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Theories On How Fosamax Causes Drug-induced Osteonecrosis Of The Jaw (ONJ)

Latest Ideas About Which Fosamax Patients Are At An Increased Risk Of Developing This Serious Side Effect

It is now generally accepted that there is an association between the use of Fosamax, an oral bisphosphonate, and osteonecrosis of the jaw (ONJ), a serious side effect which also has been referred to as jaw rot or jawbone death.

In 2006 there were two medical journal articles that provided new information about how Fosamax might cause osteonecrosis of the jaw (ONJ) and, in connection with those causation theories, what are some of the predisposing, or risk, factors for ONJ as regards patients using Fosamax and other bisphosphonates.

The first 2006 article is titled "Osteonecrosis of the Jaw -- Do Bisphosphonates Pose a Risk?"; it was published in the November 30, 2006 edition of The New England Journal of Medicine (NEJM). Therein, Dr. John P. Bilezikian offers this theory on how Fosamax and other bisphosphonates might cause ONJ:

If there is a relationship between bisphosphonates and osteonecrosis of the jaw, what might explain it? The jaw is often subject to spontaneous, local trauma as well as trauma caused by dental procedures. The mucosa of the mouth is very thin and may therefore permit unroofing of the alveolar bone immediately beneath it when trauma or infection occurs. As potent inhibitors of osteoclast activity, the nitrogen-containing bisphosphonates might retard skeletal repair processes associated with trauma to or infection of the oral mucosa that involves the underlying bone. Since the jawbones are in constant use and are characterized by active remodeling, bisphosphonates might accumulate there preferentially, resulting in concentrations that exceed those found elsewhere in the skeleton. Other potential mechanisms include the possible antiangiogenic effects of nitrogen-containing bisphosphonates and the effects of these agents on T-cell function.

Turning to the risk factors for developing ONJ, in this same article Dr. Bilezikian states: "Predisposing factors for the development of osteonecrosis of the jaw appear to be dental disease, dental surgery (e.g., tooth extraction), oral trauma, periodontitis, and poor dental hygiene."

The second 2006 article is titled "Bisphosphonate Complications Including Osteonecrosis of the Jaw", published in Hematology 2006. In this piece Dr. Bhoomi Mehrotra and Dr. Salvatore Ruggiero also discuss how bisphosphonates such as Fosamax can cause ONJ and what type of Fosamax patient is more likely to develop this serious side effect:

The mechanism of bisphosphonates-induced osteonecrosis is unclear. However, several predisposing factors have been identified. Periodontal disease, dentoalveolar surgery, prior trauma, corticosteroid therapy, immune-compromised state predisposing to increased risk of infection, possible vascular insufficiency and an underlying hypercoagulable state secondary to underlying malignancy have been implicated as possible etiologic or precipitating factors.... The unique predisposition for bony necrosis in the jaw may be related to the microenvironment in the maxilla and mandible secondary to compromised vascular supply and presence of oral microflora that may super-infect a poorly healing wound in the jaw bone. In addition, the constant microtrauma from jaw movement and lack of adequate bone remodeling in the presence of bisphosphonates may contribute to the genesis of osteonecrosis of the jaw (ONJ). Although spontaneous osteonecrosis is reported in a minority of cases, the majority of patients give a history of some prior dental or oral surgical manipulation. Several investigators have identified increasing duration of exposure, type of bisphosphonate, older age and prior history of a dental procedure as risk factors for the development of ONJ....

Referring back to the November 2006 NEJM article by Dr. Bilezikian: "Approximately two thirds of cases involve the mandible and the rest involve the maxilla."

Going further, the authors of both these 2006 medical journal articles go on to provide important information about how to recognize the early signs and symptoms of osteonecrosis of the jaw (ONJ), and also give an overview of the how doctors go about rating, or staging, ONJ when it is initially diagnosed.

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