A multicenter randomized double-masked comparative study of different preparations of alendronate in osteoporosis – monthly (four weeks) intravenous versus once weekly oral administrations

Abstract

Objective:

The aim of this study was to evaluate the efficacy and safety of intravenous alendronate (ALN) 900 µg every 4 weeks compared to oral ALN 35 mg once weekly.

Methods:

A 52-week, multicenter, randomized, double-masked, active-controlled, parallel-group, non-inferiority study was conducted in a total of 325 Japanese patients aged 48–87 years with osteoporosis. Patients were randomly assigned to an intravenous ALN (iv, n = 162) group or oral ALN (po, n = 163) group. The efficacy of the both formulations was assessed primarily by bone mineral density (BMD) measurement.

Results:

The percentage BMD change from baseline in lumbar spine (L2–L4) after 52 weeks of treatment was 6.4 ± 0.3% in the iv group and 6.0 ± 0.3% in the po group (least-squares mean ± SE). The inter-group difference in least-squares mean of percentage change from baseline in BMD was 0.37%, and its 95% confidence interval was −0.47% to 1.20%. The non-inferiority of the iv group was established against the po group with a prespecified non-inferiority margin (Δ) of 1.5%. In addition, the four bone turnover markers were reduced to a similar level by either treatment throughout the treatment period. The safety profile was also similar between the two treatment groups. Because of the limitations presented in this study, the results of the iv group may not apply to non-Japanese patients with osteoporosis.

Conclusions:

The efficacy and safety of the intravenous ALN 900 µg once every 4 weeks were similar to those of the oral ALN 35 mg once weekly, indicating that intravenous administration of ALN is an effective treatment for osteoporosis and will provide a useful alternative to oral dosing.

Key words::

• Alendronate
• Bone mineral density
• Bone turnover markers
• Intravenous administration
• Osteoporosis
• Randomized double-masked non-inferiority study

Transparency

Declaration of funding

This article was supported by Teijin Pharma Ltd (Tokyo, Japan).

Declaration of financial/other relationships

M.S. has received consulting fees from Teijin Pharma Ltd (Tokyo, Japan), Asahi Kasei Pharma, and Daiichi-Sankyo, and is on the Speakers Bureau for Ono Pharmaceuticals. T.N. has received consulting fees from Teijin Pharma, Chugai-Roche, Asahi Kasei Pharma, Astellas, Ono Pharmaceuticals and Daiichi-Sankyo. He is a member of the Advisory Boards for Amgen and MSD. T.I. has received consulting fees from Teijin Pharma. M.F. is a paid consultant for Astellas and an advisor for Asahi Kasei Pharma. A.U. is an employee of Teijin Pharma Ltd. T.S. has disclosed that he has no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

We thank Dr. T. Tomomitsu, Kawasaki College of Allied Health Professions, for his technical support. We are also indebted to Dr. Santora, Merck Research Laboratories, Rahway, New Jersey, for his kind comments and advice on the manuscript, Y. Aoki, Teijin Pharma Ltd, for his statistical analysis and H. Fujita, Teijin Pharma Ltd, for writing assistance. The following principal investigators and study sites in Japan participating in this study: Y. Kotani, S. Ohshima, M. Ito (Hokkaido University); K. Kishimoto (Tohoku University); H. Oda (Saitama Medical University); A. Yoshizaki, Y. Nomura (Yokohama City University); N. Endo (Niigata University); T. Matsumoto (Kanazawa Medical University); N. Ishiguro, S. Imagama, Y. Matsuyama (Nagoya University); H. Yamada (Fujita Health University); T. Ikeda (Kinki University); T. Miki (Osaka City University); T. Okano (Tottori University); I. Endo (Tokushima University); T. Mawatari (Kyushu University); T. Hasunuma (Kitasato University Research Center For Clinical Pharmacology); S. Okamoto (Sanyo Osteoporosis Research Foundation Okamoto Clinic); H. Naka (Aino Clinic); H. Hanashi (NS Clinic); M. Omata (Tiida Ohimachi Orthopedic Surgery Clinic); T. Ishihara (Shirahigebashi Hospital); M. Noguchi (Shinagawa East One Medical Clinic); M. Nakayama (Tiida Yokohama Motomachi Clinic); H. Shimomura (Musashino Clinic); N. Taniyasu, T. Saito (Houjin Clinic).

Notes

*Calcichew is a registered trade name of Daiichi-Sankyo Healthcare, Tokyo Japan.