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9.7.5 Acute cancer pain due to bone involvement

Primary cancers in bone and bone metastases are an important and common cause of acute
and chronic cancer pain. Whereas some bone metastases are painless, others are associated
with persistent pain with acute exacerbations precipitated by movement or mobilisation
(incident pain), pathological fractures or compression of nerves or spinal cord. Hypercalcaemia
may be a complication of bone malignancy that further heightens the pain experience.
In addition to pharmacological therapeutic options including opioids, NSAIDs, bisphosphonates
and possibly calcitonin, patients require assessment to determine whether radiation therapy,
tumour‐targeting cytotoxic or hormonal therapy, or, in the case of imminent or actual
pathological fracture or cord compression, surgical intervention may be of benefit.
Radiotherapy
Radiotherapy effectively reduces malignant bone pain and may reduce complications of bone
cancer. At 1 month after radiation therapy around 25% patients experience complete pain
relief, and 41% experience 50% pain relief (NNT for complete pain relief at one month 4.2;
95% CI 3.7 to 4.9) (McQuay et al, 2000 Level I).
One area of controversy has been the optimal fractionation schedule for radiotherapy.
A systematic review and meta‐analysis of single‐fraction versus multi‐fraction radiation
therapy considered 11 trials (3435 patients) (Sze et al, 2004 Level I). Single‐fraction treatment
was as effective as multi‐fraction radiation treatment in terms of overall pain response rates
(60% vs 59%; OR 1.03; 95% CI 0.89 to 1.19), and complete pain relief (34% vs 32%; OR 1.11;
95% CI 0.94 to 0.13); however, the definition of a pain response (reduction by at least one
category in a 4‐ or 5‐point scale), and the time of pain assessment varied between studies.
Despite equivalent pain relief outcomes, the incidence of retreatment and the pathological
fracture rate were higher after single‐dose therapy. The optimal treatment regimen must
consider the clinical scenario and patient’s life expectancy (Sze et al, 2004).
For patients with widespread bone metastases, radioisotopes had similar analgesic efficacy
but were associated with increased risk of leukocytopenia and thrombocytopenia (McQuay et
al, 2000 Level I).
Bisphosphonates
Evidence supports the use of bisphosphonates where analgesics and radiotherapy have
provided inadequate pain relief (Wong & Wiffen, 2002 Level I). In multiple myeloma, CHAPTER 9
bisphosphonates lowered the risk of vertebral pathological fracture (OR 0.59; 95% CI 0.45 to
0.78) and decreased pain (OR 0.59; 95% CI 0.46 to 0.76) (Djulbegovic et al, 2002 Level I). Similarly,
in breast cancer, bisphosphonates reduce skeletal events (median reduction 28%, range 14%
to 48%); pain was significantly better after bisphosphonates in five of eleven studies (Pavlakis et
al, 2005 Level I). Bisphosphonates for prostatic bone metastases improved pain, but not
analgesic consumption (Yuen et al, 2006 Level I).
A prospective study indicated the incidence of osteonecrosis of the jaw after bisphosphonates
to be 6.7% (17 of 252 patients); incidence may increase with time of exposure, a history of
dental exposure and type of bisphosphonate (Bamias et al, 2005 Level IV).
Although calcitonin is used to reduce metastatic bone pain and skeletal events, there is limited
evidence to support the practice. Of only two RCTS considered in a recent systematic review,
calcitonin provided no analgesic benefit relative to placebo in one trial, a non‐significant
benefit in the other, and, overall, was associated with a higher rate of adverse events
(Martinez‐Zapata et al, 2006 Level I).

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