title: Denosumab-mediated increase in hand bone mineral density associated with decreased progression of bone erosion in rheumatoid arthritis patients.
abstract: OBJECTIVE
  Periarticular osteoporosis is one of the earliest radiographic signs of bone damage in rheumatoid arthritis (RA). Denosumab, an investigational fully human monoclonal antibody that binds to RANKL, inhibits bone erosion and systemic bone loss in clinical studies of patients with RA. In this hand bone mineral density (BMD) substudy, we investigated the effects of denosumab on hand BMD and its correlation with hand erosion scores.
  
  
  METHODS
  Patients receiving methotrexate for erosive RA were randomized in a 1:1:1 ratio to receive subcutaneous placebo, denosumab 60 mg, or denosumab 180 mg at 0 and 6 months. Measurements included BMD (by dual x-ray absorptiometry [DXA]) of both hands (0, 1, 6, and 12 months), magnetic resonance images of the hands/wrists (0 and 6 months), and radiographs of the hands/wrists and feet (0, 6, and 12 months).
  
  
  RESULTS
  There were 56 patients (13 placebo, 21 denosumab 60 mg, and 22 denosumab 180 mg). Mean changes in hand BMD at 6 and 12 months were: +0.8% and +1.0%, respectively, for denosumab 60 mg; +2.0% and +2.5%, respectively, for denosumab 180 mg; and -1.2% and -2.0%, respectively, for placebo. Erosion scores remained near baseline in the denosumab groups and increased from baseline in the placebo group. A negative correlation was observed between hand BMD and erosion scores.
  
  
  CONCLUSIONS
  In patients with RA, denosumab provided protection against erosion, and not only prevented bone loss but increased hand BMD as measured by DXA.
authors.affiliation: Division of Arthritis and Rheumatic Diseases, Oregon Health & Science University, Portland, OR 97239, USA. deodhara@ohsu.edu
authors.forename: A
authors.initials: A
authors.lastname: Deodhar
authors.forename: R K
authors.initials: RK
authors.lastname: Dore
authors.forename: D
authors.initials: D
authors.lastname: Mandel
authors.forename: J
authors.initials: J
authors.lastname: Schechtman
authors.forename: W
authors.initials: W
authors.lastname: Shergy
authors.forename: R
authors.initials: R
authors.lastname: Trapp
authors.forename: P A
authors.initials: PA
authors.lastname: Ory
authors.forename: C G
authors.initials: CG
authors.lastname: Peterfy
authors.forename: T
authors.initials: T
authors.lastname: Fuerst
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: L
authors.initials: L
authors.lastname: Zhou
authors.forename: W
authors.initials: W
authors.lastname: Tsuji
authors.forename: R
authors.initials: R
authors.lastname: Newmark
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy*; D015519:Bone Density / Q000187:drug effects*; D001862:Bone Resorption / Q000209:etiology / Q000517:prevention & control*; D000069448:Denosumab; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D055103:Hypodermoclysis; D008297:Male; D008875:Middle Aged; D053245:RANK Ligand / Q000008:administration & dosage*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D053245:RANK Ligand; D000069448:Denosumab