PMID- 28277603
OWN - NLM
STAT- MEDLINE
DCOM- 20180326
LR  - 20180326
IS  - 1523-4681 (Electronic)
IS  - 0884-0431 (Linking)
VI  - 32
IP  - 7
DP  - 2017 Jul
TI  - Safety Observations With 3 Years of Denosumab Exposure: Comparison Between 
      Subjects Who Received Denosumab During the Randomized FREEDOM Trial and Subjects 
      Who Crossed Over to Denosumab During the FREEDOM Extension.
PG  - 1481-1485
LID - 10.1002/jbmr.3119 [doi]
AB  - Denosumab is a fully human monoclonal antibody against receptor activator of 
      NF-kappaB ligand (RANKL) that decreases osteoclast formation, function and survival, 
      and is approved for the treatment of postmenopausal women with osteoporosis at 
      increased or high risk for fracture, among other indications. During the pivotal 
      3-year fracture trial FREEDOM, denosumab 60 mg subcutaneously every 6 months 
      significantly reduced new vertebral (68%), hip (40%), and nonvertebral (20%) 
      fractures; increased bone mineral density (BMD); and reduced bone turnover 
      markers compared with placebo in postmenopausal women with osteoporosis. 
      Questions have arisen regarding imbalances of certain low-frequency adverse 
      events (AEs) observed in FREEDOM, as well as the top 5 most frequent adverse 
      reactions listed in the United States prescribing information (USPI; back pain, 
      pain in extremity, musculoskeletal pain, hypercholesterolemia, and cystitis). We 
      examined the incidences of these AEs in women who originally received placebo 
      during FREEDOM and then received denosumab for up to 3 years during the FREEDOM 
      Extension (Crossover Group). This provided a unique opportunity for comparison 
      with the original 3-year denosumab FREEDOM observations. We also examined the 
      incidences of these AEs over 6 years of denosumab treatment (Long-term Group; ie, 
      comparing a second 3 years of treatment with findings in the first 3 years). 
      There was no indication of increasing trends regarding the imbalances of either 
      low-frequency AEs or common AEs observed in FREEDOM. (c) 2017 American Society for 
      Bone and Mineral Research.
CI  - (c) 2017 American Society for Bone and Mineral Research.
FAU - Watts, Nelson B
AU  - Watts NB
AD  - Mercy Health, Cincinnati, OH, USA.
FAU - Brown, Jacques P
AU  - Brown JP
AD  - Laval University and CHU de Quebec Research Centre, Quebec City, Canada.
FAU - Papapoulos, Socrates
AU  - Papapoulos S
AD  - Leiden University Medical Center, Leiden, The Netherlands.
FAU - Lewiecki, E Michael
AU  - Lewiecki EM
AD  - New Mexico Clinical Research & Osteoporosis Center, Albuquerque, NM, USA.
FAU - Kendler, David L
AU  - Kendler DL
AD  - University of British Columbia, Vancouver, Canada.
FAU - Dakin, Paula
AU  - Dakin P
AD  - Amgen Inc., Thousand Oaks, CA, USA.
FAU - Wagman, Rachel B
AU  - Wagman RB
AD  - Amgen Inc., Thousand Oaks, CA, USA.
FAU - Wang, Andrea
AU  - Wang A
AD  - Amgen Inc., Thousand Oaks, CA, USA.
FAU - Daizadeh, Nadia S
AU  - Daizadeh NS
AD  - Amgen Inc., Thousand Oaks, CA, USA.
FAU - Smith, Shawna
AU  - Smith S
AD  - Amgen Inc., Thousand Oaks, CA, USA.
FAU - Bone, Henry G
AU  - Bone HG
AD  - Michigan Bone and Mineral Clinic, Detroit, MI, USA.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Observational Study
PT  - Randomized Controlled Trial
DEP - 20170403
PL  - England
TA  - J Bone Miner Res
JT  - Journal of bone and mineral research : the official journal of the American 
      Society for Bone and Mineral Research
JID - 8610640
RN  - 4EQZ6YO2HI (Denosumab)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Denosumab/*administration & dosage/adverse effects
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Middle Aged
MH  - Osteoporosis, Postmenopausal/*drug therapy/epidemiology/metabolism/pathology
MH  - United States/epidemiology
OTO - NOTNLM
OT  - DENOSUMAB
OT  - FRACTURE
OT  - OSTEOPOROSIS
OT  - PROLIA
OT  - SAFETY
EDAT- 2017/03/10 06:00
MHDA- 2018/03/27 06:00
CRDT- 2017/03/10 06:00
PHST- 2016/12/19 00:00 [received]
PHST- 2017/02/06 00:00 [revised]
PHST- 2017/02/15 00:00 [accepted]
PHST- 2017/03/10 06:00 [pubmed]
PHST- 2018/03/27 06:00 [medline]
PHST- 2017/03/10 06:00 [entrez]
AID - 10.1002/jbmr.3119 [doi]
PST - ppublish
SO  - J Bone Miner Res. 2017 Jul;32(7):1481-1485. doi: 10.1002/jbmr.3119. Epub 2017 Apr 
      3.