Osteoporosis, a health threat of major public concern, is effectively managed with the oral administration of bisphosphonates. They significantly prevent skeletal complications, particularly fractures . Although bisphosphonates are generally well tolerated and side effects are rare, bisphosphonate exposure has been linked to ONJ, which in recent years has been highlighted to potentially constitute a problem of serious clinical importance. ONJ is most prevalent in patients suffering from metastatic bone disease, who have received nitrogen-containing bisphosphonates intravenously. Cases of ONJ due to osteoporosis bisphosphonate therapy are less frequent .
Recent studies have proclaimed that the annual intravenous administration of zoledronic acid for osteoporosis therapy is safe, particularly regarding the development of ONJ . In the HORIZON study, which encompassed 3876 patients, 76% (2950 patients) received three annual infusions of zoledronic acid and completed the follow-up . Whilst no cases of ONJ were initially reported, database searches and expert adjudications identified two potential cases of ONJ (one in the placebo group and one in the zoledronic acid group). However, the reliability of ONJ diagnosis based on database searches or questionnaires (as frequently performed in retrospective studies) is questionable. Indeed, a recent study has suggested that the study design is of crucial importance and any retrospective study results in a significant underestimation of ONJ prevalence. It is certainly a drawback that the definition and diagnosis of bisphosphonate-related ONJ currently excludes histopathological evidence and relies predominantly on the medical history . Since the inclusion of stadium 0 (no exposed bone, but unspecific symptoms of infection) in the staging of bisphosphonate-related ONJ , the diagnosis of early stages has to be considered to be vague, at best. Given that patients in stage 0 and I may only have unspecific symptoms (if any), it is of paramount importance to include detailed oral examinations in any diagnosis of bisphosphonate-related ONJ.
Despite the large number of patients included in the HORIZON trial, the follow-up period was relatively short (limited to 36 months following the commencement of the study and 12 months after the third and last infusion of zoledronic acid) . In light of the fact that bisphosphonates have an extremely long half-life in bone, patients will not only continue to benefit but also remain at risk of developing bisphosphonate-related ONJ for an extended period, especially when an odontogenic infection is present or dentoalveolar surgical procedures are performed. Bisphosphonates bind to bone at around neutral pH and are released in acidic milieus. This physiologic mechanism takes place in the resorption lacunas during bone resorption, a feature that has been linked to the pathogenesis of ONJ . Acidic conditions are common during infections and the jawbone is frequently subjected to acute and chronic infections. Indeed, in older patients (aged 65 or above) the prevalence of moderate to severe infections (periodontitis) exceeds 90%. The resulting change in pH may lead to a localized release and activation of bisphosphonates, which may trigger the onset of ONJ .
Detailed regular intraoral examinations are therefore imperative in order to treat dentoalveolar inflammations and detect early stages of ONJ lesions. If diagnosed timely, the outcomes of ONJ therapy are good; surgical approaches or conservative treatment strategies result in favorable outcomes in over 80% or 60%, respectively .
All patients receiving yearly infusions of bisphosphonates for osteoporosis should be adequately informed concerning the risk of ONJ. In addition, oral examinations and (where appropriate) preventive measures are called for in order to eliminate local inflammations--thereby minimizing the risk of ONJ manifestation.