Abaloparatide treatment significantly increases bone mineral density (BMD) at the total hip, femoral neck, and lumbar spine in younger postmenopausal women at high risk for fracture, according to the results of a study published in Clinical Therapeutics.
Though studies show women aged <65 years who have experienced sentinel fractures are at an increased risk for future fractures and mortality, these women may be at particular risk for underdiagnosis and undertreatment of osteoporosis. Current treatment guidelines recommend intervention for women at any age who have a T-score of <-2.5, and therefore evaluation of the effectiveness of available therapies for the treatment of osteoporosis in this age group is warranted. The Endocrine Society recommends abaloparatide for patients who are at very high risk for fracture, such as women aged <65 years who have experienced sentinel fractures.
To determine the safety of abaloparatide and its effectiveness in preventing future fractures in this younger subset of postmenopausal women considered to be at high risk, data from 296 women with osteoporosis were analyzed in a post hoc analysis. Status as high risk for future fractures was determined based on modified healthcare insurance coverage criteria. Postmenopausal women aged 49 to 64 years with a baseline T-score at the lumbar spine, hip, or femoral neck of <-2.5 and a prevalent vertebral or ≥1 prior clinical fracture at ≤5 years before the study were included. Patients were randomly assigned to receive 80 μg of abaloparatide or matching placebo administered subcutaneously daily or 20 μg of open-label teriparatide administered subcutaneously for 18 months.
The primary end point of the study was the incidence of any new vertebral fractures, including morphometric fractures, from baseline to 18 months in women treated with abaloparatide compared with those treated with placebo. Additional end points included the percentage change in BMD at the lumbar spine, total hip, and femoral neck from baseline to 6, 12, and 18 months as well as the time to first incidence of nonvertebral, clinical, and major osteoporotic fracture.
At baseline, 31% of women had a prevalent vertebral fracture and 79% had ≥1 prior nonvertebral fracture in the preceding 5 years. A total of 94 individuals were randomly assigned to the abaloparatide group (mean age, 59.4±3.6 years), 103 to the placebo group (mean age, 59.9±3.3 years), and 99 to the teriparatide group (mean age, 58.8±3.8 years). The mean femoral neck T-score was -2.1 for the abaloparatide group and -2.0 for the placebo and teriparatide groups. The mean total hip T-scores were -1.9 for the abaloparatide group, -1.8 for the placebo group, and -1.7 for the teriparatide group. The mean lumbar spine T-scores were -3.0 for the abaloparatide and placebo groups and -2.9 for the teriparatide group.
Individuals in the abaloparatide group experienced significantly greater increases in BMD after 6 months at the total hip (P <.01), femoral neck (P <.01), and lumbar spine (P <.0001), as well as after 12 (P <.0001 for all 3 sites) and 18 months (P <.0001 for all 3 sites) compared with individuals in the placebo group. Individuals in the teriparatide group also experienced significant increases in BMD at all 3 sites (P <.0001) compared with individuals in the placebo group. Change in BMD from baseline did not significantly differ between the abaloparatide and teriparatide groups.
No significant differences in fracture incidence rates were found across treatment groups, though the fracture incidence rates were overall very low. The new vertebral fracture incidence rates were 1.3% for the abaloparatide group, 7.1% for the placebo group, and 2.3% for the teriparatide group. There was no significant difference in treatment-emergent adverse events between treatment groups.
These findings indicated that abaloparatide was a safe and effective treatment for younger postmenopausal women with osteoporosis who were at a high risk for future fractures. The study authors noted that “early access to anabolic therapy has the potential to decrease the risk of future fracture events, including downstream morbidity and mortality risks” in women who have had a “sentinel event before being diagnosed with osteoporosis.”
Limitations to this study include its small population as well as the lack of prespecified measures for family-wise type 1 error control related to subgroup analyses, which may result in chance findings in post hoc subgroup analyses.
Disclosure: Funding for this study and its author are affiliated with Radius Health, the manufacturer of abaloparatide. Please see the original reference for a full list of authors’ disclosures.
Saag KG, Williams SA, Wang Y, Weiss RJ, Cauley JA. Effect of abaloparatide on bone mineral density and fracture incidence in a subset of younger postmenopausal women with osteoporosis at high risk for fracture. Clin Ther. 2020;42(6):1099-1107.