title: Bisphosphonates in Langerhans Cell Histiocytosis: An International Retrospective Case Series.
abstract: BACKGROUND
  Bone is the most common organ of involvement in patients with Langerhans cell histiocytosis (LCH), which is often painful and associated with significant morbidity from pathological fractures. Current first-line treatments include chemotherapy and steroids that are effective but often associated with adverse effects, whereas the disease may reactivate despite an initial response to first-line agents. Bisphosphonates are osteoclast inhibitors that have shown to be helpful in treating bone lesions of LCH. To date, there are no large international studies to describe their role in treating bone lesions of LCH.
  
  
  METHODS
  We conducted a multicenter retrospective review of 13 patients with histologically proven LCH, who had received bisphosphonates either at diagnosis or at disease reactivation.
  
  
  RESULTS
  Ten patients (77%) had a single system bone disease, and 3 (23%) had bone lesions as part of multisystem disease. Median follow-up time post-bisphosphonate therapy was 4.6 years (range, 0.8 to 8.2 years). Treatment with bisphosphonates was associated with significant pain relief in almost all patients. Twelve (92%) achieved resolution of active bone lesions, and 10 out of them had no active disease for a median of 3.5 years (range, 0.8 to 5 years). One patient did not respond. No major adverse effects were reported in this series.
  
  
  CONCLUSIONS
  Bisphosphonates are well-tolerated drugs that can significantly improve bone pain and induce remission in active bone LCH. Future prospective studies evaluating the role of bisphosphonates in LCH are warranted.
authors.affiliation: Division of Hematology/Oncology and Bone Marrow Transplantation, Department of Pediatrics, The Hospital for Sick Children (SickKids), University of Toronto, Toronto, Ontario, Canada.
authors.forename: Deepak
authors.initials: D
authors.lastname: Chellapandian
authors.affiliation: Department of Endocrinology & Diabetes, 251 Hellenic Airforce & VA General Hospital, Athens, Greece.
authors.forename: Polyzois
authors.initials: P
authors.lastname: Makras
authors.affiliation: Department of Pathophysiology, National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Gregory
authors.initials: G
authors.lastname: Kaltsas
authors.affiliation: Department of Pediatric Oncology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Cor
authors.initials: C
authors.lastname: van den Bos
authors.affiliation: Hémato-oncologue pédiatrique, Centre hospitalier universitaire de Québec, Quebec City, Canada.
authors.forename: Lamia
authors.initials: L
authors.lastname: Naccache
authors.affiliation: Leukemia Service, Memorial Sloan-Kettering Cancer Center, New York, USA.
authors.forename: Raajit
authors.initials: R
authors.lastname: Rampal
authors.affiliation: Division of Hematology-Oncology, Department of Pediatrics, Centre Hospitalier Universitaire (CHU) Sainte-Justine, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Carret
authors.affiliation: Division of Hematology/Oncology and Bone Marrow Transplantation, Department of Pediatrics, The Hospital for Sick Children (SickKids), University of Toronto, Toronto, Ontario, Canada.
authors.forename: Sheila
authors.initials: S
authors.lastname: Weitzman
authors.affiliation: Division of Hematology/Oncology and Bone Marrow Transplantation, Department of Pediatrics, The Hospital for Sick Children (SickKids), University of Toronto, Toronto, Ontario, Canada.
authors.forename: R Maarten
authors.initials: RM
authors.lastname: Egeler
authors.affiliation: Division of Hematology/Oncology and Bone Marrow Transplantation, Department of Pediatrics, The Hospital for Sick Children (SickKids), University of Toronto, Toronto, Ontario, Canada.
authors.forename: Oussama
authors.initials: O
authors.lastname: Abla