What is the role of bisphosphonates in the treatment of multiple myeloma (MM)?

Updated: Jul 15, 2019
  • Author: Dhaval Shah, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Answer

Bisphosphonates are specific inhibitors of osteoclastic activity and are used to treat bone resorption. They also have a role in the secondary prevention of bony complications in MM, including hypercalcemia, pathologic fracture, and spinal cord compression. Intravenous (IV) pamidronate (Aredia) has been shown to be effective in preventing skeletal complications; zoledronic acid (Zometa) may be significantly more potent than pamidronate. A study by Morgan et al found that the early use of zoledronic acid was superior to clodronic acid in preventing skeletal-related events among patients with newly diagnosed MM, irrespective of bone disease status at baseline. [39]

A randomized placebo-controlled trial of pamidronate in subjects with MM who had experienced one skeletal event demonstrated that the medication reduced the likelihood of a second skeletal event from 41% to 24% after 9 months of therapy. [40] The investigators also noted improvements in pain, narcotic usage, and quality of life scores.

A 2007 systematic review of the use of bisphosphonates in MM confirmed a number-needed-to-treat (NNT) of 10 for the prevention of vertebral fractures, although no impact on mortality was seen. [41]

The American Society of Clinical Oncology (ASCO) issued a clinical practice guideline governing bisphosphonate therapy for MM patients who have lytic destruction of bone or compression fracture of the spine from osteopenia. [41] ASCO recommends IV pamidronate, 90 mg delivered over at least 2 hours, or zoledronic acid, 4 mg delivered over at least 15 minutes every 3-4 weeks. Because the risk for osteonecrosis of the jaw is 9.5-fold greater with zoledronic acid than with pamidronate, patients may prefer pamidronate. [41]

Zoledronic acid doses should be reduced in patients with preexisting mild to moderate renal impairment (estimated creatinine clearance, 30-60 mL/min); the drug is not recommended for use in patients with severe renal impairment. [41] All patients receiving pamidronate or zoledronic acid therapy should be screened every 3-6 months for albuminuria. If unexplained albuminuria (>500 mg/24 hours) is found, ASCO recommends discontinuation of the drug until the renal problems resolve. [41]

A study by Morgan et al revealed the anticancer properties of zoledronic acid in addition to its ability to reduce skeletal-related events in MM. [113]


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