A landmark verdict against the pharmaceutical giant Merck was recently rendered in a Fort Walton Beach Florida courtroom. It should raise wide-spead public concern over the safety of drugs called bisphosphonates prescribed for mostly women as treatment for osteoporosis and osteopenia. Bisphosphonates are a drug classification that includes Fosamax, Fosamax + D, Aredia, Boniva, Didronil, Actonel, Actonel + Ca, Reclast, Skelid, and Zometa.
Limited news reports tell the story of Shirley Boles, a 72 year old great grandmother and retired sheriff’s deputy, who was taking the drug Fosamax for osteopenia. The condition of osteopenia is a normal thinning of the bones as a person ages. It does not typically result in bone fractures unless it progresses to the disease osteoporosis. Current medical practices recommend treatment to prevent the development of osteoporosis.
Ms. Boles also had a history of periodontal disease and smoking. She began experiencing jaw problems after taking Fosamax over a 10 year period of time. She ultimately needed extraction of two teeth. Following the extraction, a very serious condition called osteonecrosis of her jaw was diagnosed. In essence, the bone in her jaw disintegrated and died. Jurors witnessed the physical decaying bone matter and infection seen from two drains in her chin. They heard how Ms. Bales only eats soft food and will need to undergo repeated surgeries to replace her dead jawbone.
How the condition osteopenia went from a research term to an actual disease classification for some people and not others, and how Merck advanced their money-losing drug Fosamax to treat the new disease is a fascinating read.
NPR broke the story during Christmas 2009. That same month, it was also reported that 10 million people in the United States had osteoporosis and most were women. That same year, 45 million bisphosphonate prescriptions were written in the US generating $4.9 billion. Given the holiday season, one must wonder how many people actually became aware of this story.
The tale actually begins with the publication of an article released by the Wall Street Journal in December 8, 2004. The story noted that in 2001, the Chief of Oral Surgery at the Long Island Jewish Medical Center, Dr. Salvatore Ruggiero, began recognizing a distinct pattern of osteonecrosis and jawbone death in 8 cancer patients taking the drug Aredia to combat bone loss. He reported his cases to the FDA. He continued to track 90 of his subsequent patients, who developed jawbone osteonecrosis while taking Aredia and Zometa. During this period, other oral surgeons were also reporting the same findings, including the Chief of Oral and Maxillofacial Surgery at the University of Miami’s Miller School of Medicine, Dr. Robert Marx.
The drug company Novartis, which makes Aredia and Zometa, first reported the side effect of osteonecrosis of the jaw (ONJ) on drug inserts in 2003. By 2004, Novartis had received 500 reported cases in cancer patients taking Aredia and Zometa. In September 2004, the FDA issued their first warning associated with intravenous bisphosphonates. In June 2006, the National Osteoporosis Foundation put out a Scientific Statement that ONJ associated with bisphosphonate therapy was seen 95% of the time in cancer patients and only rarely in the general osteoporosis patient population.
Ms. Boles did not have cancer.
The American Society of Oral and Maxillofacial Surgeons (ASOMS) put out a clinical position paper in September 2006. Their clinical research found increased risk factors for ONJ in those receiving both intravenous AND oral bisphosphonates. There was a definite risk increase in patients taking the drugs for more then 3 years, but ASOMS concluded more study was needed. In addition, ASOMS noted a seven-fold increase in patients who had a history of periodontal disease and oral abscess. Diabetes, smoking, and alcohol also increased risk.
Current drug inserts and patient information do not list (ONJ) in drug contraindications or warnings. However, under general precautions the inserts say ONJ can “occur spontaneously in association with tooth extractions, dental implants, and bony surgery. It can also occur in cancer patients receiving cancer treatments. Persons at risk include those with poor oral hygiene, periodontal disease, pre-existing dental disease, anemia, coagulopathy, and ill-fitting dentures.”
In 2009, an article was published in the Journal of the American Dental Association involving the University of Southern California dental clinics. The results were even more alarming. The researchers found out of 208 patients taking the drug Alendronate, also known as Fosamax and sold by Merck, nine had active ONJ. This represented 1 in 23 patients, 4% of the general dental clinic population. The researchers concluded the incidence may be much higher then previously reported, and the risk appears great even in short term users. The study author noted there was a 10 year half-life of the drug remaining in bone tissue. So dentists and patients need to be alerted to the risk remaining over a period of time.
Faulty drug design was the basis for Mrs. Boles $8 million dollar verdict. Merck plans to appeal. In the meantime, how many woman taking bisphosphonates remain uninformed of this potential risk?