Abstract

Osteonecrosis of the jaw (ONJ) is a frequent complication in bisphosphonate-treated multiple myeloma (MM) patients. The pathogenesis is unclear, and major risk factors are duration of bisphosphonate treatment and dental procedures. The histology of osteonecrotic bone shows osteomyelitis and inflammatory infiltrates, and, in most cases, presence of Actynomycetes. Since dental procedures are a major risk factor for ONJ development and oral microflora can be involved in the pathogenesis of the disease, we conducted a retrospective observational trial comparing ONJ occurrence and related risk factors in two groups of MM patients, who received zoledronic acid treatment at two Italian hematological centres. In one centre all patients systematically received as antibiotic prophylaxis amoxicillin-clavulanate 1 gm bid or levofloxacin 500 mg once a day starting from one day before to 3 days after any dental procedure (group A, 52 patients), while in the other centre patients did not receive any prophylaxis (group B, 61 patients). Dental procedures were categorized according to their invasivity and their supposed probability to cause ONJ. Extractions, implants, and professional cleanings were considered at high risk, while fillings were considered low risk procedures. Thirty-three group A patients (63%) and 32 group B patients (52%) received high risk procedures; 4 group A patients (8%) and 5 group B patients (8%) received low risk procedures, while 15 (29%) and 24 (39%) patients, respectively, had a denture. The duration of zoledronic acid exposure differed significantly between the two groups, with a median of 26 months for A patients and 12 months for B patients (p<0.0001). In group A no cases of ONJ were observed, while in group B 8 cases (13%) of ONJ were diagnosed, with a significant difference between the two groups (p=0.007). There was a temporal correlation between dental procedure and ONJ, with a median time of 60 days (range 37–990). The relative risk of ONJ after a dental procedure was 4.8 (p=0.01). The pooled analysis of the two groups showed that age, sex, transplant procedure, and thalidomide therapy did not correlate with ONJ. In both groups the presence of dentures was not associated with ONJ. While in group B incidence of ONJ is consistent with data reported in the literature, which range between 7% and 11%, group A patients had an unexpected low occurrence of this complication, despite a significantly longer exposure to zoledronic acid. This finding suggests a possible role of antibiotic prophylaxis in protecting from ONJ after dental procedures. Further, our observation, along with the correlation between dental procedures and ONJ development, can contribute to the proposal of a comprehensive model of ONJ pathogenesis: trauma of the alveolar bone modified by bisphosphonates induces a bacterial translocation with a subsequent induction of infection, inflammation and necrosis. In this perspective, since antibiotic prophylaxis is a simple and low cost precaution, it’s reasonable to propose it as part of standard care to zoledronic acid treated MM patients before any dental procedure.

Author notes

Disclosure: No relevant conflicts of interest to declare.