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OI0240 Genetic susceptibility to orofacial granulomatosis
OOOO Volume 117, Number 5 specific IgA antibody, using either anti-IgA or antisecretory component antisera. Sequential samples showed that change in severity scores was significantly related to change in serum IgG and IgA antibodies (P ¼ .038 and P ¼ .011, respectively). Conclusions: Serum IgG and IgA antibodies to BP180NC16a are both highly specific for diagnosing and monitoring MMP. Assay of specific salivary IgA antibody is as sensitive as specific antibody detection in serum and indicates a secretory origin. Salivary biomarkers may be useful in the diagnosis of patients with MMP. The novel finding of locally produced antibodies needs further investigation, because it might provide some insight into the pathogenesis of the disease.
OI0240 GENETIC SUSCEPTIBILITY TO OROFACIAL GRANULOMATOSIS Shalini Nayee, Natalie Prescott, Michael Escudier, Alex Mentzer, Rishi Goel, Anita Nolan, UKIBD Consortium, Jack Satsangi, John Mansfield, Jeremy Sanderson, Dental Institute, King’s College London, London, United Kingdom Objectives: Orofacial granulomatosis (OFG) is a rare, disfiguring inflammatory disorder of the mouth of which a proportion of cases also have intestinal Crohn disease (CD). The etiology remains largely unknown, although there is high prevalence of allergy in OFG with and without CD. Our objective was to investigate whether OFG and CD have shared genetic etiology or whether OFG is mediated by distinct immune-related genetic susceptibility variants. Methods: Patients were clinically assessed and determined to have either isolated oral manifestations (OFG only) or concurrent intestinal CD (CD/OFG). Genomic DNA from 263 patients was genotyped using the Immunochip, a custom Illumina microarray assessing 196 524 genetic variants across multiple immune-related disease loci. Patient data were compared with data for 4307 population controls from the UK Inflammatory Bowel Disease Genetics Consortium (UKIBD Consortium). Statistical analysis was performed using PLINK (a whole-genome association analysis program) and the R statistical package. Results: Analyses found 2 significant associations (P < 2 106) within the OFG-only cohort with single nucleotide polymorphisms (SNPs) on chromosome 11 q13.5 near the LRRC32 gene (P ¼ 1.6 109) and on chromosome 6 (P ¼ 3.9 107) within the major histocompatibility complex (MHC) class I region. The 11 q13.5 locus has previously shown association with atopic conditions, and the MHC class I region is implicated in numerous allergic and autoimmune diseases, including CD. In addition, a highly suggestive association was detected from the CD/OFG group on chromosome 5 p13 (P ¼ 2.5 106), a known risk locus for CD. Collectively, these results suggest that OFG is influenced by common variants implicated in allergy and immunity, supporting the link between OFG and allergy. However, there may also be some overlap with genetic etiology for CD. Replication in a larger independent cohort is required to substantiate our findings. Conclusions: OFG is likely to be a complex disease mediated by diverse genetic variants, sharing genetic susceptibility with allergic disorders and autoimmune conditions such as CD. Funding sources: Friends of Guy’s Hospital.
