Bisphosphonate Therapy for Treating Osteonecrosis in Pediatric Leukemia Patients: A Systematic Review

J Pediatr Hematol Oncol. 2021 Apr 1;43(3):e365-e370. doi: 10.1097/MPH.0000000000001793.


Background: Despite improved outcomes in children with leukemia, complications such as osteonecrosis are common. We conducted a systematic review to investigate the role of bisphosphonates in reducing pain, improving mobility, and stabilizing lesions in pediatric leukemia survivors.

Methods: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched the PubMed, Embase, Cochrane, Web of Science, Scopus, CINAHL, and databases. Five of 221 articles retrieved met our inclusion criteria.

Results: Bisphosphonates, especially when combined with dietary calcium and vitamin D supplements and physical therapy (supplements/PT) were associated with improved pain and mobility in 54% and 50% of patients, respectively. A significantly greater proportion of patients treated with bisphosphonates (83%) reported mild/moderate pain or no pain compared with those with supplements/PT alone (36%) (P<0.001). Sixty-six percent of patients treated with bisphosphonates achieved improved/full mobility compared with 27% of those treated with supplements/PT alone (P=0.02). However, 46% of patients showed progressive joint destruction despite bisphosphonate therapy. No adverse events were reported, except for acute phase reactions to intravenous therapies.

Conclusions: Bisphosphonates, when combined with supplements/PT, were associated with less pain and improved mobility, but not prevention of joint destruction in pediatric leukemia patients with osteonecrosis.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Systematic Review

MeSH terms

  • Antineoplastic Agents / adverse effects
  • Bone Density Conservation Agents / therapeutic use*
  • Calcium / therapeutic use
  • Child
  • Diphosphonates / therapeutic use*
  • Humans
  • Leukemia / drug therapy
  • Osteonecrosis / chemically induced
  • Osteonecrosis / drug therapy*
  • Pediatrics
  • Vitamin D / therapeutic use


  • Antineoplastic Agents
  • Bone Density Conservation Agents
  • Diphosphonates
  • Vitamin D
  • Calcium