone graft are then inserted into a core tract and the peroneal vessels are anastomosed to either the lateral circumflex artery or the ascending branch of the first perforator. Patients are typically kept on protected weight bearing for ~6 months postop. In addition to providing structural support, this procedure theoretically provides some amount of revascularization of the femoral head. Results with this technique have been highly variable {ref: 12690862}. Complications include donor site morbidity (~24% rate){ref: 9692940} and proximal femur fracture (~2.5% rate) ²⁰ . Lastly, conversion to total hip arthroplasty in patients who have undergone this procedure requires burring laterally to prevent the prosthesis from being placed in varus.

Proximal femoral osteotomy

Proximal femoral osteotomy is not widely accepted as a standard treatment in the US, however it has had more consistent results and is more commonly used in Asia. The rationale is to remove the necrotic or collapsing segment from the weight-bearing zone of the femoral head. This procedure should be considered in young patients with small to medium-size lesions (or a combined necrotic angle of less than 200). Ongoing steroid use should be considered a contraindication. The procedure is technically difficult and nonunion rates can be high. Similar to vascularized fibular grafts, success rates in the U.S. have been highly variable (as low as 30%). Additionally, the osteotomy can significantly complicate future conversion to THA due to the fact that anatomy is often distorted and retained hardware can be problematic.

Operative Treatment - Femoral Head-Sacrificing Techniques

Hemiresurfacing

One of the biggest advantages of hemiresurfacing is that proximal bone stock is conserved and the femoral canal is not violated, making later conversion to a THA easier and more successful. This is particularly important in younger patients who will likely require additional procedures. Additionally, patients are able to maintain a higher level of activity compared to those with a total hip replacement and wear debris is not an issue as opposed to metal on metal arthroplasty. Disadvantages include unpredictable relief of groin pain, which is a complaint in up to 20% of these patients. Also, this is a temporizing measure as failure will eventually occur secondary to acetabular cartilage erosion. Short-mid term results have been relatively encouraging with 5-7 year success rates are approximately 70-90%. At 10-15 years there has been a dramatic decrease in survivorship.

Metal on metal resurfacing

Metal on metal resurfacing was first used in the 1960's and had poor results. It was reintroduced in the 1990's and much improved results were seen with the improved manufacturing technology. The rate of femoral neck fracture has been reduced to 0.8% with improved technique and patient selection. Metal on metal resurfacing has similar advantages to hemiresurfacing and eliminates groin pain much more reliably. Complications include the the development of local reactions to metal wear debris and high serum levels of metal ions, however complications from this have yet to be demonstrated. Early results have been excellent with up to 95% survivorship at 5 years.

Hemiarthroplasty

Hemiarthroplasty has poor long-term results. The high activity level in this patient population results in increased polyethylene wear and osteolysis. This technique should not be used in these patients.

Total hip arthroplasty

Historical results of total hip arthroplasty for the treatment of osteonecrosis have been poor secondary to the high activity level of this population. However short to mid-term results with newer bearing surfaces and uncemented techniques have been encouraging. Success rates of up to 89% have been reported at 15 years follow-up making THA a reliable, long term option. Many argue that any surgery which may compromise future conversion to THA (such as osteotomies and vascularized bone grafts) should be used with discrimination. Some suggest that any patient over the age of 30 with collapse should be treated symptomatically until symptoms warrant arthroplasty.

Treatment Summary

When considering treatment options, there are four factors to take into consideration: 1) Patient age; 2) Activity level and general health; 3) Size and location of lesion; 4) Stage of the lesion. Small, pre-collapse lesions are typically treated with core decompression +/- bone grafting. Medium-sized precollapse lesions and postcollapse lesions with less than 2mm depression can be treated with more aggressive head-conserving approaches in younger patients. However, in light of recent improvements in materials and techniques, patients over the age of 40-50 may be better served with symptomatic treatment until symptoms warrant total hip arthroplasty. Medications such as bisphosphonates should also certainly be considered for all of the aforementioned patients. The femoral head is unlikely to be salvaged if the lesion is extensive (>30% of the femoral head) and involves the weight-bearing zone or if there is greater than 2mm of collapse. Additionally, if there is marked acetabular involvement, total hip arthroplasty is the only appropriate choice.

