New Recommendations for Use of Bisphosphonates in Treatment of Multiple Myeloma

Mayo Clinic's multiple myeloma (MM) research team has jointly issued a consensus statement regarding the use of bisphosphonates to prevent or treat bone disease in MM. Their recommendations address several controversial issues, including the type of bisphosphonate to be used and the duration of such therapy, and are available in the August issue of Mayo Clinic Proceedings.

"It was imperative that we address the issue that has been under recent intense debate due to patient safety concerns," said Martha Lacy, M.D., Mayo Clinic hematologist and lead author of the statement. "These drugs have far-ranging effects that raised concerns in the medical field, so we brought together the relevant specialists to develop a set of best practice recommendations. We published them in Mayo Clinic Proceedings in order to provide other physicians the benefit of our shared knowledge."

The Mayo Clinic team provided recommendations for the myeloma patients for whom bisphosphonates are indicated. They said pamidronate should be the bisphosphonate of choice for patients who are starting therapy, over the newer, more potent drug zoledronic acid, which is more frequently associated with serious damage to jaw bones.

Also in the interest of safety, the team recommended that patients without active disease stop bisphosphonate therapy after two years, and patients with active disease reduce the frequency at which the drugs are given.

MM is a malignant plasma cell disorder that is diagnosed in more than 15,000 people each year in the United States, and which causes more than 11,000 deaths. There are a variety of treatment options for MM, but it remains an incurable disease with current emphasis placed on enhancing quality of life while the cure is sought.

Because bone destruction causes significant problems for MM patients, and painful results include osteoporosis, lytic bone disease and skeletal fractures, clinicians seek to treat this condition aggressively. Bisphosphonates are synthetic equivalents of naturally-occurring pyrophosphate, which inhibits bone resorption and aids the body in eliminating excess calcium. These drugs reduce other bony complications related to MM as well.

Unfortunately, along with the positive effects of bisphosphonates comes the possibility of adverse reactions, including kidney function impairment and damage to the jaw bones termed "osteonecrosis of the jaw." "We have tried to balance the undisputed benefits of bisphosphonates with the increasingly well recognized safety concerns," said Vincent Rajkumar, M.D., Mayo Clinic hematologist and co-author. "These recommendations are the result of years of practical knowledge combined by our team into guidelines for use beyond our institution. We hope others will adopt them as well as continue researching other solutions."

This consensus statement was a multidisciplinary effort, in which the myeloma group worked closely with periodontists and oral/maxillofacial surgeons to assess risks and benefits. Besides Drs. Lacy and Rajkumar, the team included researchers from Mayo Clinic's three campuses in Arizona, Florida and Minnesota, including: Lief Bergsagel, M.D.; Alan Carr, D.M.D.; Robert Dalton, M.D.; David Dingli, M.D., Ph.D.; Angela Dispenzieri, M.D.; Rafael Fonseca, M.D.; Morie Gertz, M.D.; Kimberly Gollbach; Philip Greipp, M.D.; Suzanne Hayman, M.D.; Deepak Kademani, D.M.D., M.D.; Eugene Keller, D.D.S.; Shaji Kumar, M.D.; Robert Kyle, M.D.; John Lust, M.D., Ph.D.; Craig Reeder, M.D.; Vivek Roy, M.D.; Stephen Russell, M.D., Ph.D.; Keith Stewart; Christopher Viozzi, D.D.S., M.D.; Thomas Witzig, M.D.; and Steven Zeldenrust, M.D., Ph.D.