Abaloparatide Reduces Fracture Risk in Women with Osteoporosis
Landmark ACTIVE trial results with comments by lead author Paul Miller, MD and Samuel K. Cho, MD
Daily injection of abaloparatide for 18 months significantly reduced the risk of new vertebral and nonvertebral fractures in postmenopausal women with osteoporosis at high risk of fracture, according to the phase 3 ACTIVE (Abaloparatide Comparator Trial In Vertebral Endpoints) trial published in the August 16 issue of JAMA.
“The landmark ACTIVE trial results are important and further validate abaloparatide's potential to consistently, substantially and rapidly reduce both new vertebral and nonvertebral fractures in postmenopausal women with osteoporosis,” lead author Paul Miller, MD, Medical Director at the Colorado Center for Bone Research in Lakewood, Colorado, said in a press statement.
“Bisphosphonates have been the mainstay drug treatment for a long time, but they simply decrease bone loss and do not build new bone,” commented Samuel K. Cho, MD, Associate Professor of Orthopaedics and Neurosurgery at the Icahn School of Medicine at Mount Sinai, New York, NY. “Abaloparatide is a new type of drug, second of its kind, that has successfully finished phase 3 clinical trials recently. The data suggest that it builds bone more effectively than the competitor with less side effects. This is exciting news for those suffering from osteoporosis,” Dr. Cho told SpineUniverse.
Phase 3 Study Design
Dr. Miller and colleagues randomly assigned postmenopausal women (aged 49 to 86 years) with osteoporosis to receive daily injections for 18 months of placebo (n=821); abaloparatide 80 μg (n=824); or open-label teriparatide 20 μg (n=818). The women were considered to be at risk of osteoporotic fracture, with 63% of the women having a prior fracture.
The trial was conducted at 28 sites in 10 countries. Of the 2,463 women (average age, 69 years) originally enrolled in the trial, 1,901 completed the study.
Abaloparatide Lowered Risk for New Vertebral Fractures
New vertebral fractures occurred less frequently in the abaloparatide and teriparatide groups (0.58% and 0.84% groups, respectively) than in the placebo group (4.22%; P<0.001). The hazard ratio for new vertebral fracture with abaloparatide versus placebo was 0.14 (P<0.001). In addition, the estimated event rate for nonvertebral fracture was significantly lower with abaloparatide vs placebo: 2.7% vs 4.7%; P=0.049) in the placebo group. The estimated rate for nonvertebral fracture with teriparatide was 3.3%.
Favorable Bone Mineral Density Findings
Abaloparatide was linked to significantly greater increases in bone mineral density (BMD) at 18 months compared with placebo at total hip (4.18% vs -0.10%), femoral neck (3.6% vs -0.43%), and lumbar spine (11.2% vs 0.63%; P<0.001 for all comparisons). Increases in BMD also were significantly greater in the abaloparatide group versus the teriparatide group at the hip and femoral neck at 18 months (P<0.001). Differences between the two active groups were significant at the lumbar spine at 6 and 12 months, but this comparison “must be interpreted as exploratory,” the study authors noted.
Abaloparatide was linked to a significantly lower incidence of hypercalcemia compared with teriparatide (3.4% vs 6.4%; P=0.006). Overall, the groups showed a similar incidence of serious adverse events (9.7% with abaloparatide, 10.0% with teriparatide, and 11.0% with placebo).
“Further research is needed to understand the clinical importance of risk difference, the risks and benefits of abaloparatide treatment, and the efficacy of abaloparatide vs other osteoporosis treatments,” the authors wrote.
The Challenges of Spine Surgery in Patients With Osteoporosis
The findings suggest that “the spine community should consider surgical challenges that may be unique to cervical spine patients who also have osteoporosis,” Dr. Cho commented. “Based on my personal experience, surgery is just as effective for osteoporotic patient as it would for those without it. However, poor bone quality poses difficulty with surgical fixation when fusing the spine, and careful preoperative planning and execution are needed.”
“Multi-specialty approach to treat osteoporosis may improve surgical outcome in the future,” Dr. Cho noted.
The study was funded by Radius Health.