1. Aseptic Osteonecrosis in Children and Adolescents Treated for Hemato-Oncologic Diseases DR. kaji

2. 1.Aseptic Osteonecrosis in Hematologic Malignancies Pediatr Hematol Oncol Volume 27, Number 5, May 2005 2.Avascular necrosis of the femoral head October 2011 - Volume 34 · Issue 10: e593-e597 3.Effectiveness of Pamidronate as Treatment of Symptomatic Osteonecrosis Pediatr Blood Cancer DOI 10.1002/pbc

3.  avascularnecrosis, is a rare long-term complication of childhood cancer therapy that can result in significant morbidity and alteration of quality of life.  Avascular necrosis of the femoral head is usually seen in children aged 1.5 to 10 years, reaching a peak incidence between the ages of 4 and 9.

4.  both inheritance and specific environmental exposures are believed to play a role in this process(high bodymass index (BMI), age > 11 years old, white ethnicity, female gender).  Incidence rates vary widely depending on the time the study was conducted and the methods used for diagnosis.  Avascular necrosis of bone is usually multifocal, and weight-bearing joints are predominantly affected

5.  Mattano et al reported a 3-year cumulative incidence of 9% in children treated for acute lymphoblastic leukemia (ALL).  using MRI screening, AON was detected in 9 of 24 patients (38%) with ALL, 6 of whom were asymptomatic.  As AON can be detected in completely asymptomatic patients, the true incidence remains unknown.

6. Etiolog; 1)corticosteroids are considered the main etiologic factor 2)chemotherapy not containing steroids, suchas methotrexate, asparaginase, and radiotherapy 3)Cytostatic drugs, 4)immobilization 5)malignancy

7. Steroids are the second most common cause of avascular necrosis after trauma mechanism of action corticosteroids; increased osteoblast and osteoclast apoptosi increased coagulation protein concentrations

8. The clinical spectrum of AON ranges from asymptomatic patients to patients with significant bone pain and loss of function, sometimes necessitating total joint replacement. the femoral head is the most symptomatic site that often requires surgical intervention Clinical

9. Treatment of avascular necrosis  surgical or pharmacologic treatment options  Goals of avascular necrosis management are typically palliative  there is currently no proven treatment available to stop progression of the disease

10.  treatment of avascular necrosis of the femoral head includes some type of surgery  that steroid-induced avascular necrosis of the femoral head may be successfully managed without any intervention  avascular necrosis of the femoral head may run a mild course in patients with acute lymphoblastic leukemia depending on the site and size of the lesion

11.  nonoperative treatment only for patients in treatment only for patients in whom the lesion was limited to the nonweight-bearing region of the femoral head and in whom the acetabulum was intact.  when the necrotic area was small, and particularly when it was located in the nonweight-bearing area of the femoral head and the patient was clinically asymptomatic avascular necrosis of the femoral head can have a good course.

12.  In contrast, there are reports that avascular necrosis of the femoral head is persistently progressive regardless of the size and site of the lesion patients required interventional treatments.  In their study of avascular necrosis of the femoral head caused by chemotherapy in 85 children with acute lymphoblastic leukemia,5 cases of avascular necrosis of the femoral head, 3 patients needed operative intervention.

13.  Solarino et al reported a 14-year-old girl who developed multifocal osteonecrosis after treatment. Six months after beginning treatment, the patient was diagnosed with avascular necrosis of the left knee, and both hips and shoulders. total hips arthroplasty, which was still functioning well at the last follow-up visit at 5.3 years.

14.  patients received only nonoperative care consisting of temporary abduction brace, physical therapy, and anti-inflammatory drugs.  There are few reports concerning children with steroid-related bone avascular necrosis with spontaneous resolution

15.  Between 1990 and 2003, 630 consecutive children with various malignancies were treated at the University Children’s Hospital in Graz, Austria. In nine of these patients presenting with skeletal symptoms, MRI revealed AON.  the median interval between diagnosis of malignancy and onset of osteonecrosis- related symptoms was 16 months (range 6–53 months). Aseptic Osteonecrosis in Hematologic Malignancies Pediatr Hematol Oncol Volume 27, Number 5, May 2005

16.  Treatment of AON included restriction of weight-bearing, physiotherapy, and analgesics. Three patients were treated with hyperbaric oxygen therapy combined with the prostacyclin analog iloprost, and one patient also received pamidronate.  AON was observed in 1.4% of the entire study population: 3.4% of patients with ALL, 7.1% of patients with NHL, 4.4% of patients with HD, and 2% of patients with AML.

17.  The median duration of follow-up after initial improvement was 2 years  In this context dexamethasone is considered to be more toxic to the skeletal system than prednisone.  Age older than 10 years at diagnosis of malignancy has been recognized as another important risk factor for AON.

18.  Some authors argue that the maturing bones of adolescents might be more susceptible to the development of AON.  AON is reported to occur predominantly in females but in our series AON was more common in boys than girls.

19.  Most investigators propose conservative treatment including relief of weight-bearing structures, physiotherapy, and NSAIDs, followed by surgical therapy in severe cases. Other conservative treatment options (eg, HBO, iloprost, or bisphosphonates) have beenonly sporadically reported.  Iloprost, a prostacyclin analog, cause dilatation of arterioles and venules and reduction in the permeability of capillaries.

20.  Bisphosphonates might be another therapeutic option to improve bone mineralization and to reduce corticosteroid- induced osteoporosis.  the administration of iloprost in addition to the generally applied conservative treatment (physical therapy,NSAIDS), would be helpful to identify appropriate therapy for patients with AON.

21. Effectiveness of Pamidronate as Treatment of Symptomatic Osteonecrosi2012 Wiley Periodicals, Inc. DOI 10.1002/pbc.24313s Background. We assessed the effects of pamidronate compared to standard care in patients with symptomatic ON(sON) and studied whether steroids might be continued after diagnosis of ON in some patients.

22. Methods: We evaluated 17 patients with sON as complication of primary ALL treatment between 2000 and 2008. Fourteen patients were treated with pamidronate. Mobility and pain control were monitored in all patients. Affected joints were classified by magnetic resonance imaging (MRI) at ON diagnosis and after 6–72 months.

23. Results: Out of 220 patients with ALL,17 (7.7%) patients developed sON. The median age at ALL diagnosis was 11 years (range: 2.7–16.6 years) and sON occurred a median of 13.4 months (range: 2.5–34 months) after ALL diagnosis. Affected joints were hip, knee and ankle. MRI scans showed 7severe, 4 moderate, and 6 mild ON lesions. Fourteen patients showed improvement in pain (77% of patients) and motor function (59% of patients), even though corticoids were reintroduced in 4 patients.

24. Conclusions: Pamidronate seems to be effective in the management of pain and motor function recovery in sON. Further studies are needed to provide evidence as to whether bisphosphonates can be recommended for the treatment or the prevention of ON in childhood ALL patients.