What are the treatment options for pain associated with bone metastases (bone mets)?

From the Guidelines

Pain associated with bone metastases can be effectively managed with a multimodal approach, prioritizing external beam radiation therapy (EBRT) as the treatment of choice for localized moderate to severe bone pain, alongside bisphosphonates, denosumab, and radium-223 dichloride for longer-term management. For immediate relief, NSAIDs like ibuprofen (400-800mg every 6-8 hours) or naproxen (500mg twice daily) can be used alongside opioids such as morphine (starting at 5-15mg every 4 hours as needed), oxycodone (5-10mg every 4-6 hours), or fentanyl patches (25-100mcg/hour, changed every 72 hours) for more severe pain 1. Adjuvant medications including gabapentin (starting at 300mg daily, increasing to 300-1200mg three times daily) or pregabalin (starting at 75mg twice daily) can help with neuropathic components.

Key Treatment Options

• External beam radiation therapy (EBRT) is recommended for localized moderate to severe bone pain due to bone metastases, with a single 8-Gy fraction being the preferred dose 1.
• Bisphosphonates like zoledronic acid (4mg IV every 3-4 weeks) or denosumab (120mg subcutaneously every 4 weeks) can reduce pain by inhibiting bone destruction, and should be initiated at diagnosis of bone metastasis and considered throughout the course of the disease 1.
• Radium-223 dichloride is a valuable treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC) and symptomatic multiple skeletal metastases as the dominant site of disease 1.

Additional Considerations

• Prophylactic antiemetics and dexamethasone are recommended to minimize nausea/vomiting and pain flare 1.
• Structurally significant lesions in a long bone should be evaluated by an orthopaedic surgeon to provide advice on suitability for surgery, and prophylactic surgery for impending fracture is generally preferred to fixation after fracture 1.
• Patients should have a dental evaluation and, when feasible, complete invasive dental treatments before initiating a bone-modifying agent (BMA) 1.
• Correction of vitamin D deficiency and vitamin D supplementation with adequate intake of calcium throughout treatment to maintain normal serum calcium are recommended 1.

From the FDA Drug Label

1.2 Multiple Myeloma and Bone Metastases of Solid Tumors Zoledronic acid injection is indicated for the treatment of patients with multiple myeloma and patients with documented bone metastases from solid tumors, in conjunction with standard antineoplastic therapy.

• The treatment option for pain associated with bone metastases (bone mets) is Zoledronic acid injection, which is used in conjunction with standard antineoplastic therapy.
• The recommended dose of zoledronic acid injection for patients with bone metastases from solid tumors is 4 mg infused over no less than 15 minutes every 3 to 4 weeks for patients with creatinine clearance (CrCl) greater than 60 mL/min 2.

From the Research

Treatment Options for Pain Associated with Bone Metastases

The treatment options for pain associated with bone metastases include:

• Pharmacologic pain management, such as morphine, hydromorphone, fentanyl, or oxycodone, which are considered first-line therapy 3
• Non-steroid-anti-inflammatory-drugs, such as metamizole, as an alternative option 3
• Bisphosphonates, which have been shown to reduce skeletal complications in patients with bone metastases from breast cancer, with zoledronic acid demonstrating the broadest clinical activity 4
• Glucocorticoids, which are an important treatment option in advanced cancer stages 3
• Coanalgetics, such as pregabalin, for neuropathic pain 3
• Radiotherapy, which is the gold standard for pain reduction in localized bone pain, and radionuclids, such as samarium, for diffuse bone pain 3
• Interventional treatments, such as opioid therapy, radium-223, denosumab, and bisphosphonate therapy, which may be considered for patients who fail oral or transdermal medication options 5
• Pamidronate, which has been shown to have curative effects on pain induced by bone metastasis, with a higher dosage (120 mg) being more effective than a lower dosage (90 mg) 6

Specific Treatment Approaches

For breakthrough pain episodes, the provision of an on-demand opioid, such as immediate-release morphine or rapid-onset fentanyl, is mandatory 3 For patients with difficult pain syndromes, methadone may be considered, but its use should be restricted due to its complex pharmacology 3 For patients with cancer pain syndromes who are refractory to pharmacologic management and radiotherapy, invasive measures, such as neuroaxial blockage, may be an important option 3

Multidisciplinary Approach

Cancer pain management in incurable cancer is best provided as part of a multiprofessional palliative care approach, addressing all other domains of suffering, including psychosocial, spiritual, and existential aspects 3, 7