A Pooled Analysis of Fall Incidence From Placebo-Controlled Trials of Denosumab.
Pojchong ChotiyarnwongEugene V McCloskeyRichard EastellMichael R McClungEvelien GielenJohn GostageMichele McDermottArkadi ChinesShuang HuangSteven R CummingsPublished in: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research (2020)
Recent studies suggest that the RANK/RANKL system impacts muscle function and/or mass. In the pivotal placebo-controlled fracture trial of the RANKL inhibitor denosumab in women with postmenopausal osteoporosis, treatment was associated with a lower incidence of non-fracture-related falls (p = 0.02). This ad hoc exploratory analysis pooled data from five placebo-controlled trials of denosumab to determine consistency across trials, if any, of the reduction of fall incidence. The analysis included trials in women with postmenopausal osteoporosis and low bone mass, men with osteoporosis, women receiving adjuvant aromatase inhibitors for breast cancer, and men receiving androgen deprivation therapy for prostate cancer. The analysis was stratified by trial, and only included data from the placebo-controlled period of each trial. A time-to-event analysis of first fall and exposure-adjusted subject incidence rates of falls were analyzed. Falls were reported and captured as adverse events. The analysis comprised 10,036 individuals; 5030 received denosumab 60 mg subcutaneously once every 6 months for 12 to 36 months and 5006 received placebo. Kaplan-Meier estimates showed an occurrence of falls in 6.5% of subjects in the placebo group compared with 5.2% of subjects in the denosumab group (hazard ratio = 0.79; 95% confidence interval 0.66-0.93; p = 0.0061). Heterogeneity in study designs did not permit overall assessment of association with fracture outcomes. In conclusion, denosumab may reduce the risk of falls in addition to its established fracture risk reduction by reducing bone resorption and increasing bone mass. These observations require further exploration and confirmation in studies with muscle function or falls as the primary outcome. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research..
Keyphrases
- bone mineral density
- postmenopausal women
- phase iii
- placebo controlled
- body composition
- double blind
- prostate cancer
- study protocol
- phase ii
- clinical trial
- risk factors
- bone loss
- randomized controlled trial
- open label
- electronic health record
- giant cell
- machine learning
- pregnant women
- type diabetes
- soft tissue
- systematic review
- metabolic syndrome
- radical prostatectomy
- phase ii study
- big data
- smoking cessation
- bone regeneration
- polycystic ovary syndrome
- hip fracture
- middle aged
- early stage
- combination therapy