Pearls and Pitfalls

Postoperative Care

Include immediate postoperative care and rehabilitation

Outcome

Include functional and prosthetic survivorship data as applicable

Complications

Include overview of complications

Related Orthopaedia Resources

Click [here] to view a powerpoint presentation on osteonecrosis of the femoral head

Selected References

Fri Jul 30 10:23:00 PDT 2010

Footnotes
Ref	Notes
1	Jones LC, Hungerford DS, 2007. "The pathogenesis of osteonecrosis." Instr Course Lect 56: 179-96 [PubMed] Abstract: Although numerous studies concerning the pathogenesis of osteonecrosis have been published, the pathophysiologic mechanisms that may be involved continue to be debated. In the early 1980s, the concept of accumulative cell stress was advanced, which is a theory that proposes that bone cells are exposed to multiple insults or stresses, the effects of which accumulate to the point that the cells cannot sustain themselves and die. Technologic advances have led scientists to a better understanding of cell and molecular biology, and recent studies of osteonecrosis and its risk factors have indicated that this concept should be revisited. It now appears that using the term "necrosis" may be incorrect and that apoptosis may play a significant role. Research on osteoporosis, fracture healing, bone graft incorporation, hematology, and genetics may lend insight into the etiology and pathogenesis of osteonecrosis. Several studies on osteoporosis have focused on the effect of exogenous glucocorticoids on the behavior of osteocytes, osteoblasts, osteocytes, and their precursors. Recent findings on osteonecrosis and bone biology are placed into the context of what has been previously reported. [ a b ]
2	Cui Q, Wang GJ, Balian G, 1997. "Steroid-induced adipogenesis in a pluripotential cell line from bone marrow." J Bone Joint Surg Am 79 (7): 1054-63 [PubMed] Abstract: We studied the effect of steroids on the differentiation of a pluripotential mesenchymal cell with use of a cell line (D1) from mouse bone-marrow stroma. The cells were treated with increasing (10[-9], 10(-8), and 10(-7)-molar) concentrations of dexamethasone for increasing durations ranging from forty-eight hours to twenty-one days. The appearance of triglyceride vesicles in the cells indicated that this treatment had induced the differentiation of the cell into adipocytes. The number of cells that contained the triglyceride vesicles and the expression of a fat-cell-specific gene, 422(aP2), increased with longer durations of exposure to dexamethasone and with higher concentrations of the steroid. Treatment with dexamethasone also diminished the expression of alpha1 type-I collagen mRNA and osteocalcin mRNA. The data indicate that dexamethasone stimulates the differentiation of cells in bone-marrow stroma into adipocytes as well as the accumulation of fat in the marrow at the expense of expression of type-I collagen and osteocalcin mRNA, thereby suppressing differentiation into osteoblasts. CLINICAL RELEVANCE: Steroid-induced adipogenesis by bone progenitor cells in marrow may influence the development of osteonecrosis. It is therefore important to consider the investigation of a treatment, such as the inhibition of the metabolism and accumulation of fat in marrow, that can prevent the onset of osteonecrosis. [ a b ]
3	Orli�� D, Jovanovi�� S, Anticevi�� D, Zecevi�� J, 1990. "Frequency of idiopathic aseptic necrosis in medically treated alcoholics." Int Orthop 14 (4): 383-6 [PubMed] Abstract: The occurrence of idopathic aseptic necrosis of bone in multiple sites has been studied in persons who have had medical treatment for excessive consumption of alcohol. The incidence was 5.3% in 1157 such persons and there were 92 different sites in 62 patients. There were 82 lesions affecting the femoral head, 46 in the left hip and 36 in the right. In 10, it was present in the head of the humerus. Multiple foci were found in 6.1% of patients with the disease. In 2 men and 2 women both femoral heads and both humeral heads were affected. In 2 men the necrosis was present in both humeral heads and the head of the right femur.
