Management is multimodal: analgesia, bone targeted drugs, radiotherapy, surgery and treatment of the cancer.
Analgesia (stepwise, titrated to pain).
- Paracetamol: paracetamol 1 g orally every 6 hours; maximum 4 g daily (3 g daily when weight is under 50 kg, in chronic malnutrition or in hepatic impairment); monitoring: pain score, liver tests with long term use, total daily dose from all sources; adjustment: lengthen the interval to 8 hours when creatinine clearance is under 30 mL/min, reduce the dose with alcohol excess or liver disease, avoid duplicate combination products
- Opioid for moderate to severe pain: morphine sulfate immediate release 5 mg orally every 4 hours (2.5 mg in older adults) with 5 to 10 mg as needed for breakthrough pain (about one sixth of the daily dose), converted to modified release morphine every 12 hours at the same total daily dose once pain is stable; maximum: no fixed ceiling, titrate to effect and review the plan above 120 mg daily oral morphine equivalent; monitoring: pain score, sedation, respiratory rate, constipation, nausea, myoclonus; adjustment: start at 2.5 mg every 4 hours and use an alternative opioid when creatinine clearance is under 30 mL/min, co-prescribe senna 7.5 to 15 mg orally at night, reduce the new opioid dose by 25% to 50% on changing opioid because of incomplete cross-tolerance
- Neuropathic pain components: gabapentin 300 mg orally at night on day 1, 300 mg twice daily on day 2 and 300 mg three times daily on day 3, then titrated every 3 to 7 days to 900 to 1800 mg daily in 3 divided doses; maximum 3600 mg daily; monitoring: sedation, dizziness, oedema, mood, falls, respiratory depression with opioids; adjustment: creatinine clearance 30 to 59 mL/min 400 to 1400 mg daily in 2 divided doses, 15 to 29 mL/min 200 to 700 mg once daily, under 15 mL/min 100 to 300 mg once daily, taper over at least 1 week when stopping
- NSAIDs may be used short term with gastric protection and renal monitoring.
Bone modifying agents (reduce skeletal related events).
- Bisphosphonate: zoledronic acid 4 mg IV over at least 15 minutes every 4 weeks for the first 3 to 6 months and then every 12 weeks for up to 2 years (longer when benefit continues), with calcium 500 mg and vitamin D 400 to 800 units orally daily; maximum 4 mg in one dose; monitoring: creatinine before each dose, calcium, phosphate, dental review before starting, jaw and thigh pain, acute phase reaction; adjustment: reduce the dose to about 3.0 to 3.5 mg when creatinine clearance is 30 to 60 mL/min, avoid when creatinine clearance is under 30 mL/min, withhold for osteonecrosis of the jaw or pending dental surgery
- Denosumab (alternative, preferred in renal impairment): denosumab 120 mg subcutaneously every 4 weeks (every 12 weeks may be used after 1 year in selected patients), with calcium 500 mg and vitamin D 400 to 800 units orally daily; maximum 120 mg in one dose; monitoring: calcium before each dose (severe hypocalcaemia is a risk, especially with renal impairment), dental review before starting, jaw and thigh pain, rebound vertebral fractures if stopped; adjustment: no renal dose adjustment but monitor calcium closely when creatinine clearance is under 30 mL/min, correct low vitamin D before starting, do not stop abruptly (give a bisphosphonate after the last dose)
- Dental assessment before starting, and avoid invasive dental work during therapy.
Radiotherapy. A single fraction of 8 Gy gives pain relief in 60% to 70% (a second course can be repeated after 4 weeks for poor response). Multiple fractions (20 Gy in 5 or 30 Gy in 10) are used for neuropathic pain, soft tissue extension, or after surgery. Stereotactic body radiotherapy gives better durable control for oligometastatic disease.
- Pain flare prophylaxis: dexamethasone 8 mg orally on the day of radiotherapy and daily for 4 days afterwards to prevent pain flare after a single palliative fraction; maximum 8 mg daily; monitoring: glucose, mood and sleep, gastric symptoms; adjustment: give gastric protection, adjust diabetes treatment, omit if the patient already takes a higher steroid dose
Radionuclide therapy. For widespread painful sclerotic metastases:
- Radium-223: radium-223 dichloride 55 kBq/kg IV every 4 weeks for 6 injections, for castration resistant prostate cancer with symptomatic bone metastases and no visceral metastases; maximum 6 injections; monitoring: FBC before each dose (neutrophils 1.0 x 10^9/L or more and platelets 50 x 10^9/L or more are needed), creatinine, diarrhoea, fracture risk; adjustment: delay for neutrophils or platelets under these limits, avoid with abiraterone and prednisolone, give a bone protective drug in parallel, follow radiation precautions for 1 week and use contraception for 6 months
Surgery and interventional therapy. Prophylactic fixation of impending long bone fractures, intramedullary nailing or joint replacement for established fractures (followed by radiotherapy), cement augmentation of vertebral lesions, and ablation (cryoablation, radiofrequency) for painful oligometastases.
Systemic cancer treatment. Hormone therapy, chemotherapy and targeted therapy chosen for the primary cancer, with response shown by clinical and radiological assessment.
Monitoring. Pain scores at each visit, calcium and renal function every 1 to 3 months on bone targeted drugs, and imaging every 3 to 6 months in line with systemic therapy.
Referral and escalation.
- Urgent orthopaedic review for impending or established fracture.
- Same day assessment for neurological symptoms, and emergency admission for hypercalcaemia.
Special groups.
- Renal impairment: reduce zoledronic acid or prefer denosumab, and avoid NSAIDs.
- Prostate cancer: androgen deprivation therapy increases bone loss, so add bone protection.
- Frail or end-of-life patients: single fraction radiotherapy and symptom control.
