title: Denosumab treatment for juvenile Paget's disease: results from two adult patients with osteoprotegerin deficiency ("Balkan" mutation in the TNFRSF11B gene).
abstract: BACKGROUND
  Most patients with juvenile Paget's disease (JPD) have homozygous loss-of-function mutations in the TNFRSF11B gene resulting in osteoprotegerin deficiency. Because recombinant osteoprotegerin is not available for clinical use, an alternative therapeutic approach could be denosumab, which acts on the same pathway.
  
  
  OBJECTIVE
  The aim was to study the effect of denosumab on bone turnover markers in two adult patients with JPD ("Balkan" mutation) previously treated with calcitonin and bisphosphonates.
  
  
  METHODS
  The study was conducted at two tertiary hospitals in Greece.
  
  
  METHODS
  Patient 1 (a 36-year-old woman) developed a severe and long-term hypocalcemia after a single dose (3.5 mg) of zoledronic acid. Her bone disease remained active despite treatment. Patient 2 (a 67-year-old man) had satisfactorily controlled bone disease with only intermittent risedronate treatment during the last 10 years, but suffered from progressive loss of hearing and vision. Low doses (20-40 mg) of denosumab every 3-6 months were administered in both patients.
  
  
  RESULTS
  Bone markers (including total and bone-specific alkaline phosphatase, procollagen I N-terminal peptide, and osteocalcin) were reduced to normal levels in both patients, with nadir observed 2-4 months after each denosumab injection. Retinal and hearing involvement remained unchanged, but patient 2 developed a rapid progression of cataract in the right eye.
  
  
  CONCLUSIONS
  Low-dose denosumab every 3-6 months for about 2 years in two patients with JPD successfully controlled their bone disease. The long-term effect of denosumab on the nonskeletal complications remains to be elucidated.
authors.affiliation: Department of Endocrinology (S.A.P., F.A., M.K.), Ippokration General Hospital, 546 42 Thessaloniki, Greece; Department of Endocrinology, Metabolism, and Diabetes Mellitus (P.N.S., F.C.M.), St Savvas Cancer Hospital, 151 22 Athens, Greece; Department of Medicine (D.N.), Faculty of Medical & Health Sciences, University of Auckland, Auckland 1142, New Zealand; Department of Endocrinology (A.D.A.), 424 General Military Hospital, 564 29 Thessaloniki, Greece; and Biomedicine Laboratories (V.P.), 157 80 Athens, Greece.
authors.forename: Stergios A
authors.initials: SA
authors.lastname: Polyzos
authors.forename: Panagiotis N
authors.initials: PN
authors.lastname: Singhellakis
authors.forename: Dorit
authors.initials: D
authors.lastname: Naot
authors.forename: Fotini
authors.initials: F
authors.lastname: Adamidou
authors.forename: Fotini C
authors.initials: FC
authors.lastname: Malandrinou
authors.forename: Athanasios D
authors.initials: AD
authors.lastname: Anastasilakis
authors.forename: Vaia
authors.initials: V
authors.lastname: Polymerou
authors.forename: Marina
authors.initials: M
authors.lastname: Kita
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D000069448:Denosumab; D005260:Female; D006801:Humans; D054643:INDEL Mutation; D008297:Male; D010001:Osteitis Deformans / Q000188:drug therapy*; D053244:Osteoprotegerin / Q000172:deficiency / Q000235:genetics*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents; D053244:Osteoprotegerin; C506030:TNFRSF11B protein, human; D000069448:Denosumab