Bisphosphonates in Langerhans Cell Histiocytosis: An International Retrospective Case Series

Abstract

BackgroundBone 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.MethodWe conducted a multicenter retrospective review of 13 patients with histologically proven LCH, who had received bisphosphonates either at diagnosis or at disease reactivation.ResultsTen 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.ConclusionBisphosphonates 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.

Bone metabolism in Langerhans cell histiocytosis

“…A recent study has reported that cytosine arabinoside (ARA-C) is the most effective and least toxic regimen for treatment of LCH bone lesions ( 59 ). However, due to the increased incidence of adverse effects with chemotherapy, less toxic approaches such as antiresorptive agents are often considered, especially when there is solely or predominantly skeletal involvement ( 37 , 60 ).…”

“…In a Japanese survey, pamidronate resulted in the resolution of bone lesions in 75% of children with reactivated LCH ( 66 ). In a recent study, in both children and adults, bisphosphonates significantly improved bone pain and restored functional status without significant adverse effects ( 60 ). Complete remission of active bone LCH was observed in 92% of the patients.…”

“…These outcomes were not related to the type or the dose of the agent used. More importantly, bisphosphonates, especially pamidronate, have been proved to be beneficial in cases of non-ostotic LCH such as skin and soft tissue lesions ( 60 , 67 ). The most common adverse effects of bisphosphonates are hypocalcemia and acute phase reaction while a rare but clinically significant adverse effect is osteonecrosis of the jaw ( 62 , 68 ).…”

“…The most common adverse effects of bisphosphonates are hypocalcemia and acute phase reaction while a rare but clinically significant adverse effect is osteonecrosis of the jaw ( 62 , 68 ). No serious adverse effects have been reported in patients with LCH treated with bisphosphonates ( 60 ).…”

Zoledronic acid for relapsed Langerhans cell histiocytosis with isolated skull bone lesion

“…Bone involvement is frequently observed in LCH and can cause disease reactivation, resulting in permanent complications. Bisphosphonate therapy using pamidronate is effective against LCH . Zoledronate, a bisphosphonate, has demonstrated superior inhibition of bone resorption by inducing osteoclast apoptosis, showing fewer complications than pamidronate in clinical trials of adult cancer patients .…”