Denosumab versus bisphosphonates for the treatment of bone metastases from solid tumors: a systematic review

Eur J Health Econ. 2019 Jun;20(4):487-499. doi: 10.1007/s10198-018-1011-1. Epub 2018 Oct 31.


Background: Bone metastases are highly prevalent in breast, prostate, lung and colon cancers. Their symptoms negatively affect quality of life and functionality and optimal management can mitigate these problems. There are two different targeted agents to treat them: bisphosphonates (pamidronate and zoledronic acid) and the monoclonal antibody denosumab. Estimates of cost-effectiveness are still mixed.

Objective: To conduct a systematic review of economic studies that compares these two options.

Method: Literature search comprised eight databases and keywords for bone metastases, bisphosphonates, denosumab, and economic studies were used. Data were extracted regarding their methodologic characteristics and cost-effectiveness analyses. All studies were evaluated regarding to its methodological quality.

Results: A total of 263 unique studies were retrieved and six met inclusion criteria. All studies were based on clinical trials and other existing literature data, and they had high methodological quality. Most found unfavorable cost-effectiveness for denosumab compared with zoledronic acid, with adjusted ICERS that ranged from $4638-87,354 per SRE avoided and from US$57,274-4.81 M. per QALY gained, which varied widely according to type of tumor, time horizon, among others. Results were sensitive to drug costs, time to first skeletal-related event (SRE), time horizon, and utility.

Conclusions: Denosumab had unfavorable cost-effectiveness compared with zoledronic acid in most of the included studies. New economic studies based on real-world data and longer time horizons comparing these therapeutic options are needed.

Keywords: Cost-effectiveness analyses; Denosumab; Diphosphonates; Economics; Neoplasms; Pharmaceutical.

Publication types

  • Comparative Study
  • Systematic Review

MeSH terms

  • Bone Density Conservation Agents / economics
  • Bone Density Conservation Agents / therapeutic use*
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / economics
  • Bone Neoplasms / secondary*
  • Cost-Benefit Analysis
  • Denosumab / economics
  • Denosumab / therapeutic use*
  • Diphosphonates / economics
  • Diphosphonates / therapeutic use*
  • Health Care Costs
  • Humans
  • Pamidronate / economics
  • Pamidronate / therapeutic use
  • Zoledronic Acid / economics
  • Zoledronic Acid / therapeutic use


  • Bone Density Conservation Agents
  • Diphosphonates
  • Denosumab
  • Zoledronic Acid
  • Pamidronate