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  • Review Article
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Effect of bisphosphonates on pain and quality of life in patients with bone metastases

Abstract

Bone is the most common organ for tumor metastasis, especially in patients with cancers of the breast or prostate. Bone metastases disrupt skeletal metabolism and result in considerable skeletal morbidity, including intractable, chronic bone pain, hypercalcemia of malignancy, pathologic fracture and spinal-cord compression. In addition to the chronic pain caused by bone metastases, skeletal-related events (SREs) such as pathologic fractures and spinal-cord compression can result in acute increases in pain. These effects can severely impair mobility and contribute to a general decrease in quality of life. Palliative options to treat bone metastases include radiotherapy, analgesics, surgery and bisphosphonates. These drugs bind to the surface of the bone and impair osteoclast-mediated bone resorption, and reduce the tumor-associated osteolysis that is initiated by the development of skeletal metastases. In addition to preventing SREs, bisphosphonates can palliate bone pain caused by a variety of solid tumors. This Review summarizes the clinical trial data of bisphosphonates for the prevention of SREs and the palliation of bone pain. Among these agents, nitrogen-containing bisphosphonates are recognized as the most effective, and zoledronic acid has demonstrated the broadest clinical utility.

Key Points

  • Bone metastases disrupt skeletal metabolism, which can result in disabling and potentially life-limiting skeletal-related events including pathologic fracture, spinal-cord compression, the requirement for surgery or radiation therapy to bone, and hypercalcemia of malignancy

  • Bone metastases are the most frequent source of severe pain in patients with advanced cancers

  • Skeletal-related events can reduce the functional independence of patients and undermine their quality of life

  • Through the inhibition of bone resorption, bisphosphonates have demonstrated efficacy in delaying the onset and reducing the risk of skeletal-related events, as well as palliating bone pain

  • Zoledronic acid is the only bisphosphonate that has demonstrated efficacy in reducing the risk of skeletal-related events in multiple cancer types, and in the long-term palliation of bone pain in patients with breast or prostate cancer

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Figure 1: Skeletal complications reduce quality of life in patients with bone metastases from prostate cancer.
Figure 2: Zoledronic acid improves quality of life measures in patients with bone metastases from breast cancer.
Figure 3: Mean change from baseline in Brief Pain Inventory composite pain scores by treatment group and time on study.

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Robert E. Coleman, Peter I. Croucher, … Luis Costa

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Acknowledgements

Funding for medical editorial assistance was provided by Novartis Pharmaceuticals Corporation. We thank Carol Sledz, PhD, ProEd Communications, Inc., for her editorial assistance with this manuscript.

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Correspondence to Luis Costa.

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L Costa has declared associations with the following companies: Amgen, Novartis and Roche. PP Major has declared associations with the following companies: Amgen and Novartis. See the article online for full details of the relationships.

Supplementary information

Supplementary Table 2

Summary of trials with nitrogen-containing bisphosphonates* (DOC 99 kb)

Supplementary Table 3

Summary of Trials With Zoledronic Acid (4 mg) (DOC 99 kb)

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Costa, L., Major, P. Effect of bisphosphonates on pain and quality of life in patients with bone metastases. Nat Rev Clin Oncol 6, 163–174 (2009). https://doi.org/10.1038/ncponc1323

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