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Athanasios D Anastasilakis, Marina Tsoli, Gregory Kaltsas and Polyzois Makras

Langerhans cell histiocytosis (LCH) is a rare disease of not well-defined etiology that involves immune cell activation and frequently affects the skeleton. Bone involvement in LCH usually presents in the form of osteolytic lesions along with low bone mineral density. Various molecules involved in bone metabolism are implicated in the pathogenesis of LCH or may be affected during the course of the disease, including interleukins (ILs), tumor necrosis factor α, receptor activator of NF-κB (RANK) and its soluble ligand RANKL, osteoprotegerin (OPG), periostin and sclerostin. Among them IL-17A, periostin and RANKL have been proposed as potential serum biomarkers for LCH, particularly as the interaction between RANK, RANKL and OPG not only regulates bone homeostasis through its effects on the osteoclasts but also affects the activation and survival of immune cells. Significant changes in circulating and lesional RANKL levels have been observed in LCH patients irrespective of bone involvement. Standard LCH management includes local or systematic administration of corticosteroids and chemotherapy. Given the implication of RANK, RANKL and OPG in the pathogenesis of the disease and the osteolytic nature of bone lesions, agents aiming at inhibiting the RANKL pathway and/or osteoclastic activation, such as bisphosphonates and denosumab, may have a role in the therapeutic approach of LCH although further clinical investigation is warranted.

Open access

Sylvia Thiele, Anke Hannemann, Maria Winzer, Ulrike Baschant, Heike Weidner, Matthias Nauck, Rajesh V Thakker, Martin Bornhäuser, Lorenz C Hofbauer and Martina Rauner

glucocorticoid-induced osteoporosis (GIO) involves many organ systems. At the skeletal level, GCs stimulate osteoclastogenesis and profoundly inhibit bone formation ( 3 , 4 ). While an increased receptor activator of NF-κB ligand (RANKL)/osteoprotegerin (OPG

Open access

Ann-Kristin Picke, Graeme Campbell, Nicola Napoli, Lorenz C Hofbauer and Martina Rauner

, 84 ). Osteocytes coordinate osteoblast and osteoclast function via secretion of the Wnt inhibitor sclerostin and the promoter of osteoclastogenesis, receptor activator of NF-κB ligand (RANKL), respectively ( 85 , 86 ). In vitro , high concentration