Avascular Necrosis of Femoral Head Diagnosis: A Comprehensive Guide for Automotive Experts and Healthcare Professionals

Introduction to Avascular Necrosis of the Femoral Head

Avascular necrosis of the femoral head, also known as osteonecrosis, is a debilitating condition characterized by the disruption of blood supply to the proximal femur, leading to bone cell death and potential collapse of the hip joint. In the United States alone, approximately 10,000 to 20,000 new cases are diagnosed annually, highlighting the significant impact of this disease. Understanding the complexities of avascular necrosis, particularly in achieving an accurate and timely Avascular Necrosis Of Femoral Head Diagnosis, is crucial for healthcare professionals. This article provides an in-depth exploration of avascular necrosis of the femoral head, with a strong emphasis on diagnostic approaches, treatment strategies, and interprofessional management, ensuring comprehensive care for patients.

Understanding the Causes (Etiology) of Avascular Necrosis

Avascular necrosis of the femoral head can stem from a range of factors, categorized broadly as traumatic and atraumatic. Traumatic causes often involve physical injuries that directly compromise blood flow to the femoral head.

Traumatic Etiologies

Femoral neck fractures and hip dislocations are primary traumatic causes. These injuries can directly sever or compress the delicate blood vessels supplying the femoral head, leading to ischemia and subsequent necrosis. Studies indicate that osteonecrosis occurs in 15% to 50% of femoral neck fractures and 10% to 25% of hip dislocations. Prompt and effective management of these injuries is critical to minimize the risk of developing avascular necrosis.

Atraumatic Etiologies

Non-traumatic causes are diverse, with chronic steroid use and excessive alcohol consumption being the most prevalent, accounting for over 80% of cases.

Steroid-Induced Avascular Necrosis

Steroid-associated osteonecrosis is the second most common overall cause, after trauma. While the exact mechanisms are still under investigation, it is believed to be multifactorial. Proposed factors include fat emboli obstructing small blood vessels, fat cell hypertrophy increasing pressure within the bone, endothelial dysfunction affecting blood vessel health, hyperlipidemia altering blood composition, and abnormalities in bone marrow stem cells. These factors collectively contribute to reduced blood flow and bone necrosis.

Alcohol-Related Avascular Necrosis

Alcohol-induced osteonecrosis, similarly, is not fully understood. Hypothesized mechanisms are similar to steroid-induced necrosis, involving bone marrow fat cell changes, altered serum lipid levels, blood vessel occlusion, and increased intraosseous pressure, all leading to inadequate blood supply.

Sickle Cell Disease and Avascular Necrosis

Sickle cell disease is a significant hematologic cause. The characteristic sickle-shaped red blood cells can impede blood flow, causing vaso-occlusion and ischemia. The femoral head is a common site for osteonecrosis in these patients due to its vulnerable blood supply.

Autoimmune and Inflammatory Disorders

Autoimmune conditions like systemic lupus erythematosus (SLE) are associated with increased risk. While long-term steroid use in these patients is a known risk factor, avascular necrosis can also occur in steroid-naive individuals, suggesting the autoimmune process itself may play a role in vascular compromise.

Legg-Calve-Perthes Disease

Legg-Calve-Perthes disease is an idiopathic form of avascular necrosis affecting children. It disrupts blood supply to the femoral head in pediatric patients, leading to necrosis, deformity, and long-term risks of osteoarthritis and limited hip mobility. The disease progresses through four stages: initial necrosis, fragmentation, reossification, and remodeling.

Other Contributing Factors

Less common but important causes include vascular disease related to diabetes and cytotoxic agents. These factors can directly damage blood vessels or bone cells, increasing the risk of avascular necrosis.

Figure 1: Illustration depicting the intricate blood supply network to the femoral head, crucial for understanding avascular necrosis.

Epidemiology: Who is Affected?

The estimated incidence of avascular necrosis of the femoral head in the United States ranges from 20,000 to 30,000 new cases each year. This condition contributes to a significant proportion, approximately 10%, of the 250,000 total hip arthroplasties performed annually. Incidence rates are comparable in German-speaking countries (0.01%) and Japan (1.9 per 100,000 population).

