A randomized, controlled trial of once-weekly teriparatide injection versus alendronate in patients at high risk of osteoporotic fracture: primary results of the Japanese Osteoporosis Intervention Trial-05.

In this randomized, controlled trial, treatment with once-weekly subcutaneous injection of teriparatide for 72 weeks was found to be associated with a significant reduction in the incidence of morphometric vertebral fractures compared with alendronate in women with primary osteoporosis who were at high risk of fracture. Introduction To determine whether the anti-fracture efficacy of teriparatide is superior to that of alendronate, a prospective, randomized, open-label, blinded-endpoint trial was performed. Methods Japanese women aged at least 75 years were eligible for the study if they had primary osteoporosis and were at high risk of fracture. Patients were randomly assigned in a 1:1 ratio to receive sequential therapy (once-weekly subcutaneous injection of teriparatide 56.5 μg for 72 weeks followed by alendronate for 48 weeks) or monotherapy with alendronate for 120 weeks. The primary endpoint was the incidence of morphometric vertebral fractures at 72 weeks (at the end of teriparatide treatment). Results Between October 2014 and December 2017, 1011 patients (505 in the teriparatide group and 506 in the alendronate group) were enrolled. Of these, 778 patients (351 and 427, respectively) were included in the primary analysis. The incidence of morphometric vertebral fractures was significantly lower in the teriparatide group (56 per 419.9 person-years, annual incidence rate 0.1334) than in the alendronate group (96 per 553.6 person-years, annual incidence rate 0.1734), with a rate ratio of 0.78 (95% confidence interval 0.61 to 0.99, P = 0.04). In both groups, adverse events were most frequently reported in the following system organ classes: infections and infestations, gastrointestinal disorders, and musculoskeletal and connective tissue disorders. Conclusion Once-weekly subcutaneous injection of teriparatide significantly reduced the incidence of morphometric vertebral fractures compared with alendronate in women with primary osteoporosis who were at high risk of fracture. Trial registration jRCTs031180235 and UMIN000015573, March 12, 2019.