MEDICATION–RELATED OSTEONECROSIS OF THE JAW BISPHOSPHONATES AND SIMILAR DRUGS

As an oral and maxillofacial surgeon, I am often asked by referring doctors what the protocol is for dealing with patients who are taking bisphosphonates and related medications. These drugs are associated with what has been termed medically-related osteonecrosis of the jaw (MRONJ), previously referred to as bisphosphonate osteonecrosis (BRONJ).Female nurse looking at patient while adjusting IV machine for c

Define the Problem

Bisphosphonates, as a category of drug, started in wide use for bone density problems such as osteoporosis in the mid 1990s. The intravenous forms started being used along with other cancer chemotherapeutic agents and became more widely used in the early 2000s. I saw my first case of BRONJ at the beginning of 2003 and I assumed at that time that it was just some type of a bone disorder caused by trauma. Dr. Robert Marx wrote a letter to the editor in our journal that I happened to read at about the same time that I saw additional cases coming into my office. He and other researchers defined the problem. We saw many more cases between 2003 and 2008 as there was some resistance to recognizing the cause and effect. It was also found that the dosage amount, frequency, and duration had a significant effect on the development of the disorder. As the prescribing doctors realized the relationship, they started titrating the dosage better and this has resulted in a significant decrease in the number and severity of cases that we see. Some of the new intravenous forms for osteoporosis appear to again present a greater concern.

At this writing, the drugs implicated in the pathogenesis of MRONJ include bisphosphonate drugs both oral (such as Fosamax, Boniva, and Actonel) and intravenous forms (such as Zometa, Aredia, and Reclast), monoclonal antibodies Demosumab and Bevacizumab; and the multikinase inhibitor Sunitinib. These drugs are being commonly used in medicine, orthopedic and oncology for the treatment of osteoporosis, osteopenia, Paget disease, multiple myeloma and other metastatic malignancies. They have proven effective in preventing or at least minimizing fractures of the musculoskeletal system as well as controlling bone pain. This provides a better quality of life for these patients; however patients do require routine dental care and possibly emergency oral surgical treatment while taking these medications.

CTX Blood Test

CTX (c-terminal telopeptide) is a blood test that measures one of the breakdown products of type I collagen, which occurs during bone resorption. Thus, the serum levels of CTX can be used as an indicator of bone breakdown/resorption. I do not feel that this blood test is necessarily a reliable predictor for the development of osteonecrosis, but it certainly can provide a guide both to assess the risk of developing osteonecrosis, but more importantly can be a guide to physicians for adjusting dosage of the drug that they are giving. A serum level less than 100 pg/mL represent a high risk of ONJ; 100-150

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