While race is generally not a significant factor, sickle cell-related avascular necrosis is more prevalent in individuals of African descent, reflecting the higher prevalence of sickle cell disease in this population. Overall, avascular necrosis of the femoral head is more common in men than women, with reported male-to-female ratios ranging from 3:1 to 5:1. The average age at diagnosis and treatment typically falls between 33 and 38 years old, highlighting that this condition affects a relatively young and active population.

Pathophysiology: How Avascular Necrosis Develops

Regardless of the initial cause, the fundamental pathophysiology of avascular necrosis of the femoral head involves the interruption of blood supply to the bone tissue. This ischemia leads to a cascade of cellular events culminating in osteocyte and bone marrow death in the subchondral bone of the proximal femur. The lack of sufficient blood flow deprives bone cells of oxygen and nutrients, leading to necrosis.

If left untreated, the progressive bone death weakens the structural integrity of the femoral head. This weakening eventually leads to microscopic fractures, collapse of the femoral head’s articular surface, and ultimately, the development of degenerative osteoarthritis in the hip joint. Early avascular necrosis of femoral head diagnosis is paramount to intervene before irreversible damage occurs.

Recognizing the Signs: History and Physical Examination

In the early stages of avascular necrosis, patients may be asymptomatic. However, as the condition progresses, hip pain becomes the primary symptom.

Symptoms

The pain associated with avascular necrosis is typically located in the hip but may radiate to the groin and/or thigh, often making avascular necrosis of femoral head diagnosis challenging based on symptoms alone. The pain is characteristically aggravated by weight-bearing activities such as walking, standing for prolonged periods, and climbing stairs. Rest may provide some relief, but pain often persists even at rest, especially in later stages. Patients may also describe stiffness in the hip, particularly in the morning or after periods of inactivity.

Physical Examination Findings

Physical examination can reveal several signs suggestive of avascular necrosis. Restricted range of motion in the hip is a common finding, particularly with internal rotation and abduction movements. Pain is often elicited upon palpation of the hip joint and during specific hip movements, especially forced internal rotation and abduction. A limp may be observed as patients attempt to minimize weight-bearing on the affected hip.

Avascular Necrosis of Femoral Head Diagnosis: Step-by-Step Evaluation

Early and accurate avascular necrosis of femoral head diagnosis is critical for effective management and to improve patient outcomes. Diagnosis relies on a combination of clinical assessment and advanced imaging techniques.

Imaging Modalities

Plain Radiography (X-rays)

Initial imaging often includes plain radiographs (X-rays) of the hip, typically in anterior-posterior and frog-leg lateral views. In early stages, X-rays may appear normal. However, as the disease progresses, characteristic radiographic signs may emerge. Subchondral radiolucency, known as the “crescent sign,” is a pathognomonic finding, indicating subchondral bone collapse. Sclerosis (increased bone density) and cystic changes within the femoral head may also be visible. While X-rays are readily available and cost-effective, they are less sensitive in detecting early avascular necrosis compared to other imaging modalities.

Radionuclide Bone Scanning

Radionuclide bone scanning, using Technetium-99m, can be more sensitive than X-rays in detecting early bone changes. In avascular necrosis, a “donut sign” may be observed, characterized by a ring of increased radiotracer uptake surrounding a central area of reduced uptake (“cold center”). This pattern represents increased bone turnover and repair activity at the boundary between necrotic and viable bone. Bone scans, while more sensitive than X-rays, are less specific for avascular necrosis and may be abnormal in other bone conditions.

Magnetic Resonance Imaging (MRI) – The Gold Standard

Magnetic resonance imaging (MRI) is considered the gold standard for avascular necrosis of femoral head diagnosis due to its high sensitivity and specificity, especially in early stages. MRI can detect subtle changes in bone marrow composition and blood supply long before they are visible on X-rays.

MRI allows for detailed visualization of:

• Bone marrow edema: Early indicator of ischemia.
• Size and location of the necrotic lesion: Crucial for staging and prognosis.
• Effect on articular cartilage: Assessment of joint damage.
• Subchondral collapse and its extent.
• Acetabular involvement.

MRI findings are instrumental in determining prognosis, guiding treatment decisions, and monitoring disease progression.

Steinberg Staging System

Once imaging confirms avascular necrosis, the extent of necrosis is classified using staging systems. The Steinberg staging system is the most widely used classification, providing a standardized approach to categorize the severity of avascular necrosis and guide treatment strategies.

