Abaloparatide vs. Alendronate for Osteoporosis

Current pharmacologic therapies for patients with osteoporosis include anti-resorptive drugs, such as bisphosphonates (e.g., alendronate and risedronate) and anabolic agents, such as abaloparatide and teriparatide. Researchers have previously published findings of the Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) study, which demonstrated the efficacy of abaloparatide in preventing fractures in postmenopausal women with osteoporosis.¹ The study was followed by the ACTIVExtend trial, which demonstrated sustained reduction of fracture risk with alendronate in abaloparatide-treated participants from ACTIVE.² Although the results of these two studies have been published, up until now, investigators have not used the data to compare the efficacy of abaloparatide with anti-resorptive therapies.

Recently, researchers performed this analysis, with results suggesting that initial treatment with abaloparatide may result in greater vertebral fracture reduction than alendronate in postmenopausal women with osteoporosis. Benjamin Z. Leder, MD, an endocrinologist at Massachusetts General Hospital, Boston, and colleagues published their findings in the March issue of the Journal of Clinical Endocrinology and Metabolism. This study is the first to prospectively compare the effect of initial treatment with abaloparatide to that of bisphosphonates on fracture incidence in this patient population.³

The investigators analyzed data from participants in ACTIVE who were randomly assigned in a 1:1:1 ratio to receive 80 μg of subcutaneous abaloparatide daily, 20 μg of subcutaneous, open-label teriparatide or matching placebo in a double-blind fashion daily for 18 months. The participants then had the option of participating in ACTIVExtend, during which they received 70 mg of alendronate weekly for 24 months. ACTIVE included 1,243 participants, 1,139 of who participated in ACTIVExtend. The authors note that a relatively small number of fractures occurred in both the abaloparatide and alendronate groups.

A comparison of the fracture rates from the abaloparatide group from ACTIVE with the fracture rates from the group that received alendronate in ACTIVExtend following placebo treatment in ACTIVE revealed the vertebral fracture rate was lower during abaloparatide treatment in ACTIVE (0.47 fractures per 100 patient-years) than during alendronate treatment in ACTIVExtend (1.66 fractures per 100 patient-years). This difference translated into a relative risk reduction of 71%.

The vertebral fracture rate in alendronate-treated women represented a reduction compared with the rate during the placebo-treatment phase, but the comparison did not reach statistical significance. However, patients who switched from placebo in the ACTIVE trial to alendronate in ACTIVExtend experienced a decrease in the rate of new vertebral fractures from 2.49 to 1.66 fractures per 100 patient-years. Those who switched from abaloparatide to alendronate experienced a decrease from 0.47 to 0.19 fractures per 100 patient-years.

Next, the researchers performed a sensitivity analysis that included all participants enrolled in ACTIVE, even those not enrolled in ACTIVExtend. They found a vertebral fracture rate of 3.15 per 100 patient-years among patients who received placebo during ACTIVE and a fracture rate of 1.66 per 100 patient-years among patients who received alendronate in the placebo/alendronate arm of ACTIVExtend. From this finding, the investigators calculated a 1.48 per 100 patient-years reduction after transition from placebo to alendronate.

The reduction in vertebral fractures in the alendronate group was similar to that seen in previous studies examining the effect of alendronate treatment on postmenopausal women with osteoporosis. The investigators saw no differences in the rates of nonvertebral fractures and clinical fractures.

Lara C. Pullen, PhD, is a medical writer based in the Chicago area.

References

1. Miller PD, Hattersley G, Riis BJ, et al. Effect of abaloparatide vs. placebo on new vertebral fractures in postmenopausal women with osteoporosis: A randomized clinical trial. JAMA. 2016 Aug 16;316(7):722–773.
2. Bone HG, Cosman F, Miller PD, et al. ACTIVExtend: 24 months of alendronate after 18 months of abaloparatide or placebo for postmenopausal osteoporosis. J Clin Endocrinol Metab. 2018 Aug 1;103(8):2949–2957.
3. Leder BZ, Mitlak B, Hu MY, et al. Effect of abaloparatide vs. alendronate on fracture risk reduction in postmenopausal women with osteoporosis. J Clin Endocrinol Metab. 2020 Mar 1;105(3):938–943.