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Bone-growth drugs may increase jaw disease risk

New study finds link between common drug and jawbone death

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5:36pm, January 2, 2009
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Some drugs meant to build bone for people with osteoporosis could increase the risk of developing a devastating jaw infection, a new study suggests. Even short-term use of some osteoporosis drugs may raise the risk of the jaw disease, called osteonecrosis. The results appear January 1 in the Journal of the American Dental Association.

Drugs called bisphosphonates — which include the widely prescribed alendronate (Fosamax), ibandronate (Boniva) and risedronate (Actonel) — are taken orally and commonly prescribed to combat osteoporosis, a disease that is marked by weak bones and affects over 10 million people in the United States.

Jawbone disease is “absolutely rare, and one of the least likely bones to get infected,” says study coauthor Parish Sedghizadeh, a dentist and researcher at the University of Southern California in Los Angeles. Over the last several years, Sedghizadeh and other dentists at the University of Southern California noticed a rise in the number of patients who came in with the unusual and hard-to-treat jaw infection. “All of a sudden, we saw this raging epidemic of jawbone infections,” prompting the researchers to scrutinize the electronic medical records of dental patients at USC.

From sifting through thousands of such records, the researchers found that nine of 208 current USC patients — or four percent — who were taking or had taken bisphosphonates for any amount of time in the past five years also had jawbone necrosis diagnoses. Of the 13,522 control patients not taking the bone-building drugs, none were diagnosed with jawbone necrosis.

But Aliya Khan, a doctor at McMaster University in Hamilton, Canada, points out that four of the nine patients found by the new study to have jaw necrosis had “additional risk factors,” including cancer, diabetes and steroid treatment. “From this study it cannot be concluded that the alendronate was a causal factor in the development of osteonecrosis,” says Khan, who has consulted for drug companies including Merck. “We need to obtain prospective, good quality data” on the causes and incidence of jaw osteonecrosis.”

Clinical trials involving more than 17,000 patients and conducted by Merck, the maker of alendronate, found no reports of jaw osteonecrosis, according to a statement released by the company in 2007.

However, Sedghizadeh says that these trials have not been evaluated in any peer-reviewed journal, and may not have had adequate dental oversight. “Better, larger studies are really needed to clarify the risk,” Sedghizadeh says.

All of the nine patients with jawbone necrosis developed it after undergoing a dental procedure, such as a tooth extraction, that exposed the jawbone to bacteria in the mouth. In early 2008, Sedghizadeh coauthored a separate report showing that biofilms, communities of bacteria, had invaded the jawbone of four osteonecrosis patients who were taking bisphosphonates. Once situated in the jawbone, these dense lawns of bacteria coat the bone and slowly destroy it.

In response to a 2005 request from the FDA, Merck now includes the following statement with Fosamax prescriptions: “Osteonecrosis of the jaw, generally associated with tooth extraction and/or local infection, often with delayed healing, has been reported in patients taking bisphosphonates.”

Researchers don’t yet know why these bone-building drugs may leave patients vulnerable to jawbone infections. Sedghizadeh’s guess is that the drugs may change the surface characteristics of the jawbone, making the bones a more hospitable place for bacteria to land and stick.

Until more data are collected, Sedghizadeh recommends that patients on these bone-building drugs be classified as “at-risk” for developing jawbone infections after dental procedures. Minimizing the bacteria in the mouth with extensive antibacterial mouth rinses for weeks before and after a tooth extraction may decrease jawbone infections in these patients, Sedghizadeh says.

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