title: The effect of three or six years of denosumab exposure in women with postmenopausal osteoporosis: results from the FREEDOM extension.
abstract: BACKGROUND
  The Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) extension is evaluating the long-term efficacy and safety of denosumab for up to 10 years.
  
  
  OBJECTIVE
  The objective of the study was to report results from the first 3 years of the extension, representing up to 6 years of denosumab exposure.
  
  
  METHODS
  This was a multicenter, international, open-label study of 4550 women.
  
  
  METHODS
  Women from the FREEDOM denosumab group received 3 more years of denosumab for a total of 6 years (long-term) and women from the FREEDOM placebo group received 3 years of denosumab (crossover).
  
  
  METHODS
  Bone turnover markers (BTMs), bone mineral density (BMD), fracture, and safety data are reported.
  
  
  RESULTS
  Reductions in BTMs were maintained (long-term) or achieved rapidly (crossover) after denosumab administration. In the long-term group, BMD further increased for cumulative 6-year gains of 15.2% (lumbar spine) and 7.5% (total hip). During the first 3 years of denosumab treatment, the crossover group had significant gains in lumbar spine (9.4%) and total hip (4.8%) BMD, similar to the long-term group during the 3-year FREEDOM trial. In the long-term group, fracture incidences remained low and below the rates projected for a virtual placebo cohort. In the crossover group, 3-year incidences of new vertebral and nonvertebral fractures were similar to those of the FREEDOM denosumab group. Incidence rates of adverse events did not increase over time. Six participants had events of osteonecrosis of the jaw confirmed by adjudication. One participant had a fracture adjudicated as consistent with atypical femoral fracture.
  
  
  CONCLUSIONS
  Denosumab treatment for 6 years remained well tolerated, maintained reduced bone turnover, and continued to increase BMD. Fracture incidence remained low.
authors: MD, Michigan Bone and Mineral Clinic, 22201 Moross Road, Suite 260, Detroit, Michigan 48236. hgbone.md@att.net.
authors: Henry G
authors: HG
authors: Bone
authors: Roland
authors: R
authors: Chapurlat
authors: Maria-Luisa
authors: ML
authors: Brandi
authors: Jacques P
authors: JP
authors: Brown
authors: Edward
authors: E
authors: Czerwinski
authors: Marc-Antoine
authors: MA
authors: Krieg
authors: Dan
authors: D
authors: Mellström
authors: Sebastião C
authors: SC
authors: Radominski
authors: Jean-Yves
authors: JY
authors: Reginster
authors: Heinrich
authors: H
authors: Resch
authors: Jose A Román
authors: JA
authors: Ivorra
authors: Christian
authors: C
authors: Roux
authors: Eric
authors: E
authors: Vittinghoff
authors: Nadia S
authors: NS
authors: Daizadeh
authors: Andrea
authors: A
authors: Wang
authors: Michelle N
authors: MN
authors: Bradley
authors: Nathalie
authors: N
authors: Franchimont
authors: Michelle L
authors: ML
authors: Geller
authors: Rachel B
authors: RB
authors: Wagman
authors: Steven R
authors: SR
authors: Cummings
authors: Socrates
authors: S
authors: Papapoulos
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D015519:Bone Density / Q000187:drug effects; D018592:Cross-Over Studies; D000069448:Denosumab; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology / Q000517:prevention & control*; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000453:epidemiology; D010919:Placebos; D053245:RANK Ligand / Q000037:antagonists & inhibitors*; D012307:Risk Factors; D013995:Time
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D010919:Placebos; D053245:RANK Ligand; D000069448:Denosumab
references: Bone. 2011 Apr 1;48(4):677-92
references: 21145999
references: N Engl J Med. 2004 Mar 18;350(12):1189-99
references: 15028823
references: Lancet. 2006 Jun 17;367(9527):2010-8
references: 16782492
references: J Bone Miner Res. 1993 Sep;8(9):1137-48
references: 8237484
references: Osteoporos Int. 2013 Jan;24(1):227-35
references: 22776860
references: Stat Med. 2010 May 10;29(10):1127-36
references: 20209478
references: N Engl J Med. 2009 Aug 20;361(8):756-65
references: 19671655
references: J Bone Miner Res. 2010 Nov;25(11):2267-94
references: 20842676
references: Curr Opin Pharmacol. 2005 Dec;5(6):618-25
references: 16188502
references: J Bone Miner Res. 2010 Aug;25(8):1886-94
references: 20222106
references: Lancet Oncol. 2010 Sep;11(9):815
references: 20816372
references: Nature. 2003 May 15;423(6937):337-42
references: 12748652
references: J Bone Miner Res. 2004 Jul;19(7):1059-66
references: 15176987
references: J Bone Miner Res. 2012 Mar;27(3):694-701
references: 22113951
references: N Engl J Med. 2006 Feb 23;354(8):821-31
references: 16495394
references: J Bone Miner Res. 2012 Mar;27(3):687-93
references: 22095631
references: N Engl J Med. 2006 May 25;354(21):2250-61
references: 16723616