Steinberg Staging System for Avascular Necrosis of the Femoral Head

Stage	Features
0	Normal radiograph, bone scan, and MRI
I	Normal radiograph, abnormal bone scan and/or MRI
IA	Mild (involves less than 15% of the femoral head)
IB	Moderate (involves 15% to 30% of the femoral head)
IC	Severe (involves over 30% of the femoral head)
II	Cystic and sclerotic changes of the femoral head (seen on radiograph)
IIA	Mild (involves less than 15% of the femoral head)
IIB	Moderate (involves 15% to 30% of the femoral head)
IIC	Severe (involves more than 30% of the femoral head)
III	Subchondral collapse (crescent sign) without flattening of the femoral head (seen on radiograph)
IIIA	Mild (involves under 15% of the femoral head)
IIIB	Moderate (involves 15% to 30% of the femoral head)
IIIC	Severe (involves over 30% of the femoral head)
IV	Flattening of the femoral head/femoral head collapse (seen on radiograph)
IVA	Mild (involves under 15% of the femoral head)
IVB	Moderate (involves 15% to 30% of the femoral head)
IVC	Severe (involves greater than 30% of the femoral head)
V	Joint space narrowing and/or acetabular changes (osteoarthritis)
VA	Mild
VB	Moderate
VC	Severe
VI	Advanced degenerative joint disease

Laboratory Investigations

While imaging is central to avascular necrosis of femoral head diagnosis, laboratory tests play a supporting role, primarily to rule out other causes of hip pain and identify potential underlying risk factors. A standard workup may include:

• Complete Blood Count (CBC): To assess for anemia (e.g., in sickle cell disease) and infection.
• Lipid Panel: To evaluate for hyperlipidemia, a potential contributing factor.
• Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP): Inflammatory markers, elevated in some differential diagnoses.
• Rheumatoid Factor (RF) and Anti-Nuclear Antibody (ANA): To screen for autoimmune conditions (though non-specific).
• Anti-Cyclic Citrullinated Peptide (anti-CCP): More specific for rheumatoid arthritis.
• Hemoglobin Electrophoresis: To detect hemoglobinopathies like sickle cell disease.

Elevated ANA and/or RF may suggest an autoimmune process, while elevated ESR and CRP indicate inflammation. Elevated anti-CCP is suggestive of rheumatoid arthritis, and HbS detected on hemoglobin electrophoresis points to sickle cell disease. CBC findings such as normocytic or microcytic anemia with elevated reticulocyte count are also consistent with sickle cell disease. These lab tests help differentiate avascular necrosis from other conditions presenting with hip pain and identify predisposing systemic diseases.

Biopsy and Angiography

Biopsy is rarely needed for avascular necrosis of femoral head diagnosis as imaging and clinical findings are usually sufficient. However, if performed, histological examination reveals trabecular necrosis (more than 50% empty osteocytic lacunae) and necrotic bone marrow without inflammation, tumor cells, or sepsis. Angiography studies are also not routinely performed clinically but may be used in research to visualize the vasculature of the femoral head and further understand disease pathology.

Figure 2: X-ray demonstrating dysbaric osteonecrosis of the hip, illustrating radiographic changes in avascular necrosis.

Differential Diagnosis: Ruling Out Other Conditions

The symptoms of avascular necrosis of the femoral head can overlap with several other conditions, making a thorough differential diagnosis essential.

Bone Marrow Edema Syndrome (BMES)

Bone marrow edema syndrome (BMES), also known as transient osteoporosis, is a condition characterized by rapid-onset hip pain, sometimes atraumatic, often triggered by minor injury, increased activity, or osteoarthritis. BMES is self-limiting, typically resolving within a year. MRI in BMES shows widespread bone marrow edema, distinguishing it from the more focal necrosis seen in avascular necrosis.

Subchondral Fracture

Subchondral fractures, particularly insufficiency fractures, can mimic avascular necrosis, especially in elderly patients with osteoporosis following minor trauma. These fractures occur due to bone insufficiency rather than vascular compromise.

