Resumen de Periodontal Disease as a Risk Factor for Bisphosphonate-Related Osteonecrosis of the Jaw
Background: Previous case reports and animal studies suggest that periodontitis is associated with bisphosphonate-related osteonecrosis of the jaw (BRONJ). This case-control study is conducted to evaluate the association between clinical and radiographic measures of periodontal disease and BRONJ.
Methods: Twenty-five patients with BRONJ were matched with 48 controls. Trained examiners measured probing depth, clinical attachment level (CAL), and bleeding on probing on all teeth except third molars and gingival and plaque indices on six index teeth. Alveolar bone height was measured from orthopantomograms. Most patients with BRONJ were using antibiotics (48%) or a chlorhexidine mouthrinse (84%) at enrollment. Adjusted comparisons of patients with BRONJ versus controls used multiple linear regression.
Results: The average number of bisphosphonate (BP) infusions was significantly higher in patients with BRONJ compared with controls (38.4 versus 18.8, P = 0.0001). In unadjusted analyses, patients with BRONJ had more missing teeth (7.8 versus 3.1, P = 0.002) and higher average CAL (2.18 versus 1.56 mm, P = 0.047) and percentage of sites with CAL =3 mm (39.0 versus 23.3, P = 0.039) than controls. Also, patients with BRONJ had lower average bone height (as a fraction of tooth length, 0.59 versus 0.62, P = 0.004) and more teeth with bone height less than half of tooth length (20% versus 6%, P = 0.001). These differences remained significant after adjusting for age, sex, smoking, and number of BP infusions.
Conclusions: BRONJ patients have fewer teeth, greater CAL, and less alveolar bone support compared with controls after adjusting for number of BP infusions. Group differences in antibiotics and chlorhexidine rinse usage may have masked differences in the other clinical measures.
Case reports suggest that periodontitis may predispose patients to developing bisphosphonate-related osteonecrosis of the jaw (BRONJ).1,2 In a seminal paper, Marx et al.1 noted that 84% of patients with BRONJ had periodontal disease, including 29% with advanced disease. Similarly, a large chart review study by Hoff et al.3 noted a high prevalence (41%) of periodontitis in patients with BRONJ. Ficarra et al.4 reported a series of nine patients with severe periodontal disease in whom BRONJ was noted after extraction of periodontally �hopeless� teeth.
Periodontal pathogens also have been isolated from BRONJ lesions. In a retrospective study, Badros et al.2 identified Prevotella, Porphyromonas, Fusobacterium, Peptostreptococcus, Streptococcus sp., and Eikenella species in nine of 17 patients with BRONJ. Lesions in the remaining eight patients contained Actinomyces species. Likewise, Sedghizadeh et al.5 showed that bone sections from BRONJ sites contained microbial biofilms comprising predominantly Fusobacterium, Actinomyces, Staphylococcus, Streptococcus, Selenomonas, and Treponemes species. The contribution of these organisms to BRONJ development is unknown, and it is important to determine whether specific bacteria contribute to BRONJ development or merely colonize previously exposed bone.
Researchers also have studied the role of periodontal disease in BRONJ development using animal models.6,7 Aghaloo et al.6 noted that 47% of zoledronate-treated rats showed histologic and radiologic evidence of osteonecrosis and 21% showed evidence of exposed bone in the presence of ligature-induced periodontitis, whereas none in the control group showed evidence of exposed bone. Similarly, Aguirre et al.7 noted that high doses of zoledronate exacerbated the inflammatory response and periodontal tissue damage and induced BRONJ-like lesions in rats.
Although observations in both humans and animals suggest that periodontal disease may affect risk for BRONJ development,2,8-10 there are few epidemiologic studies evaluating the association between periodontal disease and BRONJ in humans. Therefore, this case-control study is conducted to evaluate the association between clinical and radiographic measures of periodontal disease and BRONJ development.
