Pain outcomes in patients with bone metastases from advanced cancer: assessment and management with bone-targeting agents

Abstract

Bone metastases in advanced cancer frequently cause painful complications that impair patient physical activity and negatively affect quality of life. Pain is often underreported and poorly managed in these patients. The most commonly used pain assessment instruments are visual analogue scales, a single-item measure, and the Brief Pain Inventory Questionnaire-Short Form. The World Health Organization analgesic ladder and the Analgesic Quantification Algorithm are used to evaluate analgesic use. Bone-targeting agents, such as denosumab or bisphosphonates, prevent skeletal complications (i.e., radiation to bone, pathologic fractures, surgery to bone, and spinal cord compression) and can also improve pain outcomes in patients with metastatic bone disease. We have reviewed pain outcomes and analgesic use and reported pain data from an integrated analysis of randomized controlled studies of denosumab versus the bisphosphonate zoledronic acid (ZA) in patients with bone metastases from advanced solid tumors. Intravenous bisphosphonates improved pain outcomes in patients with bone metastases from solid tumors. Compared with ZA, denosumab further prevented pain worsening and delayed the need for treatment with strong opioids. In patients with no or mild pain at baseline, denosumab reduced the risk of increasing pain severity and delayed pain worsening along with the time to increased pain interference compared with ZA, suggesting that use of denosumab (with appropriate calcium and vitamin D supplementation) before patients develop bone pain may improve outcomes. These data also support the use of validated pain assessments to optimize treatment and reduce the burden of pain associated with metastatic bone disease.

Cost-effectiveness of denosumab for the prevention of skeletal-related events in patients with solid tumors and bone metastases in the United States

“…Patients with solid tumors and bone metastases are at an increased risk for bone complications (also known as skeletal-related events [SREs]): rates of bone complications are $40% (19 months) in patients with prostate cancer and 54% (24 months) in patients with breast cancer 3,4 . Bone complications are associated with decreased survival and considerable morbidity, pain, impaired mobility, and decreased quality-of-life 3,[5][6][7][8][9][10] . Healthcare costs for patients with bone complications are substantial 3,[11][12][13][14][15][16] .…”

Nonresponsiveness and Susceptibility of Opioid Side Effects Related to Cancer Patients’ Clinical Characteristics: A Post‐Hoc Analysis

“…Up to now, this topic has been only partially investigated in the literature. It has been described that cancer progression, the site of primary tumor, the presence of metastases, and negative psychological conditions could influence the pain experienced . Also, the features of pain, as in cases of neuropathic and breakthrough pain (BTP), often have been related to worse experienced pain and a poorer response to analgesics .…”

Decreased sensory nerve excitation and bone pain associated with mouse Lewis lung cancer in TRPV1-deficient mice

“…Bone pain is induced as a consequence of sensitization and excitation of sensory nerves (SNs) innervating bone by mechanical, chemical and/or thermal noxious stimuli that are produced under complex interactions among cancer cells, bone cells (osteoclasts, osteoblasts and osteocytes), bone marrow stromal cells and immune cells (11,12). Although the precise mechanism by which these noxious stimuli excite SNs and evoke bone pain remains unclear, clinical observations that bone-targeting agents including bisphosphonates and denosumab significantly relieve bone pain in cancer patients with bone metastases (13) indicate a critical role of osteoclasts in the pathophysiology of cancer-induced bone pain. Osteoclasts, which play a central role in the development and progression of bone metastasis by establishing the vicious cycle with metastatic cancer cells (1,14,15), destroy bone by releasing protons via the plasma membrane a3 isoform vacuolar proton pump (16), thereby creating acidic microenvironments in bone metastases.…”