Other Differential Diagnoses

Other conditions to consider include:

• Complex Regional Pain Syndrome
• Inflammatory Synovitis
• Neoplastic Bone Conditions (bone tumors)
• Osteomyelitis (bone infection)
• Osteoarthritis
• Osteoporosis
• Soft Tissue Trauma around the hip

Careful clinical evaluation, combined with appropriate imaging, is crucial to differentiate avascular necrosis from these other conditions and ensure accurate avascular necrosis of femoral head diagnosis.

Treatment and Management Strategies

Management of avascular necrosis of the femoral head is tailored to the individual patient and depends on factors such as disease stage, patient age, pain level, extent of necrosis, and presence of femoral head collapse. Treatment strategies range from conservative non-operative approaches to invasive surgical interventions. Ideally, treatments are implemented in the pre-collapse stages to preserve the hip joint. Untreated avascular necrosis can progress to subchondral fracture and collapse within 2 to 3 years.

Conservative Management

Non-operative treatments are considered primarily for early-stage, pre-collapse avascular necrosis or when surgery is not feasible. Conservative options include:

• Physical Therapy: To maintain range of motion and muscle strength around the hip.
• Restricted Weight-Bearing: Using crutches or other aids to reduce stress on the femoral head and potentially slow disease progression.
• Alcohol Cessation and Discontinuation of Steroids: Addressing modifiable risk factors.
• Pain Control Medications: Analgesics and NSAIDs for pain management.
• Targeted Pharmacologic Therapy: Several medications have been used off-label to attempt to improve blood flow and bone health, including vasodilators (e.g., iloprost), statins, bisphosphonates (e.g., alendronate), and anticoagulants (e.g., enoxaparin). However, there is no strong consensus on the effectiveness of these agents. Intra-articular steroid injections are generally avoided as they may worsen avascular necrosis.

Surgical Options

Surgical interventions are often necessary for more advanced stages or when conservative measures fail. Surgical options can be broadly categorized as joint-preserving or joint-reconstructive.

Joint-Preserving Procedures

• Core Decompression: This involves drilling into the femoral head to reduce intraosseous pressure, improve blood flow, and stimulate bone healing. It is most effective in pre-collapse stages. Cell therapies, such as bone marrow aspirate concentrate, are sometimes used as adjuncts to core decompression to enhance bone regeneration.
• Bone Grafting: Involves replacing necrotic bone with healthy bone graft. Grafts can be autografts (from the patient’s own body), vascularized bone grafts (including blood supply), or allografts (from a donor). Vascularized bone grafts may offer better revascularization and outcomes.
• Osteotomy: Surgical reshaping of the bone to shift weight-bearing away from the necrotic area of the femoral head. Procedures include rotational or angular osteotomies.

Joint-Reconstructive Procedures

• Hip Arthroplasty (Total Hip Replacement): Indicated for advanced avascular necrosis with femoral head collapse, acetabular involvement, or severe osteoarthritis. Hip replacement involves replacing the damaged hip joint with a prosthetic implant. Modern hip replacement techniques and implants have significantly improved outcomes in patients with osteonecrosis.

Prognosis and Factors Influencing Outcomes

The prognosis of avascular necrosis of the femoral head is variable and depends on several factors, most importantly the stage at avascular necrosis of femoral head diagnosis. Early diagnosis and intervention generally lead to better outcomes.

Factors Associated with Poorer Prognosis

• Advanced stage at diagnosis.
• Lateral femoral head involvement.
• Involvement of more than one-third of the weight-bearing portion of the femoral head (on MRI).
• Age over 50 years at diagnosis.

Even with these factors, individual prognosis varies, and a qualified orthopedic physician should determine it after comprehensive evaluation.

Potential Complications of Untreated AVN

If left untreated, avascular necrosis of the femoral head can lead to progressive joint damage and significant complications:

• Worsening Hip Pain: Pain typically increases over time and becomes more constant.
• Restricted Range of Motion: Hip stiffness and limited mobility.
• Osteoarthritis: Degenerative joint disease, leading to chronic pain and disability.
• Femoral Head Collapse: Structural failure of the hip joint.
• Need for Hip Replacement: In advanced cases, hip arthroplasty becomes necessary to restore function and relieve pain.

