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OBJECTIVE: This literature review was performed to elucidate the relationship between bisphosphonate use and development of osteonecrosis of the jaw (ONJ) in patients receiving oral bisphosphonates for the treatment of osteoporosis. METHODS: MEDLINE, the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, and EMBASE were searched for English-language articles published from 1966 to September 2006 whose titles included the term osteonecrosis of the jaw in conjunction with bisphosphonates, alendronate, risedronate, ibandronate, etidronate, clodronate, zoledronic acid, or pamidronate. Articles were included in the review if the population consisted of adults with ONJ; patients received bisphosphonates for the treatment of osteoporosis only; the reported data included baseline characteristics of the study population (age; sex; comorbidities; concomitant medications; history of dental surgery, trauma, or infection), characteristics of bisphosphonate treatment (specific bisphosphonate, dose, duration of treatment, mode of administration), clinical features of ONJ (signs, symptoms, site), the treatment protocol used to manage ONJ, or the prevalence of ONJ in patients with osteoporosis treated with bisphosphonates; and the publication involved a case report, case series, or observational study. RESULTS: After application of the search strategy and the inclusion/exclusion criteria, 11 publications reporting 26 cases of ONJ in patients receiving bisphosphonates for the treatment of osteoporosis were included in the review. The most commonly affected site was the mandible (16 patients), followed by the maxilla (6 patients). Among the 23 patients whose age was reported, 18 (78%) were aged >or=60 years. Among the 23 patients whose sex was reported, only 3 (13%) were men. Of 15 patients with a history of invasive dental treatment, 12 (80%) had undergone dental surgery or experienced dental trauma at the site of ONJ. Among the 10 patients for whom the duration of bisphosphonate treatment was reported, no clear relationship between the duration of bisphosphonate treatment and the development of ONJ was observed. CONCLUSIONS: Considering that millions of patients have been prescribed bisphosphonates for the treatment of osteoporosis, the relative prevalence of ONJ in these patients was low. Age >or=60 years, female sex, and previous invasive dental treatment were the most common characteristics of those who developed ONJ. However, it is not possible to draw further conclusions about the potential association between oral bisphosphonate use and ONJ in the identified studies because of incomplete reporting and the presence of confounding factors.

Original publication




Journal article


Clin ther

Publication Date





1548 - 1558


Administration, Oral, Adult, Age Factors, Aged, Aged, 80 and over, Bone Density Conservation Agents, Diphosphonates, Female, Humans, Jaw Diseases, Male, Middle Aged, Oral Surgical Procedures, Osteonecrosis, Osteoporosis, Prevalence, Risk Assessment, Risk Factors, Sex Factors