4	Laroche M, 2002. "Intraosseous circulation from physiology to disease." Joint Bone Spine 69 (3): 262-9 [PubMed] Abstract: Blood flow within bones is unique in two ways: (1) the blood circulates within a closed cavity in which pressure must remain constant, a feat achieved in part thanks to the considerable distensibility of the intraosseous vessels and, above all, veins; (2) the intraosseous circulation allows traffic of minerals between the blood and bone tissue and sends the blood cells produced within the bone marrow into the systemic circulation. In contrast, the arterioles and capillaries within bones have the same anatomic structure as those located elsewhere in the body and are susceptible to arteriosclerosis, arteritis, or thrombosis. The mechanisms that regulate blood flow within bone are incompletely understood, probably because they are difficult to study in vivo. The cytokines and growth factors that regulate intraosseous angiogenesis also regulate bone remodeling, and close links exist between the blood supply to bone and bone formation and resorption: most diseases characterized by increased bone resorption are associated with increased bone vascularization. The vascular bud located at the center of bone multicellular units (BMUs) may determine the timing of bone resorption and bone formation. Avascular bone necrosis and bone infarction may result from acute blood vessel occlusion (thrombosis, lipid emboli, fat cell hypertrophy with compression of intraosseous capillaries), whereas arteriosclerosis may contribute to the development of osteoporosis.
5	Wang GJ, Sweet DE, Reger SI, Thompson RC, 1977. "Fat-cell changes as a mechanism of avascular necrosis of the femoral head in cortisone-treated rabbits." J Bone Joint Surg Am 59 (6): 729-35 [PubMed] Abstract: Large doses of cortisone were given to growing and adult rabbits over a five-month period to produce avascular necrosis of the femoral head. The cortisone caused an increase in the serum cholesterol, fatty metamorphosis of the liver, and fat emboli visible in sections of the femur and humerus. These emboli partially obliterated the microcirculation of the subchondral vessels of both femoral and humeral heads. The average diameter of the marrow fat cells also increased more than ten micrometers. This increase in cell volume might be significant because in the closed chamber of the femoral head it could increase tissue pressure, diminish perfusion, and be the mechanism for avascular necrosis induced by cortisone.
6	Jones LC, Mont MA, Le TB, Petri M, Hungerford DS, Wang P, Glueck CJ, 2003. "Procoagulants and osteonecrosis." J Rheumatol 30 (4): 783-91 [PubMed] Abstract: OBJECTIVE: To study the relationship between hypofibrinolysis, thrombophilia, and osteonecrosis. We evaluated the frequency of abnormal concentrations of 9 coagulation factors in patients diagnosed with osteonecrosis. METHODS: Blood samples were drawn from 45 patients diagnosed with osteonecrosis. Etiologic associations included systemic lupus erythematosus (n = 9), inflammatory bowel disease (n = 1), corticosteroid therapy (n = 20), or history of heavy alcohol (n = 4) or tobacco (n = 3) use. No associated risk factors were identified in 5 patients; these individuals were labeled "idiopathic." The patient cohort was matched to a similarly studied cohort of 40 healthy individuals without documented osteonecrosis. The following factors were analyzed: plasminogen activator inhibitor (PAI-Fx), stimulated tissue plasminogen activator, lipoprotein (a), resistance to activated protein C, anticardiolipin antibodies (aCL IgG, IgM), protein C, protein S (free), and homocysteine. RESULTS: Thirty-seven of the 45 patients (82.2%) with osteonecrosis were found to have at least one coagulopathy, versus 30% of controls (p < 0.0001). Twenty-one patients (46.7%) were identified with 2 or more abnormal test results versus 2.5% of controls (p < 0.0001). Patients were more likely than controls to have high levels of the hypofibrinolytic plasminogen activator inhibitor activity (42% vs 3%; p < 0.0001), and high anticardiolipin antibody IgG (34% vs 10%; p = 0.008). At least one coagulation factor abnormality was detected in all 5 idiopathic patients; elevated aCL IgG and PAI-Fx were evident in 4 patients. CONCLUSION: This study revealed a high incidence of thrombophilic and hypofibrinolytic coagulation abnormalities in patients with osteonecrosis. These findings have major implications for the diagnosis as well as the treatment of this disease. Since some of these abnormalities may be the result of autosomal dominant disorders, it may be possible to detect individuals at risk for development of this disease.
