Preventing or controlling periodontitis reduces the occurrence of osteonecrosis of the jaw (ONJ) in rice rats (Oryzomys palustris).

INTRODUCTION: Osteonecrosis of the jaw (ONJ) is an adverse event that requires association of both systemic risk factors, such as powerful anti-resorptives (pARs; e.g. zoledronic acid [ZOL]), and local oral risk factors (e.g. tooth extraction, periodontitis). Whereas optimal oral health prior to initiate pARs is recognized as critically important for minimizing ONJ risk, the efficacy of preventive/maintenance measures in patients who are taking pARs is understudied. Rice rats fed a standard diet (STD), rich in insoluble fiber, develop localized periodontitis. STD-rats with localized periodontitis treated with ZOL for 18-24 wk develop ONJ. Hence, we hypothesized that controlling/preventing localized periodontitis in the ZOL-treated rats, reduces ONJ occurrence. METHODS: We used two approaches to attempt reducing periodontitis prevalence: 1) periodontal cleaning (PC); and 2) replacing the STD-diet with a nutritionally-equivalent diet high in soluble fiber (SF). 75 four-week-old male rats were weight-randomized into five groups (n = 15) in a 24-week experiment. Three groups ate the STD-diet and two the high SF-diet. STD-diet groups received intravenous (IV) vehicle (VEH) q4wks (STD + VEH), 80 µg/kg ZOL q4wks IV (STD + ZOL), or ZOL plus PC q2wks (STD + ZOL + PC). The SF-diet groups received VEH (SF + VEH) or ZOL (SF + ZOL). Jaws were processed for histopathology and evaluated for ONJ prevalence and tissue-level periodontitis. RESULTS: 1) 40% of STD + VEH rats developed maxillary localized periodontitis with no ONJ; 2) 50% of STD + ZOL rats developed ONJ; 3) 7% of STD + ZOL + PC rats developed ONJ (p < 0.01 vs. STD + ZOL); and 4) one SF + ZOL rat developed localized periodontitis, and no SF + VEH or SF + ZOL rats developed ONJ (p < 0.001 vs. STD + ZOL). CONCLUSIONS: 1) Periodontal cleaning in ZOL-treated rats decreases localized periodontitis severity and reduces ONJ prevalence; and 2) feeding a SF-diet to ZOL-treated rats reduces both incidence of localized periodontitis and ONJ. Our data indicates strong oral microbial community shifts according to oral health condition and trends in the shifts associated with diet.

Anti-vascular endothelial growth factor antibody monotherapy causes destructive advanced periodontitis in rice rats (Oryzomys palustris).

OBJECTIVE: Angiogenesis inhibitors (AgI) are commonly used in combination chemotherapy protocols to treat cancer, and have been linked to osteonecrosis of the jaw (ONJ). However, it is unknown if AgI therapy alone is sufficient to induce ONJ. We have previously established an ONJ model in rice rats with localized periodontitis that receive zoledronic acid (ZOL). The purpose of this study was to use this model to determine the role of anti-vascular endothelial growth factor A (anti-VEGF) antibody treatment of rice rats with localized maxillary periodontitis. We hypothesized that rice rats with localized maxillary periodontitis given anti-VEGF monotherapy will develop oral lesions that resemble ONJ, defined by exposed, necrotic alveolar bone. METHODS: At age 4 weeks, 45 male rice rats were randomized into three groups (n = 15): 1) VEH (saline), 2) ZOL (80 µg/kg body weight, intravenously once monthly), and 3) anti-VEGF (5 mg B20-4.1.1/kg body weight, subcutaneously twice weekly). After 24 weeks, rats were euthanized, jaws were excised and a high-resolution photograph of each quadrant was taken to assign a severity grade based on gross appearance. Jaws were then fixed, scanned by MicroCT, decalcified and sectioned for histopathologic and immunohistochemical analyses. RESULTS: 40-80% of the rats in the three groups developed gross oral lesions. 50% of ZOL rats developed ONJ. In contrast, 80% of the anti-VEGF rats developed destructive advanced periodontitis that was characterized by extreme alveolar bone loss and fibrosis. Anti-VEGF rats never developed exposed, necrotic bone. Furthermore, only anti-VEGF rats developed mild to severe mandibular periodontitis. Compared to VEH rats, more T-cells were found in periodontal lesions of anti-VEGF rats and more cells of the monocyte lineage were found in ONJ lesions of ZOL rats. CONCLUSIONS: Anti-VEGF monotherapy administered to a validated rodent model of ONJ caused a destructive advanced form of periodontitis that differed significantly from ONJ.

Zoledronic acid increases the prevalence of medication-related osteonecrosis of the jaw in a dose dependent manner in rice rats (Oryzomys palustris) with localized periodontitis.

