title: Impact of denosumab on the peripheral skeleton of postmenopausal women with osteoporosis:  bone density, mass, and strength of the radius, and wrist fracture.
abstract: OBJECTIVE
  The aim of this study was to report the effects of denosumab on radius cortical and trabecular bone density, mass, and strength, and wrist fracture incidence in the FREEDOM (Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months) study.
  
  
  METHODS
  In the FREEDOM study, postmenopausal women with osteoporosis (N = 7,808) received placebo or 60 mg of denosumab every 6 months for 36 months. Radius bone mineral density (BMD), bone mineral content, and strength (polar moment of inertia) were evaluated in two prespecified substudies using dual-energy x-ray absorptiometry (placebo, n = 209; denosumab, n = 232) or quantitative CT (placebo, n = 48; denosumab, n = 62). Prespecified analysis assessed wrist fracture incidence in all FREEDOM participants (placebo, N = 3,906; denosumab, N = 3,902), and post hoc subgroup analyses evaluated those with higher fracture risk (baseline femoral neck T-score ≤-2.5; placebo, N = 1,406; denosumab, N = 1,384).
  
  
  RESULTS
  Denosumab significantly increased areal BMD (assessed by dual-energy x-ray absorptiometry) and volumetric BMD, bone mineral content, and polar moment of inertia (assessed by quantitative CT), compared with placebo, in radius cortical and trabecular bone at all time points evaluated (all P < 0.05). Wrist fracture incidence was 2.9% for placebo and 2.5% for denosumab (relative risk reduction, 16%; P = 0.21) on month 36. Participants with a femoral neck T-score of -2.5 or lower were at increased risk for wrist fracture, and denosumab significantly reduced wrist fracture incidence compared with placebo (placebo, 4.0%; denosumab, 2.4%; relative risk reduction, 40%; absolute risk reduction, 1.6%; P = 0.03).
  
  
  CONCLUSIONS
  Denosumab significantly improves radius bone density, mass, and strength compared with placebo. In higher-risk women, denosumab significantly reduces wrist fracture risk.
authors.affiliation: George Washington University, Washington DC, USA. jsimon@JamesASimonMD.com
authors.forename: James A
authors.initials: JA
authors.lastname: Simon
authors.forename: Christopher
authors.initials: C
authors.lastname: Recknor
authors.forename: Alfred H
authors.initials: AH
authors.lastname: Moffett
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Adachi
authors.forename: Edward
authors.initials: E
authors.lastname: Franek
authors.forename: E Michael
authors.initials: EM
authors.lastname: Lewiecki
authors.forename: Michael R
authors.initials: MR
authors.lastname: McClung
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Mautalen
authors.forename: Sergio
authors.initials: S
authors.lastname: Ragi-Eis
authors.forename: Geoffrey C
authors.initials: GC
authors.lastname: Nicholson
authors.forename: Christian
authors.initials: C
authors.lastname: Muschitz
authors.forename: Ranuccio
authors.initials: R
authors.lastname: Nuti
authors.forename: Ove
authors.initials: O
authors.lastname: Törring
authors.forename: Andrea
authors.initials: A
authors.lastname: Wang
authors.forename: Cesar
authors.initials: C
authors.lastname: Libanati
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001842:Bone and Bones / Q000187:drug effects / Q000503:physiopathology*; D000069448:Denosumab; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000503:physiopathology; D010919:Placebos; D053245:RANK Ligand / Q000037:antagonists & inhibitors*; D011884:Radius / Q000000981:diagnostic imaging / Q000503:physiopathology*; D011885:Radius Fractures / Q000453:epidemiology / Q000517:prevention & control; D012306:Risk; D014057:Tomography, X-Ray Computed; D014458:Ulna Fractures / Q000453:epidemiology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents; D010919:Placebos; D053245:RANK Ligand; D000069448:Denosumab