Intravenous zoledronate for pediatric langerhans cell histiocytosis with bone involvement

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-positive), 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.