{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T12:06:44Z","timestamp":1777637204910,"version":"3.51.4"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:p>Bone involvement in pediatric Langerhans cell histiocytosis (LCH) causes pain, functional impairment, and frequent relapse, creating a need for adjunctive therapies with rapid skeletal benefit. At National University Hospital, Singapore, a tertiary pediatric hematology-oncology referral centre, we retrospectively evaluated eight children with osseous LCH treated with intravenous zoledronate between January 2020 and December 2025. Three had multisystem disease (two risk-organ\u2013positive), four had multifocal bone LCH, and one had unifocal bone LCH. Pain response (clinical improvement) and radiologic outcome (lesion stability or sclerosis) and adverse effects, and concurrent therapies were recorded. Prior treatment exposure was heterogeneous, ranging from no prior systemic therapy to multi-agent chemotherapy, oral maintenance therapy, targeted therapy, radiotherapy, pamidronate, and indomethacin. Zoledronate was given for painful active bone lesions, particularly in weight-bearing sites, and in selected patients for progressive relapsed osseous disease, poor tolerance of oral chemotherapy, or as a chemotherapy-sparing bone-directed approach. Zoledronate was started at a median age of 60 months. All 4 symptomatic patients experienced pain improvement (100%), with a median time to improvement of 18 days post-infusion. Among 8 patients with imaging follow-up, 2 exhibited complete radiographic resolution and 6 showed improvement. The treatment was well tolerated; transient fever occurred in 4 patients. Three patients received concomitant oral chemotherapy for active systemic disease, either in other systems or in new bone lesions. No cases of clinically significant hypocalcemia or osteonecrosis of the jaw were observed.<\/jats:p>","DOI":"10.3389\/fped.2026.1825076","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T06:04:06Z","timestamp":1777442646000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Intravenous zoledronate for pediatric langerhans cell histiocytosis with bone involvement"],"prefix":"10.3389","volume":"14","author":[{"given":"Jann Adriel","family":"Sy","sequence":"first","affiliation":[{"name":"Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore","place":["Singapore, Singapore"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thuan Chong","family":"Quah","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore","place":["Singapore, Singapore"]},{"name":"Khoo Teck Puat - National University Children\u2019s Medical Institute, National University Health System","place":["Singapore, Singapore"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pian Pian","family":"Tee","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Sabah Women and Children Hospital","place":["Sabah, Malaysia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cindy Wei Li","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore","place":["Singapore, Singapore"]},{"name":"Khoo Teck Puat - National University Children\u2019s Medical Institute, National University Health System","place":["Singapore, Singapore"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1319","DOI":"10.1182\/blood.2019000934","article-title":"Langerhans cell histiocytosis","volume":"135","author":"Rodriguez-Galindo","year":"2020","journal-title":"Blood"},{"key":"B2","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1016\/j.jpeds.2008.05.002","article-title":"Reactivations in multisystem Langerhans cell histiocytosis: data of the international LCH registry","volume":"153","author":"Minkov","year":"2008","journal-title":"J Pediatr"},{"key":"B3","doi-asserted-by":"publisher","first-page":"5006","DOI":"10.1182\/blood-2012-09-455774","article-title":"Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis","volume":"121","author":"Gadner","year":"2013","journal-title":"Blood"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1032","DOI":"10.4065\/83.9.1032","article-title":"Bisphosphonates: mechanism of action and role in clinical practice","volume":"83","author":"Drake","year":"2008","journal-title":"Mayo Clin Proc"},{"key":"B5","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1081\/CNV-120014886","article-title":"The new bisphosphonate, Zometa \u00ae (zoledronic acid), decreases skeletal complications in both osteolytic and osteoblastic lesions: a comparison to pamidronate","volume":"20","author":"Lipton","year":"2002","journal-title":"Cancer Invest"},{"key":"B6","doi-asserted-by":"publisher","first-page":"256","DOI":"10.21037\/tp.2017.09.10","article-title":"Zoledronic