What Are The Current Causation Theories And Which Patients Are At An Increased Risk
As reported previously, there is increasing attention being paid to the association between the use of oral bisphosphonates and osteonecrosis of the jaw (ONJ), the serious side effect which is commonly called jawbone death, bone decay, or jaw rot.
Two recent medical journal articles provide information about how osteonecrosis of the jaw (ONJ) may be caused by Fosamax and other bisphosphonates as well as identify some of the predisposing, or risk, factors for developing ONJ.
We start with an article called "Osteonecrosis of the Jaw -- Do Bisphosphonates Pose a Risk?", published in the November 30, 2006 edition of The New England Journal of Medicine (NEJM), where Dr. John P. Bilezikian offers this on causation:
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.
As for the ONJ risk factors, 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."
Further discussion about how bisphosphonates such as Fosamax causes ONJ and when that side effect is more likely to develop can be found in the article by Dr. Bhoomi Mehrotra and Dr. Salvatore Ruggiero called "Bisphosphonate Complications Including Osteonecrosis of the Jaw", published in Hematology 2006:
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....
According to Dr. Bilezikian's November 2006 NEJM article: "Approximately two thirds of cases involve the mandible and the rest involve the maxilla."
In part two of this series, sub-titled "What Patients Should Know About The Signs And Symptoms As Well As Diagnostic Staging", we get from these same two medical journal articles some important information about the early signs and symptoms of osteonecrosis of the jaw (ONJ) as well as the extent, or staging, of ONJ upon diagnosis.
(Posted by: Tom Lamb)