Chronically altering calcium balance impairs new bone formation

In 2003 oral and maxillofacial surgeons began reporting cases of nonhealing, exposed bone in the jaws of patients receiving intravenous (IV) bisphosphonates. Reports linking osteonecrosis of the jaw (ONJ) to bisphosphonate treatment have increased and now include a few cases among patients taking less-potent oral bisphosphates. “Clinicians should understand the risks for osteonecrosis and optimize patient’s oral health before starting bisphosphonate therapy,” says Peter D. Waite, MPH, DDS, MD, director of UAB’s Division of Oral and Maxillofacial Surgery.

More than 2000 cases of bisphosphonate-related ONJ, which occurs more often in the mandible but also can affect the maxilla, have been reported in the last 3 years. Patients with mild ONJ can be asymptomatic, but sequelae can be devastating, with some severe cases requiring removal of sections of the jaw.

Bisphosphonates are potent inhibitors of osteoclastic bone resorption that persist in the body for years. Long-term effects of the drugs, available for a decade, are not well studied. IV bisphosphates reduce bone pain and skeletal complications in patients with multiple myeloma and metastatic cancers, significantly improving their quality of life.

“Bisphosphonates are important drugs that offer many benefits. Although new complications of ONJ have been report-ed, this should not prevent use of these drugs for medical therapy,” Waite says. “Inhibiting osteoclasts may reduce bone remodeling and new bone formation and increase the jaws’ vulnerability to trauma,” he says. “Healing seems especially impaired in people with cancers and other comorbidities, including poor oral health.”

Risk for ONJ increases along with potency of the bisphosphonate and duration of use. More than 90% of cases are among patients with multiple myeloma or metastatic cancer receiving powerful nitrogen-containing IV bisphosphonates including alendronate, risedronate, pamidronate, and zoledronic acid. People on oral bisphosphates have a much lower risk of ONJ, though Waite has seen several cases in postmenopausal women taking the drugs for osteoporosis.

Tooth extraction is the most frequent precipitating event for ONJ. Patients receiving IV bisphosphates who undergo invasive dental procedures are at least 7 times more likely to develop the condition. Other risk factors include poor oral health, smoking, chemotherapy, head and neck radiotherapy, steroid use, and vascular disease.

“Before starting bisphosphonates, patients should undergo thorough oral evaluation and aggressive dental management. Teeth in need of removal should be extracted and other dental surgeries completed,” he says. “Patients also should be educated about the risk of ONJ, its signs and symptoms, and the importance of maintaining good oral hygiene, including regular checkups. Discontinuing bisphosphonate therapy in patients with ONJ is often considered, but seems to have no effect on established disease. Physicians must weigh severity of bone degeneration against the benefit of continued therapy. Individuals also need to consider the benefits and risks of chronic bisphosphonate therapy — these drugs stay in the body for decades, and more study is needed to define their role.”

For more information
Dr. Peter Waite
1.800.UAB.MIST
mist@uabmc.edu