Pathogenesis of Osteosclerotic Change Following Treatment with an Antibody Against RANKL for Giant Cell Tumour of the Bone.
Giant cell tumours (GCTs) of the bone are intermediate tumours that are locally aggressive. Denosumab, an antibody against receptor activator of nuclear factor kappa-B ligand (RANKL), was recently developed; however, it induces osteosclerotic change through an unknown mechanism. We determined whether osteosclerotic change could be induced by neoplastic stromal cells of giant cell tumours (GCTs).



Participants included four patients with GCT of the bone who were treated with neoadjuvant denosumab. Expression of alkaline phosphatase (ALP), osteocalcin (OCN), RANKL and histone H3K36 trimethylation were assessed through immunohistochemistry of biopsy and surgical specimens.



OCN expression was significantly elevated after denosumab treatment, whereas ALP and RANKL expressions were not significantly elevated. Immunofluorescence staining revealed OCN expression and H3K36 trimethylation while their co-localisation was confirmed in the surgical specimens.



Denosumab promoted OCN expression and might induce the osteogenic differentiation of GCT stromal cells.
Department of Orthopaedic Surgery, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.|Department of Orthopaedics, East Avenue Medical Center, Quezon City, Philippines.
Mamer
M
Rosario
Department of Orthopaedic Surgery, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan a_take@med.kanazawa-u.ac.jp.
Akihiko
A
Takeuchi
Department of Orthopaedic Surgery, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
Norio
N
Yamamoto
Department of Orthopaedic Surgery, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
Katsuhiro
K
Hayashi
Department of Orthopaedic Surgery, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
Shinji
S
Miwa
Department of Orthopaedic Surgery, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
Takashi
T
Higuchi
Department of Orthopaedic Surgery, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
Kensaku
K
Abe
Department of Orthopaedic Surgery, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
Yuta
Y
Taniguchi
Department of Orthopaedic Surgery, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
Hisaki
H
Aiba
Division of Musculoskeletal Oncology, National Cancer Center Hospital, Tokyo, Japan.
Yoshikazu
Y
Tanzawa
Department of Orthopaedic Surgery, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
Hideki
H
Murakami
Department of Orthopaedic Surgery, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.
Hiroyuki
H
Tsuchiya
D000328:Adult; D000469:Alkaline Phosphatase / Q000096:biosynthesis; D050071:Bone Density Conservation Agents / Q000276:immunology / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D000069448:Denosumab / Q000276:immunology / Q000627:therapeutic use*; D005260:Female; D018212:Giant Cell Tumor of Bone / Q000188:drug therapy* / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008239:Lysine / Q000378:metabolism; D008297:Male; D008745:Methylation / Q000187:drug effects; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D015675:Osteocalcin / Q000096:biosynthesis; D010012:Osteogenesis / Q000187:drug effects; D053245:RANK Ligand / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000276:immunology
D050071:Bone Density Conservation Agents; D006657:Histones; D053245:RANK Ligand; D015675:Osteocalcin; D000069448:Denosumab; D000469:Alkaline Phosphatase; D008239:Lysine
Denosumab; RANKL; alkaline phosphatase; giant cell tumour of the bone; giant cell tumour stromal cells; osteocalcin; osteosclerotic change