Chinese Experts' Consensus on the Diagnosis and Treatment of Osteonecrosis of the Femoral Head in Adults

Introduction

Avascular necrosis or osteonecrosis of the femoral head (ONFH) is a recalcitrant and common disease characterized by death of the osteocytes and the bone marrow, and is caused by inadequate blood supply to the affected segment of the subchondral bone. Experts' suggestions of the diagnosis and treatment osteonecrosis of the femoral head were described for diagnosis, treatment and evaluation of ONFH in 2006. The Group of Microsurgery, Chinese Orthopaedic Association, Chinese Medical Association, and Group of Bone defect and Osteonecrosis, Chinese Association of Reparative and Reconstructive Surgery, and the editorial board of the Chinese Journal of Orthopaedics sponsored the senior experts' seminar on ONFH and updated the experts' suggestions in March 2012. All members of the Microsurgery groups and senior experts were invited to discuss the latest concepts and debate on the diagnosis and treatment of ONFH. Finally, an experts' consensus was given to provide a current basis for diagnosis, treatment and evaluation of ONFH.

Overview

The Association Research Circulation Osseous (ARCO) and the American Academy of Orthopaedic Surgeons (AAOS) states that ONFH is not a specific diagnostic entity, but is considered a final common pathway for many diseases that can disrupt blood supply to the femoral head causing cell death within the femoral head. Histologically, ONFH is characterized by dead osteocytes, necrotic marrow elements, and lack of vasculature in a defined region in the femoral head; in most cases, these changes ultimately lead to collapse of the subchondral bone and the destruction of the hip joint in patients1.

The etiology of ONFH includes traumatic and non‐traumatic causes. ONFH commonly occurs after direct trauma, such as hip dislocation or femoral neck fracture. Pathogenesis of non‐traumatic ONFH is not well understood, and in China the main risk factors include corticosteroid use, alcoholism, decompression sickness, and sickle cell anemia etc2, 3, 4.

Diagnostic Criteria

The diagnostic criteria was decided by making a reference to Japanese Investigation Committee (JIC) and Mont's criteria for osteonecrosis of the femoral head5, 6:

1. Clinical symptoms, signs and medical histories: Although early in the disease process the condition is painless, the chief complaint of a patient with osteonecrosis is pain with limitation of movement. The pain is usually localized to the groin area but occasionally to the ipsilateral buttock and knee, or greater trochanteric area. The pain has been described as a deep, intermittent, throbbing pain, with an insidious onset that can be sudden. The pain is exacerbated with weight bearing and relieved by rest. Physical examination reveals pain with both, active and passive range of motion, especially with forced internal rotation. A limitation of passive abduction is usually elicited, and passive internal and external rotation of the extended leg can cause pain. Medical history usually includes excessive corticosteroid use, alcohol abuse, smoking, coagulopathies, hemoglobinopathy, gout, systemic lupus erythematosus and chemotherapy or exposure to radiotherapy. The patient with traumatic ONFH will provide a history of hip injury that includes dislocations and fractures.

2. X‐rays: Standard anteroposterior and frog‐leg (Lowenstein) lateral radiographs should be obtained in both legs as part of a patient's work‐up since bilateral disease is common. It may be difficult to delineate small areas of ONFH on plain radiographs, but the most common early findings are alternating areas of subchondral sclerosis and lucency. The presence of the crescent sign corresponds with the progress of ONFH, reflecting the discrepancy in densities of the femoral head due to subchondral bone collapse. The final stages of joint space narrowing, acetabular changes, or both, and advanced degenerative changes can also be made out.

3. Computed tomography scan: CT scans of the femoral head show the necrotic and repairing bone is in the surrounding sclerotic bone. Perhaps subchondral bone fracture may also be made out, but CT scan is less sensitive than MRI.

4. Magnetic resonance imaging: MRI achieves excellent sensitivity for early ONFH detection. This is particularly relevant in patients who show signs and symptoms of the disease with no changes appreciated on radiographs. A circumscribed subchondral “band‐like” lesion with low signal intensity on T1‐W images is pathognomonic. The “double‐line” sign is seen on T2‐W images.

