Osteonecrosis in Acute Lymphoblastic Leukaemia (ALL)

Corticosteroids are an important component of treatment of childhood ALL. The use of corticosteroids ahs been associated with osteonecrosis. The estimates of osteonecrosis have varied from 7.4%-44%.  About 25% of these patients need surgical intervention for symptom or functional deficit.

Factors Predisposing to Osteonecrosis

  1. Age: Increasing age predisposes to ON. ON is uncommon below the age of 10 years and increases thereafter. The extent of ON is adults with ALL is not characterized.
  2. Gender: Females are at a greater risk of ON than males.
  3. Steroid Use:  ON is more common with the use of dexamethasone. Administering dexamethasone on alternate weeks in late intensification has been shown to be associated with a lower incidence of osteonecrosis. Patients who have a poor  dexamethasone clearance have a higher risk of ON.
  4. Other Factors: ON has been reported to be more common in patients with a low albumin and elevated. High body-mass index is associated with increased risk of ON.

Mechanism of Osteonecrosis

The mechanism of ON in ALL patients is unknown. The proposed etiologies are:

  1. Steroid induced hypercoagulable state resulting in the development of microthrombi
  2. Steroid induced intramedullary lipocyte proliferation and hypertrophy causing a reduced blood flow
  3. Suppression of osteoblasts and apoptosis of osteocytes

Clinical Presentation

The median time to occurrence of symptoms is 14-27 months. Ninety-five percent of the patients have ON of weight-bearing joints The usual presentation if of pain in the hip and knees. In severe cases the joints may collapse.

Management

The treatment of ON is mainly supportive. Surgical intervention, including joint replacement where needed, may be needed in a about one-fourth of the patient for pain or functional deficit.  Bisphosphonates have been used to slow progression but their role is uncertain. The value of discontinuing steroids is not certain but most discontinue steroids but most discontinue steroids.

Prevention and Monitoring

MRI can detect ON before it becomes symptomatic but it’s use outside clinical trials is not recommended.

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