7	Glueck CJ, Freiberg RA, Wang P, 2008. "Heritable thrombophilia-hypofibrinolysis and osteonecrosis of the femoral head." Clin Orthop Relat Res 466 (5): 1034-40 [PubMed] Abstract: We hypothesized that inherited thrombophilia and hypofibrinolysis were risk factors for osteonecrosis of the femoral head. We compared measures of thrombophilia and hypofibrinolysis in referred new adult patients with idiopathic osteonecrosis (n = 71) or secondary osteonecrosis (n = 62) with the same measures in sex- and race-matched healthy control subjects. Heritable thrombophilic Factor VIII and hypofibrinolytic Lp(a) were more frequently high in the 71 patients with idiopathic osteonecrosis than in control subjects. High Factor VIII, Factor V Leiden heterozygosity, and resistance to activated protein C, all heritable thrombophilias, were more frequently present in the 62 patients with secondary osteonecrosis than in control subjects. Our data suggest inherited thrombophilia and hypofibrinolysis are risk factors for both idiopathic and secondary osteonecrosis of the head of the femur.
8	Mont MA, Marulanda GA, Jones LC, Saleh KJ, Gordon N, Hungerford DS, Steinberg ME, 2006. "Systematic analysis of classification systems for osteonecrosis of the femoral head." J Bone Joint Surg Am 88 Suppl 3: 16-26 [PubMed] Abstract: BACKGROUND: Multiple classification systems for osteonecrosis of the hip have been developed to assist physicians in the diagnosis and treatment of this potentially debilitating disorder. The purpose of this analysis was to delineate the classification systems utilized in reports published since 1985 and, through a comparison of the most commonly used systems, to identify consistent factors that would allow for cross-publication comparisons to be made. METHODS: We performed a PubMed search for reports of outcome studies concerning treatment methods for osteonecrosis of the hip. All studies of reported outcomes with greater than ten patients were included in the analysis. Various classification systems were tabulated to determine usage frequencies. The four most commonly used systems were then analyzed to determine common factors used for classification. RESULTS: One hundred and fifty-seven studies were available for analysis. Sixteen major classification systems that made use of more than one radiographic factor were identified, and nine of these systems had one to five modifications reported throughout the literature. Additionally, eleven other systems made use of single factors obtained from either magnetic resonance imaging or anatomic data. The review revealed that four classification systems accounted for greater than 85.4% of the reported studies. Parameters for these four systems were stratified to allow for uniformity of patient or study evaluation. CONCLUSIONS: This analysis of the reported classification systems for osteonecrosis of the femoral head revealed several similarities between the most commonly used systems. An analysis of patients can be made with any of the four major systems if specific data are collected according to various magnetic resonance imaging and radiographic findings. This approach will allow for easier comparison of studies across different centers. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions to Authors on jbjs.org for a complete description of levels of evidence.
9	Lieberman JR, Berry DJ, Mont MA, Aaron RK, Callaghan JJ, Rajadhyaksha AD, Urbaniak JR, 2003. "Osteonecrosis of the hip: management in the 21st century." Instr Course Lect 52: 337-55 [PubMed] Abstract: Osteonecrosis of the femoral head is a progressive condition that often leads to collapse of the femoral head. The ultimate goal in the treatment for osteonecrosis of the hip is preservation of the femoral head. However, the condition is difficult to treat because it is associated with a number of different diseases, and the etiology and natural history of the condition have not been definitively determined. The delineation of new information regarding the etiology, pathogenesis, and natural history of osteonecrosis is ongoing. Core decompression, vascularized and nonvascularized bone grafting procedures, and arthroplasty procedures play an important role in treatment.
10	Min BW, Song KS, Cho CH, Lee SM, Lee KJ, 2008. "Untreated asymptomatic hips in patients with osteonecrosis of the femoral head." Clin Orthop Relat Res 466 (5): 1087-92 [PubMed] Abstract: Because there is no consensus regarding the factors predicting femoral head collapse in asymptomatic osteonecrosis of the hip, we studied the risk factors for collapse. Between 1990 and 2000, we used MRI to confirm asymptomatic osteonecrosis of the femoral head in 81 patients (81 hips) whose other hip had nontraumatic symptomatic osteonecrosis and we monitored them prospectively. The minimum followup was 5 years (mean, 8.3 years; range, 5-16 years). At the latest followup, 31 hips (38%) were symptomatic and 26 hips (32%) had collapsed. The mean interval between diagnosis and collapse was 4.1 years. We observed no correlation between femoral head collapse and patients' age, gender, weight, presumed cause of osteonecrosis, or length of followup. With combined factors, only extent of large necrotic lesion (hazard ratio, 4.06; 95% confidence interval, 1.29-12.77) and location of Type C2 necrotic lesion (hazard ratio, 6.35; 95% confidence interval, 1.18-34.11) predicted collapse.