5. Radionuclide bone scan: Bone scintigraphy with ^99mTc‐methylene diphosphonate, shows high sensitivity for early detection. For symptomatic disease the method is able to provide positive findings within 2–3 days after the onset of symptoms (“cold within hot”) and later “hot lesion” reflecting revascularization. These findings can be matched with MRI findings.

6. Bone histologic examination: Histologic examination of the diseased femoral head shows bone empty lacuna were more than 50% in bone trabeculae, with damage of many adjacent bone trabeculae and bone marrow necrosis.

• Experts' consensus: The presence of two or more of the above criteria confers the diagnosis of ONFH. Except the 1^st and 5^th criteria, any other one criterion can diagnose ONFH.

Differential Diagnosis

Table 1 represents the various clinical features and diagnostic characteristics of conditions that can mimic ONFH:

1. Mid‐late term osteoarthritis: Osteoarthritis is the most common cause of chronic joint pain among middle‐aged and older people. Osteoarthritis involves the entire joint, including the nearby muscles; underlying bone, ligaments, joint lining (synovium), and the joint cover (capsule) and hip joint space narrowing. CT scans show sclerotic bone and cystic changes; the crescent sign can be seen on MRI.

2. Acetabular dysplasia secondary osteoarthritis: This condition most commonly affects female children and young adults, bilaterally. X‐rays show dislocation of hip joint, hip joint space narrowing, and features of secondary osteoarthritis.

3. Ankylosing spondylitis involving the hip: Ankylosing spondylitis (AS) is a common inflammatory rheumatic disease that affects the axial skeleton, causing characteristic inflammatory back pain, which can lead to structural and functional impairments and a decrease in quality of life. The pathogenesis of AS is poorly understood, immune mediated mechanisms involving human leucocyte antigen (HLA)‐B27 are associated with pathogenesis. Involvement of the hip is common among patients with AS, and is understood to be a result of inflammation of the subchondral bone marrow. Hip involvement often affects bilateral femoral heads, and radiography shows sacroiliac joint erosions and iliac side subchondral sclerosis.

4. Rheumatoid arthritis: Rheumatoid arthritis (RA) is a symmetric polyarticular arthritis that primarily affects the small diarthrodial joints of the hands and feet. RA often affects bilateral hip joints in middle‐aged and older women. The radiography shows hip joint space narrowing and changes consistent with secondary osteoarthritis.

5. Chondroblastoma in the femoral head: Chondroblastoma is a benign bone tumor arising most often in the epiphyses of long bones, but can also affect the proximal femur. Nearly 90% occur in patients between the ages of 5 and 25 years. MRI shows the high signal intensity on T2‐W images; CT scans show irregular dissolved bone7.

6. Fibrous dysplasia in femoral head: Fibrous dysplasia is a rare, non‐neoplastic condition of unknown etiology that affects many bones including the proximal femur. It is usually diagnosed in children and young adolescents. No significant sex preponderance has been reported consistently. It frequently is asymptomatic. Bilateral involvement is rare. Classic shepherd's crook deformity of proximal femur is the typical X‐ray appearance.

7. Idiopathic transient osteoporosis of the hip (ITOH): Idiopathic transient osteoporosis of the hip occurs mostly in middle‐aged men, but sometimes in women, usually in late pregnancy. There is increasing pain and a limp, with some local muscle wasting. An abnormal bone scan may precede radiographic osteoporosis of the femoral head and neck. Symptoms reach a plateau then resolve, and bone density returns to normal. MRI shows low signal intensity on T1‐W images and high signal intensity on T2‐W images, extending from the femoral head to the intertrochanteric region8.

8. Subchondral insufficiency fracture (SIF): SIF occurs mostly in women over 60 years old, with osteoporosis. The initial symptom is acute onset of hip pain. Radiologically, a subchondral collapse, mainly in the superolateral segment of the femoral head is noted. One of the characteristic MRI findings is the shape of the low‐intensity band on T1‐weighted images, and high‐intensity T2 weighted images (bone marrow edema pattern) that is generally irregular, serpiginous, convex to the articular surface, and often discontinuous8.