When to Consult a Specialist

If avascular necrosis of the femoral head is suspected based on symptoms or initial imaging, consultation with a qualified orthopedic surgeon is essential. An orthopedic specialist can provide expert evaluation, confirm the avascular necrosis of femoral head diagnosis, determine the stage of disease, and recommend the most appropriate treatment plan.

Deterrence and Patient Education

Patient education and awareness are crucial for early detection and prevention. Patients should be advised to seek medical attention if they experience persistent hip, groin, or thigh pain, especially if associated with risk factors for avascular necrosis.

Patient Populations at Higher Risk

• Patients on long-term steroid therapy.
• Individuals with excessive alcohol consumption.
• Patients with hemoglobinopathies (e.g., sickle cell disease).
• Patients undergoing chemotherapy or radiation.
• Individuals with a history of hip trauma or surgery.

Screening high-risk individuals may be considered, particularly those with hip symptoms. Education should also focus on lifestyle modifications to reduce risk factors, such as moderating alcohol intake and using corticosteroids judiciously.

Interprofessional Team Approach for Enhanced Care

Optimal management of avascular necrosis of the femoral head requires a collaborative interprofessional healthcare team. Team members may include:

• Physicians (Primary Care, Orthopedic Surgeons, Rheumatologists).
• Nurse Practitioners and Physician Assistants.
• Pharmacists.
• Nurses.
• Physical Therapists.

Each team member plays a vital role in patient care. Pharmacists can review medication regimens and advise on potential drug-related risks. Nurses are crucial for patient education, pre- and post-operative care, and monitoring treatment efficacy and adverse effects. Physical therapists guide rehabilitation programs. Primary care clinicians and nurses play a key role in risk factor education, early symptom recognition, and referral to specialists. Effective communication and coordination among team members are essential to improve patient outcomes in avascular necrosis of the femoral head.

Conclusion: Early Diagnosis is Key to Managing Avascular Necrosis of the Femoral Head

Avascular necrosis of the femoral head is a serious condition that can lead to significant hip pain, disability, and joint destruction. Early and accurate avascular necrosis of femoral head diagnosis is paramount for effective management and to improve patient prognosis. Healthcare professionals must maintain a high index of suspicion for avascular necrosis in patients presenting with hip pain, especially those with known risk factors. Utilizing appropriate imaging modalities, particularly MRI, and staging systems like Steinberg, allows for timely diagnosis and tailored treatment strategies. A comprehensive, interprofessional approach, focusing on early intervention and patient education, is crucial to optimize outcomes and enhance the quality of life for individuals affected by avascular necrosis of the femoral head.

