Osteonecrosis – Causes, Symptoms, Diagnosis, Treatment and Ongoing care

Basics

Definition: Cellular death (“necrosis”) of the elements of bone (“osteo”) due to interruption of the blood supply to that bone. Classified as traumatic (most common) vs nontraumatic.

Description

Primarily involves the epiphysis of long bones (most commonly femoral head, humeral head, and the femoral condyles) but small bones also affected in the hand, foot, ankle and faceSystem(s) affected: MusculoskeletalSynonym(s): Idiopathic osteonecrosis; avascular necrosis (AVN); lunatomalacia/Kienböck disease (involving lunate); subchondral fracture; aseptic necrosis; Legg-Calve-Perthes syndrome (children with idiopathic necrosis of the femoral head)

Epidemiology

Predominant age: 3rd–5th decadePredominant sex: Male > Female ratio 4–8:1

Incidence

10,000–20,000 new cases reported in the US per yearDisease is bilateral in at least 50% of all nontraumatic cases and in 75–95% of cases associated with steroid use (1).

Prevalence

Hip: Occurs in approximately 10% of undisplaced femoral neck fractures, 15–30% of displaced femoral neck fractures, and 10% of hip dislocationsJaw: Occurs in 3–12% of oncology patients taking high-dose IV bisphosphonates at 36 months of exposure and in <1% of nononcology patients with osteoporosis (2)Special population: Occurs in 21–25% of patients during early postoperative period following renal transplant (3)

Risk Factors

Top 3: Trauma, prolonged corticosteroid use, alcoholismOthers: Bisphosphonate use, sickle cell disease, diabetes mellitus, type II or IV hyperlipemia, oral contraceptives, pregnancy, decompression sickness (aka “bends,” “caisson disease,” “divers disease”), chronic pancreatitis, Crohn disease, myeloproliferative disorders, radiation treatment, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), chronic renal failure and hemodialysis, Gaucher disease, organ transplant, trauma, tobacco use, HIV, hypercoagulable state, developmental hip dysplasia, idiopathic

General Prevention

Limiting alcohol use: Dose-dependent relationship with RR of 3.3 for <400 mg/week consumed compared to RR of 17.9 for >1,000 mL/week consumed (4)Smoking cessation: Smokers with RR of 3.9 vs nonsmokers with no significance found to cumulative effect (4)Limiting corticosteroid use: Use the minimum effective dose of systemic corticosteroids as highest daily dose and cumulative dose is directly correlated to increased risk of osteonecrosis (5)[B].Screening: No definitive evidence but screening of asymptomatic patients at high risk for osteonecrosis may be of value if prophylactic treatment of asymptomatic osteonecrosis is proven useful (6).

Pathophysiology

Pathophysiology is multifactorial and not fully understood, but the final common pathway is interruption of blood flow to the bone.Lack of blood supply leads to hyperemia, demineralization, trabecular thinning and subchondral plate fracture, which eventually leads to collapse of the necrotic segment (1)Collapse of bone is irreversible, painful, often requires surgery for symptom relief, and is a risk factor for developing osteoarthritis.

Etiology

Traumatic: Disruption of blood supply due to physical disruption of a vessel due to fracture or dislocationNontraumatic: Possible mechanisms include: Impedance of blood flow due to vascular compression/vasospasmExtraluminal obliteration from marrow edemaIntraluminal obstruction from thromboembolism, nitrogen bubbles, fat emboli, intravascular coagulation, or vascular stasis (1)

 

Diagnosis

Consider AVN in any individual with bone pain and history of trauma or other risk factors.Pain in the affected joint is typically the presenting symptom.

History

Hip/femoral head: Dull aching groin/hip pain that is progressive and worsened with weight bearingKnee: Dull aching knee pain that is worsened with weight bearing, stair climbing, and at nightHumeral head: Shoulder pain that is severe and poorly localized, worsened at night and with activityLunate (Kienböck disease): Pain and stiffness to dorsal wrist of dominant hand

Physical Exam

Hip/femoral head: Decreased hip range of motion especially in rotation and abductionAntalgic or Trendelenburg gaitSynovitis = pain throughout range of motionKnee: Pseudolocking secondary to pain, effusion, or muscle contractureHumeral head: Active motion inhibited by painPassive motion and strength preservedLunate (Kienböck disease): Dorsal swelling with tenderness over radiocarpal jointRestricted and painful dorsiflexion of wristWeakness of grip

