PMID- 33211870
OWN - NLM
STAT- MEDLINE
DCOM- 20210920
LR  - 20210929
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 106
IP  - 2
DP  - 2021 Jan 23
TI  - Denosumab Safety and Efficacy Among Participants in the FREEDOM Extension Study 
      With Mild to Moderate Chronic Kidney Disease.
PG  - 397-409
LID - 10.1210/clinem/dgaa851 [doi]
AB  - CONTEXT: The effects of long-term exposure to denosumab in individuals with renal 
      insufficiency are unknown. OBJECTIVE: This post hoc analysis evaluates the 
      long-term safety and efficacy of denosumab in individuals with mild-to-moderate 
      chronic kidney disease (CKD) (stages 2 and 3) using data from the pivotal phase 
      3, double-blind, 3-year FREEDOM (NCT00089791) and open-label, 7-year extension 
      (NCT00523341) studies. PARTICIPANTS AND METHODS: Women age 60 to 90 years with a 
      bone mineral density (BMD) T-score of less than -2.5 to greater than -4.0 at the 
      total hip or lumbar spine were randomly assigned 1:1 to receive denosumab 60 mg 
      subcutaneously every 6 months (long-term arm) or placebo (cross-over arm) in 
      FREEDOM; eligible participants could enroll in the extension to receive denosumab 
      60 mg subcutaneously every 6 months. Change in estimated glomerular filtration 
      rate (eGFR) from study baseline and annualized rates of fracture and adverse 
      events (AEs) were the main outcome measures. RESULTS: Most participants 
      (1259/1969 [64%] long-term arm; 1173/1781 [66%] crossover arm) with baseline CKD 
      stage 2 or 3 remained within the same CKD subgroup at study completion; less than 
      3% progressed to CKD stage 4. Participants in all eGFR subgroups showed similar, 
      persistent BMD gains over time and a low incidence of fractures. The percentage 
      of participants reporting serious AEs was similar among renal subgroups (normal, 
      CKD stage 2, CKD stage 3a, CKD stage 3b) both for the long-term (54% vs 52% vs 
      57% vs 58%) and crossover (43% vs 42% vs 43% vs 68%) arms, except CKD stage 3b 
      subgroup, crossover arm. CONCLUSION: The safety and efficacy of denosumab did not 
      differ among participants with mild to moderate CKD.
CI  - (c) The Author(s) 2020. Published by Oxford University Press on behalf of the 
      Endocrine Society.
FAU - Broadwell, Aaron
AU  - Broadwell A
AD  - Rheumatology and Osteoporosis Specialists, Shreveport, Louisiana, USA.
FAU - Chines, Arkadi
AU  - Chines A
AD  - Amgen Inc, Thousand Oaks, California, USA.
FAU - Ebeling, Peter R
AU  - Ebeling PR
AD  - Monash University, Clayton, Victoria, Australia.
FAU - Franek, Edward
AU  - Franek E
AD  - Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
FAU - Huang, Shuang
AU  - Huang S
AD  - Amgen Inc, Thousand Oaks, California, USA.
FAU - Smith, Shawna
AU  - Smith S
AD  - Amgen Inc, Thousand Oaks, California, USA.
FAU - Kendler, David
AU  - Kendler D
AD  - University of British Columbia, Vancouver, British Columbia, Canada.
FAU - Messina, Osvaldo
AU  - Messina O
AD  - University of Buenos Aires, Buenos Aires, Argentina.
FAU - Miller, Paul D
AU  - Miller PD
AD  - Colorado Center for Bone Research, Lakewood, Colorado, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT00523341
SI  - ClinicalTrials.gov/NCT00089791
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Bone Density Conservation Agents)
RN  - 4EQZ6YO2HI (Denosumab)
SB  - IM
CIN - J Clin Endocrinol Metab. 2021 Jun 16;106(7):e2833-e2834. PMID: 33954779
MH  - Aged
MH  - Aged, 80 and over
MH  - *Bone Density
MH  - Bone Density Conservation Agents/*administration & dosage/adverse effects
MH  - Clinical Trials, Phase III as Topic
MH  - Cross-Over Studies
MH  - Denosumab/*administration & dosage/adverse effects
MH  - Double-Blind Method
MH  - Female
MH  - Follow-Up Studies
MH  - Fractures, Bone/chemically induced/*pathology
MH  - Global Health
MH  - Humans
MH  - Hypocalcemia/chemically induced/*pathology
MH  - Middle Aged
MH  - Multicenter Studies as Topic
MH  - Osteoporosis, Postmenopausal/chemically induced/*pathology
MH  - Prognosis
MH  - Randomized Controlled Trials as Topic
MH  - Renal Insufficiency, Chronic/*drug therapy/pathology
PMC - PMC7823314
OTO - NOTNLM
OT  - bone mineral density
OT  - chronic kidney disease
OT  - denosumab
OT  - fracture
OT  - safety
EDAT- 2020/11/20 06:00
MHDA- 2021/09/21 06:00
PMCR- 2020/11/19
CRDT- 2020/11/19 17:12
PHST- 2020/04/08 00:00 [received]
PHST- 2020/11/20 06:00 [pubmed]
PHST- 2021/09/21 06:00 [medline]
PHST- 2020/11/19 17:12 [entrez]
PHST- 2020/11/19 00:00 [pmc-release]
AID - 5992310 [pii]
AID - dgaa851 [pii]
AID - 10.1210/clinem/dgaa851 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2021 Jan 23;106(2):397-409. doi: 10.1210/clinem/dgaa851.