Results of a recent study indicate that a history of smoking, the use of the bisphosphonate Aredia, and five genetic variations may put multiple myeloma patients at an increased risk of developing osteonecrosis of the jaw, a rare but serious side effect of bisphosphonate treatment.  Several of the genes the study authors identified are involved in bone formation, osteoporosis, and wound healing.

The study authors noted that if their findings can be confirmed in larger studies, they could be used to tailor bisphosphonate treatment for patients carrying these genetic variations, thus decreasing the occurrence of osteonecrosis of the jaw.

Osteonecrosis of the jaw is a condition that is associated with a loss of blood supply to the jaw, causing the jawbone tissue to die. It can occur in a small fraction of multiple myeloma patients during bisphosphonate treatment. 

Bisphosphonates are a class of drugs that prevent bone from breaking down.  In multiple myeloma, they are commonly given to decrease bone pain and reduce the development of bone disease associated with myeloma.

Since not all myeloma patients develop osteonecrosis of the jaw when receiving bisphosphonate treatment, researchers from the University of Florida hypothesized that genetic and clinical factors may play a role in the development of the complication.

In their study, the researchers analyzed data from 78 multiple myeloma patients on intravenous bisphosphonate therapy. Of the 78 patients, 12 had developed osteonecrosis of the jaw during treatment.  The median time to the onset of osteonecrosis of the jaw was 28 months.

The researchers found that multiple myeloma patients with a history of smoking were four times more likely to develop osteonecrosis of the jaw while on bisphosphonate therapy than those with no history of smoking.  

Furthermore, those patients taking the bisphosphonate Aredia ^[1] (pamidronate), or taking Aredia before switching to the bisphosphonate Zometa ^[2] (zoledronic acid), were four times more likely to develop osteonecrosis of the jaw than those on Zometa.

In order to determine the role of genetic factors in the development of osteonecrosis of the jaw, the researchers compared the genetic variations between the patients who developed osteonecrosis of the jaw and those who did not.

They identified five genetic variations that increased the risk for developing osteonecrosis of the jaw.  They found that patients who had variations in all five of these genes were 11 times more likely to develop osteonecrosis of the jaw while on bisphosphonates than those patients who had fewer than five of these variations.

The researchers concluded that their findings indicate that multiple genes are involved in the development of bisphosphonate-induced osteonecrosis of the jaw, rather than a single gene. 

For more information on the study or the specific genetic variations associated with the development of osteonecrosis of the jaw, please see the International Journal of Oral & Maxillofacial Surgery ^[3] (abstract).