title: Effect of denosumab on bone mineral density in women receiving adjuvant aromatase inhibitors for non-metastatic breast cancer: subgroup analyses of a phase 3 study.
abstract: Denosumab increased lumbar spine bone mineral density (BMD) versus placebo in a 2-year, randomized, placebo-controlled, phase 3 study of patients with hormone-receptor-positive, non-metastatic breast cancer and low bone mass who were receiving adjuvant aromatase inhibitor therapy. In subgroup analyses at 12 and 24 months, we evaluated factors (duration and type of aromatase inhibitor, tamoxifen use, age, time since menopause, body mass index, T-score) that might influence BMD at the lumbar spine, total hip, femoral neck, and 1/3 radius. Patients were randomized to receive placebo (n = 125) or 60 mg denosumab (n = 127) subcutaneously every 6 months. In all subgroups, 12 or 24 months' treatment with denosumab was associated with larger BMD gains than placebo across multiple skeletal sites. Most increases were statistically significant (P < 0.05). Twice-yearly administration of denosumab, regardless of patient subgroup or skeletal site, resulted in consistent increases in BMD versus placebo at 12 and 24 months.
authors.affiliation: Seattle Cancer Care Alliance, 825 Eastlake Avenue East, Mail Stop G3-200, Seattle, WA, 98109-1023, USA. gellis@u.washington.edu
authors.forename: Georgiana K
authors.initials: GK
authors.lastname: Ellis
authors.forename: Henry G
authors.initials: HG
authors.lastname: Bone
authors.forename: Rowan
authors.initials: R
authors.lastname: Chlebowski
authors.forename: Devchand
authors.initials: D
authors.lastname: Paul
authors.forename: Silvana
authors.initials: S
authors.lastname: Spadafora
authors.forename: Michelle
authors.initials: M
authors.lastname: Fan
authors.forename: Dennis
authors.initials: D
authors.lastname: Kim
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use; D047072:Aromatase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D015519:Bone Density / Q000187:drug effects*; D001943:Breast Neoplasms / Q000150:complications / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D000069448:Denosumab; D004334:Drug Administration Schedule; D004967:Estrogens; D005260:Female; D005272:Femur Neck / Q000000981:diagnostic imaging / Q000187:drug effects; D006801:Humans; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000187:drug effects; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000150:complications / Q000188:drug therapy*; D015663:Osteoporosis, Postmenopausal / Q000139:chemically induced / Q000188:drug therapy*; D053245:RANK Ligand / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000276:immunology / Q000627:therapeutic use*; D013629:Tamoxifen / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D004967:Estrogens; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D013629:Tamoxifen; D000069448:Denosumab