title: Denosumab for the treatment of adult multisystem Langerhans cell histiocytosis.
abstract: An etiological treatment is currently lacking for Langerhans Cell Histiocytosis (LCH). Receptor activator of nuclear factor κB ligand (RANKL) appears to play a central role in the lesional immunological process inducing compensatory osteoprotegerin (OPG) activation. In a preliminary study we aimed to evaluate for the first time the use of denosumab, a RANKL inhibitor, as a targeted treatment strategy in LCH in order to support and enhance endogenous OPG action in order to control or alter the lesional immunological process.
  
  
  
  Two adult female patients with painful osteolytic bone lesions and concomitant pulmonary involvement received bimonthly denosumab 120mg in a total of 4 doses.
  
  
  
  Both patients reported an immediate pain relief within the first two weeks following the 1st dose of denosumab. One month following the last dose an almost full remission of the initial osteolytic and lung lesions was observed, although an apparent new bone lesion was detected in one patient that was treated with a single intralesional steroid injection. No adverse events were recorded throughout the treatment period. Both patients have no active disease 6months following the last denosumab dose.
  
  
  
  Denosumab could be considered an effective treatment option in adults with multisystem LCH also exerting a significant analgesic effect in bone lesions, warranting further investigation.
authors.affiliation: Department of Endocrinology and Diabetes, 251 Hellenic Air Force General Hospital, 3 Kanellopoulou St., 11525, Athens, Greece. Electronic address: pmakras@gmail.com.
authors.forename: Polyzois
authors.initials: P
authors.lastname: Makras
authors.affiliation: Department of Pathophysiology, National University of Athens, 75 Mikras Asias St., 11527, Athens, Greece.
authors.forename: Marina
authors.initials: M
authors.lastname: Tsoli
authors.affiliation: Department of Endocrinology, 424 Military Hospital, 3 Gr. Lambraki St., 54638, Thessaloniki, Greece.
authors.forename: Athanasios D
authors.initials: AD
authors.lastname: Anastasilakis
authors.affiliation: REA Maternity Hospital, 383 A. Singrou Ave., P. Faliro, 17564, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Thanou
authors.affiliation: Department of Pathophysiology, National University of Athens, 75 Mikras Asias St., 11527, Athens, Greece.
authors.forename: Gregory
authors.initials: G
authors.lastname: Kaltsas
mesh_terms: D000328:Adult; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001847:Bone Diseases / Q000188:drug therapy / Q000209:etiology; D000069448:Denosumab / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006646:Histiocytosis, Langerhans-Cell / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy*; D006801:Humans; D008171:Lung Diseases / Q000188:drug therapy / Q000209:etiology; D008279:Magnetic Resonance Imaging; D053244:Osteoprotegerin / Q000096:biosynthesis / Q000235:genetics; D010146:Pain / Q000188:drug therapy / Q000209:etiology; D049268:Positron-Emission Tomography; D053245:RANK Ligand / Q000037:antagonists & inhibitors; D016896:Treatment Outcome
chemical_list: D050071:Bone Density Conservation Agents; D053244:Osteoprotegerin; D053245:RANK Ligand; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D000069448:Denosumab
keywords: Denosumab; Langerhans cell histiocytosis; RANKL; Treatment