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Archives of Osteoporosis

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01-12-2019 | Review Article

Oral bisphosphonates and incidence of cancers in patients with osteoporosis: a systematic review and meta-analysis

Authors: Yingfang Deng, Zhen Zhang, Xi Jia, Wenke Cheng, Xixi Zhou, Yi Liu, Miaozhou Wang

Published in: Archives of Osteoporosis | Issue 1/2019

Abstract

Purpose

Several previous studies have shown that oral bisphosphonates (BPs) are associated with the incidence of 13 specific cancers, including lung cancer, esophageal cancer, gastric cancer, and colorectal cancer (CRC). However, the findings are heterogeneous.

Methods and results

Relevant studies published in databases such as PubMed, Embase database, and Cochrane library were systematically retrieved from inception to August 25th, 2018, regardless of language, by two investigators independently. Afterwards, the maximum adjusted hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were extracted from the retrieved studies. Finally, 13 cohort studies involving 1,510,763 participants were enrolled into this meta-analysis. No significant relationship was found between oral BPs and the risk of all-cause cancer in osteoporosis (OP) patients among the entire population (HR 0.97, 95% CI 0.80–1.18; I² 92.5%). Besides, oral BPs could remarkably reduce the incidence of breast cancer (HR 0.79, 95% CI 0.68–0.92; I² 54%) and endometrial cancer (HR 0.79, 95% CI 0.64–0.96; I² 0%) in postmenopausal OP females. In addition, oral BPs were also found to evidently reduce the incidence of upper gastrointestinal cancer in OP patients among the entire population (HR 0.73, 95% CI 0.54–0.98; I² 36.1%). However, oral BPs may lead to increased risk of liver cancer in mixed genders (HR 1.69, 95% CI 1.03–2.77; I² 30.7%).

Conclusions

Taken together, oral BPs do not increase the risk of incidence of all-cause cancer; instead, they can reduce the incidence of breast, endometrial, and upper gastrointestinal cancers among the postmenopausal OP females. Our analysis stratified by gender suggests that oral BPs may increase the incidence of liver cancer in mixed genders, while no significant association was observed in females. Careful analysis of post-marketing data should be conducted to address the clinical relevance of our results on the putative association of oral BP use and liver cancer suggested by our meta-analysis.

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North American Menopause Society (2010) Position statement: management of osteoporosis in postmenopausal woman: 2010. Menopause 17:25–54 quiz 55-6CrossRef

Van Acker HH, Anguille S, Willemen Y et al (2016) Bisphosphonates for cancer treatment: mechanisms of action and lessons from clinical trials. Pharmacol Ther 158:24–40CrossRef

Lee WY, Sun LM, Lin MC, Liang JA, Chang SN, Sung FC, Muo CH, Kao CH (2012) A higher dosage of oral alendronate will increase the subsequent cancer risk of osteoporosis patients in Taiwan: a population-based cohort study [J]. PLoS One 7(12):e53032CrossRef

Chiang CH, Huang CC, Chan WL, Huang PH, Chen TJ, Chung CM, Lin SJ, Chen JW, Leu HB (2012) Oral alendronate use and risk of cancer in postmenopausal women with osteoporosis: a nationwide study[J]. J Bone Miner Res 27(9):1951–1958CrossRef

Vestergaard P (2011) Occurrence of gastrointestinal cancer in users of bisphosphonates and other antiresorptive drugs against osteoporosis[J]. Calcif Tissue Int 89(6):434–441CrossRef

Abrahamsen B, Pazianas M, Eiken P, Russell RGG, Eastell R (2012) Esophageal and gastric cancer incidence and mortality in alendronate users[J]. J Bone Miner Res 27(3):679–686CrossRef

Passarelli MN, Newcomb PA, LaCroix AZ, Lane DS, Ho GYF, Chlebowski RT (2013) Oral bisphosphonate use and colorectal cancer incidence in the Women's Health Initiative[J]. J Bone Miner Res 28(9):2043–2048CrossRef

Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of observational studies in epidemiology (MOOSE) group. JAMA 283:2008–2012CrossRef

Wells GA, Shea B, O’Connell D et al (2014) The Newcastle Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed 30 Aug 2016

10.

Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560CrossRef

11.

Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50:1088–1101CrossRef

12.

Tao MH, Chen S, Freudenheim JL, Cauley JA, Johnson KC, Mai X, Sarto GE, Wakelee H, Boffetta P, Wactawski-Wende J (2018) Oral bisphosphonate use and lung cancer incidence among postmenopausal women[J]. Ann Oncol 29(6):1476–1485CrossRef

13.

Cardwell CR, Abnet CC, Cantwell MM, Murray LJ (2010) Exposure to oral bisphosphonates and risk of esophageal cancer[J]. Jama 304(6):657–663CrossRef

14.

Cardwell CR, Abnet CC, Veal P, Hughes CM, Cantwell MM, Murray LJ (2012) Exposure to oral bisphosphonates and risk of cancer[J]. Int J Cancer 131(5):E717–E725CrossRef

15.

Khalili H, Huang ES, Ogino S, Fuchs CS, Chan AT (2012) A prospective study of bisphosphonate use and risk of colorectal cancer[J]. J Clin Oncol 30(26):3229–3233CrossRef

16.

Newcomb PA, Passarelli MN, Phipps AI, Anderson GL, Wactawski-Wende J, Ho GYF, O'Sullivan MJ, Chlebowski RT (2015) Oral bisphosphonate use and risk of postmenopausal endometrial cancer[J]. J Clin Oncol 33(10):1186–1190CrossRef

17.

Pazianas M, Abrahamsen B, Eiken PA, Eastell R, Russell RGG (2012) Reduced colon cancer incidence and mortality in postmenopausal women treated with an oral bisphosphonate—Danish National Register Based Cohort Study[J]. Osteoporos Int 23(11):2693–2701CrossRef

18.

Vestergaard P, Fischer L, Mele M, Mosekilde L, Christiansen P (2011) Use of bisphosphonates and risk of breast cancer[J]. Calcif Tissue Int 88(4):255–262CrossRef

19.

Fournier A, Mesrine S, Gelot A, Fagherazzi G, Baglietto L, Clavel-Chapelon F, Boutron-Ruault MC, Chabbert-Buffet N (2017) Use of bisphosphonates and risk of breast Cancer in a French cohort of postmenopausal women[J]. J Clin Oncol 35(28):3230–3239CrossRef

20.

Greenland S. Quantitative methods in the review of epidemiologic literature[J] (1987) Epidemiol Rev 9(1):1–30CrossRef

21.

Monsees GM, Malone KE (2011) Tang MT, et al:bisphosphonate use after estrogen receptorpositive breast cancer and risk of contralateral breast cancer. J Natl Cancer Inst 103:1752–1760CrossRef

Title: Oral bisphosphonates and incidence of cancers in patients with osteoporosis: a systematic review and meta-analysis
Authors: Yingfang Deng
Zhen Zhang
Xi Jia
Wenke Cheng
Xixi Zhou
Yi Liu
Miaozhou Wang
Publication date: 01-12-2019
Publisher: Springer London
Published in: Archives of Osteoporosis / Issue 1/2019
Print ISSN: 1862-3522
Electronic ISSN: 1862-3514
DOI: https://doi.org/10.1007/s11657-018-0552-3

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Oral bisphosphonates and incidence of cancers in patients with osteoporosis: a systematic review and meta-analysis

Abstract

Purpose

Methods and results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Purpose

Methods and results

Conclusions

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