References

1. Petek D, Hannouche D, Suva D. Osteonecrosis of the femoral head: pathophysiology and current concepts of treatment. EFORT Open Rev. 2019 Mar;4(3):85-97. [PMC free article: PMC6440301] [PubMed: 30993010]
2. Gold M, Munjal A, Varacallo M. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Jul 25, 2023. Anatomy, Bony Pelvis and Lower Limb, Hip Joint. [PubMed: 29262200]
3. Itokazu M, Takahashi K, Matsunaga T, Hayakawa D, Emura S, Isono H, Shoumura S. A study of the arterial supply of the human acetabulum using a corrosion casting method. Clin Anat. 1997;10(2):77-81. [PubMed: 9058012]
4. Narayanan A, Khanchandani P, Borkar RM, Ambati CR, Roy A, Han X, Bhoskar RN, Ragampeta S, Gannon F, Mysorekar V, Karanam B, V SM, Sivaramakrishnan V. Avascular Necrosis of Femoral Head: A Metabolomic, Biophysical, Biochemical, Electron Microscopic and Histopathological Characterization. Sci Rep. 2017 Sep 06;7(1):10721. [PMC free article: PMC5587540] [PubMed: 28878383]
5. Baig SA, Baig MN. Osteonecrosis of the Femoral Head: Etiology, Investigations, and Management. Cureus. 2018 Aug 21;10(8):e3171. [PMC free article: PMC6197539] [PubMed: 30357068]
6. Xie XH, Wang XL, Yang HL, Zhao DW, Qin L. Steroid-associated osteonecrosis: Epidemiology, pathophysiology, animal model, prevention, and potential treatments (an overview). J Orthop Translat. 2015 Apr;3(2):58-70. [PMC free article: PMC5982361] [PubMed: 30035041]
7. Jaffré C, Rochefort GY. Alcohol-induced osteonecrosis–dose and duration effects. Int J Exp Pathol. 2012 Feb;93(1):78-9; author reply 79. [PMC free article: PMC3311024] [PubMed: 22264288]
8. Adesina O, Brunson A, Keegan THM, Wun T. Osteonecrosis of the femoral head in sickle cell disease: prevalence, comorbidities, and surgical outcomes in California. Blood Adv. 2017 Jul 11;1(16):1287-1295. [PMC free article: PMC5728545] [PubMed: 29296770]
9. Mok MY, Farewell VT, Isenberg DA. Risk factors for avascular necrosis of bone in patients with systemic lupus erythematosus: is there a role for antiphospholipid antibodies? Ann Rheum Dis. 2000 Jun;59(6):462-7. [PMC free article: PMC1753161] [PubMed: 10834864]
10. Mills S, Burroughs KE. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Jul 10, 2023. Legg-Calve-Perthes Disease. [PubMed: 30020602]
11. Rampal V, Clément JL, Solla F. Legg-Calvé-Perthes disease: classifications and prognostic factors. Clin Cases Miner Bone Metab. 2017 Jan-Apr;14(1):74-82. [PMC free article: PMC5505718] [PubMed: 28740529]
12. Tripathy SK, Goyal T, Sen RK. Management of femoral head osteonecrosis: Current concepts. Indian J Orthop. 2015 Jan-Feb;49(1):28-45. [PMC free article: PMC4292325] [PubMed: 25593355]
13. Moya-Angeler J, Gianakos AL, Villa JC, Ni A, Lane JM. Current concepts on osteonecrosis of the femoral head. World J Orthop. 2015 Sep 18;6(8):590-601. [PMC free article: PMC4573503] [PubMed: 26396935]
14. Hofmann S, Kramer J, Plenk H. [Osteonecrosis of the hip in adults]. Orthopade. 2005 Feb;34(2):171-83; quiz 184. [PubMed: 15714357]
15. Ikeuchi K, Hasegawa Y, Seki T, Takegami Y, Amano T, Ishiguro N. Epidemiology of nontraumatic osteonecrosis of the femoral head in Japan. Mod Rheumatol. 2015 Mar;25(2):278-81. [PubMed: 25036228]
16. Vardhan H, Tripathy SK, Sen RK, Aggarwal S, Goyal T. Epidemiological Profile of Femoral Head Osteonecrosis in the North Indian Population. Indian J Orthop. 2018 Mar-Apr;52(2):140-146. [PMC free article: PMC5858207] [PubMed: 29576641]
17. Arbab D, König DP. Atraumatic Femoral Head Necrosis in Adults. Dtsch Arztebl Int. 2016 Jan 22;113(3):31-8. [PMC free article: PMC4748149] [PubMed: 26857510]
18. Karim R, Goel KD. Avascular necrosis of the hip in a 41-year-old male: a case study. J Can Chiropr Assoc. 2004 Jun;48(2):137-41. [PMC free article: PMC1840046] [PubMed: 17549225]
19. Mangla A, Ehsan M, Agarwal N, Maruvada S. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Sep 4, 2023. Sickle Cell Anemia. [PubMed: 29489205]