OBJECTIVE: Investigate role of dose/duration of zoledronic acid (ZOL), a powerful anti-resorptive (pAR), on prevalence of medication-related osteonecrosis of the jaw (MRONJ) in rice rats (Oryzomys palustris), a species with natural susceptibility to food impaction-induced localized periodontitis (FILP). We hypothesize that ZOL induces MRONJ lesions in rice rats with FILP, and that the prevalence of MRONJ rises with increasing dose and duration of ZOL treatment. METHODS: We performed a toxicology experiment with clinically-relevant doses of ZOL in female rats (N=230) fed standard (STD) rodent chow. At age 4weeks (baseline), 12 rats were necropsied. The rest were randomized into five groups that began to receive 0, 8, 20, 50 or 125µg/kg ZOL IV/q 4weeks. After 12, 18, 24 and 30weeks, subgroups (N=9-16) from each of the dose groups were necropsied. High-resolution macroscopic photos of all jaw quadrants were given a gross quadrant grade (GQG) (0-4 or MRONJ) that classified FILP lesion severity and determined presence of gross MRONJ. Quadrants with GQG≥1 were examined histopathologically. Logistic regression analysis (ZOL dose/duration) of MRONJ prevalence was completed. RESULTS: We found: 1) 75% of 0µg/kg ZOL rats developed FILP lesions; 2) baseline rats and rats treated with 0µg/kg ZOL had no MRONJ; 3) 29 gross MRONJ cases were identified; 4) all gross MRONJ cases were confirmed histopathologically by the observation of exposed necrotic bone, and 53 new cases were discovered (total=82); 5) ZOL dose (P<0.001), but not duration (P=0.326), was a significant predictor of MRONJ prevalence; 6) 13% prevalence of gross MRONJ among all rats, with 22% prevalence among rats exposed to ZOL oncologic doses (20-125µg/kg); 7) 38% prevalence of histopathologic MRONJ among all rats, with 73% prevalence among rats exposed to ZOL oncologic doses. CONCLUSIONS: This is the first experiment to show a dose response relationship between clinically relevant doses of ZOL and MRONJ prevalence.

Prevalence of dental caries and fluorosis in seven- to 12-year-old children in northern Newfoundland and Forteau, Labrador.

In 1993, a cross-sectional oral health survey of 739 randomly selected seven- to 12-year-old Canadian school children was conducted in Forteau (Labrador), Roddickton (northern Newfoundland), and Flower's Cove (northern Newfoundland) to determine the prevalence of dental caries and fluorosis. Children in grades two through six (n = 838) were selected to participate in the survey, which achieved a response rate of 88.2 per cent. Caries prevalence was estimated using modified World Health Organization (WHO) criteria (non-cavitated carious pits and fissures were coded separately from cavitated carious lesions). Fluorosis was measured using the Tooth Surface Index of Fluorosis (TSIF). In-school examinations were carried out by three dentists using portable equipment. There was a significantly higher percentage of caries-free children in Forteau (17.6 per cent) than in Roddickton (7.1 per cent) or Flower's Cove (8.3 per cent). Less than 20 per cent of the children surveyed in all regions had fluorosis. When fluorosis was present, it was mostly of the "very mild" type. Children from Forteau had a significantly lower mean number of decayed permanent teeth than children from the two other regions (1.6 in Forteau, versus 2.7 in Roddickton and 3.4 in Flower's Cove). The mean number of sealed teeth was significantly higher in Forteau children (mean = 1.1) compared with children from Roddickton (mean = 0.3) and Flower's Cove (mean = 0.03). In Forteau children, the F/DMFS2 (non-cavitated carious lesions excluded) ratio was 57 per cent, compared to a ratio of 29 per cent in children from Roddickton and 25 per cent in children from Flower's Cove. Similarly, the mean number of non-cavitated carious pits and fissures were higher than cavitated tooth surfaces by a ratio of 1.5 to 1. The risk markers significantly associated with lower DMFS scores were the number of sealants, lower grade level, college or university education of parents, and residence in Forteau. However, dental caries is endemic in the region and there is a clear need for an accessible school- and community-based oral health promotion and treatment program. In conclusion, this survey found that sealants are effective in preventing dental caries.

The risk of fluorosis in students exposed to a higher than optimal concentration of fluoride in well water.

OBJECTIVES: In December 1991 the residents of the community of Rigolet, Labrador, Canada, discovered that they were exposed to higher than 2.0 ppm fluoride in the drinking water from the new town well, which became operational in December 1983. In 1993 an investigation of the occurrence of fluorosis in children exposed to the high-fluoride water during different ages of life was carried out. METHODS: A dental examination for fluorosis was conducted using Pendrys' Fluorosis Risk Index. Out of 84 students in Rigolet, 74 were examined and the parents of 60 students agreed to be interviewed. Out of the 60 students, 48 lived all of their first six years of life in Rigolet. RESULTS: Of the 48 children with life-long residence, the odds ratio of fluorosis on enamel zones that began forming during the first year of life was 8.31 (95% CI = 1.84, 38.59) for children exposed since birth or during the first year of life relative to those exposed after 1 year of age. The odds that a child had a maxillary central incisor with fluorosis were 5.69 (95% CI = 1.34, 24.15) times higher if exposure occurred during the first yea of life compared with exposure after 1 year of age. Only those exposed to the high-fluoride water during the first year of life developed fluorosis on the mandibular central incisors. CONCLUSIONS: Within the limitations of this small population study, age relative to the date when the new water well became operational was a significant risk factor in development of fluorosis. The first year of life was a significant period for developing fluorosis on the mandibular and maxillary central incisors.

Stress in dental patients undergoing routine procedures.

A method was devised to record graphically the stress that patients experience during routine dental procedures. Heart rate was used as the indicator and the variations in it showed which parts of the treatment provoked the maximum stress reactions. This pilot study indicated that by using this method it is possible to study specific dental problems and methods for treating them.