title: Denosumab reduces the risk of osteoporotic fractures in postmenopausal women, particularly in those with moderate to high fracture risk as assessed with FRAX.
abstract: Denosumab has been shown to reduce the incidence of vertebral, nonvertebral, and hip fractures. The aim of the current study was to determine whether the antifracture efficacy of denosumab was dependent on baseline fracture probability assessed by FRAX. The primary data of the phase 3 FREEDOM study of the effects of denosumab in women with postmenopausal osteoporosis were used to compute country-specific probabilities using the FRAX tool (version 3.2). The outcome variable comprised all clinical osteoporotic fractures (including clinical vertebral fractures). Interactions between fracture probability and efficacy were explored by Poisson regression. At baseline, the median 10-year probability of a major osteoporotic fracture (with bone mineral density) was approximately 15% and for hip fracture was approximately 5% in both groups. In the simplest model adjusted for age and fracture probability, treatment with denosumab over 3 years was associated with a 32% (95% confidence interval [CI] 20% to 42%) decrease in clinical osteoporotic fractures. Denosumab reduced fracture risk to a greater extent in those at moderate to high risk. For example, at 10% probability, denosumab decreased fracture risk by 11% (p = 0.629), whereas at 30% probability (90th percentile of study population) the reduction was 50% (p = 0.001). The reduction in fracture was independent of prior fracture, parental history of hip fracture, or secondary causes of osteoporosis. A low body mass index (BMI) was associated with greater efficacy. Denosumab significantly decreased the risk of clinical osteoporotic fractures in postmenopausal women. Overall, the efficacy of denosumab was greater in those at moderate to high risk of fracture as assessed by FRAX.
authors.affiliation: WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield, Sheffield, United Kingdom. e.v.mccloskey@shef.ac.uk
authors.forename: Eugene V
authors.initials: EV
authors.lastname: McCloskey
authors.forename: Helena
authors.initials: H
authors.lastname: Johansson
authors.forename: Anders
authors.initials: A
authors.lastname: Oden
authors.forename: Matt
authors.initials: M
authors.lastname: Austin
authors.forename: Ethel
authors.initials: E
authors.lastname: Siris
authors.forename: Andrea
authors.initials: A
authors.lastname: Wang
authors.forename: E Michael
authors.initials: EM
authors.lastname: Lewiecki
authors.forename: Roman
authors.initials: R
authors.lastname: Lorenc
authors.forename: Cesar
authors.initials: C
authors.lastname: Libanati
authors.forename: John A
authors.initials: JA
authors.lastname: Kanis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D015992:Body Mass Index; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D000069448:Denosumab; D005260:Female; D017102:Fracture Healing; D006801:Humans; D008875:Middle Aged; D010024:Osteoporosis / Q000188:drug therapy* / Q000517:prevention & control*; D058866:Osteoporotic Fractures / Q000517:prevention & control*; D010919:Placebos; D017698:Postmenopause; D011336:Probability; D016016:Proportional Hazards Models; D012306:Risk; D018570:Risk Assessment
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents; D010919:Placebos; D000069448:Denosumab