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Randomized Controlled Trial
. 2023 Jan;34(1):189-199.
doi: 10.1007/s00198-022-06570-0. Epub 2022 Oct 14.

Sequential therapy with once-weekly teriparatide injection followed by alendronate versus monotherapy with alendronate alone in patients at high risk of osteoporotic fracture: final results of the Japanese Osteoporosis Intervention Trial-05

Satoshi Mori  1 , Hiroshi Hagino  2 , Toshitsugu Sugimoto  3 , Shiro Tanaka  4 , Yuji Mitomo  4 , Kaito Takahashi  4 , Teruki Sone  5 , Toshitaka Nakamura  6 , Satoshi Soen  7
Affiliations
Randomized Controlled Trial

Sequential therapy with once-weekly teriparatide injection followed by alendronate versus monotherapy with alendronate alone in patients at high risk of osteoporotic fracture: final results of the Japanese Osteoporosis Intervention Trial-05

Satoshi Mori et al. Osteoporos Int. 2023 Jan.

Abstract

In this randomized, controlled trial, sequential therapy with once-weekly subcutaneous injection of teriparatide for 72 weeks, followed by alendronate for 48 weeks resulted in a significantly lower incidence of morphometric vertebral fracture than monotherapy with alendronate for 120 weeks in women with osteoporosis at high risk of fracture.

Purpose: To determine whether the anti-fracture efficacy of sequential therapy with teriparatide, followed by alendronate is superior to that of monotherapy with 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 if they were at high risk of fracture. Patients were randomly assigned (1:1) to receive the 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 in the final analysis was the incidence of morphometric vertebral fracture during the 120-week follow-up period.

Results: Between October 2014 and June 2020, 505 patients in the sequential therapy group and 506 in the monotherapy group were enrolled. Of these, 489 and 496, respectively, were included in the main analysis. The incidence of morphometric vertebral fracture during the 120-week follow-up period in the sequential therapy group (64 per 627.5 person-years, annual incidence rate 0.1020) was significantly lower than that in the monotherapy group (126 per 844.2 person-years, annual incidence rate 0.1492), with a rate ratio of 0.69 (95% confidence interval 0.54 to 0.88, P < 0.01). After 72 weeks, no patient had a severe adverse event that was considered related to the study drug.

Conclusion: Once-weekly injection of teriparatide, followed by alendronate resulted in a significantly lower incidence of morphometric vertebral fracture than alendronate monotherapy in women with osteoporosis who were at high risk of fracture. TRIAL REGISTRATION NUMBER, DATE OF REGISTRATION: jRCTs031180235 and UMIN000015573, March 12, 2019.

Keywords: Alendronate; Anabolic agent; Osteoporosis; Sequential therapy; Teriparatide; Vertebral fracture.

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Conflict of interest statement

H. Hagino has received lecture fees or grants outside the submitted work from Amgen Inc., Asahi Kasei Pharma Corp., Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan Co., Ltd., Mitsubishi Tanabe Pharma Corp., Mochida Pharma Corp., Ono Pharmaceutical Co., Ltd., Pfizer Inc., Taisho Pharmaceutical Co., Ltd., Teijin Pharma Co., Ltd., and UCB Japan.

T. Sugimoto has received research grants from Asahi Kasei Pharma Corp., Astellas Pharma, Taisho Toyama Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Pfizer, and Teijin Pharma Ltd., as well as consulting fees from Kissei Pharmaceutical Co., Ltd., Shimadzu Corp., and Takeda Pharmaceutical Co., Ltd.

S. Tanaka has received lecture fees from Bayer Yakuhin, Amgen Astellas BioPharma K.K., and Research Institute of Healthcare Data Science. He has received consultation fees and outsourcing fees from Daiichi Sankyo Company, Limited, Boehringer Ingelheim, Satt, and the Public Health Research Foundation. He has received research grants from the Japan Agency for Medical Research and Development, the Japanese Ministry of Health Labor and Welfare, the Japanese Ministry of Education, Science, and Technology, and Novo Nordisk. He engaged in a research project of the Japan Agency for Medical Research and Development.

T. Sone has received research grants from Astellas Pharma, Eisai, Daiichi-Sankyo, Chugai Pharmaceutical, and Eli Lilly Japan, as well as consulting and/or lecture fees from Asahi Kasei Pharma, MSD, and Daiichi-Sankyo.

T. Nakamura has received personal fees and other from Asahi Pharma, Teijin Pharma, Daiichi-Sankyo Pharma, UCB Pharma, Amgen Inc., Astellas Pharma, and Chugai Pharma, as well as personal fees and others from MERCK.

S. Soen has received consulting fees, speaking fees, and/or honoraria from Asahi Kasei Pharma, Amgen, Astellas Pharma, Daiichi Sankyo, Eli Lilly Japan, Teijin Pharma, and UCB Japan.

S. Mori, Y. Mitomo, and K. Takahashi have nothing to disclose.

Figures

Fig. 1
Fig. 1
Flowchart of the patients enrolled in the Japanese Osteoporosis Intervention Trial-05
Fig. 2
Fig. 2
Changes in bone mineral density at the lumbar spine and bone turnover markers over 120 weeks by treatment group. Percent changes in bone mineral density were 9.0% (n = 192), 12.3% (n = 165), 15.0% (n = 151), and 20.2% (n = 129) at each time point in the sequential group and 7.2% (n = 228), 10.7% (n = 220), 13.5% (n = 208), and 14.8% (n = 177) at each time point in the monotherapy group. Percent changes in osteocalcin were 54.2% (n = 364), 50.1% (n = 338), 35.2% (n = 288), 33.1% (n = 263), and − 28.9% (n = 221) at each time point in the sequential group and − 8.5% (n = 424), − 19.6% (n = 416), − 25.9% (n = 392), − 28.7% (n = 362), and − 28.3% (n = 308) at each time point in the monotherapy group. Percent changes in P1NP were 21.9% (n = 364), 18.7% (n = 338), 7.9% (n = 288), 7.9% (n = 263), and − 42.5% (n = 221) at each time point in the sequential group and − 30.3% (n = 424), − 38.7% (n = 416), − 39.9% (n = 392), − 42.4% (n = 362), and − 37.3% (n = 308) at each time point in the monotherapy group. Percent changes in TRACP-5b were − 2.1% (n = 363), − 5.3% (n = 338), − -11.8% (n = 288), − 10.4% (n = 263), and − 24.3% (n = 221) at each time point in the sequential group and − 23.1% (n = 425), − 26.3% (n = 416), − 28.3% (n = 392), − 27.0% (n = 362), and − 21.6% (n = 308) at each time point in the monotherapy group. Abbreviations: BMD, bone mineral density; P1NP, procollagen type I amino-terminal propeptide; TRACP-5b, tartrate-resistant acid phosphatase 5b. The term “teriparatide to alendronate” means the sequential therapy group, whereas “alendronate to alendronate” means the monotherapy group
Fig. 3
Fig. 3
Rate ratios for the incidence of morphometric vertebral fracture stratified by baseline characteristics. Abbreviations: BMI, body mass index; HbA1c, hemoglobin A1c; SQ, semiquantitative; BMD, bone mineral density
See this image and copyright information in PMC

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