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KOS 2007: The Role of Bisphosphonates in the Management of Myeloma
By James Berenson, MD
James Berenson, MD
Institute for Myeloma and Bone Cancer Research
Los Angeles, CA, USA

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Institute for Myeloma and Bone Cancer Research
Los Angeles, CA, USA

by Lynne Lederman, PhD

Dr. Berenson observed that the use of bisphosphonates is causing a lot of consternation these days. He noted that in the recent pivotal phase 3 study comparing intravenous pamidronate to intravenous zolendronic acid, all patients received 400 I.U. of vitamin D and 500 mg of calcium, supplements that he recommends to patients. Bisphosphonates reduce the incidence of skeletal events, preserving quality of life, and also have a direct anti-tumor effect via activity on the bone marrow microenvironment. Skeletal events, markers of bone destruction (e.g., NTX or N-telopeptides), and IgA M-protein are all predictive of poor survival. Bone alkaline phosphatase (BALP), a marker of bone formation, is associated with bone pain, bone lesions, and fractures in untreated myeloma and higher levels also increase the risk of a negative outcome. Dr. Berenson discussed osteonecrosis of the jaw (ONJ), which he defined as exposed bone in the maxillofacial area in association with dental surgery or occurring spontaneously without healing within 6 months of occurrence. Chart reviews suggest an incidence of about 10% and a median time to development of 52 months after initiation of zolendronic acid. Excellent oral hygiene, limiting the use of alcohol, eliminating the use of tobacco, a complete dental assessment and completion of any extractions or implants before therapy are recommended to reduce the risk of ONJ. He recommends avoiding surgical intervention to treat ONJ. Although recent guidelines recommend discontinuation of bisphosphonates after 2 years of therapy, Dr. Berenson believes this puts patients at risk for skeletal events, and there is no evidence that discontinuation will decrease the incidence of ONJ which is related to the time from first dose rather than the number of doses.

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