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Fosamax-Induced Osteonecrosis of the Jaw More Common Than Previously Thought

Posted by medconsumers on March 1, 2009

Dentists have been in the forefront of identifying a severe complication of Fosamax, the osteoporosis drug widely prescribed to prevent fractures. The January issue of the Journal of the American Dental Association published a study describing a significant risk of osteonecrosis of the jaw from even oral use of Fosamax. Until this small study of 208 dental patients was published, jaw osteonecrosis was thought to be rare and limited to people with cancer who received large doses of Fosamax intravenously to treat bone metastases.

Dental School Patients Studied

In this study conducted at the University of Southern California School of Dentistry, 4% of the dental patients taking oral Fosamax had osteonecrosis of the jaw. All had suffered dental trauma—either a tooth extraction or ill-fitting dentures that resulted in jawbone exposure; all were women, average age 73 years, who had been taking the drug for 12 months or longer. Osteonecrosis is defined as “the presence of exposed bone in the mouth, which fails to heal after appropriate intervention over a period of six or eight weeks.”

Parish P. Sedghizadeh, DDS, and colleagues at the USC School of Dentistry found no cases of osteonecrosis of the jaw among their 4,384 dental patients not taking Fosamax who underwent tooth extraction. Fosamax was the first and most aggressively promoted of all drugs in a class called bisphosphonates, which also includes Actonel, Boniva, Aredia, Zometa, Reclast, and Bonefos. In 2011, the FDA issued a warning about serious adverse effects, stating that they apply to  all  bisphosphonates.

4% Risk is Not Rare

Sedghizadeh and colleagues say their findings contradict Merck’s claim that jaw osteonecrosis is a rare side effect of its drug. “We have been told that the risk with oral bisphosphates is negligible, but 4% is not negligible,” said Dr. Sedghizadeh. (The benefit of Fosamax could also be described as rare because the drug reduces the risk of hip fracture from 2% to 1%, as demonstrated in premarketing trials.) Prior to receiving FDA approval, Fosamax was tested in trials that lasted only three to five years. Ever since this drug first came on the market in 1996, the unanswered question has been: How long can people safely take Fosamax—or any one of other bisphosphonates, which are known to suppress bone turnover.

Drugs Have a Long Half-Life

This warning came from the USC Dental School research team: Bisphosphonates have half-lives of ten years or more, and people taking the drug orally may ultimately reach the same high dose level as that given intravenously to treat bone metastases in cancer patients. Sedghizadeh and colleagues also explained that because bisphosphonates stay in the bone for a long time, the risk of osteonecrosis remains even after people go off the drugs. The half-life of a drug describes how long it takes for half of it to be eliminated from the bloodstream.

The USC study is not the last word on the frequency of osteonecrosis of the jaw in people taking bisphosphonates. A much larger study is needed; ideally, one that takes place in many dental schools. Researchers at other institutions are trying to determine the prevalence of osteonecrosis of the jaw in cancer patients treated with bisphosphonates for cancer metastases. In the journal Bone, Dr. I.R. Reid, University of Auckland, estimated that it is 5% among people with myeloma, breast cancer or prostate cancer.

What to do

Thirteen years after Fosamax was launched, severe adverse effects have been showing up that may not be as rare as the public has been led to believe. Last year, the FDA reported that all bisphosphonates carry the risk of severe and sometimes incapacitating musculoskeletal pain. And case reports in several medical journals describe an unusual type of severe fracture of the femur associated with bisphosphonate use. In 2007 an increase in serious cases of atrial fibrillation was reported in people given the relatively new once-a-year bisphosphonate injection for fracture prevention (Zometa).

Osteonecrosis Treatments

As for osteoporosis of the jaw, more information is needed about how to prevent and treat it successfully—if that’s possible. Sedghizadeh and colleagues at USC Dental School did not have too much to offer on this topic. They advise unnamed alternate treatment options be considered for “nonnecessary extractions;” reducing the amount of the bacteria with a chlorhexidine rinse for those who must undergo a procedure; and daily antibiotics for those with denture trauma. For the exposed bone that fails to heal, the researchers name a procedure called “mucosal coverage.”

University of New Zealand’s Dr. Reid put it more succinctly “Management focuses on prevention, treatment of infection and cessation of bisphosphonate. The role of surgery is unclear.”

For more information: Read my 2008 article about Fosamax and this 2008 article about Evista. For an overview of how the definition of osteoporosis was expanded by the pharmaceutical industry: read “The marketing of osteoporosis: how a risk factor became a disease,” which appeared in the April 2009 issue of the American Journal of Nursing.

Maryann Napoli, Center for Medical Consumers©

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