Document Detail


Denosumab and changes in bone turnover markers during androgen deprivation therapy for prostate cancer.
MedLine Citation:
PMID:  21898590     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Androgen deprivation therapy (ADT) for prostate cancer increases fracture risk, decreases bone mineral density, and increases bone turnover markers (BTMs) including serum type 1 C-telopeptide (sCTX), tartrate-resistant alkaline phosphatase 5b (TRAP-5b), and procollagen-1 N-terminal telopeptide (P1NP). In a prespecified exploratory analysis of a phase 3, multicenter, double-blind study, we evaluated the effects of denosumab (60 mg subcutaneously every 6 months for 3 years) versus placebo (1468 patients, 734 in each group) on BTM values. BTMs were measured at baseline, month 1, and predose at months 6, 12, 24, and 36 in the overall population. BTMs at month 1 are also reported for subgroups based on age (<  70 years versus ≥  70 years), prior duration of ADT (≤  6 months versus > 6 months), and baseline BTM (≤  median versus >  median BTM values). Treatment with denosumab provided a rapid and sustained decrease of BTM values compared with placebo. The median change in sCTX levels at month 1 was -90% in the denosumab group and -3% in the placebo group (p  <  0.0001). The median change in TRAP-5b levels at month 1 was -55% in the denosumab group and -3% in the placebo group (p <  0.0001). The maximal median change in P1NP was -64% in the denosumab group and -11% in the placebo group, (p  <  0.0001). Significantly greater decreases in BTM for denosumab were also seen in subgroup analyses based on age, prior ADT treatment, and baseline BTM values. Suppression of bone turnover markers was consistent with marked increases in bone mineral density reported previously.
Authors:
Matthew R Smith; Fred Saad; Blair Egerdie; Paul Sieber; Teuvo Lj Tammela; Benjamin Z Leder; Chunlei Ke; Carsten Goessl
Publication Detail:
Type:  Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research     Volume:  26     ISSN:  1523-4681     ISO Abbreviation:  J. Bone Miner. Res.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-11-22     Completed Date:  2012-03-13     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  8610640     Medline TA:  J Bone Miner Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2827-33     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 American Society for Bone and Mineral Research.
Affiliation:
Massachusetts General Hospital Cancer Center, Genitourinary Oncology Program, Boston, MA, USA. smith.matthew@mgh.harvard.edu
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00089674
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MeSH Terms
Descriptor/Qualifier:
Acid Phosphatase / blood
Aged
Antibodies, Monoclonal / pharmacology*,  therapeutic use*
Antibodies, Monoclonal, Humanized
Biological Markers / blood
Bone Density / drug effects
Bone Remodeling / drug effects*
Collagen Type I / blood
Humans
Isoenzymes / blood
Male
Peptide Fragments / blood
Peptides / blood
Procollagen / blood
Prostatic Neoplasms / blood,  drug therapy*,  physiopathology*
Statistics, Nonparametric
Grant Support
ID/Acronym/Agency:
5K24CA121990/CA/NCI NIH HHS; K24 CA121990-05/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antibodies, Monoclonal, Humanized; 0/Biological Markers; 0/Collagen Type I; 0/Isoenzymes; 0/Peptide Fragments; 0/Peptides; 0/Procollagen; 0/collagen type I trimeric cross-linked peptide; 0/procollagen Type I N-terminal peptide; 4EQZ6YO2HI/denosumab; EC 3.1.3.-/tartrate-resistant acid phosphatase; EC 3.1.3.2/Acid Phosphatase
Comments/Corrections

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