Denosumab may mitigate fall risk in osteoporosis
Click Here to Manage Email Alerts
A post hoc analysis of five randomized controlled trials suggests that older adults with osteoporosis assigned denosumab therapy were 20% less likely to experience a fall during follow-up compared with those assigned placebo, according to findings published in the Journal of Bone and Mineral Research.
“Most fractures, including virtually all nonvertebral fractures, occur in the setting of a fall-related injury, leading to the use of two parallel management strategies, namely to reduce falls risk and improve bone strength,” Pojchong Chotiyarnwong, MD, PhD, a researcher in the department of orthopedic surgery at Siriraj Hospital, Mahidol University, Bangkok, and colleagues wrote. “The possibility that treatments targeted to one strategy might impact on the other is not new; for example, it has long been assumed that the effects of vitamin D supplementation might have beneficial effects on both, though the effects are modest. However, the observation that therapies developed as specific bone-targeted agents, such as denosumab, might also impact muscle function and falls-risk is a novel development.”
Chotiyarnwong and colleagues analyzed data from 10,036 adults (16.9% men; mean age, 72 years) participating in one of five placebo-controlled trials: postmenopausal women with osteoporosis (FREEDOM), postmenopausal women with low bone mass, men with osteoporosis, women receiving adjuvant aromatase inhibitors for breast cancer, and men receiving androgen deprivation therapy for prostate cancer. For each study, participants were randomly assigned 60 mg denosumab (Prolia, Amgen; n = 5,030) or placebo injection (n = 5,006) once every 6 months for 12 to 36 months. Calcium and vitamin D supplementation varied across trials but was applied equally to the denosumab and placebo groups (median baseline vitamin D level, 21 ng/mL). No studies included advice about fall prevention. Participants reported falls via questionnaires during study visits. Researchers used Cox proportional hazard models to estimate HRs for incident falls during denosumab treatment vs. placebo, using individual study data and pooled data. Median follow-up was 36 and 35.9 months for the pooled denosumab and placebo groups, respectively.
“In the main analysis, all falls were included in the outcome, regardless of whether a fracture occurred on the same day; all analyses were then repeated for falls excluding those reports that contained a fracture event on the same day,” the researchers wrote.
Across trials, 4.6% of participants in the denosumab groups and 5.8% of participants in the placebo groups reported at least one fall. Of 520 incident falls overall, 7.7% were considered serious adverse events. Exposure-adjusted incidence rate of falls, calculated as the number of participants who experienced the event divided by the sum of exposure time in years, was 1.8 in the pooled denosumab group and 2.3 in the pooled placebo group, for a rate ratio of 0.77 (95% CI, 0.66-0.9).
In Kaplan-Meier estimates, researchers found that 5.2% of participants in the denosumab group and 6.5% of participants in the placebo group experienced falls, for a pooled HR of 0.79 (95% CI, 0.66-0.93). Results persisted after adjusting for baseline age, total hip bone mineral density T-score and nonvertebral fracture history.
“The apparent reduction in falls risk observed here is of clinical importance, and is similar in magnitude to that achieved by interventions targeted directly at falls risk,” the researchers wrote.
The researchers noted that none of the trials were designed to prospectively or retrospectively collect and validate falls data, and causes of falls were not collected during trials.
“In addition to the bone turnover and density-mediated fracture risk reduction in subjects with postmenopausal osteoporosis, low bone mass, male osteoporosis and cancer treatment-induced bone loss, denosumab may also reduce the risk of falls in these patients,” the researchers wrote. “This observation identifies the need for further high-quality, appropriately powered and designed studies to explore the effect of denosumab on muscle mass and function.” – by Regina Schaffer
Disclosures: Amgen sponsored this study. Chotiyarnwong reports he received speaking fees from Amgen, Eli Lilly, MSD, Novartis, Pfizer Consumer and Roche, and received travel assistance from Amgen and Teva. Please see the study for all other authors’ relevant financial disclosures.
Read more about
Click Here to Manage Email Alerts