Biphosphonate-induced osteonecrosis of the jaws (ONJ) was first described in the literature in 2003. Biphosphonates, which are structural analogues of inorganic pyrophosphate, inhibit the formation, aggregation and dissolution of calcium phosphate crystals; they have a high affinity for the mineralised bone matrix and can inhibit osteoclast-mediated osseous resorption. They are divided into non-aminobiphosphonates (etidronate, clodronate, tiludronate) and aminobiphosphonates (alendronate, ibandronate, neridronate, risedronate, pamidronate, zoledronate), which have a more powerful inhibitory effect on osteoclast-mediated osseous resorption. In 2009 the AAOMS estimated the incidence of i.v. biphosphonate-induced ONJ to be 0.8–12%, and that of ONJ induced by oral biphosphonates to be 0.01–0.1%. In recent years, preventive measures have been introduced, to be adopted in all patients about to begin biphosphonate treatment, as well as behavioural measures to be adopted in patients under bisphosphonate therapy requiring dental treatment to prevent ONJ.
To establish the incidence of the disease over the years, and whether this incidence fell in 2009; to investigate correlations between ONJ and gender, age, underlying disease, type of biphosphonate taken and duration of biphosphonate treatment; to investigate treatments instituted.
Materials and methods:
We collected data on all cases of ONJ diagnosed at the Careggi Hospital in Florence up to December 2009: the sample was made up of 59 patients (24 men, 35 women). We performed a statistical analysis of the data in our possession. No patient was excluded from the study.
The incidence of the disease was higher in the women (59.32% versus 40.68%) and this difference was statistically significant. The mean age at diagnosis was 66 years, 8 months, with a difference emerging between the women (67 yrs 6 mths) and the men (65 yrs 3 mths). The drug responsible for the highest number of cases of ONJ was zoledronate (86.44%), followed by alendronate and pamidronate (both 5.08%), and risendronate (3.40%). The most frequent of the underlying diseases requiring the use of biphosphonates was multiple myeloma (32.20%), followed by breast cancer (25.42%) and osteoporosis (10.17%). These were followed, in order of frequency, by prostate cancer, lung cancer, lymphomas and leukaemia. The oldest diagnoses dated back to 2004. The year with the smallest number of diagnosed cases was 2009, in which 4 cases of ONJ were detected (6.78% of the total). Of these, 3 patients had taken alendronate (in 2 cases for osteoporosis) and 1 zometa. The duration of treatment varied, ranging from 3 months to 11 years (mean 30.4 months).
The appearance of the lesions was due to: tooth extractions (77.97%), trauma caused by dental prostheses (15.25%), endodontics (1.69%), implantology (1.69%), no dental intervention (1.69%). In most cases the lesions were mandibular (57.6%), in 27.1% maxillary and in 15.2% of cases present at both levels.
At diagnosis, 56 patients were at stage 2 (95%) and 3 at stage 3 (5%) of the AAOMS staging system. The stage 3 patients were treated with surgical mandibular resection and vascularised graft, while the stage 2 patients received pharmacological therapy, in some cases associated with minor surgery and hyperbaric oxygen therapy (HBOT).
From the data gathered in recent years on patients diagnosed with ONJ at our service, we can conclude that zoledronate caused most of the cases of ONJ. It was thus confirmed as the drug with the greatest potency and affinity, as has been shown by the literature. It can be noted that osteoporosis was found to be the third most frequent underlying disease and that the incidence of ONJ fell in 2009, presumably due to increased understanding of the condition, but that, contrary to the overall mean, in 2009 half of the cases were osteoporosis patients who had taken alendronate.