title: Treatment of Paget's Disease of Bone with Denosumab: Case Report and Literature Review.
abstract: Paget's disease is a condition involving focal overactivity of bone cells (osteoblasts and osteoclasts), which can result in significant skeletal morbidity. It is unclear in which bone cells the causative lesion resides. It is managed effectively with potent bisphosphonates, but treatment is difficult if these drugs are contraindicated. We describe a 75-year-old woman with Paget's disease involving the skull who was intolerant of bisphosphonates, so was treated with denosumab. This intervention normalized serum alkaline phosphatase for 4-8 months after each injection and led to some symptomatic improvement. Scintigraphic activity in the lesion was improved but not normalized. We conclude that reduction in RANKL activity by denosumab only partially corrects pagetic activity, indicating that the osteoclast overactivity of Paget's disease is not wholly mediated by RANKL. Denosumab has some clinical utility in Paget's disease and may become a second-line agent in those with contraindications to intravenous bisphosphonates.
authors.affiliation: Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand. i.reid@auckland.ac.nz.|Department of Endocrinology, Auckland District Health Board, Auckland, New Zealand. i.reid@auckland.ac.nz.
authors.forename: Ian R
authors.initials: IR
authors.lastname: Reid
authors.affiliation: Department of Endocrinology, Auckland District Health Board, Auckland, New Zealand.
authors.forename: Sonakshi
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand.|Department of Rheumatology, Auckland District Health Board, Auckland, New Zealand.
authors.forename: Ramanamma
authors.initials: R
authors.lastname: Kalluru
authors.affiliation: Department of Endocrinology, Middlemore Hospital, Counties Manukau District Health Board, Auckland, New Zealand.
authors.forename: Carl
authors.initials: C
authors.lastname: Eagleton
mesh_terms: D000368:Aged; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology; D000069448:Denosumab / Q000627:therapeutic use*; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D010001:Osteitis Deformans / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D010006:Osteoblasts / Q000187:drug effects / Q000473:pathology; D010010:Osteoclasts / Q000187:drug effects*
chemical_list: D004164:Diphosphonates; D000069448:Denosumab
keywords: Alendronate; Denosumab; Paget’s disease