11	Hernigou P, Poignard A, Nogier A, Manicom O, 2004. "Fate of very small asymptomatic stage-I osteonecrotic lesions of the hip." J Bone Joint Surg Am 86-A (12): 2589-93 [PubMed] Abstract: BACKGROUND: The prognosis for a patient with osteonecrosis of the hip is generally considered to be worse if a large volume of the femoral head is involved, the patient is symptomatic, and the stage of the lesion is advanced. In 1990, we began a prospective study to detect collapse in asymptomatic hips with a very small stage-I osteonecrotic lesion in the femoral head. We hypothesized that such patients would have a favorable prognosis. These hips were followed for a minimum of ten years after the diagnosis. METHODS: A small asymptomatic stage-I osteonecrotic lesion (not seen on plain radiographs) was diagnosed with magnetic resonance imaging in forty patients (forty hips) contralateral to a hip with symptomatic osteonecrosis. The criterion for inclusion in the study was a lesion with a volume of <5 cm(3) involving <10% of the volume of the femoral head. Plain radiographs were made annually in six different projections for all patients. At the most recent follow-up evaluation (average, eleven years), patients with a symptomatic hip but without evidence of collapse on plain radiographs underwent a computerized tomography scan. RESULTS: Thirty-five (88%) of the forty hips became symptomatic, and twenty-nine (73%) demonstrated collapse. The mean interval between the diagnosis and the first symptoms was eighty months. Symptoms always preceded collapse by at least six months. The mean interval between the diagnosis and the collapse was ninety-two months (range, seventy-two to 140 months). The diagnosis of collapse could be made on only one or two of the six radiographic views obtained for each patient at each evaluation. The diagnosis of collapse for two patients was made only on a computerized tomography scan at the most recent follow-up evaluation. At the time of final follow-up, the twenty-nine hips with collapse had symptoms of intractable pain and required surgery. CONCLUSIONS: This study confirms that the diagnosis of collapse is difficult in hips with a very small stage-I osteonecrotic lesion. Multiple radiographic views and computerized tomography scans may be required to demonstrate small areas of collapse. Clinical and radiographic signs of progression of the disease in asymptomatic hips with a very small asymptomatic lesion progress more slowly than do those signs in hips with a large symptomatic stage-II lesion. Because hips with a small area of osteonecrosis do collapse in a large percentage of patients, such patients should be followed carefully over a long period of time. LEVEL OF EVIDENCE: Prognostic study, Level I-1 (prospective study). See Instructions to Authors for a complete description of levels of evidence.
12	Pritchett JW, 2001. "Statin therapy decreases the risk of osteonecrosis in patients receiving steroids." Clin Orthop Relat Res (386): 173-8 [PubMed] Abstract: Osteonecrosis is a devastating complication of systemic steroid use. Prolonged steroid use produces a hyperlipidemic state in most patients and puts them at risk for osteoporosis and osteonecrosis. The fat content within the femoral head increases, resulting in increased intracortical pressure that may lead to sinusoidal collapse and osteonecrosis. Statins are lipid-clearing agents that dramatically reduce lipid levels in blood and tissues. Statins are widely used to prevent cardiovascular disease and have been shown to reduce the adverse effects of steroids on lipid metabolism. The purpose of this study was to determine whether the use of statin drugs affects later development of osteonecrosis in patients receiving steroids. The records of 284 patients who were taking statin drugs at the time they were started on high dose steroids were examined to determine whether osteonecrosis had developed. The patients remained on statin drugs during the entire time of steroid exposure. Magnetic resonance imaging scans were used to verify the osteonecrosis unless it was visible by radiograph. After an average of 7.5 years (minimum followup, 5 years), only three patients (1%) from the group had osteonecrosis develop. This 1% incidence is much less than the 3% to 20% incidence usually reported for patients receiving high-dose steroids. Statins may offer some protection against having osteonecrosis develop when steroid treatment is necessary.