OI0271 TIME TO BISPHOSPHONATE-ASSOCIATED OSTEONECROSIS OF THE JAW DIAGNOSIS: RESULTS FROM A LARGE MULTICENTER STUDY Polly Pok-Lam Fung, Aviva Petrie, Stephen Porter, Stefano Fedele; on
ABSTRACTS Abstracts e335 behalf of the GENVABO Consortium, Oral Medicine Unit, University College London Eastman Dental Institute, London, United Kingdom Objectives: There has been limited evidence on the time to bisphosphonate-associated osteonecrosis of the jaw (BONJ), particularly its association with any potential factors. This study aimed (1) to report time elapsed from first bisphosphonate use to BONJ diagnosis in a large multicenter cohort and (2) to investigate its association with a large number of potential factors using robust statistics. Methods: This is a retrospective study of 348 patients with BONJ recruited from 20 European centers. Time to BONJ was the primary outcome, and was defined as the period from the initiation of bisphosphonates to BONJ diagnosis. The secondary outcome was the association between the primary outcome (dependent variable) and 11 potential factors, regarding demography, bisphosphonate therapy, medical history, and dental history (independent variables). The association was first investigated with univariable analyses, consisting of linear regression, MannWhitney tests, and Kruskal-Wallis tests. Factors that were statistically significant at the 10% level in the univariable analyses were entered into a multivariable linear regression using a significance level of 5%. All analyses were performed in Stata 11.0. Results: The median time to BONJ diagnosis was 39.5 months. Multivariable linear regression found that, on average, (1) individuals with metastatic prostate cancer (P ¼ .011) or multiple myeloma (P ¼ .044) had significantly shorter time to BONJ than osteoporosis patients; (2) individuals exposed to zoledronate (P ¼ .003) had significantly shorter time to BONJ than those on alendronate; and (3) individuals with previous dentoalveolar surgery (P ¼ .007) had significantly longer time to BONJ than those with no previous surgery. Conclusions: The current study investigated time to BONJ diagnosis in the largest cohort of patients to date, recruited from the largest number of centers, and it analyzed the largest number of factors. The current study confirms that malignancy and zoledronate are risk factors for early BONJ. This is also the first study showing that dentoalveolar surgery delays BONJ occurrence.
OI0308 CLASS IV LASER THERAPY IN PEDIATRICS AFFECTED BY CHEMOTHERAPY-INDUCED ORAL MUCOSITIS Maddalena Chermetz, Margherita Gobbo, Giulia Ottaviani, Serena Zacchigna, Roberto Di Lenerda, Matteo Biasotto, Dental Science Department, Division of Oral Medicine and Pathology, Trieste, Italy Objectives: Oral mucositis (OM) is a debilitating side effect of chemotherapy. Laser therapy has recently proved efficacious in its management. This prospective study evaluates the efficacy of class IV high-power laser therapy (HPLT) in healing OM and in reducing related pain. Methods: 18 oncohematologic pediatric patients receiving cancer therapies and affected by OM were enrolled 7.5 3.0 days after the end of a chemotherapy cycle. Patients were treated with HPLT during 4 consecutive days (970 nm, 5 W (50%), 35-6000 Hz, 230 s). At first visit, assessment of OM was performed with the WHO scale, and pain was evaluated with a visual analog scale (VAS). Patients were reevaluated by a blinded operator at day 11 (11 days after the beginning of laser therapy). Neutrophil counts and white blood cell (WBC) counts were recorded on days 1, 4, and 11. Data were analyzed using SPSS, version 11.0. Categorical variables were presented as absolute frequencies and
OI0240 GENETIC SUSCEPTIBILITY TO OROFACIAL GRANULOMATOSIS Shalini Nayee, Natalie Prescott, Michael Escudier, Alex Mentzer, Rishi Goel, Anita Nolan, UKIBD Consortium, Jack Satsangi, John Mansfield, Jeremy Sanderson, Dental Institute, King’s College London, London, United Kingdom Objectives: Orofacial granulomatosis (OFG) is a rare, disfiguring inflammatory disorder of the mouth of which a proportion of cases also have intestinal Crohn disease (CD). The etiology remains largely unknown, although there is high prevalence of allergy in OFG with and without CD. Our objective was to investigate whether OFG and CD have shared genetic etiology or whether OFG is mediated by distinct immune-related genetic susceptibility variants. Methods: Patients were clinically assessed and determined to have either isolated oral manifestations (OFG only) or concurrent intestinal CD (CD/OFG). Genomic DNA from 263 patients was genotyped using the Immunochip, a custom Illumina microarray assessing 196 524 genetic variants across multiple immune-related disease loci. Patient data were compared with data for 4307 population controls from the UK Inflammatory Bowel Disease Genetics Consortium (UKIBD Consortium). Statistical analysis was performed using PLINK (a whole-genome association analysis program) and the R statistical package. Results: Analyses found 2 significant associations (P < 2 106) within the OFG-only cohort with single nucleotide polymorphisms (SNPs) on chromosome 11 q13.5 near the LRRC32 gene (P ¼ 1.6 109) and on chromosome 6 (P ¼ 3.9 107) within the major histocompatibility complex (MHC) class I region. The 11 q13.5 locus has previously shown association with atopic conditions, and the MHC class I region is implicated in numerous allergic and autoimmune diseases, including CD. In addition, a highly suggestive association was detected from the CD/OFG group on chromosome 5 p13 (P ¼ 2.5 106), a known risk locus for CD. Collectively, these results suggest that OFG is influenced by common variants implicated in allergy and immunity, supporting the link between OFG and allergy. However, there may also be some overlap with genetic etiology for CD. Replication in a larger independent cohort is required to substantiate our findings. Conclusions: OFG is likely to be a complex disease mediated by diverse genetic variants, sharing genetic susceptibility with allergic disorders and autoimmune conditions such as CD. Funding sources: Friends of Guy’s Hospital.
