title: Effects of RANK-ligand antibody (denosumab) treatment on bone turnover markers in a girl with juvenile Paget's disease.
abstract: BACKGROUND
  Juvenile Paget's disease (JPD) is an extremely rare, yet painful and debilitating bone disease with onset occurring during early childhood. JPD can be caused by loss of function of osteoprotegerin, resulting in subsequent stimulation of osteoclasts via the receptor activator of nuclear factor-κB (RANK) pathway. Increased bone turnover and lack of bone modeling lead to severe deformities, frequent fractures, short stature, and loss of hearing.
  
  
  METHODS
  The treatment for JPD is challenging and has previously been based on administration of either calcitonin or bisphosphonates. However, with the development of denosumab, a receptor activator of nuclear factor-κB-ligand (RANKL) antibody, a treatment targeting the pathophysiology of JPD may be available. We report the effects of denosumab treatment on an 8-year-old girl with a severe form of JPD.
  
  
  METHODS
  Before starting the denosumab treatment regimen, the patient had been treated for 3.5 years with iv pamidronate.
  
  
  RESULTS
  The administration of denosumab resulted in improved disease control compared with bisphosphonate, as assessed by monitoring markers of bone turnover. Alkaline phosphatase levels dropped within the normal range and remained at normal levels for 5 months after the final dose of denosumab. Additionally, bone pain was more efficiently controlled with denosumab. However, concomitant with the first injection, severe hypocalcemia developed, for which the patient was hospitalized and iv calcium supplementation was required for 13 days.
  
  
  CONCLUSIONS
  Denosumab appears to be significantly effective for osteoclast inhibition for the treatment of JPD. However, in our patient, denosumab administration was associated with severe hypocalcemia, indicating that close monitoring of calcium levels is required during treatment.
authors.affiliation: Kinderklinik II, Department of Pediatric Endocrinology, Hufelandstrasse 55, 45122 Essen, Germany. corinna.grasemann@uk-essen.de
authors.forename: Corinna
authors.initials: C
authors.lastname: Grasemann
authors.forename: Michael M
authors.initials: MM
authors.lastname: Schündeln
authors.forename: Matthias
authors.initials: M
authors.lastname: Hövel
authors.forename: Bernd
authors.initials: B
authors.lastname: Schweiger
authors.forename: Christoph
authors.initials: C
authors.lastname: Bergmann
authors.forename: Ralf
authors.initials: R
authors.lastname: Herrmann
authors.forename: Dagmar
authors.initials: D
authors.lastname: Wieczorek
authors.forename: Bernhard
authors.initials: B
authors.lastname: Zabel
authors.forename: Regina
authors.initials: R
authors.lastname: Wieland
authors.forename: Berthold P
authors.initials: BP
authors.lastname: Hauffa
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood; D000596:Amino Acids / Q000652:urine; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D015415:Biomarkers; D016723:Bone Remodeling; D002648:Child; D024042:Collagen Type I / Q000652:urine; D000069448:Denosumab; D005260:Female; D006801:Humans; D010001:Osteitis Deformans / Q000188:drug therapy* / Q000378:metabolism; D010281:Parathyroid Hormone / Q000097:blood; D010455:Peptides / Q000652:urine; D053245:RANK Ligand / Q000037:antagonists & inhibitors*
chemical_list: D000596:Amino Acids; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D024042:Collagen Type I; D010281:Parathyroid Hormone; D010455:Peptides; D053245:RANK Ligand; C052929:collagen type I trimeric cross-linked peptide; D000069448:Denosumab; C036020:deoxypyridinoline; D000469:Alkaline Phosphatase