Bisphosphonates are a class of commonly prescribed drugs that primarily act to decrease the resorption of bone by inhibiting osteoclastic activity, thereby decreasing bone turnover. With the Food and Drug Administration’s approval of alendronate (Fosamax; Merck, Whitehouse Station, NJ) in 1995, they have become among the most prescribed drugs in the United States. Osteoporosis treatment is the most common application of bisphosphonate therapy, and the oral forms of medication that treat this condition account for over 99% of bisphosphonate prescriptions. Alendronate, ibandronate, and risedronate are oral agents used primarily to prevent or treat osteoporosis, although some are also used in the treatment of Paget’s disease and osteogenesis imperfecta. The more potent intravenously administered bisphosphonates—pamidronate and zoledronic acid—are the current standard of care for the reduction of bone pain, hypercalcemia of malignancy, and skeletal complications in patients with multiple myeloma and lung, breast, and other cancers.

Although the reduction in morbidity and mortality from the various conditions mentioned previously is desirable, osteoclast suppression has been linked to a severe adverse side effect: osteonecrosis of the jaws. In 2003, Marx alerted the dental community to the possible relationship between intravenous bisphosphonate therapy and necrosis of the jaws. He reported on 36 patients who were receiving intravenous bisphosphonates, all with cases of bone exposure that were unresponsive to surgical or medical treatments. His letter to the editor prompted others to review their records and report on similar findings; Ruggerio et al published a review of 56 patients with osteonecrosis of the jaws associated with bisphosphonate therapy, 7 of whom were receiving the oral bisphosphonate alendronate or risedronate for the treatment of osteoporosis. One year later, Migliorati et al presented 18 patients with osteonecrosis of the jaws, 17 of whom were receiving pamidronate or zoledronic acid as part of their cancer regimen; 1 patient was receiving alendronate for the treatment of osteopenia. Additional insight was provided by Marx et al in 2005, when they reviewed 119 cases of bisphosphonate-related bone exposure to determine the type, dosage, and duration of bisphosphonate therapy that the patients had received. They found that many osteonecrotic sites were related to extractions, periodontal diseases, periodontal surgeries, placement of dental implants, and apicoectomies, although spontaneous osteonecrosis occurred in 30 of the 119 patients. Most concerning were the 3 osteonecrotic cases related to the oral administration of alendronate for the treatment of osteoporosis. An estimated 18 million prescriptions for alendronate were written in 2005, and the half-life of the drug is estimated to be greater than 10 years, so there was concern that more patients with alendronate-associated necrosis of the jaw would surface. A systematic review in 2006 of all reports concerning bisphosphonates and osteonecrosis of the jaws uncovered a total of 368 cases. The authors noted that most cases involved intravenous bisphosphonates used to treat multiple myeloma or various metastatic diseases, although 15 cases of osteonecrosis were associated with the treatment of osteoporosis and oral bisphosphonates. The results of the systematic review should be viewed cautiously, however, since it was written before the establishment of the American Association of Oral and Maxillofacial Surgeons’ definition of osteonecrosis. Two nationwide studies in Japan showed an increased prevalence of osteonecrosis after improved awareness and monitoring.

Whereas the literature relating aspects of bisphosphonate use to osteonecrosis of the jaws is fairly well established, the research relating bisphosphonate use to orthodontic-specific complications has been largely anecdotal, relying heavily on biologic plausibility, animal studies, and scattered case reports. Decreased orthodontic tooth movement has been found in mice and rats that were administered bisphosphonates. Fujimura et al also used scanning electron micrographs and histologic stains to determine that bisphosphonates decrease osteoclast formation during orthodontic tooth movement in mice. A few case reports detailing the orthodontic treatment of patients who were taking bisphosphonates have been published. One report described 3 patients who underwent orthodontic treatment, with varying results. The first patient was a 60-year-old woman taking alendronate for osteoporosis. Her nonsurgical, nonextraction orthodontic treatment proceeded for 4.5 years before it was discontinued by the orthodontist because of decreased tooth movement and fear of osteonecrosis. The second patient was a 50-year-old woman who began taking alendronate before the extraction of a mandibular premolar and the start of orthodontic therapy to close the space. Despite discontinued bisphosphonate use within 6 months from the start of orthodontic bonding, slow tooth movement and poor root parallelism were observed throughout treatment. The third patient was a 74-year-old woman who had been taking alendronate for 3 years. In this case, the bisphosphonate was discontinued 3 months before the necessary incisor extraction and during the orthodontic treatment. Normal extraction healing, parallel roots, and space closure were achieved. Two case reports by Rinchuse et al offer additional insight. Their first patient was a 35-year-old woman taking oral bisphosphonates. She had extractions of the right first premolars, and the authors reported difficulty in closing these extraction spaces. In addition, treatment time was prolonged, and the finished results were less than ideal. The second patient reported on was 77 years old, and she was referred for space closure after removal of a mandibular incisor. Tooth movements and space closures were extremely difficult. After 11 more months, orthodontic treatment was discontinued because of a developing area of osteonecrosis in the posterior mandible. The spaces were incompletely closed, and the authors stated that any space closure that was achieved was the result of tipping, rather than bodily movement of the teeth.

Adults currently comprise over 20% of all orthodontic patients. Among this patient population are postmenopausal women, who are at an increased risk of developing osteoporosis due to decreased estrogen secretion and the complementary increase in osteoclastic activity. It is estimated that women comprise 80% of the approximately 12 million Americans older than age 50 who have osteoporosis and 80% of the approximately 40 million Americans over age 50 with osteopenia, contributing to the more than 24 million prescriptions for bisphosphonates issued in the United States during 2007. Although the American Dental Association has released updated dental management guidelines for specialists treating patients receiving oral bisphosphonate therapy, the orthodontic-specific guidelines are minimal. As a result of this lack of information and the perceived risks, many orthodontists are apprehensive about treating patients who take bisphosphonates.

With many postmenopausal women seeking orthodontic therapy, some of whom have been treated for osteoporosis with bisphosphonates, it is important to investigate the treatment outcomes and risks of osteonecrosis of the jaws in this population. The purposes of this retrospective study are to describe bisphosphonate use among an orthodontic population of older women and to determine the extent to which bisphosphonate therapy predisposes them to poor orthodontic outcomes, as measured by incomplete space closure, prolonged treatment time, nonparallel roots, incisor malalignment, and osteonecrosis of the jaws.