13	Nishida K, Yamamoto T, Motomura G, Jingushi S, Iwamoto Y, 2008. "Pitavastatin may reduce risk of steroid-induced osteonecrosis in rabbits: a preliminary histological study." Clin Orthop Relat Res 466 (5): 1054-8 [PubMed] Abstract: Several animal and human studies suggest pharmacological approaches may prevent steroid-induced osteonecrosis (ON). We asked whether the newly developed 3-hydroxymethyl-3-glutaryl-CoA (HMG-CoA) reductase inhibitor, pitavastatin, could prevent steroid-induced ON in rabbits. We injected 65 adult male Japanese white rabbits once with 20 mg/kg of methylprednisolone acetate into the right gluteus medius muscle. The rabbits were divided into two groups; one group of 35 rabbits received pitavastatins (PS), and the other group of 30 rabbits received no prophylaxis (CTR). Hematological examinations were performed just before the steroid injection (0 weeks) and at 1 and 2 weeks after steroid injection; both the femora and the humeri were histologically examined 2 weeks postinjection. The incidence of histologic changes consistent with early ON in the PS group (13 of 35; 37%) was lower in comparison to the CTR group (21 of 30; 70%). The size of the bone marrow fat cells in the PS group (56.6 +/- 10 microm) was smaller than those in the CTR group (60 +/- 4 microm). The data suggest pitavastatin has the potential to lower the incidence of steroid-induced ON in rabbits.
14	Lai KA, Shen WJ, Yang CY, Shao CJ, Hsu JT, Lin RM, 2005. "The use of alendronate to prevent early collapse of the femoral head in patients with nontraumatic osteonecrosis. A randomized clinical study." J Bone Joint Surg Am 87 (10): 2155-9 [PubMed] Abstract: BACKGROUND: Osteonecrosis of the femoral head is the most common diagnosis leading to total hip arthroplasty in young adults. Joint-preserving treatment options have been mainly surgical, with inconsistent results. Alendronate (a bisphosphonate agent) has been shown to lower the prevalence of vertebral compression fractures and could potentially retard the collapse of an osteonecrotic femoral head. The purpose of this study was to test the effect of alendronate in preventing early collapse of the femoral head in patients with nontraumatic osteonecrosis. METHODS: Forty patients with Steinberg stage-II or III nontraumatic osteonecrosis of the femoral head and a necrotic area of >30% (class C) were randomly divided into alendronate and control groups of twenty patients each. Patients in the alendronate group took 70 mg of alendronate orally per week for twenty-five weeks, while the patients in the control group did not receive this medication or a placebo. The patients were observed for a minimum of twenty-four months. Harris hip scores, plain radiographs, and magnetic resonance imaging scans were obtained. RESULTS: During the study period, only two of twenty-nine femoral heads in the alendronate group collapsed, whereas nineteen of twenty-five femoral heads in the control group collapsed (p < 0.001). One hip in the alendronate group underwent total hip arthroplasty, whereas sixteen hips in the control group underwent total hip arthroplasty (p < 0.001). CONCLUSIONS: Alendronate appeared to prevent early collapse of the femoral head in the hips with Steinberg stage-II or IIIC nontraumatic osteonecrosis. A longer duration of follow-up is needed to confirm whether alendronate prevents or only retards collapse. LEVEL OF EVIDENCE: Therapeutic Level I.
15	Glueck CJ, Freiberg RA, Sieve L, Wang P, 2005. "Enoxaparin prevents progression of stages I and II osteonecrosis of the hip." Clin Orthop Relat Res (435): 164-70 [PubMed] Abstract: In a prospective pilot study, we hypothesized that enoxaparin (60 mg/day for 12 weeks) would prevent progression of Stages I and II osteonecrosis of the hip associated with thrombophilia or hypofibrinolysis or both over > or = 108 weeks of followup versus untreated historic controls, with different treatment responses in primary versus corticosteroid-associated secondary osteonecrosis. Patients with one or more thrombophilic-hypofibrinolytic disorder and Ficat Stages I or II osteonecrosis of at least one hip were included. A