Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Jun 9:11:1758835919855235.
doi: 10.1177/1758835919855235. eCollection 2019.

The incidence and relative risk of adverse events in patients treated with bisphosphonate therapy for breast cancer: a systematic review and meta-analysis

Yan-Li Yang  1 , Zi-Jian Xiang  2 , Jing-Hua Yang  2 , Wen-Jie Wang  2 , Ruo-Lan Xiang  3
Affiliations

The incidence and relative risk of adverse events in patients treated with bisphosphonate therapy for breast cancer: a systematic review and meta-analysis

Yan-Li Yang et al. Ther Adv Med Oncol. .

Abstract

Background: Adjuvant bisphosphonates reduce the rate of breast cancer recurrence in the bone and improve breast cancer survival. However, the risk of adverse events associated with bisphosphonate therapy for breast cancer remains poorly defined.

Methods: A literature search was conducted using the PubMed, EMBASE, Cochrane and Web of Science libraries. Risk ratio (RR) was calculated to evaluate the adverse events of the meta-analytic results. Osteonecrosis of the jaw (ONJ) incidence was calculated using the random effect model (D+L pooled) for meta-analysis.

Results: A total of 47 studies comprising 20,607 patients were included; 23 randomized controlled studies (RCTs) provided data of adverse events for bisphosphonate therapy versus without bisphosphonates. Bisphosphonates were significantly associated with influenza-like illness (RR = 4.52), fatigue (RR = 1.08), fever (RR = 1.82), dyspepsia (RR = 1.25), anorexia (RR = 1.29), and urinary tract infection (RR = 1.32). No differences were observed in other adverse events. We combined the incidence of ONJ in 24 retrospective studies to analyze the incidence of ONJ using bisphosphonates. The pooled probability of ONJ toxicity in the bisphosphonates group was 2%.

Conclusions: Bisphosphonates were significantly associated with influenza-like illness, fatigue, fever, dyspepsia, anorexia, and urinary tract infection. Furthermore, bisphosphonates increase the risk of ONJ toxicity.

Keywords: adverse events; bisphosphonates; breast cancer; neoadjuvant therapy; osteonecrosis of the jaw.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest statement: The authors declare that there is no conflict of interest.

Figures

Figure 1.
Figure 1.
Flowchart of selection of studies for inclusion in meta-regression.
Figure 2.
Figure 2.
(a) Risk of bias graph: review authors’ judgments about each risk of bias item presented as percentages across all included randomized controlled trial (RCT) studies. (b) Risk of bias summary: review authors’ judgements about each risk of bias item for each included RCT study.
Figure 3.
Figure 3.
Summary figure demonstrating the risk ratio (RR) for adverse events for patients with and without exposure to bisphosphonates. CI, Confidence interval.
Figure 4.
Figure 4.
Meta-analysis of incidence of bisphosphonates-associated osteonecrosis of the jaw. CI, Confidence interval.
Figure 5.
Figure 5.
Results of Egger’s test (a), Begg’s test (b), and the fill method (c) for bisphosphonates-associated osteonecrosis of the jaw (ONJ).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Palmieri C, Fullarton JR, Brown J. Comparative efficacy of bisphosphonates in metastatic breast and prostate cancer and multiple myeloma: a mixed-treatment meta-analysis. Clin Cancer Res 2013; 19: 6863–6872. - PubMed
    1. Clement-Demange L, Clezardin P. Emerging therapies in bone metastasis. Curr Opin Pharmacol 2015; 22: 79–86. - PubMed
    1. Saad F, Lipton A, Cook R, et al. Pathologic fractures correlate with reduced survival in patients with malignant bone disease. Cancer 2007; 110: 1860–1867. - PubMed
    1. Van Poznak CH, Temin S, Yee GC, et al. American society of clinical oncology executive summary of the clinical practice guideline update on the role of bone-modifying agents in metastatic breast cancer. J Clin Oncol 2011; 29: 1221–1227. - PubMed
    1. Landesberg R, Eisig S, Fennoy I, et al. Alternative indications for bisphosphonate therapy. J Oral Maxillofac Surg 2009; 67: 27–34. - PubMed

LinkOut - more resources