Osteonecrosis – Interesting Facts

15 Interesting Facts of Osteonecrosis

1. Osteonecrosis (ON) most commonly involves the femoral head.
2. The most common risk factors for ON are glucocorticoid (GC) use and alcohol abuse.
3. If you have sufficient clinical suspicion of ON and x-rays are normal, magnetic resonance imaging (MRI) must be performed.
4. Nonoperative therapy for early disease includes protected weight-bearing, bisphosphonates, statins, and anticoagulants.
5. Operative therapy includes core decompression with or without grafting and total joint replacement.
6. Osteonecrosis is a degenerative bone condition characterized by death of cellular components of bone owing to interruption of the subchondral blood supply; resorptive component of the repair process results in loss of structural integrity 
7. Main risk factors for osteonecrosis of the femoral head are glucocorticoid use, alcohol consumption of 1000 mL or more per week, smoking, and trauma and prior surgery involving the affected joint 
8. Patients typically present with history of slow-onset, insidious joint pain
9. Primary physical signs are tenderness and limited joint range of motion
10. MRI is the diagnostic modality of choice, with high sensitivity and specificity for osteonecrosis 
11. Surgery is the only definitive treatment for osteonecrosis, especially in advanced stages 
12. Surgical treatment of early-stage osteonecrosis is important, because patients diagnosed with precollapse osteonecrosis are likely to progress to collapse within 3 years 
13. Nonoperative options, including bisphosphonates, have limited benefit 
14. Patients diagnosed with precollapse osteonecrosis who receive no treatment have 70% to 80% chance of collapse within 3 years 
15. Once severe subchondral collapse has occurred in knee osteonecrosis, procedures for salvaging the joint are rarely successful; joint arthroplasty is necessary to relieve pain

Synonyms for Osteonecrosis

• Avascular necrosis,
• aseptic necrosis,
• atraumatic necrosis, and
• ischemic necrosis

How is Osteonecrosis defined?

ON refers to death of the cellular component of bone (osteocytes) and contiguous bone marrow resulting from ischemia. Although inciting factors for such ischemia are varied, their end results are clinically indistinguishable.

What skeletal regions are predisposed to developing Osteonecrosis?

Bones are most vulnerable in those areas having both limited vascular supply and restricted collateral circulation, which are areas that are also typically covered by articular cartilage.

The area most frequently affected is the femoral head. At-risk areas include femoral head, carpal bones (scaphoid, lunate), humeral head, talus, femoral condyles, tarsal navicular, proximal tibia, and metatarsals.

Additional Info on Osteonecrosis

Pitfalls

• Nonoperative options, including bisphosphonates, have limited benefit 
• Total hip or knee replacement procedures generally have lower success rates when performed for osteonecrosis (versus osteoarthritis) 
• Advanced cases in young patients treated with total hip replacement often demonstrate good initial results but are prone to early failure 

Osteonecrosis is a degenerative bone condition characterized by death of cellular components of bone owing to interruption of the subchondral blood supply; resorptive component of the repair process results in loss of structural integrity 

Also called avascular necrosis

Usually affects epiphysis of long bones at weight-bearing joints

Femoral head is most commonly affected

Humerus and knee are the next most frequently affected sites

Less often, affects smaller bones and jaw

Classification 

• Various classification systems are available for osteonecrosis of the femoral head
  • Modified Ficat-Arlet system: most commonly used clinically 
    • Stage I: patient presents with ischemic pain in the groin, with or without radiation down front of thigh
    • Stage II: subchondral cyst formation and sclerosis
      • Flattening of contour of femoral head (out-of-round sign)
    • Stage III: femoral head flattening, subchondral collapse, and crescent sign (represents subchondral fracture)
    • Stage IV: decreased joint space, degenerative changes, and collapse of femoral head
  • Association Research Circulation Osseous system 
    • Stage I: normal radiographic findings in a patient with clinical manifestations, such as pain
    • Stage II: demarcating sclerosis in femoral head and no collapse
    • Stage III: femoral head collapse, crescent sign, and no joint space narrowing
      • IIIA: collapse less than 3 mm
      • IIIB: collapse greater than 3 mm
    • Stage IV: osteoarthritic degenerative changes
  • University of Pennsylvania classification system 
    • Stage I: normal radiographic findings in a patient with clinical manifestations, such as pain
    • Stage II: femoral head lucency/sclerosis
    • Stage III: subchondral collapse (without femoral head flattening) and crescent sign
    • Stage IV: subchondral collapse, femoral head flattening, and normal joint space
    • Stage V: flattening with joint space narrowing and/or acetabular changes
    • Stage VI: advanced degenerative changes and secondary osteoarthritis
• For shoulder (humeral head), Cruess classification is used: 
  • Stage I: normal radiographic findings, with possible changes on MRI
  • Stage II: sclerosis (wedged, mottled) and osteopenia
  • Stage III: crescent sign indicating a subchondral fracture
  • Stage IV: flattening and collapse
  • Stage V: degenerative changes extend to glenoid

