title: Denosumab and changes in bone turnover markers during androgen deprivation therapy for prostate cancer.
abstract: 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: Massachusetts General Hospital Cancer Center, Genitourinary Oncology Program, Boston, MA, USA. smith.matthew@mgh.harvard.edu
authors: Matthew R
authors: MR
authors: Smith
authors: Fred
authors: F
authors: Saad
authors: Blair
authors: B
authors: Egerdie
authors: Paul
authors: P
authors: Sieber
authors: Teuvo Lj
authors: TLj
authors: Tammela
authors: Benjamin Z
authors: BZ
authors: Leder
authors: Chunlei
authors: C
authors: Ke
authors: Carsten
authors: C
authors: Goessl
mesh_terms: D000135:Acid Phosphatase / Q000097:blood; D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects*; D024042:Collagen Type I / Q000097:blood; D000069448:Denosumab; D006801:Humans; D007527:Isoenzymes / Q000097:blood; D008297:Male; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D011347:Procollagen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D018709:Statistics, Nonparametric; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D024042:Collagen Type I; D007527:Isoenzymes; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D000069448:Denosumab; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase