title: Denosumab treatment in postmenopausal women with osteoporosis does not interfere with fracture-healing: results from the FREEDOM trial.
abstract: BACKGROUND
  Fracture is the major complication of osteoporosis, and it allows the identification of individuals needing medical intervention for osteoporosis. After nonvertebral fracture, patients often do not receive osteoporosis medical treatment despite evidence that this treatment reduces the risk of subsequent fracture. In this pre planned analysis of the results of the three-year, placebo-controlled FREEDOM trial, we evaluated the effect of denosumab administration on fracture-healing to address theoretical concerns related to initiating or continuing denosumab therapy in patients presenting with a nonvertebral fracture.
  
  
  METHODS
  Postmenopausal women aged sixty to ninety years with osteoporosis were randomized to receive 60 mg of denosumab (n = 3902) or a placebo (n = 3906) subcutaneously every six months for three years. Investigators reported complications associated with a fracture or its management and with fracture-healing for all nonvertebral fractures that occurred during the study. Delayed healing was defined as incomplete fracture-healing six months after the fracture.
  
  
  RESULTS
  Six hundred and sixty-seven subjects (303 treated with denosumab and 364 who received a placebo) had a total of 851 nonvertebral fractures (386 in the denosumab group and 465 in the placebo group), including 199 fractures (seventy-nine in the denosumab group and 120 in the placebo group) that were treated surgically. Delayed healing was reported in seven subjects (two in the denosumab group and five in the placebo group), including one with subsequent nonunion (in the placebo group). Neither delayed healing nor nonunion was observed in any subject who had received denosumab within six weeks preceding or following the fracture. A complication associated with the fracture or intervention occurred in five subjects (2%) and twenty subjects (5%) in the denosumab and placebo groups,respectively (p = 0.009).
  
  
  CONCLUSIONS
  Denosumab in a dose of 60 mg every six months does not seem to delay fracture-healing or contribute to other complications, even when it is administered at or near the time of the fracture.
authors.affiliation: Faculty of Medicine & Surgery, University of Verona, P. le Scuro 10, 37134, Verona, Italy.
authors.forename: Silvano
authors.initials: S
authors.lastname: Adami
authors.forename: Cesar
authors.initials: C
authors.lastname: Libanati
authors.forename: Steven
authors.initials: S
authors.lastname: Boonen
authors.forename: Steven R
authors.initials: SR
authors.lastname: Cummings
authors.forename: Pei-Ran
authors.initials: PR
authors.lastname: Ho
authors.forename: Andrea
authors.initials: A
authors.lastname: Wang
authors.forename: Ethel
authors.initials: E
authors.lastname: Siris
authors.forename: Joseph
authors.initials: J
authors.lastname: Lane
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Adachi
authors.forename: Mohit
authors.initials: M
authors.lastname: Bhandari
authors.forename: Luiz
authors.initials: L
authors.lastname: de Gregorio
authors.forename: Nigel
authors.initials: N
authors.lastname: Gilchrist
authors.forename: George
authors.initials: G
authors.lastname: Lyritis
authors.forename: Gerd
authors.initials: G
authors.lastname: Möller
authors.forename: Santiago
authors.initials: S
authors.lastname: Palacios
authors.forename: Karel
authors.initials: K
authors.lastname: Pavelka
authors.forename: Resch
authors.initials: R
authors.lastname: Heinrich
authors.forename: Christian
authors.initials: C
authors.lastname: Roux
authors.forename: Daniel
authors.initials: D
authors.lastname: Uebelhart
mesh_terms: D015502:Absorptiometry, Photon / Q000379:methods; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D015519:Bone Density / Q000502:physiology; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D016009:Chi-Square Distribution; D000069448:Denosumab; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D005593:Fracture Fixation, Internal / Q000379:methods*; D017102:Fracture Healing / Q000187:drug effects*; D005598:Fractures, Spontaneous / Q000000981:diagnostic imaging / Q000209:etiology* / Q000601:surgery; D006801:Humans; D007279:Injections, Subcutaneous; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D011446:Prospective Studies; D012016:Reference Values; D018570:Risk Assessment; D016103:Spinal Fractures / Q000000981:diagnostic imaging / Q000209:etiology / Q000601:surgery; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents; D000069448:Denosumab