Clinical Presentation

History

• For osteonecrosis at any anatomic site, history of slow-onset, or insidious joint pain
  • With humoral head osteonecrosis, pain is in shoulder area 
  • With femoral head osteonecrosis, pain is in groin
  • Femoral head osteonecrosis may be unilateral or bilateral
    • 75% of all femoral head osteonecrosis cases are bilateral 
    • Incidence of bilateral femoral head osteonecrosis is connected with presence versus absence of glucocorticoid use in history 
      • Cases with no glucocorticoids in history: 50% bilateral
      • Cases with glucocorticoids in history: 80% bilateral
  • Jaw osteonecrosis typically presents as exposed bone in areas where patient has been experiencing pain; patient may have a history of using medications known to be associated with osteonecrosis of the jaw (ie, antiresorptive and antiangiogenic medications) 
  • Osteoradionecrosis of the jaw involves nonhealing exposed necrotic bone in a previously irradiated site that has been present for at least 3 months 
• For osteonecrosis at any location 
  • Pain at night
  • Joint stiffness
  • Symptoms generally amplified with bearing weight and relieved with rest

Physical examination

• Any of the following signs:
  • Tenderness around affected joint
    • With femoral head osteonecrosis: 
      • Logrolling (passive internal and external rotation) elicits pain
      • Apprehension with passive internal rotation of hip
    • With shoulder osteonecrosis, movement of joint elicits pain 
    • With jaw osteonecrosis, pain can worsen when examiner moves jaw 
  • Limited joint range of motion
    • With femoral head osteonecrosis, hip abduction and internal rotation particularly are limited
  • Click or crepitus when a joint is put through range of motion
    • Particularly common in femoral head osteonecrosis (hip joint)
  • Stiffness and contractures in late stage

Causes

• Reduction of subchondral blood flow, owing to any of the following: 
  • Vascular interruption from fractures and/or dislocation
  • Intravascular occlusion caused by thrombi or embolic fat
  • Intraosseous extravascular compression caused by lipocyte hypertrophy or Gaucher cells

Risk factors and/or associations

Age

• Typically occurs between ages 35 and 45 years 

Sex

• Males are affected up to 3 times more often than females 

Genetics

• Genetic factors are implicated but causal gene has not been identified 
• COL2A1 gene has been reported to be associated in some studies 
  • In a Japanese family, mutations of this gene were reported in association with bilateral femoral head osteonecrosis, with autosomal dominant inheritance
  • In another study, associated with hip joint pathology that presented as femoral head osteonecrosis along with precocious hip osteoarthritis and Legg-Calvé-Perthes disease

Other risk factors/associations

• Major risk factors: account for 75% to 90% of cases 
  • Glucocorticoid use
  • 1000 mL or more alcohol per week 
  • Smoking 
  • Trauma and prior surgery involving the affected joint
• Sickle cell disease 
• Organ transplant 
• Antiresorptive (eg, bisphosphonates) and antiangiogenic (eg, bevacizumab) medications carry risk of jaw osteonecrosis, although oral bisphosphonates are used to treat osteonecrosis of the femoral head 
• Radiation therapy 
  • Called osteoradionecrosis
  • Generally from radiation doses greater than 60 Gy 
  • Occurs particularly in mandible, after radiation therapy for oro-nasal-pharyngeal malignancy, but other areas prone to osteoradionecrosis are: 
    • Spine
    • Chest wall–shoulder–humerus–scapula
    • Pelvis
• Decompression sickness 
  • Called dysbaric osteonecrosis
  • Occurs via disruption of vasculature by nitrogen bubbles
• Other conditions and factors affecting the femoral head 
  • Systemic lupus erythematosus
  • Chronic liver disease
  • History of slipped capital femoral epiphysis
  • Coagulopathy
    • Thrombophilia
    • Disseminated intravascular coagulation
  • HIV infection
  • Hyperlipidemia
  • Fat emboli syndrome
  • Treatment of developmental hip dysplasia
  • Previous chemotherapy
  • Gaucher disease
  • Gout
  • Metabolic bone disease

How is Osteonecrosis diagnosed?

