title: Effect of denosumab treatment on the risk of fractures in subgroups of women with postmenopausal osteoporosis.
abstract: Denosumab reduces the risk of new vertebral and nonvertebral fractures. Previous trials suggest that the efficacy of antiresorptives on fractures might differ by patients' characteristics, such as age, bone mineral density (BMD), and fracture history. In the FREEDOM study, 7808 women aged 60 to 90 years with osteoporosis were randomly assigned to receive subcutaneous injections of denosumab (60 mg) or placebo every 6 months for 3 years. New vertebral and nonvertebral fractures were radiologically confirmed. Subgroup analyses described in this article were prospectively planned before study unblinding to evaluate the effect of denosumab on new vertebral and nonvertebral fractures across various subgroups. Compared with placebo, denosumab decreased the risk of new vertebral fractures in the overall study population over 3 years. This effect did not significantly differ for any of the nine subgroups analyzed (p > 0.09 for all potential interactions). Denosumab also reduced all nonvertebral fractures by 20% in the full study cohort over 3 years. This risk reduction was statistically significant in women with a baseline femoral neck BMD T-score ≤ -2.5 but not in those with a T-score > -2.5; in those with a body mass index (BMI) < 25 kg/m(2) but not ≥ 25 kg/m(2); and in those without but not with a prevalent vertebral fracture. These differential treatment effects were not explained by differences in BMD responses to denosumab. Denosumab 60 mg administered every 6 months for 3 years in women with osteoporosis reduced the risk of new vertebral fractures to a similar degree in all subgroups. The effect of denosumab on nonvertebral fracture risk differed by femoral neck BMD, BMI, and prevalent vertebral fracture at baseline.
authors: Oregon Osteoporosis Center, Portland, OR 97213, USA. mmcclung@orost.com
authors: Michael R
authors: MR
authors: McClung
authors: Steven
authors: S
authors: Boonen
authors: Ove
authors: O
authors: Törring
authors: Christian
authors: C
authors: Roux
authors: René
authors: R
authors: Rizzoli
authors: Henry G
authors: HG
authors: Bone
authors: Claude-Laurent
authors: CL
authors: Benhamou
authors: Willem F
authors: WF
authors: Lems
authors: Salvatore
authors: S
authors: Minisola
authors: Johan
authors: J
authors: Halse
authors: Hans C
authors: HC
authors: Hoeck
authors: Richard
authors: R
authors: Eastell
authors: Andrea
authors: A
authors: Wang
authors: Suresh
authors: S
authors: Siddhanti
authors: Steven R
authors: SR
authors: Cummings
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use*; D015519:Bone Density / Q000187:drug effects; D000069448:Denosumab; D005260:Female; D005272:Femur Neck / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D058866:Osteoporotic Fractures / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D012307:Risk Factors; D016103:Spinal Fractures / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000069448:Denosumab