A pooled analysis of fall incidence from five placebo-controlled studies showed that the RANKL inhibitor denosumab may reduce the risk of falls, as well as provide established fracture risk reduction by reducing bone resorption and increasing bone mass.
The analysis in the Journal of Bone and Mineral Research noted that recent studies suggest that the nuclear factor-kappaB ligand (RANKL)/RANK system impacts muscle function and/or mass. For example, the pivotal placebo-controlled fracture trial of denosumab in women with postmenopausal osteoporosis found that treatment was associated with a lower incidence of non-fracture-related falls (P = 0.02).
The current ad hoc exploratory analysis pooled data from five denosumab studies to determine if there was consistency across studies in the reduction of fall incidence. The studies included women with postmenopausal osteoporosis and low bone mass, men with osteoporosis, women receiving adjuvant aromatase inhibitors for breast cancer, and men undergoing androgen deprivation therapy for prostate cancer.
The analysis was stratified by study and only included data from the placebo-controlled period of each study. A time-to-event analysis of first fall and exposure-adjusted subject incidence rates of falls was also calculated. Falls were reported and captured as adverse events.
The analysis comprised 10,036 individuals, of whom 16.9% were men. The mean age was roughly 72 years, and slightly less than 50% of patients had a prior fracture. Baseline characteristics were comparable for both sexes, with median vitamin D values approximately 21 ng/mL (53 nmol/L) in all subjects.
Calcium and vitamin D supplementation differed between the studies, but was applied equally to the denosumab and placebo groups.
“A fall was defined as a sudden, unintentional coming to rest on the ground, floor, or other lower level, regardless of whether an injury had occurred as a result,” the authors wrote.