HEALTH NEWS

Study Title:

Bone Drugs and Jaw Disease

Study Abstract

Background. Initial reports of osteonecrosis of the jaw (ONJ) secondary to bisphosphonate (BP) therapy indicated that patients receiving BPs orally were at a negligible risk of developing ONJ compared with patients receiving BPs intravenously. The authors conducted a study to address a preliminary finding that ONJ secondary to oral BP therapy with alendronate sodium in a patient population at the University of Southern California was more common than previously suggested.

Methods. The authors queried an electronic medical record system to determine the number of patients with a history of alendronate use and all patients receiving alendronate who also were receiving treatment for ONJ.

Results. The authors identified 208 patients with a history of alendronate use. They found that nine had active ONJ and were being treated in the school’s clinics. These patients represented one in 23 of the patients receiving alendronate, or approximately 4 percent of the population.

Conclusions. This is the first large institutional study in the United States with respect to the epidemiology of ONJ and oral bisphosphonate use. Further studies along this line will help delineate more clearly the relationship between oral BP use and ONJ.

Clinical Implications. The findings from this study indicated that even short-term oral use of alendronate led to ONJ in a subset of patients after certain dental procedures were performed. These findings have important therapeutic and preventive implications.

From press release:

Researchers at the University Of Southern California, School Of Dentistry release results of clinical data that links oral bisphosphonates to increased jaw necrosis. The study is among the first to acknowledge that even short-term use of common oral osteoporosis drugs may leave the jaw vulnerable to devastating necrosis, according to a new report.

Osteoporosis currently affects 10 million Americans. Fosomax is the most widely prescribed oral bisphosphonate, ranking as the 21st most prescribed drug on the market since 2006, according to a 2007 report released by IMS Health.

This is the first large institutional study in the U.S. to investigate the relationship between oral bisphosphonate use and jaw bone death, said principal investigator Parish Sedghizadeh, assistant professor of clinical dentistry with the USC School of Dentistry.

After controlling for referral bias, nine of 208 healthy School of Dentistry patients who take or have taken Fosamax for any length of time were diagnosed with osteonecrosis of the jaw (ONJ). The study's results are in contrast to drug makers' prior assertions that bisphosphonate-related ONJ risk is only noticeable with intravenous use of the drugs, not oral usage, Sedghizadeh said. "We've been told that the risk with oral bisphosphonates is negligible, but four percent is not negligible," he said.

Most doctors who have prescribed bisphosphonates have not told patients about any oral health risks associated with the use of the drugs, despite even short-term usage posing a risk due to the drug's tenacious 10-year half life in bone tissue. Lydia Macwilliams of Los Angeles said no one told her about the risk posed by her three years of Fosamax usage until she became a patient of Sedghizadeh at the School of Dentistry. "I was surprised," she said. "My doctor who prescribed the Fosamax didn't tell me about any possible problems with my teeth."

Macwilliams was especially at risk for complications because she was to have three teeth extracted. The infection is a biofilm bacterial process, meaning that the bacteria infecting the mouth and jaw tissues reside within a slimy matrix that protects the bacteria from many conventional antibiotic treatments, and bisphosphonate use may make the infection more aggressive in adhering to the jaw, Sedghizadeh said. The danger is especially pronounced with procedures that directly expose the jaw bone, such as tooth extractions and other oral surgery. After her extractions, two of the three extraction sites had difficulty healing due to infection, Macwilliams said. Luckily, with treatment as well as the rigorous oral hygiene regimen USC dentists developed especially for patients with a history of bisphosphonate usage, the remaining sites slowly but fully healed. "It took about a year to heal," she said, "but it's doing just fine now."

Sedghizadeh hopes to have other researchers confirm his findings and thus encourage more doctors and dentists to talk with patients about the oral health risks associated with the widely used drugs. The results confirm the suspicions of many in the oral health field, he said. "Here at the School of Dentistry we're getting two or three new patients a week that have bisphosphonate-related ONJ," he said, "and I know we're not the only ones seeing it."

Study Information

Parish P. Sedghizadeh, DDS, MS, Kyle Stanley, BS, Matthew Caligiuri, BA, Shawn Hofkes, BS, Brad Lowry, BS and Charles F. Shuler, DMD, PhD
Oral bisphosphonate use and the prevalence of osteonecrosis of the jaw.
J Am Dent Assoc
2009 January
University Of Southern California, School Of Dentistry.