J Korean Med Sci.  2020 Dec;35(46):e403. 10.3346/jkms.2020.35.e403.

Osteoporotic Fractures of the Spine, Hip, and Other Locations after Adjuvant Endocrine Therapy with Aromatase Inhibitors in Breast Cancer Patients: a Meta-analysis

• Lee YK
• Lee EG
• Kim HY
• Lee Y
• Lee SM
• Suh DC
• Yoo JI
• Lee S

• KMID: 2509039
• DOI: http://doi.org/10.3346/jkms.2020.35.e403

Abstract

Background
Aromatase inhibitors (AIs) play an important role in the endocrine therapy of postmenopausal breast cancer patients, with a recent tendency to extend the duration of their use. However, AIs may increase the risk of osteoporotic bone fractures. This meta-analysis evaluated the risk of osteoporotic fractures of the hip, spine, and other locations in breast cancer patients using AIs.
Methods
We performed a systematic search to identify randomized controlled clinical trials that investigated osteoporotic fractures in breast cancer patients on AI therapy. The main outcomes were the incidence and risk of osteoporotic fractures in general and of hip, vertebral, and non-vertebral fractures in AI users and controls.
Results
The systematic review found a total of 30 randomized controlled trials including 117,974 participants. The meta-analysis showed a higher incidence of osteoporotic fracture in AI users: The crude risk ratio for all osteoporotic fractures was 1.35 (95% confidence interval [CI], 1.29–1.42;P < 0.001), for hip fractures 1.18 (95% CI, 1.02–1.35; P < 0.001), for vertebral fractures 1.84 (95% CI, 1.36–2.49; P < 0.001), and for non-vertebral fractures 1.18 (95% CI, 1.02–1.35; P < 0.001), respectively, compared to the controls.
Conclusion
Our meta-analysis suggested an increased risk of osteoporotic fractures for AI therapy in patients with breast cancer that was most expressed for vertebral fractures. Breast cancer patients on AIs need to be monitored for osteoporosis and osteoporotic fractures, and active prevention measures should be implemented.

Keyword

Aromatase Inhibitors; Hip Fractures; Breast Malignant Neoplasm; Meta-analysis; Osteoporosis; Post-menopausal; Spinal Fractures

Figure

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  Fig. 1 Preferred Reporting Items for Systematic Reviews and Meta-Analysis flow diagram for the study selection in this meta-analysis of the risk of osteoporotic fractures in breast cancer patients on aromatase inhibitor treatment.RCT = randomised controlled trial.

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  Fig. 2 Forest plots of the effect of aromatase inhibitors on osteoporotic fractures in women with breast cancer determined by fixed-effects meta-analysis.RR = risk ratio, CI = confidence interval.

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  Fig. 3 Forest plots of the effect of aromatase inhibitors on hip fractures in women with breast cancer determined by fixed-effects meta-analysis.RR = risk ratio, CI = confidence interval.

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  Fig. 4 Forest plots of the effect of aromatase inhibitors on vertebral fractures in women with breast cancer determined by random-effects meta-analysis.RR = risk ratio, CI = confidence interval.

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  Fig. 5 Forest plots of the effect of aromatase inhibitors on non-vertebral fractures in women with breast cancer determined by random-effects meta-analysis.RR = risk ratio, CI = confidence interval.

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