9. Pigmented villonodular synovitis (PVNS): Pigmented villonodular synovitis is a rare disorder affecting joints and a benign proliferative disorder of the synovium of uncertain cause. PVNS occurs mostly in the second and the fourth decade of life. No significant sex preponderance has been reported. It may involve tendon sheaths, bursae, or joints, the latter occurring as diffuse involvement or a localized nodule. X‐rays and CT scans show narrowing of the hip joint space. MRI shows extensive thickening of the joint lining or an extensive mass, possibly with destructive bone changes.

10. Bone infarction: Bone infarct occurs with ischemic death of the cellular elements of the bone and marrow. This condition affects bilateral hip joints. MRI shows high signal intensity on T2‐W images, and the appearance of the characteristic double‐line sign, which consists of a hyperintense inner ring and a hypointense outer ring.

Table 1.

Differential diagnosis of diseases analogous to osteonecrosis of the femoral head (ONFH)

Diseases	Age predilection	Sex predilection	Etiology	Unilateral or Bilateral	Acetabulum involved or not	Diagnosis elements
Osteoarthritis	Middle‐age and older	No gender differences	Degeneration	Bilateral	Yes	CT: sclerotic bone and cystic change MRI: crescent sign
Acetabular dysplasia secondary osteoarthritis	Children and Youth	Female	Genetic factors	Bilateral	Yes	X rays: hip joint dislocation, hip joint space narrowing and features of secondary osteoarthritis
Ankylosing spondylitis involving the hip	Teenagers	Male	Genetic factors and environment	Bilateral	Yes	HLA‐B27(+), sacroiliac joint erosions and iliac side subchondral sclerosis
Rheumatoid arthritis	Middle‐aged and older	Female	Unclear	Bilateral	Yes	X rays: hip joint space narrowing and features of secondary osteoarthritis
Chondroblastoma in femoral head	Children and Teenagers	Male	Unclear	Unilateral	No	MRI: high signal intensity on T2‐W images; CT: irregular dissolved bone.
Fibrous dysplasia	Children and Youth	Female	Unclear	Unilateral	N0	X rays: classic shepherd's crook deformity of the proximal femur
Idiopathic transient osteoporosis of the hip	Middle‐aged and youth	No gender differences	None	Unilateral	No	MRI: low signal intensity on T1WI, high signal intensity on T2‐WI, extending from the femoral head to the intertrochanteric region
Subchondral insufficiency fracture	Elderly	Female	Osteoporosis	Unilateral	No	X rays: femoral head becomes flat; MRI: subchondral low signal intensity on T1‐WI and T2‐WI, with bone marrow edema pattern
Pigmented villonodular synovitis	Young adults	No gender differences	None	Unilateral	Yes	X‐rays and CT: hip joint space narrowing; MRI: extensive thickening of the joint lining or an extensive mass, possibly with destructive bone changes
Bone Infarction	Unclear	Unclear	Unclear	Bilateral	No	MRI: high signal intensity on T2‐WI, characteristic double‐line sign, which consists of a hyperintense inner ring and a hypointensity outer ring

Staging

Staging is developed as a method to treat a disease during the various developmental phases. A number of classification systems for ONFH staging have been developed, including the ARCO9 (Association Research Circulation Osseous), Stulberg10 and Ficat11. The experts' consensus suggested that the ARCO international classification system is considered most useful: Early stage (ARCO 0 stage–I stage), middle stage (ARCO II stage–IIIb stage) and lately stage (ARCO IIIc–IV stage).

Treatment of ONFH

Management alternatives for ONFH vary from joint salvaging procedures including non‐operative treatment and operative treatment. Factors affecting the outcome of these procedures include patient's age, etiology and stage of osteonecrosis, in addition to the size and location of the osteonecrotic lesion.

Non‐operative Treatment

Non‐surgical management can only be selected for early stages and very small lesions, or among patients in whom surgical management is contraindicated.

1. Weight‐bearing: The use of two crutches can reduce pain, but wheelchair use must not be encouraged1.

2. Treatment with drugs: Lipid‐lowering drugs, anticoagulants, vasodilators, and bisphosphonates that address specific physiological risk factors for osteonecrosis such as lipid emboli, adipocyte hypertrophy, venous thrombosis, increased intraosseous pressure, and resorption of bone, have been tried12.

