Zhu, M., Liang, R., Pan, L.H., Huang, B., Qian, W., Zhong, J.H., . . . Li, C.L. (2013). Zoledronate for metastatic bone disease and pain: A meta-analysis of randomized clinical trials. Pain Medicine, 14, 257–264.

STUDY PURPOSE: To determine the efficacy and safety of zoledronate in treating pain related to metastatic bone disease

TYPE OF STUDY: Meta-analysis and systematic review

DATABASES USED: PubMed, EMBASE, and the Cochrane Library up to October 2011

KEYWORDS: Zoledronic acid and bone metastasis, and these two terms in combination with zoledronate and bone pain

INCLUSION CRITERIA: Patient had at least one site of bone metastasis; Eastern Cooperative Oncology Group performance status of 2 or less; the study evaluated the effects of at least one type of zoledronate on skeletal-related events (SREs) or bone pain in patients with any type of metastatic bone disease; study was a placebo-controlled RCT; and study reported Brief Pain Inventory (BPI) scores at all time points examined

EXCLUSION CRITERIA: None listed

TOTAL REFERENCES RETRIEVED = 150 studies

EVALUATION METHOD AND COMMENTS ON LITERATURE USED: Two reviewers used the Jadad composite scale to score the methodologic quality of the studies for the studies that were included in the analysis

• FINAL NUMBER STUDIES INCLUDED = 12
• SAMPLE RANGE ACROSS STUDIES, TOTAL PATIENTS INCLUDED IN REVIEW: 4,450 patients (range of sample size = 20–440)
• KEY SAMPLE CHARACTERISTICS: No key sample characteristics listed

• PHASE OF CARE: Multiple phases of care     
• APPLICATIONS: Palliative care

Ten of the 12 RCTs provided data on SREs. Patients receiving zoledronate had a significantly lower rate of SREs than the placebo group (RR 0.75, 95% Cl 0.69–0.81, p < 0.001). Six studies that reported BPI scores found the zoledronate group to have significantly reduced scores at three months (WMD -0.53, 95% Cl -0.72–-0.35, p < 0.001), 12 months (WMD 0.39, 95% Cl -0.62–-0.16, p < 0.001), and 24 months (WMD -0.48, 95% Cl -0.77–-0.19, p < 0.001). The incidence of pyrexia (RR 1.43, 95% Cl 1.12–1.70, p < 0.001), fatigue (RR 1.26. 95% Cl 1.11–1.43, p < 0.001), and anemia (RR 1.33. 95% Cl 1.14–1.55, p < 0.001) was higher in the zoledronate group than the placebo group for the pooled results from five to six studies.

Zoledronate was more effective in preventing SREs and bone pain than a placebo for up to 24 months in patients with metastatic bone disease. Adverse effects were a class effect related to bisphosphonates; thus, they were not specific to zoledronate. Renal effects, which are associated with this classification of drugs, were not found to be a significant adverse event among patients in these studies receiving 4 mg zoledronate in a 15-minute infusion.

A limitation was that 50% of the studies (n = 6) included in the meta-analysis received a low quality score of 2 or less. However, the authors did report that a sensitivity analysis of the pooled results was unchanged with the removal of these studies’ data from the analysis.

Nurses need to be knowledgeable about the potential adverse effects of zoledronate (more common: pyrexia, fatigue, and anemia; less common: nausea and emesis), which are the same adverse effects of other bisphosphonates. In addition, to prevent renal toxicity, the dose should not be more than 4 mg and should be delivered IV in a 100 ml solution over 15 minutes. Lastly, nurses should be aware that patients can safely receive this drug every three weeks over a period of 24 months with continued pain relief and prevention of SREs.