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ACE inhibitors and the risk of fractures: a meta-analysis of observational studies

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Abstract

A meta-analysis was conducted to evaluate the effect of treatment with angiotensin-converting enzyme inhibitors on the risk of fractures. All the included articleswere retrieved from MEDLINE, EMBASE and the Cochrane Database. Trial eligibility and methodological quality were assessed before data extraction. Relative risk (RR) with corresponding 95% confidence intervals (95% CI) were used to assess the effect. Six case-control studies with11,387,668 participants met the inclusion criteria and were included in the meta-analysis. A small but significant risk effect on fractures was shown in the overall analysis of angiotensin-converting enzyme inhibitor users compared with nonusers (Pooled RR 1.27; 95% CI 1.01–1.60), although a relatively high heterogeneity was found across studies. In the stratified analysis, therewas no statistically significant association in the subgroups of hip fracture (Pooled RR 1.14; 95% CI 0.73–1.76) and the study quality (Pooled RR 1.13; 95% CI 0.89–1.44), while the over 65-year-old angiotensin-converting enzyme inhibitor users showed a stronger risk effect on fractures (Pooled RR 2.06; 95% CI 1.53–3.17). Moreover, age was found to be contributed a large part of the high heterogeneity across the included studies. This study demonstrated that the use of angiotensin-converting enzyme inhibitors might have a small but significant risk effect on fractures, especially for the over 65-year-old users. These results should be interpreted with caution as the relatively high heterogeneity across studies. Additional multiple observational studies and high quality data from randomized controlled trials are needed to confirm these findings.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant No. 81270966, No.81500679), the Natural Science Foundation of Guangdong Province, China (Grant No. S2012010009494, 2014A030310036 and 2014A030310472), Science and technology plan of Guangdong province (Grant No. 2016A020215097) and the Natural Science Foundation of Southern Medical University, Guangdong Province, China (Grant No. PY2013N050).

Author contributions

Y. Cheng and Z. Huang wrote the main manuscript text, Z. Shen, H. Wu, J. Peng performed data extraction and quality assessment, M. Waye, S. Rao and L. Yang performed statistical analysis and overall design of the meta-analysis. All authors reviewed the manuscript.

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    1. Department of Endocrinology, Zhujiang Hospital of Southern Medical University, Guangzhou, China

      Yan-Zhen Cheng & Li Yang

    2. Department of the Second Clinical Medical College, Zhujiang Hospital of Southern Medical University, Guangzhou, China

      Zhen-Zi Huang, Ze-Feng Shen, Hai-Yang Wu & Jia-Xin Peng

    3. School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, N.T., Hong Kong SAR, China

      Mary Miu Yee Waye & Shi-Tao Rao

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    Cheng, YZ., Huang, ZZ., Shen, ZF. et al. ACE inhibitors and the risk of fractures: a meta-analysis of observational studies. Endocrine 55, 732–740 (2017). https://doi.org/10.1007/s12020-016-1201-5

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