3. Traditional Chinese medicine (TCM) treatment: According to the holistic concept of TCM13, the principles of dynamic and static combination, equal emphasis on bones and muscles, combined internal and external therapy, doctor‐patient cooperation methods are followed. Activating blood circulation14, clearing damp and dissolving phlegm15 and Bushen Jiangu16 are other TCM techniques to treat early stages of ONFH.

4. Physiotherapy: Various external, biophysical, non‐operative modalities have been used to treat ONFH. These include electromagnetic stimulation, extracorporeal shock‐wave therapy, and hyperbaric oxygen17.

5. Immobilization and traction: These methods may be adopted in the early and (ARCO 0 stage–I stage) and the middle stages (ARCO II stage–IIIb stage) of ONFH.

Operative Treatment

Non‐operative treatment is usually not very effective in ONFH, hence most patients of ONFH choose operative treatment to alleviate pain and retain mobility. Management alternatives for ONFH include joint salvaging procedures including core decompression, non‐vascularized bone‐grafting, osteotomy, vascularized bone‐grafting, and joint arthroplasty. The most commonly used procedures are core decompression and vascularized bone‐grafting in early (ARCO 0 stage–I stage) and middle stages (ARCO II stage–IIIb stage).

• 1 Core decompression: Core decompression is currently the most common procedure in the early stages of ONFH. Core decompression aims to decrease the intraosseous pressure and possibly enhance vascular ingrowth, thereby alleviating pain and delaying or negating the need for total hip arthroplasty. This technique uses a tunnel or multiple small holes that are drilled through the proximal femur into the necrotic lesion17, 18. Core decompression showed that its success rate was significantly higher than that of nonsurgical management of early‐stage disease. The experts recommended that multiple small holes should be drilled to maximize efficacy of the procedure.

Core decompression is usually combined with implants of bone marrow stromal cells19, 20, 21(implantation of autologous bone‐marrow cells). Many studies have reported the efficacy of this surgical technique22, 23.

The experts suggested that the core decompression with bone marrow stromal cells can be used for ONFH in established centers in large numbers that used a long‐term follow‐up reporting system.

• 2.  Non‐vascularized bone‐grafting: This procedure provides decompression of the femoral head, removal of necrotic bone, and structural support and scaffolding to allow repair and remodeling of subchondral bone. The methods include impaction bone grafting and strut bone graft with autogenous bone, allogeneic bone, and bone substitution material.
• 3.  Osteotomy: Osteotomies are used to move the segment of necrotic bone away from the weight‐bearing region, thereby relieving stress. There are two general types of osteotomies: angular intertrochanteric (varus and valgus) and rotational transtrochanteric. Total hip replacements performed after an osteotomy are often technically more difficult than those done in patients with ONFH who have never had an osteotomy, and may not be successful in the long‐term24.
• 4.  Vascularized bone‐grafting: The rationale for vascularized bone‐grafting is that it allows decompression, provides structural support, and restores a vascular supply that had been deficient or non‐existent for a long period of time. There have been multiple published reports on the use of vascularized around hip and fibular grafts. Presently, there are seven distinct approaches for around hip bone graft: (i) iliac graft vascularization25; (ii) vascularized greater trochanter graft26; (iii) greater trochanter flap with branch of transverse lateral circumflex femoral vascular27; (iv) vascularized pedicled bone flap of deep iliac circumflex vessels; (v) greater trochanter flap with branch of transverse lateral circumflex femoral vascular and iliac graft vascularization28; (vi) iliac graft with deep branch of medial circumflex femoral artery or pedicled ilium periosteal flap; and (vii) quadratus femoris muscle pedicle29, 30, 31. The surgical technique of vascularized iliac bone flap combined with tantalum screw has a good short‐term effect32, 33. The result of vascularized fibular grafts was confirmed34, 35. According to grafts' technical characteristics and surgeons' proficiency choose using graft36.

The experts' advice was to use vascularized hip bone graft, because of its small wound, good curative effect, and relatively easy surgical procedure.