blinded committee interpreted anteroposterior and frog-leg lateral radiographs at entry in the study and every 36 weeks to > or = 108 weeks. Maintenance of the disease at Stages I and II versus progression of the osteonecrosis to Stages III and IV requiring total hip replacement was the major end point. Sixteen patients had primary osteonecrosis (25 hips; 13 Stage I, 12 Stage II), and 12 had secondary osteonecrosis (15 hips; five Stage I, 10 Stage II). With no Enoxaparin-related complications, 19 of 20 hips (95%) with primary osteonecrosis were unchanged from Stages I and II osteonecrosis at > or = 108 weeks; 12 of 15 hips (80%) with secondary osteonecrosis progressed to Stages III and IV osteonecrosis. In primary osteonecrosis at > or = 108 weeks, survival of 95% hips, or 76% (19/25 hips, based on intent to treat), compared favorably with untreated historical controls (approximately 20% 2-year survival), comparable to 20% survival in secondary hip osteonecrosis. Enoxaparin may prevent progression of primary hip osteonecrosis, decreasing the incidence of total hip replacement. LEVEL OF EVIDENCE: Therapeutic study, II-1 (prospective cohort study).
16	Mont MA, Ragland PS, Etienne G, 2004. "Core decompression of the femoral head for osteonecrosis using percutaneous multiple small-diameter drilling." Clin Orthop Relat Res (429): 131-8 [PubMed] Abstract: Osteonecrosis is a disease with a wide ranging etiology and poorly understood pathogenesis seen commonly in young patients. Core decompression has historically been used in patients with small-sized or medium-sized precollapse lesions in an attempt to forestall disease progression. Typically, an 8-10 mm wide cannula trephine is used to do this procedure. The authors report on a new technique using multiple small drillings with a 3-mm Steinman pin to effectuate the core decompression. In this report, there were 32 of 45 hips (71%; 35 patients) with a successful clinical result at a mean followup of 2 years (range, 20-39 months). Twenty four of 30 Stage I hips (80%; 23 patients) had successful outcomes compared with 8 of 15 Stage II hips (57%; 12 patients) with no surgical complications occurring with this technique. This procedure is technically straightforward and led to minimal morbidity with no surgical complications. It may be effective in delaying the need for total hip arthroplasty in young patients with early (precollapse) stages of femoral head osteonecrosis. [ a b ]
17	Lieberman JR, Conduah A, Urist MR, 2004. "Treatment of osteonecrosis of the femoral head with core decompression and human bone morphogenetic protein." Clin Orthop Relat Res (429): 139-45 [PubMed] Abstract: A retrospective evaluation was done of 15 patients (17 hips) with symptomatic osteonecrosis of the hip treated with core decompression combined with an allogeneic, antigen-extracted, autolyzed fibula allograft and 50 mg of partially purified human bone morphogenetic protein and noncollagenous proteins. The average duration of clinical followup of the patients was 53 months (range, 26-94 months). The osteonecrotic involvement of the hip was classified by plain radiographs using a modification of the Ficat staging system and MRI evaluations. Fifteen hips were classified as Ficat Stage IIA, one hip (one patient) was classified as Ficat Stage IIB, and one hip (one patient) was classified as Ficat Stage III. Fourteen hips had involvement of 50% or less of the femoral head and 2/3 or less involvement of the weight-bearing surface of the femoral head, based on a magnetic resonance imaging evaluation. The procedures were a clinical success in 14 of 15 hips (93%; 13 patients) with Stage IIA disease. Three of 17 hips (three patients) had radiographic progression (Ficat Stages IIA, IIB, and III) of the femoral head and were converted to total hip replacements. Only one of seven hips (six patients) with 50% or less involvement of the femoral head and between 1/3 and 2/3 of the weightbearing surface of the femoral head developed radiographic progression of the femoral head. There was no radiographic progression in the 3 hips with less than 1/3 involvement of the weightbearing surface of the femoral head. Further evaluation of the potential efficacy of bone morphogenetic protein is required in randomized trials.
