Oral Bisphosphonate Use Linked to Osteonecrosis of the Jaw

Four percent of patients at dental school with history of oral bisphosphonate use have jaw problem

11 jan 2009-- Osteonecrosis of the jaw may be more common in people who have used the oral bisphosphonate Fosamax than data has previously reported, especially following tooth extraction, according to an article published online Jan. 1 in the Journal of the American Dental Association.

Parish P. Sedghizadeh, D.D.S., of the University of Southern California in Los Angeles, and colleagues analyzed the USC School of Dentistry's electronic records system to identify patients with a history of Fosamax use, as well as patients on the drug being managed for active osteonecrosis of the jaw.

The authors found 208 patients with a history of Fosamax use. Of these, nine had active osteonecrosis of the jaw, which represented roughly 4 percent of Fosamax-using patients. Patients' ages ranged from 63 to 80; all were females who took the drug for at least 12 months for osteoporosis. All cases occurred after tooth extraction or denture trauma with exposure of bone, the report indicates.

"Current data like ours suggesting a risk of osteonecrosis of the jaw in oral bisphosphonate users has prompted us to actively screen every patient who comes to the school with updated consent and patient medical history forms reflecting the need for increased awareness and early risk or disease assessment. We have also updated our consent for dental surgery (e.g. extractions) with the American Dental Association recommended statement: 'Because you are taking a type of drug called bisphosphonate, you may be at risk of developing osteonecrosis (bone death) of the jaw and certain dental treatment may increase that risk,'" the authors write.

Abstract
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Oral Bisphosphonates Triple Aseptic Osteonecrosis Rate

By John Gever
VANCOUVER, British Columbia, Jan. 18 -- Patients with severe bone necrosis are almost three times more likely to have been treated with oral bisphosphonates for osteoporosis than those without aseptic osteonecrosis, researchers here found. In a study of 196 aseptic osteonecrosis patients requiring hospitalization, the adjusted risk ratio for having a history of oral bisphosphonate drug therapy was 2.87 (95% CI: 1.71 to 5.05), compared with 1,960 age-matched controls, reported Mahyar Etminan, Pharm.D., M.Sc., of Vancouver General Hospital, and colleagues online in the Journal of Rheumatology. Case reports and small case series have been published of osteonecrosis, particularly osteonecrosis of the jaw, in patients with a history of bisphosphonate use, including alendronate (Fosamax), risedronate (Actonel), and etidronate (Didronel). This association was reported primarily in patients receiving intravenous bisphosphonates.
Dr. Etminan and colleagues' findings came from analysis of 87,837 case records from Quebec, involving cardiovascular patients ages 65 or older. The records database includes information on prior prescriptions as well as hospitalizations, diagnoses, and procedures.
For each of the 196 cases of osteonecrosis requiring hospitalization who were identified, the investigators obtained records for 10 control patients matched by age, date of treatment, and length of follow-up.
Raw data showed that 14.8% of cases had taken bisphosphonates at some point, compared with 3.8% of controls, suggesting a crude risk ratio of 4.61.
But adjusting for factors including age, comorbidity, coronary artery surgery, history of fractures, malignancies, all medication use, corticosteroid use, diabetic medications, and dental procedures reduced the risk ratio to 2.87.
A history of statin or ACE inhibitor drug use did not show a similar pattern of increased osteonecrosis, Dr. Etminan and colleagues reported.
When patients currently taking bisphosphonate were separated from those with a previous bisphosphonate history, both groups still showed a significant association with osteonecrosis.
Among those with current use, the adjusted risk ratio was 3.14 (95% CI: 1.68 to 5.88). The adjusted risk ratio for those with only previous use was 2.52 (95% CI: 1.01 to 6.26).
"Additional studies are needed not only to confirm these preliminary observations but also to investigate further the role of specific bisphosphonates, their dose-response relationship, duration of therapy, and the exact sites of bone necrosis," Dr. Etminan and colleagues wrote.
They pointed out that their data did not include information on necrosis site. Because corticosteroid use was more than three times as common among cases versus controls, the researchers said it was likely that most cases involved sites other than the jaw, particularly the hip.
Because the study was observational, it did not prove causality, the investigators noted.
Nevertheless, Dr. Etminan said in an interview that the study bolsters the cautions expressed by the FDA and others about musculoskeletal side effects of bisphosphonates.
"Obviously a lot of people are taking these medications … and are benefiting from them," he said. Nevertheless, he added, they involve a tradeoff of risks and benefits. He said patients and physicians need to be aware of the side effects, which may often go unreported.
The FDA issued an alert this month on unexplained sudden and severe musculoskeletal pain associated with these drugs, although this effect's relationship to the reports of osteonecrosis was not detailed.
The FDA has said it plans to evaluate the reports of severe musculoskeletal pain with bisphosphonates by July. Labeling information for all drugs in this class currently include cautions about this side effect.
One co-author reported receiving financial support from le Fonds de la Recherche en Santé du Québec.
Primary source: Journal of RheumatologySource reference:Etminan M, et al "Use of oral bisphosphonates and the risk of aseptic osteonecrosis: a nested case-control study" J Rheumatology 2008.

New method predicts hip joint decay from chemotherapy

St. Jude study shows that the extent of hip decay is key to predicting which survivors of leukemia/lymphoma who develop osteonecrosis of the femoral head will suffer hip joint collapse requiring surgical repair
Investigators at St. Jude Children's Research Hospital say they have found the best way for predicting when patients will need future surgery to repair hip joints that have deteriorated because of pediatric leukemia or lymphoma treatment.
The investigators found that if more than 30 percent of the head of the bone fitting into the hip socket is deteriorated, it is at high risk of collapsing and requiring reconstructive surgery within two years.
The study is significant because the intensive use of corticosteroid drugs that have been implicated in development of osteonecrosis, or bone deterioration, is a major component of chemotherapy for pediatric leukemia and lymphoma. The drugs have been key to raising the survival rates of children with these cancers, and currently there is no adequate substitute for their use. Therefore, it is important for clinicians to monitor patients during treatment and identify those at highest risk for this complication. Eventually, genetic or other tests may be developed to help predict these patients. This is a subject of ongoing study.
A report on this work appears in the April 20 issue of "Journal of Clinical Oncology."
Hip collapse occurs following deterioration of the ball-like top part of the upper leg bone, or femur, which fits into the hip socket. Degeneration of this area, called osteonecrosis of the capital femoral epiphysis, is a common problem among children undergoing chemotherapy for leukemia or lymphoma.
"Being able to predict which children are likely to experience serious bone deterioration in the future will help investigators identify and monitor survivors who are at particularly high risk for developing this problem," said Sue Kaste, D.O., a member of the Radiological Sciences department at St. Jude. Kaste is the paper's senior author.