Increased bone pain

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2 studies · 1 recommendation

Last updated: February 25, 2026

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Progressive bone pain escalation signals impending skeletal-related events requiring prompt evaluation

Two cohort studies analyzing a pooled population of 5,543 patients with solid tumors and bone metastases across three phase 3 trials demonstrated that increasing bone pain serves as a critical warning sign. The proportion of patients experiencing moderate to severe pain progressively increased during the 6 months preceding skeletal-related events (SREs), including pathological fracture, spinal cord compression, and need for radiation or surgery to bone. All SRE types were significantly associated with increased risk of progression to moderate/severe pain and strong opioid use. Patients without SREs maintained relatively stable pain levels over time. Worsening pain also correlated with greater interference in physical function, emotional well-being, and daily activities. Any new or escalating bone pain in patients with known bone metastases warrants timely clinical assessment to detect and potentially prevent these complications.

Evidence

Pain and analgesic use associated with skeletal-related events in patients with advanced cancer and bone metastases

Authors: A Hussain, A Lipton, A Lipton, Ada Braun, Alison Stopeck, AM Abdulhalim, Arun Balakumaran, AT Stopeck, Blair Egerdie, C Nieder, Charles Cleeland, CS Cleeland, CS Cleeland, CS Cleeland, CS Cleeland, D Henry, Danail Damyanov, DF Cella, DH Henry, Donald L. Patrick, E Chow, F Saad, Felipe Salvador Palazzo, G Oster, Gavin Marx, GD Roodman, GR Mundy, GV Scagliotti, JA Ford, Janet Brown, Jean-Jacques Body, K Cetin, K Fizazi, K Fizazi, K Lemay, K Webster, KC Chung, L Costa, L Costa, L Costa, Lesley Fallowfield, LS Rosen, M Maltoni, M Norgaard, M Yong, MR Smith, N Sathiakumar, N Sathiakumar, R Moos von, R Moos von, RE Coleman, RE Coleman, Roger von Moos, S Vadhan-Raj, Yi Qian, Ying Zhou

Published: January 1, 2015

In a pooled cohort of 5,543 patients with solid tumors and bone metastases across three phase 3 trials, the proportion of patients experiencing moderate/severe pain progressively increased during the 6 months preceding a skeletal-related event (SRE) and remained elevated afterward. Regression analysis showed all SRE types — pathological fracture, radiation to bone, surgery to bone, and spinal cord compression — were significantly associated with increased risk of progression to moderate/severe pain. Pain interference with physical function was significantly greater across all SRE types. In contrast, patients without SREs maintained relatively consistent pain levels over time.

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Pain and analgesic use associated with skeletal-related events in patients with advanced cancer and bone metastases

Authors: Roger von Moos, Jean-Jacques Body, Blair Egerdie, Alison Stopeck, Janet Brown, Lesley Fallowfield, Donald L. Patrick, Charles Cleeland, Danail Damyanov, Felipe Salvador Palazzo, Gavin Marx, Ying Zhou, Ada Braun, Arun Balakumaran, Yi Qian, RE Coleman, RE Coleman, R Moos von, S Vadhan-Raj, GR Mundy, GD Roodman, JA Ford, A Lipton, F Saad, LS Rosen, L Costa, CS Cleeland, K Lemay, CS Cleeland, M Maltoni, L Costa, CS Cleeland, R Moos von, L Costa, AT Stopeck, K Fizazi, DH Henry, D Henry, GV Scagliotti, A Lipton, CS Cleeland, KC Chung, DF Cella, K Webster, N Sathiakumar, N Sathiakumar, K Fizazi, M Yong, M Norgaard, K Cetin, C Nieder, E Chow, MR Smith, A Hussain, AM Abdulhalim, G Oster

Published: September 6, 2005

In a pooled cohort of 5,543 patients with solid tumors and bone metastases from three phase 3 trials, the proportion of patients experiencing moderate to severe pain and requiring strong opioids progressively increased during the 6 months preceding a skeletal-related event (SRE), while pain levels remained relatively stable over time in patients who did not experience an SRE. Regression analysis demonstrated that all SRE types—pathological fracture, radiation to bone, surgery to bone, and spinal cord compression—were significantly associated with increased risk of progression to moderate/severe pain and strong opioid use. Pathological fracture, radiation to bone, and spinal cord compression were also significantly associated with greater pain interference with overall daily functioning, emotional well-being, and physical function.

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