18	Mont MA, Einhorn TA, Sponseller PD, Hungerford DS, 1998. "The trapdoor procedure using autogenous cortical and cancellous bone grafts for osteonecrosis of the femoral head." J Bone Joint Surg Br 80 (1): 56-62 [PubMed] Abstract: We have reviewed the results of 30 operations performed on 23 patients with Ficat stage-III or stage-IV osteonecrosis of the femoral head in which autogenous cortical and cancellous bone grafting had been performed through a so-called trapdoor made in the femoral head. At a mean of 56 months (30 to 60) after operation 20 of 24 stage-III hips (83%) had a good or excellent result as determined by the Harris hip-scoring system. Two of six stage-IV hips (33%) had good or excellent results. Eighteen of 21 hips (86%) with a combined necrotic angle of 200 degrees had good or excellent clinical results compared with only four of nine hips (44%) with a combined necrotic angle of more than 200 degrees. Six of the eight hips which had fair or poor results were in patients who had received corticosteroids; five of these six hips had lesions with a combined necrotic angle of greater than 200 degrees or were in a late stage (stage IV). There were no perioperative complications. Our results suggest that the trapdoor procedure with autogenous cancellous and cortical bone grafting can be successful in Ficat and Arlet stage-III osteonecrosis of the hip in patients with small- to medium-sized lesions. [ a b ]
19	Seyler TM, Marker DR, Ulrich SD, Fatscher T, Mont MA, 2008. "Nonvascularized bone grafting defers joint arthroplasty in hip osteonecrosis." Clin Orthop Relat Res 466 (5): 1125-32 [PubMed] Abstract: A variety of nonvascularized bone grafting techniques have been proposed with varying degrees of success as treatment alternatives for osteonecrosis of the femoral head. The success of these procedures may be enhanced using ancillary growth and differentiation factors. We retrospectively reviewed 33 patients (39 hips) with osteonecrosis of the hip who had nonvascularized bone grafting procedures with supplemental OP-1. We compared the outcomes in this cohort to similar patients treated nonoperatively or with other nonvascularized bone grafting procedures. We used a trapdoor to make a window at the head-neck junction to remove necrotic bone and packed the excavated area with autogenous cancellous bone graft, marrow, and OP-1. The minimum followup was 24 months (mean, 36 months; range, 24-50 months). We performed no further surgery in 25 of 30 small- and medium-sized lesions (80%) but did in two of nine large lesions. Hips with Ficat Stage II disease were not reoperated in 18 of 22 cases during the followup periods. Our short-term results compare similarly to nonoperative treatment and other reports of nonvascularized bone grafting. With the addition of ancillary growth factors, these procedures effectively reduce donor site morbidity and may defer joint arthroplasty in selected patients.
20	Aluisio FV, Urbaniak JR, 1998. "Proximal femur fractures after free vascularized fibular grafting to the hip." Clin Orthop Relat Res (356): 192-201 [PubMed] Abstract: The management of symptomatic femoral head osteonecrosis in young, active patients is troublesome and controversial. At the authors' institution, 707 consecutive free vascularized fibular grafts were performed for femoral head osteonecrosis between October 1979 and October 1995. Patients who underwent this procedure were at increased risk for proximal femur fractures because of the 16 to 21 mm core drilled through the lateral femoral cortex for removal of the avascular bone and placement of the fibular graft. An ongoing prospective database of patients who underwent this procedure was accessed to determine the incidence of and factors associated with postoperative subtrochanteric femur fractures. Eighteen subtrochanteric fractures occurred for an overall incidence of 2.5%. All fractures occurred through the core decompression site in the lateral femoral cortex. The treatment was nonoperative in seven patients and operative in 11. Fourteen of 18 fractures (77%) healed with an average of 4.1 months until radiographically documented union. Four fractures had nonunions develop, three of which later healed with bone grafting and internal fixation, whereas the fourth eventually required conversion to total hip arthroplasty. Twelve fractures in 251 patients occurred when the weightbearing regimen was touchdown weightbearing for the first 6 weeks and five fractures in 456 patients occurred when the weightbearing regimen was changed to nonweightbearing. The results indicate that nonweightbearing in the immediate postoperative period is associated with the lowest fracture rate.

Mont et al. OKU 3: Hip and Knee Reconstruction. AAOS. 2006. Ch. 44: Osteonecrosis of the hip. 511-19.

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