Diagnostic Tests & Interpretation

No specific physical findings or laboratory tests can reliably establish the diagnosis.Clinically suspected osteonecrosis can be confirmed only by diagnostic imaging or biopsy.Screening of a patient who is at high risk for osteonecrosis may be of value if prophylactic treatment of asymptomatic osteonecrosis is proven useful (6)[B].Imaging options: Plain films: 1st line Early stages: UnremarkableMild-to-moderate AVN: Sclerosis and changes in bone densityAdvanced disease: Bony deformities such as flattening, subchondral radiolucent lines (crescent sign), and osseus collapseViews to order based on location: Hip/femoral head: Order anteroposterior (AP) and frog lateral views of both hips; knee: Order AP, lateral, and tunnel view of knee; humeral head: Order AP, true AP, and axillary views of shoulder; lunate: Order wrist filmsMRI: Gold standard for diagnosis with sensitivity and specificity >98% (7)[B]; obtain if x-ray findings are normal and clinical suspicion is high Early stages: Decreased signal intensity of the subchondral region on both T1- and T2-weighted images (water signal)Mild-to-moderate AVN: High signal intensity line within 2 parallel rims of decreased signal intensity on T2-weighted scans (double line sign)Advanced disease: Deformity and calcification of the articular surfaceBone scan: Alternative to MRI, when used with SPECT imaging is 85% sensitive and 100% specific (8) Central area of decreased uptake surrounded by an area of increased uptake (doughnut sign)

Lab

Consider testing for sickle cell disease (Hb electrophoresis), hyperlipidemia (fasting lipid profile), and coagulopathies (protein C, protein S, factor V Leiden) with atraumatic etiology

Imaging

Bone marrow edema on MRI should be considered a marker for potential progression to advanced osteonecrosis and collapse of the femoral head (9)[B].Several different staging systems available for classifying osteonecrosis of femoral head (10) FICAT: Stages 0–4 based on symptoms, x-ray, and MRI findingsSteinberg: Stages 0–6 based on imaging and subdivided into categories based on percentage of femoral head affectedARCO (international classification of osteonecrosis of the femoral head): Stages 0–6 based on clinical symptoms and imaging findings with focus on status of the femoral head

Differential Diagnosis

Hip/femoral head: Osteoarthritis, femoral neck fracture, labral tear, osteomyelitis, muscle strain, groin injury, transient synovitis, bone marrow edema syndromeKnee: Osteoarthritis, septic arthritis, meniscal tear, bone bruise, transient osteopenia of the knee, pes anserine bursitis, osteochondritis desiccansHumeral head:Adhesive capsulitis, rotator cuff tear/tendonitis, osteomyelitisLunate (Kienböck disease): TFCC injury, tenosynovitis of extensor compartments, rheumatoid arthritis, degenerative joint disease, occult ganglion, other carpal bone injury

Treatment

Treatment depends on age, location, stage of the disease and overall health of the patient.Goal of therapy is to preserve the native joint for as long as possible.Early diagnosis is important to maximize treatment options.

Medication

No medical treatment has been proven effective for arresting the disease process.NSAIDs and other analgesics as needed for pain reliefProphylactic alendronate at 70 mg/week orally for 25 weeks found to prevent collapse of femoral head (NNT = 2) and need for total hip arthroplasty (NNT = 2) at 2 years in patients with Steinberg stage 2 or 3 nontraumatic AVN of femoral head with necrotic area >30% (11)[B]

Additional Treatment

General Measures

Usually managed as an outpatient but may be inpatient if surgery indicatedCrutches or other assistive devices to avoid weight bearing in early disease if weight bearing joint is affected

Issues for Referral

Evaluation by orthopedic surgeon once diagnosis is made to determine if surgery is appropriate

Complementary and Alternative Medicine

Noninvasive modalities of electrical stimulation, shock wave therapy, and electromagnetic field therapy undergoing trials but currently no evidence to support (12)[C]

Surgery/Other Procedures

Surgical options depend on severity and site of disease.Hip/femoral head: Early stages (precollapse) treated surgically with bone decompression and possible bone graftLater stages (postcollapse) treated with total hip arthroplastyKnee: Arthroscopy, osteochondral grafts, high tibial osteotomy, core decompression, unicompartmental knee arthroplasty, total knee arthroplastyHumeral head: Arthroscopy, core decompression, hemiarthroplasty, total shoulder arthroplastyLunate (Kienböck disease): Lunate excision with or without replacement, joint-leveling procedures, inter-carpal fusions, revascularization, salvage procedures

Ongoing Care

Physical therapy and occupational therapy as adjunctive treatmentSickle cell patients: No evidence that adding hip core decompression to physical therapy achieves clinical improvement in people with avascular necrosis of bone compared to physical therapy alone, per Cochrane Review (13)[A]

Patient Education

Physicians prescribing bisphosphonates should counsel their patients about potential oral complications linked to using these medications and advise patients to notify their dentists that they are taking the drugs (14)[C].Other high-risk patients should be educated about the risk of developing osteonecrosis and should be advised to report symptoms as soon as possible.

