Bisphosphonates for bone pain
Bisphosphonates are used for treatment or prophylaxis of cancer-related bone pain, an especially useful modality in addition to other analgesics like NSAIDs or opiates for cancer related bone pain.
The mechanism of action is thought to be related to inhibition of bone resorption. All bisphosphonates inhibit osteoclast activity and some also inhibit the maturation of mononuclear precursors into active osteoclasts.

Analgesic therapy
Breast cancer and multiple myeloma have been found to be the most responsive tumors to bisphosphonates. Pain relief has been shown to a lesser degree in lung, GI and prostate carcinomas.

Standard starting doses:
- pamidronate 90 mg IV administered over 2 hours.
- zoledronic acid 4 mg IV over 15 minutes

50-70% of patients achieve a 30% reduction in pain within days or a week. The average duration of pain relief is 12 weeks after a single 90 mg infusion of pamidronate. If analgesia is not achieved within a week, the patient can be retreated.

Typically patients are treated every three-four weeks to achieve maximal effect. If the pain is well controlled the dosing interval can be extended to a longer period without change in effect.

Prophylaxis
In patients with breast cancer or multiple myeloma, monthly bisphosphonates decrease skeletal-related events (SRE) by 30% (pathologic fracture, spinal cord compression, surgery to bone, or radiation therapy to bone). The dosages of pamidronate and zoledronic acid are the same as used in analgesic therapy. There is no evidence that these medications prevent SRE in patients without known bone involvement.

Toxicity
Pamidronate and zoledronic acid have the same safety profiles. Both cause an injection site reaction and a flu-like syndrome that responds well to acetaminophen. Less common side effects include hypocalcemia and scleritis. Renal dysfunction is a side effect of long-term, high dose or short interval/frequency use of bisphosphonates, this is typically reversible with discontinuation of the drug.

Bisphosphonates are contraindicated in renal failure and with patients who experience an increase in creatinine (>0.5 over baseline or >1.0 in patients with pre-existing renal insufficiency). In patients moderate renal insufficiency (Cr 73.0 mg/dl), the dose of both agents should be reduced and/or the infusion time increased.

Adapted from Weinstein E and Arnold R. Palliative Care Network of Wisconsin. Fast facts and concepts #113. Bisphosphonates for fone pain. Internet. Accessed on January 25, 2016.