• 5.  Joint arthroplasty: Total hip replacement is indicated once the femoral head has collapsed and the hip joint has degenerated such that the articulation is compromised37. Recently, however, there has been enthusiasm among some investigators who anticipate better results from resurfacing due to improvements in techniques and biomaterials. Some elements should be taken into consideration: (i) corticosteroid use increases rates of infection; (ii) osteoporosis leads to the prosthetic into the acetabulum; (iii) high difficulty of operation in association with hip replacements after operative treatment; and (iv) the curative effect of traumatic ONFH is better than non‐traumatic.

Experts' Consensus on Choice of Treatment Methods

Stages and Treatment

• ARCO I stage: core decompression (with implants included bone marrow stromal cells).

• ARCO II stage: core decompression (with implants included bone marrow stromal cells), vascularized bone‐grafting, nonvascularized bone‐grafting (15% < necrosis volume <30%).

• ARCO IIIa, IIIb stage: vascularized bone‐grafting.

• ARCO IIIc, IV stage: vascularized bone‐grafting (youngster) and joint arthroplasty.

Age and Choice of Treatment

Young adults: core decompression (with implants included bone marrow stromal cells), vascularized bone‐grafting, and non‐vascularized bone‐grafting (15% < necrosis volume <30%).

Middle‐age: core decompression, vascularized bone‐grafting, non‐vascularized bone‐grafting and joint arthroplasty.

Older people (>55 years old): joint arthroplasty, bipolar/tripolar hemiarthroplasty or total hip replacement.

Therapy Assessment and Rehabilitation

Assessment of ONFH therapy can be determined by clinical and imaging evaluations.

The hip rate scale system (Harris38, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) 39, 40, Chinese Orthopaedic Association41, etc.) can be used to evaluate clinical outcomes. Meanwhile, gait analysis is recommended to aid the clinical data.

Imaging evaluation can be conducted by X‐ray and MRI scans. A concentric circle template can be used to observe the shape of femoral head, joint space, and the change in the acetabulum. Additional Digital Subtraction Angiography should be done in the vascular bone transplant cases, to assess the blood supplement and recovery42.

Experts suggested that it is necessary to establish detailed record‐keeping for continual assessment of therapy outcomes in ONFH. Rehabilitation training is an effective way to restore function and prevent the ONFH patient from getting muscle disuse atrophy. Rehabilitation training should be focused on active rather than adjuvant treatment, gradually increasing the time and intensity and choosing an adequate way to exercise according to the stage of ONFH, the treatment, the hip rate scale and the result of the gait analysis43, 44. The following exercises were the consensus among the experts.

1. Lie supine with leg lifts: The patient lies supine and raises the affected leg, with hip and knee flexed at 90°, 200 times per day but divided into three to four sessions. These exercises are especially useful in the conservative treatment for ONFH and postoperative period while the patient is recuperating in the hospital bed.

2. Division and reunion: The patient sits on a chair, feet at shoulder width, with hands on knees, shifts left leg to the left and right one to the right, stretching fully in front and adducting the limb. This should be done 300 times per day but divided into three to four sessions. These exercises also are used in the conservative treatment for ONFH and postoperative partial weight‐bearing stage.

3. Raise the leg in erect position: The patient is asked to hand hold onto a fixture, keeping the erect position, raising the affected leg and keeping the body and legs at 90°, hip and knee flexed at 90°, repeated up to 300 times per day but divided into three to four sessions. These exercises may also be useful in the conservative treatment for ONFH and postoperative in the partial weight‐bearing stage.

4. Squat with the help of a fixture: The patient is asked to hand hold onto the fixture, maintaining the erect position, feet at shoulder width, then squat and stand up. This is repeated up to 300 times per day but divided into three to four sessions. This could be useful in the conservative treatment for ONFH and postoperative period during the total weight‐bearing stage.

5. Adduction and abduction: The patient is asked to hand hold onto a fixture, adduct, abduct and circle movement of the affected limb for at least 300 times per day but divided into three to four sessions. These exercises are used in the conservative treatment for ONFH and postoperative in the total weight‐bearing stage.

6. Walking with a pair of crutches or cycling training: This may be used in the conservative treatment for ONFH and postoperative during the total weight‐bearing stage.