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Network meta-analysis of bisphosphonates in the treatment of bone metastases from breast cancer 

Li-Wen Zhang, An Huang, Hong-Fang Ma, and Jun Shen

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Volume 64 (2026) p. 470 - 481

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 64 – No. 9/2026 (470-481)

Network meta-analysis of bisphosphonates in the treatment of bone metastases from breast cancer 

Li-Wen Zhang¹*, An Huang²*, Hong-Fang Ma³, and Jun Shen¹

¹Department of Surgical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou City, ²Department of Breast Surgery, Maternal and Child Health Hospital, Yiwu City, and ³Department of Plastic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
Objective: Through a network meta-analysis, this study aimed to systematically evaluate the efficacy and safety of bisphosphonates in reducing skeletal-related events in patients with bone metastases from breast cancer, providing clinical guidance for treatment selection.
Materials and methods: Randomized controlled trials (RCTs) on bisphosphonate therapy for bone metastases in breast cancer were retrieved from PubMed, Cochrane, and Embase databases from inception to January 2025. Statistical analyses were performed using Stata software.
Results: 22 studies involving 14,934 patients were included. The bisphosphonates evaluated were pamidronate, zoledronate, clodronate, and ibandronate. Regarding the reduction of pathological fractures, the efficacy ranking was clodronate > ibandronate > pamidronate > zoledronate. Significant differences were found between clodronate and pamidronate (OR = –1.41, 95% CI: –2.78 to –0.04) and between clodronate and zoledronate (OR = –1.44, 95% CI: –2.85 to –0.04). For hypercalcemia reduction, zoledronate was more effective than clodronate and pamidronate, though differences were not statistically significant (p > 0.05). In terms of safety, ibandronate showed fewer adverse reactions than clodronate and zoledronate, with a significant difference between ibandronate and zoledronate (OR = –1.14, 95% CI: –1.99 to –0.28).
Conclusion: Clodronate was most effective in reducing pathological fractures, zoledronate was superior in controlling hypercalcemia, and ibandronate demonstrated the best safety profile. Further clinical studies are warranted to clarify the comparative advantages of each bisphosphonate and support individualized treatment decisions.

*Both authors contributed equally to this study.Correspondence to:
Jun Shen, MD
Department of Surgical Oncology
Sir Run Run Shaw Hospital
Zhejiang University School of Medicine
No. 3. East road of Qingchun
Hangzhou 310016, Zhejiang Province, China
Email: [email protected]

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