acid in pediatric metabolic bone disorders","volume":"6","author":"Bowden","year":"2017","journal-title":"Transl Pediatr"},{"key":"B7","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1111\/j.1365-2796.1989.tb00038.x","article-title":"Experiences of clodronate treatment of multifocal eosinophilic granuloma of bone","volume":"225","author":"Elomaa","year":"1989","journal-title":"J Intern Med"},{"key":"B8","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1007\/s12185-011-0839-2","article-title":"Treatment of Langerhans cell histiocytosis bone lesions with zoledronic acid: a case series","volume":"93","author":"Sivendran","year":"2011","journal-title":"Int J Hematol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1111\/ped.13774","article-title":"Zoledronic acid for relapsed Langerhans cell histiocytosis with isolated skull bone lesion","volume":"61","author":"Kudo","year":"2019","journal-title":"Pediatr Int"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4084\/mjhid.2016.033","article-title":"Bisphosphonates in Langerhans cell histiocytosis: an international retrospective case series","volume":"8","author":"Chellapandian","year":"2016","journal-title":"Mediterr J Hematol Infect Dis"},{"key":"B11","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1111\/j.1365-2141.2011.08654.x","article-title":"Resolution of bone lysis in Langerhans cell histiocytosis by bisphosphonate therapy","volume":"154","author":"Tsuda","year":"2011","journal-title":"Br J Haematol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1926","DOI":"10.1359\/jbmr.2002.17.11.1926","article-title":"Bisphosphonate induces remission of refractory osteolysis in Langerhans cell histiocytosis","volume":"17","author":"Kamizono","year":"2002","journal-title":"J Bone Miner Res"},{"key":"B13","first-page":"1145","article-title":"Bisphosphonate therapy for refractory Langerhans cell histiocytosis: a case report","volume":"98","author":"Takpradit","year":"2015","journal-title":"J Med Assoc Thail"},{"key":"B14","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1097\/00043426-200101000-00013","article-title":"Treatment of Langerhans cell histiocytosis with pamidronate","volume":"23","author":"Farran","year":"2001","journal-title":"Am J Pediatr Hematol Oncol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1002\/pbc.22703","article-title":"Nationwide survey of bisphosphonate therapy for children with reactivated Langerhans cell histiocytosis in Japan","volume":"56","author":"Morimoto","year":"2011","journal-title":"Pediatr Blood Cancer"},{"key":"B16","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1056\/NEJM200107193450318","article-title":"Pamidronate for bone pain from osteolytic lesions in Langerhans\u2019-cell histiocytosis","volume":"345","author":"Arzoo","year":"2001","journal-title":"N Engl J Med"},{"key":"B17","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1084\/jem.20041785","article-title":"Presence of osteoclast-like multinucleated giant cells in the bone and nonostotic lesions of Langerhans cell histiocytosis","volume":"201","author":"da Costa","year":"2005","journal-title":"J Exp Med"},{"key":"B18","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1111\/j.1600-0609.1998.tb01073.x","article-title":"Long-term oral pamidronate treatment inhibits osteoclastic bone resorption and bone turnover without affecting osteoblastic function in multiple myeloma","volume":"61","author":"Abildgaard","year":"1998","journal-title":"Eur J Haematol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1080\/080352598750031437","article-title":"Elevated erythrocyte sedimentation rate and thrombocytosis as possible indicators of active disease in Langerhans\u2019 cell histiocytosis","volume":"87","author":"Calming","year":"1998","journal-title":"Acta Paediatr"},{"key":"B20","doi-asserted-by":"publisher","first-page":"466","DOI":"10.3389\/fped.2020.00466","article-title":"A \u201cwait-and-see\u201d approach to quiescent single-system Langerhans cell histiocytosis to spare children from chemotherapy","volume":"8","author":"Oh","year":"2020","journal-title":"Front Pediatr"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1825076\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T06:04:08Z","timestamp":1777442648000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1825076\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,29]]},"references-count":20,"alternative-id":["10.3389\/fped.2026.1825076"],"URL":"https:\/\/doi.org\/10.3389\/fped.2026.1825076","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,29]]},"article-number":"1825076"}}