Clinical, Economic and Humanistic Burdens of Skeletal-related Events Associated with Bone Metastases

John A Carter; Xiang Ji; Marc F Botteman


Expert Rev Pharmacoeconomics Outcomes Res. 2013;13(4):469-482. 

In This Article

Abstract and Introduction


Despite effective skeletal-related event (SRE)-limiting therapies such as zoledronic acid and denosumab, SREs continue to place a meaningful burden on patients, providers and payers. However, studies of SRE-related effects on clinical (i.e., survival), economic (i.e., cost per event) and humanistic (i.e., quality of life) outcomes often report results in a composite manner and frequently do not differentiate the effects by SRE-type (i.e., bone radiation, bone surgery, hypercalcemia, pathological fracture and spinal cord compression). Nevertheless, understanding the differential burdens of individual SRE types, which vary in severity and duration of effect, is an important consideration – particularly in pharmacoeconomic evaluations of SRE-limiting therapies. In this review of the clinical, economic and humanistic SRE burden, it was found that SRE types can be differentiated by these outcomes, although economic outcomes are far more frequently reported than clinical or humanistic.


Bisphosphonates have been used to prevent skeletal-related events (SREs) associated with bone metastases.[1] In particular, the efficacy of zoledronic acid in reducing SREs in patients with metastatic bone disease has been established in many solid tumor types.[2–4] Recently, the US FDA approved denosumab,[101] a monoclonal antibody, for the prevention of SREs in breast cancer and castrate-resistant prostate cancer patients with metastatic bone disease; two indications for which zoledronic acid has been the most widely approved and most commonly used treatment in the USA and Europe. Therefore, it is likely that healthcare decision-makers and clinicians will require analyses that differentiate the two agents with respect to clinical, humanistic and economic outcomes.

In assessing the benefits of SRE reduction, it is essential to recognize that not all SREs (i.e., hypercalcemia, bone fracture, spinal cord compression, radiotherapy and bone surgery) impact the disease burden equally. However, these effects are often reported in a composite manner. That is, studies often refer to the effect of SREs averaged across SRE types without reporting the effects per event type. The purpose of this study was to review the published literature to understand the different clinical, economic and quality-of-life burdens each SRE type imposes on patients.