Prognosis

Poor prognostic factors include age >50, advanced disease at time of diagnosis, necrosis of >1/3 of the femoral head weight bearing area, lateral femoral head involvement, and nonmodifiable risk factors.Progression of asymptomatic osteonecrosis of the femoral head proportional to lesion size with small lesions (<15% involvement) unlikely to progress and large lesions (>30% involvement) likely to progress (15)[B]More than 50% of patients with osteonecrosis require surgical treatment within 3 years of diagnosis.Osteonecrosis of the humeral head accounts for 10% of total joint replacement procedures performed annually in US (7).

Complications

Secondary to surgery-induced trauma, including nonunion, malunion, peroneal nerve palsy, deep venous thrombosis, intraoperative fracture, and post-op dislocation (7)Progression of disease leads to OA of the involved joint to a varying degree.

References

1. Lafforgue P. Pathophysiology and natural history of avascular necrosis of bone. Joint Bone Spine. 2006;73(5):500–7.

2. Khan AA, Sándor GK, Dore E, et al. Bisphosphonate associated osteonecrosis of the jaw. J Rheumatol. 2009;36:478–90.

3. Kubo T, Yamazoe S, Sugano N, et al. Initial MRI findings of non-traumatic osteonecrosis of the femoral head in renal allograft recipients. Magn Reson Imaging. 1997;15:1017–23.

4. Matsuo K, Hirohata T, Sugioka Y, et al. Influence of alcohol intake, cigarette smoking and occupational status on idiopathic osteonecrosis of the femoral head. Clin Orthop Relat Res. 1998;115–23.

5. Powell C, Chang C, Naguwa SM, et al. Steroid induced osteonecrosis: An analysis of steroid dosing risk. Autoimmun Rev. 2010;9:721–43.

6. American College of Radiology (ACR) Appropriateness Criteria for avascular necrosis of the hip. National Guideline Clearinghouse. 2010;31:15734.

7. Assouline-Dayan Y, Chang C, Greenspan A, et al. Pathogenesis and natural history of osteonecrosis. Semin Arthritis Rheum. 2002;32:94–124.

8. Collier BD, Carrera GF, Johnson RP, et al. Detection of femoral head avascular necrosis in adults by SPECT. J Nucl Med. 1985;26:979–87.

9. Iida S, Harada Y, Shimizu K, et al. Correlation between bone marrow edema and collapse of the femoral head in steroid-induced osteonecrosis. AJR Am J Roentgenol. 2000;174:735–43.

10. Steinberg ME, Steinberg DR. Classification systems for osteonecrosis: an overview. Orthop Clin North Am. 2004;35:273–83, vii–viii.

11. Lai K-A, Shen W-J, Yang C-Y, et al. The Use of Alendronate to Prevent Early Collapse of the Femoral Head in Patients with Nontraumatic Osteonecrosis. The Journal of Bone and Joint Surgery (American).2005;87:2155–2159.

12. Mont MA, Jones LC, Seyler TM, et al. New treatment approaches for osteonecrosis of the femoral head: an overview. Instr Course Lect. 2007;56:197–212.

13. Martí-Carvajal AJ, Solà I, Agreda-Pérez LH. Treatment for avascular necrosis of bone in people with sickle cell disease. Cochrane Database of Systematic Reviews 2009, Issue 3. Art. No.: CD004344. DOI:10.1002/14651858.CD004344.pub3.

14. Study: Physicians need to educate patients about use of bisphosphonates. AAFP News Now. 6/11/2010.

15. Hungerford DS, Jones LC, et al. Asymptomatic osteonecrosis: should it be treated? Clin Orthop Relat Res. 2004;124–30.

Additional Reading

National Institute of Arthritis and Musculoskeletal and Skin Diseases: Osteonecrosis. http://www.niams.nih.gov/health_info/osteonecrosis/

17. Tofferi J, Gilliland W. E-Medicine Rheumatology: Avascular Necrosis. http://emedicine.medscape.com/article/333364-overview

See Also (Topic, Algorithm, Electronic Media Element)

Arthritis, Osteo; Legg-Calvé-Perthes Disease

Codes

ICD9

733.40 Aseptic necrosis of bone, site unspecified733.41 Aseptic necrosis of head of humerus733.42 Aseptic necrosis of head and neck of femur733.43 Aseptic necrosis of medial femoral condyle733.44 Aseptic necrosis of talus733.45 Aseptic necrosis of jaw733.49 Aseptic necrosis of other bone sites

Snomed

398199007 aseptic necrosis of bone (disorder)83453001 aseptic necrosis of head of humerus (disorder)29281007 aseptic necrosis of head AND/OR neck of femur (disorder)17926002 aseptic necrosis of medial femoral condyle (disorder)43453000 aseptic necrosis of talus (disorder)441809006 aseptic necrosis of bone of jaw (disorder)

Clinical Pearls

Trauma, alcoholism, and prolonged glucocorticoid use are most common risk factors for the development of osteonecrosis.Identify at-risk patients and suspect osteonecrosis in this population if presenting with bone or joint pain.Initiate workup with appropriate radiographs, then proceed to MRI if indicated (6)[A].