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. 2023 Dec 5;33(12):633-639.
doi: 10.2188/jea.JE20220099. Epub 2023 Mar 31.

Antiresorptive Drugs and the Risk of Femoral Shaft Fracture in Men and Women With Osteoporosis: A Cohort Study Using the National Database of Health Insurance Claims of Japan

Takumi Imai  1 , Takayuki Hosoi  2 , Hiroshi Hagino  3 , Takanori Yamamoto  4 , Tatsuhiko Kuroda  5 , Hiroshi Watanabe  6 , Shiro Tanaka  7
Affiliations

Antiresorptive Drugs and the Risk of Femoral Shaft Fracture in Men and Women With Osteoporosis: A Cohort Study Using the National Database of Health Insurance Claims of Japan

Takumi Imai et al. J Epidemiol. .

Abstract

Background: This cohort study aimed to estimate incidence rates of femoral shaft fracture in patients who were treated with antiresorptive drugs.

Methods: We used data from the National Database of Health Insurance Claims of Japan from April 2009 and October 2016. All patients with new use of an antiresorptive drug, prescription-free period of ≥3 months, and no prior femoral fractures were included. Femoral shaft fractures were identified using a validated definition based on International Classification of Diseases, 10th revision (ICD-10) codes. Incidence rate ratios were estimated using Poisson regression, with adjustment for sex, age, and the Charlson Comorbidity Index.

Results: We identified 7,958,655 patients (women: 88.4%; age ≥75 years: 51.2%). Femoral shaft fractures were identified in 22,604 patients. Incidence rates per 100,000 person-years were 74.8 for women, 30.1 for men, 30.1 for patients aged ≤64 years, 47.7 for patients aged 65-74 years, and 99.0 for patients aged ≥75 years. Adjusted incidence rate ratios in patients taking versus not taking each type of antiresorptive drug were 1.00 (95% confidence interval [CI], 0.98-1.03) for bisphosphonates, 0.46 (95% CI, 0.44-0.48) for selective estrogen receptor modulators, 0.24 (95% CI, 0.18-0.32) for estrogens, 0.75 (95% CI, 0.71-0.79) for calcitonins, and 0.93 (95% CI, 0.84-1.03) for denosumab. The adjusted incidence rate ratio for alendronate was 1.18 (95% CI, 1.14-1.22).

Conclusion: The incidence rates of femoral shaft fracture varied across patients treated with different antiresorptive drugs. Further research on a specific antiresorptive drug can increase understanding of the risk of femoral shaft fracture.

Keywords: Japanese population; claims database; femoral shaft fracture; osteoporosis; pharmacoepidemiology.

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Conflict of interest statement

Conflicts of interest: ST received lecture fees from Bayer Yakuhin, Amgen Astellas BioPharma, and Research Institute of Healthcare Data Science. He has received consultation fees and outsourcing fees from Daiichi Sankyo Company, Boehringer Ingelheim, Satt, and Public Health Research Foundation. He has received research grants from the Japan Agency for Medical Research and Development; the Japanese Ministry of Health, Labour and Welfare; the Japanese Ministry of Education, Science and Technology; and Novo Nordisk. He was engaged in a research project of the Japan Agency for Medical Research and Development. TI received lecture fees from JCR Pharmaceuticals and Kyowa Kirin and outsourcing fees from the Organization for Clinical Medicine Promotion. HH has received lecture fees or grants outside the submitted work from Amgen, Asahi Kasei Pharma, Astellas Pharma, Chugai Pharmaceutical, Daiichi Sankyo, Eisai, Eli Lilly Japan, Pfizer Japan, Mitsubishi Tanabe Pharma, Mochida Pharma, Ono Pharmaceutical, Taisho Pharmaceutical, and Teijin Pharma; and UCB Japan. TY is an employee of Eli Lilly Japan, which owns the patent and manufactures for one of the study drugs (raloxifene). Eli Lilly Japan provided funding to support only the infrastructure to convert the format of the raw data to an analysis data set. Eli Lilly Japan confirmed whether the progress of this project was aligned with the original purpose of the partnering contract, but suggestions from the company was scientifically judged by primary investigator of this study, which was independent from the company. TK is an employee of Asahi Kasei. The other authors declare that they have no conflicts of interest with respect to this article.

Figures

Figure 1.
Figure 1.. Flowchart showing identification of patients treated with antiresorptive drugs and incidence of femoral shaft fracture
See this image and copyright information in PMC

References

    1. Bilezikian JP. Efficacy of bisphosphonates in reducing fracture risk in postmenopausal osteoporosis. Am J Med. 2009;122(2 Suppl):S14–S21. 10.1016/j.amjmed.2008.12.003 - DOI - PubMed
    1. Odvina CV, Zerwekh JE, Rao DS, Maalouf N, Gottschalk FA, Pak CY. Severely suppressed bone turnover: a potential complication of alendronate therapy. J Clin Endocrinol Metab. 2005;90:1294–1301. 10.1210/jc.2004-0952 - DOI - PubMed
    1. Armamento-Villareal R, Napoli N, Panwar V, Novack D. Suppressed bone turnover during alendronate therapy for high-turnover osteoporosis. N Engl J Med. 2006;355(19):2048–2050. 10.1056/NEJMc062268 - DOI - PubMed
    1. Goh SK, Yang KY, Koh JS, et al. . Subtrochanteric insufficiency fractures in patients on alendronate therapy: a caution. J Bone Joint Surg Br. 2007;89:349–353. 10.1302/0301-620X.89B3.18146 - DOI - PubMed
    1. Lenart BA, Lorich DG, Lane JM. Atypical fractures of the femoral diaphysis in postmenopausal women taking alendronate. N Engl J Med. 2008;358:1304–1306. 10.1056/NEJMc0707493 - DOI - PubMed

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