title: A randomized, double-blind phase 2 clinical trial of blosozumab, a sclerostin antibody, in postmenopausal women with low bone mineral density.
abstract: Sclerostin, a SOST protein secreted by osteocytes, negatively regulates formation of mineralized bone matrix and bone mass. We report the results of a randomized, double-blind, placebo-controlled multicenter phase 2 clinical trial of blosozumab, a humanized monoclonal antibody targeted against sclerostin, in postmenopausal women with low bone mineral density (BMD). Postmenopausal women with a lumbar spine T-score -2.0 to -3.5, inclusive, were randomized to subcutaneous blosozumab 180 mg every 4 weeks (Q4W), 180 mg every 2 weeks (Q2W), 270 mg Q2W, or matching placebo for 1 year, with calcium and vitamin D. Serial measurements of spine and hip BMD and biochemical markers of bone turnover were performed. Overall, 120 women were enrolled in the study (mean age 65.8 years, mean lumbar spine T-score -2.8). Blosozumab treatment resulted in statistically significant dose-related increases in spine, femoral neck, and total hip BMD as compared with placebo. In the highest dose group, BMD increases from baseline reached 17.7% at the spine, and 6.2% at the total hip. Biochemical markers of bone formation increased rapidly during blosozumab treatment, and trended toward pretreatment levels by study end. However, bone specific alkaline phosphatase remained higher than placebo at study end in the highest-dose group. CTx, a biochemical marker of bone resorption, decreased early in blosozumab treatment to a concentration less than that of the placebo group by 2 weeks, and remained reduced throughout blosozumab treatment. Mild injection site reactions were reported more frequently with blosozumab than placebo. In conclusion, treatment of postmenopausal women with an antibody targeted against sclerostin resulted in substantial increases in spine and hip BMD. These results support further study of blosozumab as a potential anabolic therapy for osteoporosis.
authors.affiliation: Osteoporosis Research Center, Creighton University, Omaha, NE, USA.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Recker
authors.forename: Charles T
authors.initials: CT
authors.lastname: Benson
authors.forename: Toshio
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Michael A
authors.initials: MA
authors.lastname: Bolognese
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Robins
authors.forename: Jahangir
authors.initials: J
authors.lastname: Alam
authors.forename: Alan Y
authors.initials: AY
authors.lastname: Chiang
authors.forename: Leijun
authors.initials: L
authors.lastname: Hu
authors.forename: John H
authors.initials: JH
authors.lastname: Krege
authors.forename: Hideaki
authors.initials: H
authors.lastname: Sowa
authors.forename: Bruce H
authors.initials: BH
authors.lastname: Mitlak
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Myers
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D015519:Bone Density / Q000187:drug effects*; D019485:Bone Morphogenetic Proteins / Q000276:immunology*; D016723:Bone Remodeling / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D005819:Genetic Markers / Q000276:immunology*; D006801:Humans; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy; D010919:Placebos; D017698:Postmenopause / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; D010919:Placebos; C422903:SOST protein, human; C000593189:blosozumab
keywords: ANABOLICS; BLOSOZUMAB; BONE MINERAL DENSITY; OSTEOPOROSIS TREATMENT; SCLEROSTIN ANTIBODY