Fast Fact and Concept #113: Bisphosphonates for Bone Pain

Author(s): E. Weinstein; R. Arnold

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. In the United States, two preparations are used: zoledronic acid or pamidronate.

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 include: Zoledronic acid 4mg IV over 15 minutes or and pamidronate 90mg IV administered over 2 hours. 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 discontiuation 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.

Cost
The average wholesale price for zoledronic acid 4mg is $856; where the AWP of pamidronate 90mg is $88. In considering the cost difference between these two drugs it is important to acknowledge the added costs to patients, physicians and medical facilities for the infusion time of pamidronate (average appointment time 2h 52 min vs. 1h 6min for zoledronic acid).

References:

1. Hillner B, Ingle J, Chlebowski RT, al. e. ASCO 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer. JCO. 2003;21(21):4042-4057.
2. Pereira J. Management of Bone Pain. In: Topics in Palliative Care Volume 3 editors Portenoy RK, Bruera E. New York Oxford University Press, Inc. 1998, 79-116.
3. Body JJ, Mancini I. Bisphosphonates for cancer patients: why, how and when? Support Care Cancer 2002 Jul: 10(5): 399-407
4. Body JJ. Dosing regimens and main adverse events of bisphosphonates. Semin Oncol. 2001 Aug; 28(4 Suppl 11):49-53.
5. Strang P. Analgesic effect of bisphosphonates on bone pain in breast cancer patients: a review article. Acta Oncol. 1996; 35 Suppl 5:50-54.
6. Berenson JR, Rosen LS Howell A, et al: Zoledronic acid reduces skeletal-related events in patients with osteolytic metastases. Cancer 91:1191-1200, 2001.
7. DesHarnais CL, Bajwa K, Markle JP, et al: A microcosting analysis of zoledronic acid and pamidronate therapy in patients with metastatic bone disease. Support Cancer Care 9:545-551, 2001.

Fast Facts were edited by David Weissman MD, Palliative Care Center, Medical College of Wisconsin until January 2007.  For comments/questions write to the current editor, Drew Rosielle MD: drosiell@mcw.edu. The complete set of Fast Facts is available at EPERC: www.eperc.mcw.edu

Copyright/Referencing Information: Users are free to download and distribute Fast Facts for educational purposes only. Citation for referencing: Weinstein E and Arnold A. Fast Facts and Concepts #113. Bisphosphonates for bone pain. April 2004. End-of-Life/Palliative Education Resource Center www.eperc.mcw.edu.

Disclaimer: Fast Facts provide educational information, this information is not medical advice. Health care providers should exercise their own independent clinical judgment. Some Fast Fact information cites the use of a product in dosage, for an indication, or in a manner other than that recommended in the product labeling. Accordingly, the official prescribing information should be consulted before any such product is use.

Creation Date: 4/2004

Purpose: Instructional Aid, Self-Study Guide, Teaching

Audience(s)

ACGME Competencies: Medical Knowledge, Patient Care

Keyword(s): Pain>non-opioids; cancer

Specific Disease and Organ System Category(s): Cancer