• Imaging is the primary diagnostic tool; MRI is the modality of choice

Imaging

• MRI 
  • Imaging modality of choice owing to high sensitivity and specificity for osteonecrosis 
  • T1 shows: 
    • Single density line representing interface between viable and necrotic bone
    • Serpiginous bandlike lesion with low signal intensity
  • T2 shows: 
    • Double density line (double-line sign); high signal intensity reparative interface of vascular reactive bone adjacent to necrotic subchondral bone
• Radionuclide bone scan
  • Indicated for detection of inflammatory activity in femoral head when MRI is contraindicated (eg, owing to cardiac pacemaker or ferromagnetic implants) 
  • Less sensitive and specific than MRI 
  • Shows increased uptake on delayed scan 
• Plain radiography
  • Highly specific for more advanced osteonecrosis (Ficat-Arlet II or III) 
  • Not sensitive for early changes (Ficat-Arlet I); therefore, not indicated in patients whose clinical assessment (history and physical) suggests mild to moderate disease 
  • Shows increased bone density

Differential Diagnosis

Most common

• Osteoarthritis
• Osteomyelitis in adults
• Postmenopausal osteoporosis

Treatment Goals

• Slow progression
• Restore joint function

Admission criteria

• Hospital admission is required only for patients with osteonecrosis who are electing surgical procedures that must be performed on an inpatient basis, such as total hip or knee replacement

Recommendations for specialist referral

• All patients suspected of having osteonecrosis in a long bone should be referred to an orthopedic surgeon
• Osteonecrosis of the jaw requires referral to specialists in dentistry, oncology, and maxillofacial surgery 

Treatment Options

Surgery is the only definitive treatment for osteonecrosis, especially in advanced stages; main surgical options are: 

• Core decompression
• Bone grafting
  • Nonvascularized graft
  • Vascularized graft
• Osteotomy
• Arthrodesis
• Joint arthroplasty

Surgical treatment of early-stage osteonecrosis is important, because patients diagnosed with precollapse osteonecrosis are likely to progress to collapse within 3 years 

Nonoperative options, including bisphosphonates, have limited benefit 

For medication-related osteonecrosis of the jaw, the most important goals of treatment are primarily the control of infection, bone necrosis progression, and pain; initial approach should be as conservative as possible 

• Multidisciplinary team approach including a dentist, an oncologist, and a maxillofacial surgeon is recommended to determine the best therapy on a case-by-case basis 

Drug therapy

• Bisphosphonates
  • Alendronate has been used 
  • Benefit has been demonstrated, particularly with femoral head osteonecrosis if stage is early and necrotic size is small 
  • Controversy surrounds benefit versus adverse effects and complications (eg, headache, nausea, vomiting, esophagitis, esophageal ulceration) 
  • Alendronate Sodium Oral tablet; Adults: 10 mg PO once daily. 

Nondrug and supportive care

Measures to offload force on the affected hip

• For early-stage disease only; limited success in preventing disease progression
• Options include:
  • Cane/walker
  • Activity modification
  • Physical therapy

Other nonoperative measures

• Smoking and alcohol abstinence
• Extracorporeal shockwave therapy
• Hyperbaric oxygen therapy (for osteoradionecrosis of the jaw) 
  • May reduce the chance of osteoradionecrosis after tooth extraction in an irradiated field 

Procedures

Extracorporeal shockwave therapy 

General explanation

• Diseased tissue is bombarded with sound waves under local anesthesia
• Could slow or block the progression of osteonecrosis of the femoral head, therefore reducing the demand for surgery 

Indication

• Early-stage osteonecrosis of the femoral head

Contraindications

• Neurologic or vascular insufficiencies
• Bleeding diathesis or medications that interfere with blood clotting
• Nerve entrapment syndrome

Hyperbaric oxygen therapy 

General explanation

• Exposure to 100% oxygen inside a chamber that is pressurized beyond 1 ATA
• Hemoglobin is saturated with oxygen
• Oxygen is dissolved into plasma to hyperoxygenate the blood
• May reduce the chance of osteoradionecrosis after tooth extraction in an irradiated field 

Indication

• Routine use for the prevention or management of osteoradionecrosis of the jaw is not recommended
• Adjunctive use may be considered on a case‐by‐case basis in patients considered to be at exceptionally high risk who have failed conservative therapy and subsequent surgical resection

