title: Use of bisphosphonates for the treatment of osteonecrosis as a complication of therapy for childhood acute lymphoblastic leukaemia (ALL).
abstract: BACKGROUND
  Osteonecrosis is a well-recognised complication of current childhood acute lymphoblastic leukaemia (ALL) therapy. There are few studies on the medical management of osteonecrosis in this setting. We studied the therapeutic and radiological effects of oral and intravenous bisphosphonate use compared with standard care as treatment for osteonecrosis in this population.
  
  
  METHODS
  Patients who developed osteonecrosis as a complication of ALL therapy between 1994 and 2007 were treated at a single paediatric institution. Of 17 patients, 9 were commenced on bisphosphonates and 8 treated conservatively. Both groups were observed with time. Pain, analgesic requirement and musculoskeletal function were assessed monthly. Affected joints were radiologically imaged at set intervals. Each scan was graded using an ellipsoid method to give the total volume of osteonecrosis, by blinded radiologic examination.
  
  
  RESULTS
  Three of six patients treated with oral alendronate showed clinical improvement. The three patients that had no improvement were subsequently treated with intravenous pamidronate. All six patients treated with intravenous pamidronate showed clinical improvement. Seven of eight conservatively treated patients deteriorated clinically. All patients demonstrated reduction in the radiological burden of osteonecrosis with time. There was no difference in the rate of reduction between conservative and bisphosphonate arms.
  
  
  CONCLUSIONS
  Bisphosphonate use, in particular pamidronate, improved pain scores, analgesic requirement and musculoskeletal function in patients with osteonecrosis occurring as a complication of childhood ALL therapy. Objective radiologic benefit of bisphosphonate treatment could not be demonstrated. Risks, benefits and long-term outcome of bisphosphonate use in this population should be addressed in a larger prospective, randomised trial.
authors.affiliation: Department of Haematology and Oncology, Princess Margaret Hospital, Perth, Western Australia, Australia. rishi.kotecha@health.wa.gov.au
authors.forename: Rishi S
authors.initials: RS
authors.lastname: Kotecha
authors.forename: Neil
authors.initials: N
authors.lastname: Powers
authors.forename: Senq-J
authors.initials: SJ
authors.lastname: Lee
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Murray
authors.forename: Tina
authors.initials: T
authors.lastname: Carter
authors.forename: Catherine
authors.initials: C
authors.lastname: Cole
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D019386:Alendronate / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D002118:Calcium / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D015994:Incidence; D007262:Infusions, Intravenous; D008297:Male; D010020:Osteonecrosis / Q000139:chemically induced* / Q000188:drug therapy* / Q000453:epidemiology; D010146:Pain / Q000188:drug therapy / Q000209:etiology; D000077268:Pamidronate; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D011878:Radiotherapy; D012307:Risk Factors; D014807:Vitamin D / Q000627:therapeutic use
chemical_list: D000305:Adrenal Cortex Hormones; D004164:Diphosphonates; D014807:Vitamin D; D000077268:Pamidronate; D002118:Calcium; D019386:Alendronate