OI0271 TIME TO BISPHOSPHONATE-ASSOCIATED OSTEONECROSIS OF THE JAW DIAGNOSIS: RESULTS FROM A LARGE MULTICENTER STUDY Polly Pok-Lam Fung, Aviva Petrie, Stephen Porter, Stefano Fedele; on
ABSTRACTS Abstracts e335 behalf of the GENVABO Consortium, Oral Medicine Unit, University College London Eastman Dental Institute, London, United Kingdom Objectives: There has been limited evidence on the time to bisphosphonate-associated osteonecrosis of the jaw (BONJ), particularly its association with any potential factors. This study aimed (1) to report time elapsed from first bisphosphonate use to BONJ diagnosis in a large multicenter cohort and (2) to investigate its association with a large number of potential factors using robust statistics. Methods: This is a retrospective study of 348 patients with BONJ recruited from 20 European centers. Time to BONJ was the primary outcome, and was defined as the period from the initiation of bisphosphonates to BONJ diagnosis. The secondary outcome was the association between the primary outcome (dependent variable) and 11 potential factors, regarding demography, bisphosphonate therapy, medical history, and dental history (independent variables). The association was first investigated with univariable analyses, consisting of linear regression, MannWhitney tests, and Kruskal-Wallis tests. Factors that were statistically significant at the 10% level in the univariable analyses were entered into a multivariable linear regression using a significance level of 5%. All analyses were performed in Stata 11.0. Results: The median time to BONJ diagnosis was 39.5 months. Multivariable linear regression found that, on average, (1) individuals with metastatic prostate cancer (P ¼ .011) or multiple myeloma (P ¼ .044) had significantly shorter time to BONJ than osteoporosis patients; (2) individuals exposed to zoledronate (P ¼ .003) had significantly shorter time to BONJ than those on alendronate; and (3) individuals with previous dentoalveolar surgery (P ¼ .007) had significantly longer time to BONJ than those with no previous surgery. Conclusions: The current study investigated time to BONJ diagnosis in the largest cohort of patients to date, recruited from the largest number of centers, and it analyzed the largest number of factors. The current study confirms that malignancy and zoledronate are risk factors for early BONJ. This is also the first study showing that dentoalveolar surgery delays BONJ occurrence.
OI0308 CLASS IV LASER THERAPY IN PEDIATRICS AFFECTED BY CHEMOTHERAPY-INDUCED ORAL MUCOSITIS Maddalena Chermetz, Margherita Gobbo, Giulia Ottaviani, Serena Zacchigna, Roberto Di Lenerda, Matteo Biasotto, Dental Science Department, Division of Oral Medicine and Pathology, Trieste, Italy Objectives: Oral mucositis (OM) is a debilitating side effect of chemotherapy. Laser therapy has recently proved efficacious in its management. This prospective study evaluates the efficacy of class IV high-power laser therapy (HPLT) in healing OM and in reducing related pain. Methods: 18 oncohematologic pediatric patients receiving cancer therapies and affected by OM were enrolled 7.5 3.0 days after the end of a chemotherapy cycle. Patients were treated with HPLT during 4 consecutive days (970 nm, 5 W (50%), 35-6000 Hz, 230 s). At first visit, assessment of OM was performed with the WHO scale, and pain was evaluated with a visual analog scale (VAS). Patients were reevaluated by a blinded operator at day 11 (11 days after the beginning of laser therapy). Neutrophil counts and white blood cell (WBC) counts were recorded on days 1, 4, and 11. Data were analyzed using SPSS, version 11.0. Categorical variables were presented as absolute frequencies and