Abstract
BackgroundZoledronic 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.MethodsRelevant randomized clinical trials were selected by searching the electronic database PubMed, and a meta-analysis was conducted.ResultsFour 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).ConclusionsOur 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.
Highlights
More patients with early breast cancer have been diagnosed with the development of screening techniques [1]
Randomized clinical trials were included if they met the following criteria: (1) Zoledronic acid (ZOL) used in breast cancer patients in adjuvant setting; (2) ZOL used with a control group receiving no treatment or placebo, or upfront ZOL versus delayed ZOL; (3) enough published data for estimated a risk ratio (RR) with 95% confidence interval (CI)
Compared to patients without ZOL treatment, patients treated with ZOL had a significantly higher risk of arthralgia (RR: 1.162, 95% CI: 1.096-1.232, P = 0.466 for heterogeneity) (Figure 1)
Summary
More patients with early breast cancer have been diagnosed 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 [2,3,4]. Both adjuvant chemotherapy and endocrine therapy cause bone loss to these patients. Zoledronic acid (ZOL) can prevent bone loss in early breast cancer patients [10]. Previous randomized clinical trials [14,15,16,17] showed that musculoskeletal disorders occurred in more than 20% patients treated with ZOL and in more than 10% patients without ZOL treatment. Zoledronic acid (ZOL) is widely used for preventing bone loss in early breast cancer patients. No precise estimation of musculoskeletal disorders has been made
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