Malignant bone pain: pathophysiology and treatment.

The presence of bone metastases predicts the presence of pain and is the most common cause of cancer-related pain. Although bone metastases do not involve vital organs, they may determine deleterious effects in patients with prolonged survival. Bone fractures, hypercalcaemia, neurologic deficits and reduced activity associated with bone metastases result in an overall compromise in the patient's quality of life. A metastasis is a consequence of a cascade of events including a progressive growth at the primary site, vascularization phase, invasion, detachment, embolization, survival in the circulation, arrest at the site of a metastasis, extravasion, evasion of host defense and progressive growth. Once cancer cells establish in the bone, the normal process of bone turnover is disturbed. The different mechanisms responsible for osteoclast activation correspond to typical radiologic features showing lytic, sclerotic or mixed metastases, according to the primary tumor. The release of chemical mediators, the increased pressure within the bone, microfractures, the stretching of periosteum, reactive muscle spasm, nerve root infiltration and compression of nerves by the collapse of vertebrae are the possible mechanisms of malignant bone pain. Pain is often disproportionate to the size or degree of bone involvement. A comprehensive assessment including a trusting relationship with the patient, taking a careful history of the pain complaint, the characteristics of the pain, the evaluation of the psychological status of the patient, neurological examination, the reviewing of diagnostic studies and laboratory findings, and individualization of the therapeutic approach, should precede any treatment. Radiotherapy is the cornerstone of the treatment. Low doses given in a single session are safe and effective, and reduce distress and inconvenience associated with repeated session. Radioisotopes are more imprecise in delivering specific doses of radiation, but have less toxicity and easy administration as well as effectiveness in subclinical sites of metastases, although storage, dispensing and administration should be under strict control. Chemotherapy and endocrine therapy are difficult to measure in terms of pain relief. Prophylactic fixation surgery can lead to improved survival and quality of life of patients with bone metastases. Surgical treatment should be undertaken when fracture occurs. Careful selection of patients for surgical spinal decompression is required. The potential benefits of surgical interventions have to be tempered with patient survival. The use of analgesics according to the WHO ladder is recommended. There is no clear evidence that non-steroidal anti-inflammatory drugs (NSAIDs) have a specific efficacy in malignant bone pain. The difficulty with incident pain is not a lack of response to systemic opioids, but rather that the doses required to control the incidental pain produce unacceptable side-effects at rest. Alternative measures are often required. The inhibition of bone resorption and hypercalcaemia can be reduced by the use of bisphosphonates. This class of drugs potentiate the effects of analgesics in improving metastatic bone pain. Invasive techniques are rarely indicated, but may provide analgesia in the treatment of pain resistant to the other modalities. Neural blockade should never be used as the sole modality for malignant bone pain, but should be considered as a helpful in specific pain situations. Careful appraisal and the application of a correct approach should enable the patient with bone metastases to obtain an acceptable pain relief despite the advanced nature of their malignant disease.