20. Zabinski SJ, Sculco TP, Dicarlo EF, Rivelis M. Osteonecrosis in the rheumatoid femoral head. J Rheumatol. 1998 Sep;25(9):1674-80. [PubMed: 9733445]
21. Mukisi-Mukaza M, Gomez-Brouchet A, Donkerwolcke M, Hinsenkamp M, Burny F. Histopathology of aseptic necrosis of the femoral head in sickle cell disease. Int Orthop. 2011 Aug;35(8):1145-50. [PMC free article: PMC3167438] [PubMed: 20830473]
22. Zlotorowicz M, Czubak J, Kozinski P, Boguslawska-Walecka R. Imaging the vascularisation of the femoral head by CT angiography. J Bone Joint Surg Br. 2012 Sep;94(9):1176-9. [PubMed: 22933487]
23. Hsu H, Nallamothu SV. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Aug 8, 2023. Hip Osteonecrosis (Archived) [PubMed: 29763129]
24. Claßen T, Becker A, Landgraeber S, Haversath M, Li X, Zilkens C, Krauspe R, Jäger M. Long-term Clinical Results after Iloprost Treatment for Bone Marrow Edema and Avascular Necrosis. Orthop Rev (Pavia). 2016 Mar 21;8(1):6150. [PMC free article: PMC4821225] [PubMed: 27114807]
25. Pritchett JW. Statin therapy decreases the risk of osteonecrosis in patients receiving steroids. Clin Orthop Relat Res. 2001 May;(386):173-8. [PubMed: 11347831]
26. Glueck CJ, Freiberg RA, Sieve L, Wang P. Enoxaparin prevents progression of stages I and II osteonecrosis of the hip. Clin Orthop Relat Res. 2005 Jun;(435):164-70. [PubMed: 15930934]
27. Lai KA, Shen WJ, Yang CY, Shao CJ, Hsu JT, Lin RM. 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. 2005 Oct;87(10):2155-9. [PubMed: 16203877]
28. Agarwala S, Shah S, Joshi VR. The use of alendronate in the treatment of avascular necrosis of the femoral head: follow-up to eight years. J Bone Joint Surg Br. 2009 Aug;91(8):1013-8. [PubMed: 19651826]
29. Immonen I, Friberg K, Grönhagen-Riska C, von Willebrand E, Fyhrquist F. Angiotensin-converting enzyme in sarcoid and chalazion granulomas of the conjunctiva. Acta Ophthalmol (Copenh). 1986 Oct;64(5):519-21. [PubMed: 3028032]
30. Piuzzi NS, Chahla J, Schrock JB, LaPrade RF, Pascual-Garrido C, Mont MA, Muschler GF. Evidence for the Use of Cell-Based Therapy for the Treatment of Osteonecrosis of the Femoral Head: A Systematic Review of the Literature. J Arthroplasty. 2017 May;32(5):1698-1708. [PubMed: 28162838]
31. Chughtai M, Piuzzi NS, Khlopas A, Jones LC, Goodman SB, Mont MA. An evidence-based guide to the treatment of osteonecrosis of the femoral head. Bone Joint J. 2017 Oct;99-B(10):1267-1279. [PubMed: 28963146]
32. Piuzzi NS, Chahla J, Jiandong H, Chughtai M, LaPrade RF, Mont MA, Muschler GF, Pascual-Garrido C. Analysis of Cell Therapies Used in Clinical Trials for the Treatment of Osteonecrosis of the Femoral Head: A Systematic Review of the Literature. J Arthroplasty. 2017 Aug;32(8):2612-2618. [PubMed: 28392136]
33. Lespasio MJ, Sodhi N, Mont MA. Osteonecrosis of the Hip: A Primer. Perm J. 2019;23 [PMC free article: PMC6380478] [PubMed: 30939270]
34. Kim YH, Kim JS, Park JW, Joo JH. Contemporary total hip arthroplasty with and without cement in patients with osteonecrosis of the femoral head: a concise follow-up, at an average of seventeen years, of a previous report. J Bone Joint Surg Am. 2011 Oct 05;93(19):1806-10. [PubMed: 22005866]
35. Choi HR, Steinberg ME, Y Cheng E. Osteonecrosis of the femoral head: diagnosis and classification systems. Curr Rev Musculoskelet Med. 2015 Sep;8(3):210-20. [PMC free article: PMC4596207] [PubMed: 26088795]
36. Goker B, Block JA. Risk of contralateral avascular necrosis (AVN) after total hip arthroplasty (THA) for non-traumatic AVN. Rheumatol Int. 2006 Jan;26(3):215-9. [PubMed: 15761731]
37. Niimi R, Sudo A, Hasegawa M, Uchida A. Course of avascular necrosis of femoral head without collapse of femoral head at first examination: minimum 8-year follow-up. Orthopedics. 2008 Aug;31(8):755. [PubMed: 19292420]
38. Hauzeur JP, De Maertelaer V, Baudoux E, Malaise M, Beguin Y, Gangji V. Inefficacy of autologous bone marrow concentrate in stage three osteonecrosis: a randomized controlled double-blind trial. Int Orthop. 2018 Jul;42(7):1429-1435. [PubMed: 28988340]