Zhou et al. Journal of Experimental & Clinical Cancer Research 2011, 30:72 http://www.jeccr.com/content/30/1/72 R E S E A R C H Open Access Innegligible musculoskeletal disorders caused by zoledronic acid in adjuvant breast cancer treatment: a meta-analysis Wen-Bin Zhou1, Peng-Ling Zhang2, Xiao-An Liu1, Tao Yang3 and Wei He3* Abstract Background: Zoledronic acid (ZOL) is widely used for preventing bone loss in early breast cancer patients. However, the adverse effects caused by ZOL itself should not be neglected. Musculoskeletal disorders were common after ZOL administration and distressing to the patients. Up to now, no precise estimation of musculoskeletal disorders has been made. Methods: Relevant randomized clinical trials were selected by searching the electronic database PubMed, and a meta-analysis was conducted. Results: Four trials reported musculoskeletal disorders of ZOL treatment versus no ZOL, including 2684 patients treated with ZOL and 2712 patients without ZOL treatment. Compared to patients without ZOL treatment, patients treated with ZOL had a significantly higher risk of arthralgia (risk ratio (RR): 1.162, 95% confidence interval (CI): 1.096-1.232, P = 0.466 for heterogeneity) and bone pain (RR: 1.257, 95% CI: 1.149-1.376, P = 0.193 for heterogeneity). Three clinical trials reported the complications of upfront versus delayed ZOL treatment, including 1091 patients with upfront ZOL and 1110 patients with delayed ZOL. The rate of bone pain in upfront group (119/ 824) was significantly higher than that in delayed group (74/836) (RR: 1.284, 95% CI: 1.135-1.453, P = 0.460 for heterogeneity). Conclusions: Our meta-analysis suggested that treatment with ZOL was significantly associated to the occurrence of arthralgia and bone pain. Moreover, higher rate of bone pain was observed in patients treated with upfront ZOL compared with delayed ZOL treatment. More attentions should be paid to patients treated with ZOL, especially for immediate ZOL. For patients with low risk of osteoporosis, immediate ZOL may be not needed due to additional musculoskeletal disorders and little benefit. Or it can be stopped after the occurrence of these adverse events. Keywords: zoledronic acid, musculoskeletal disorders, breast cancer, meta-analysis Introduction More patients with early breast cancer have been diag- nosed with the development of screening techniques [1]. Following adjuvant chemotherapy and endocrine therapy can significantly improve disease-free survival (DFS) and overall survival (OS) in early breast cancer patients [2-4]. However, both adjuvant chemotherapy and endo- crine therapy cause bone loss to these patients. Patients * Correspondence: hewei1007@sina.cn 3Department of Endocrinology and Metabolism, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, 210029 Nanjing, China Full list of author information is available at the end of the article with amenorrhea after chemotherapy [5,6] and postme- nopausal patients receiving aromatase inhibitors (AIs) are at high risk of bone loss [3,4,7-9]. Zoledronic acid (ZOL) can prevent bone loss in early breast cancer patients [10]. Furthermore, ZOL also has antitumor and antimetastatic properties. The previous meta-analysis [11] suggested that the use of ZOL was associated with a statistically significant lower risk for disease recurrence. In addition, ZOL has several poten- tial advantages compared to the oral bisphosphonates, including good bioavailability, gastrointestinal tolerance, and adequate compliance [12]. Thus, less adverse effects, such as gastrointestinal disorders and vascular disorders, © 2011 Zhou et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.