Contraindications

• Absolute
  • Untreated pneumothorax
• Relative
  • Asthma
  • History of bleomycin treatment, which may exacerbate the development of pulmonary oxygen toxicity
  • Congenital spherocytosis, which may cause severe hemolysis

Complications

• Barotraumatic lesions
• Oxygen toxicity
• Confinement anxiety
• Ocular effects

Core decompression 

General explanation

• Trephine and/or drill is used to access marrow cavity, thereby relieving marrow pressure
• Can be combined with a grafting procedure

Indication

• Precollapse osteonecrosis stage (corresponding to stage I/II in the case of femoral head osteonecrosis, but this concept can be applied to the knee and shoulder) 

Contraindications

• Osteonecrosis that has progressed to subchondral collapse

Nonvascularized bone graft 

General explanation

• Harvested bone tissue is implanted at osteonecrotic site without need to connect the new tissue surgically to a blood supply

Indication

• Osteonecrosis with subchondral collapse less than 2 mm

Contraindications

• End-stage disease (eg, stage IV in femoral head osteonecrosis, stage V in shoulder osteonecrosis)

Vascularized bone graft 

General explanation

• Harvested bone tissue is implanted at osteonecrotic site with direct, surgically connected blood supply

Indication

• Osteonecrosis stage II or III in a young patient desiring to be highly physically active

Contraindications

• End-stage disease

Osteotomy 

General explanation

• Bone cut and repositioned to alter mechanical axis and offload the diseased area from direct loading

Indication

• Controversial, but may be indicated in some patients in stage III/IV femoral head osteonecrosis, without steroid-associated disease, and with smaller necrotic fragment

Contraindications

• Relative
  • Possibility that conversion to total hip replacement will be desired, since osteotomy can make total hip replacement more difficult

Arthrodesis 

General explanation

• Bones are fused together

Indication

• Can be helpful in some young patients with unilateral stage III/IV disease caused by trauma

Contraindications

• Lack of healthy bone in locations where hardware must be placed to fuse adjacent bones

Total hip or knee replacement 

General explanation

• Distal portion of affected long bone is removed and replaced with an artificial device
• Concerns about failure and dislocation (in case of hip); generally lower success rate when performed for osteonecrosis (versus osteoarthritis)

Indication

• Young patient desiring high level of activity
• With knee osteonecrosis, once severe subchondral collapse has occurred, joint arthroplasty is necessary to relieve pain

Contraindications 

• Significant medical disease in which risk of surgery outweighs expected benefit
• Psychiatric disease or dementia
• Systemic infections

Comorbidities

• The following contribute to inferior outcomes and thus may affect benefit-versus-risk decisions regarding treatment: 
  • Alcohol abuse
  • Systemic lupus erythematosus
  • Other inflammatory disorders

Complications

• Subchondral collapse and joint deterioration
  • Patients diagnosed with precollapse osteonecrosis who receive no treatment have 70% to 80% chance of collapse within 3 years 

Prognosis

• Femoral head osteonecrosis
  • Prognosis significantly improved with early diagnosis, before articular collapse (pre–stage III) 
  • With nonsurgical treatment, femoral head preservation rates: 
    • Stage I: 35%
    • Stage II: 31%
    • Stage III: 13%
  • With core decompression, femoral head preservation rates: 
    • Stage I: 84%
    • Stage II: 65%
    • Stage III: 47%
  • Advanced cases in young patients treated with total hip replacement often demonstrate good initial results but are prone to early failure 
  • Osteonecrosis associated with sickle cell disease has a particularly poor prognosis 
• Knee osteonecrosis 
  • Joint-preserving surgical techniques may successfully postpone the need for joint arthroplasty
  • Once severe subchondral collapse has occurred, procedures for salvaging the joint are rarely successful; joint arthroplasty is necessary to relieve pain

Screening

At-risk populations

• Patients on prolonged glucocorticoid therapy

Screening tests

• MRI screening 
  • In patients older than 10 years, early screening with MRI can identify extensive asymptomatic lesions in those who would be eligible for intervention studies of treatments for prevention or delay of joint collapse, particularly with femoral head osteonecrosis

Prevention

• Elimination of modifiable risk factors, such as smoking and alcohol consumption
• Dental screening and adequate treatment are fundamental to reduce the risk of osteonecrosis in patients on antiresorptive or antiangiogenic therapy, or before initiating their administration 

Sources

Shah KN et al: Pathophysiology and risk factors for osteonecrosis. Curr Rev Musculoskelet Med. 8(3):201-9, 2015 Reference