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Patterns of Maxillofacial Ischemic Bone Disease -- First Cadaver Investigation
ORAL MEDICINE e114 Abstracts Methods: Clinical and radiographic records of patients with established medication-related osteonecrosis of the jaw treated with either an oral regimen of pentoxifylline with vitamin E or low energy laser therapy were examined to determine if these treatments provided therapeutic benefit. The patients involved had been treated for a gastrointestinal stromal tumor (n¼1), multiple myeloma (n¼3) or metastatic breast cancer (n¼4). The treatment regimens applied to these patients involved zoledronic acid alone (n¼4), denosumab alone (n¼1) or combination therapy with zoledronic acid and denosumab (n¼1), zoledronic acid with pamidronate (n¼1) or zoledronic acid with sunitinib (n¼1). Results: Patients treated with low level laser therapy reported more immediate relief of symptoms than those on pentoxifylline with vitamin E. Patients on pentoxifylline with vitamin E demonstrated a gradual diminishment in the involved area of bone observed by Panoramic radiograph, but only after several years of treatment. Conclusions: Our case series illustrates that pentoxifylline with vitamin E and low energy laser therapy may be safe and effective adjuncts in the management of medication-related osteonecrosis of the jaw. Further investigation in the form of a pilot study is proposed.
INNOVATIVE APPROACH FOR RISK STRATIFICATION OF PATIENTS ON BISPHOSPHONATES NOAM YAROM, MERAV LEIBA, RAN YAHALOM, AYA PESSING, YAN GONG, NOA DAVIS, NOAM SHOMRON, JOSEPH KATZ. SCHOOL OF DENTAL MEDICINE, TEL AVIV UNIVERSITY, ISRAEL. Objectives: Osteonecrosis of the jaw (ONJ) may affect up to 18% of cancer patients treated with bisphosphonates. In many cases, dento-alveolar surgery is associated with the development of bisphosphonate-related ONJ (BRONJ). To date, there is no reliable assay to predict the risk of developing BRONJ. This reported trial is a multi-center, international study, aiming to unravel SNPs associated with BRONJ and to stratify the risk for ONJ. Methods: We sequenced 125 exomes of subjects receiving bisphosphonates due to multiple myeloma (106 patients) or other cancers (19 patients). Of these, 69 patients had BRONJ and 56 were disease-free for at least two years. Bioinformatics was performed as follows: short reads were mapped to a reference human genome with BWA aligner and variant calling was performed using the FreeBayes pipeline. Samples were divided into Training/Testing sets. We used PLINK to find candidate SNPs in the Training set and then to test them in the Testing set. Results: We found six SNPs that were associated with BRONJ (Thresholds were: P < .05 with False Positive Rate <20% in both sets). Additionally, 13 SNPs located in three genes showed association with the disease in an ethnicity-dependent manner. Some of these SNPs reside in genes with biological functions possibly relevant to the etiology of BRONJ. A statistical model yielded 93% sensitivity among cancer patients who developed BRONJ, and 68% specificity among BRONJ-free cancer patients. Conclusions: The 19 SNPs associated with BRONJ were discovered on a single sample set and tested on an independent set, which strengthens their reliability. Since there is no effective treatment for BRONJ, combining these SNPs into a predicting algorithm is instrumental in stratifying BRONJ risk in patients administrated with bisphosphonates who are candidate for dental surgery. Moreover, a predictive algorithm may be utilized by
OOOO October 2016 oncologists for the management of high-risk patients, and by dentists for personalized treatment plan.
PATTERNS OF MAXILLOFACIAL ISCHEMIC BONE DISEASE – FIRST CADAVER INVESTIGATION JERRY BOUQUOT, WESLEY SHANKLAND, FIROOZEH SAMIM. THE MAXILLOFACIAL CENTER FOR EDUCATION & RESEARCH, USA. Objectives: Chronic ischemic bone disease (CIBD) has very unique histopathologic, imaging and gross anatomic characteristics, including multi-site involvement and bone cavitations. While the gross appearances are well established in long bones, they remain largely unknown for the jaws, despite the fact that jaws are among the most commonly affected bones. The purpose of this investigation was to characterize CIBD in mandibles from a cadaver cohort representing patients with high risk of chronic systemic ischemia. Methods: 66 well-preserved mandibles, 62.2% from females, were harvested from cadavers with death from malignancy, cardiovascular and certain autoimmune diseases. The average age at death was 69.0 years (range: 42-91 years). Radiographs were taken and hemimandibles were sectioned sagittally after formic acid decalcification. Representative samples of cancellous bone were removed for microscopic evaluation from the third molar and premolar regions, as well as all grossly abnormal regions. Results: 24 mandibles (33.4%) had 34 areas of grossly abnormal bone, with an average lesion size of 14x4 mm (range: 5x3 to 31x9 mm.). The typical grossly visible lesion (n ¼ 34) was a soft brown discoloration (79.3%), with ischemic cavitations only in 11.8% & osteosclerosis in 5.9%; 79.4 of lesions were touching or surrounding the inferior mandibular nerve. 40.7% of positive gross sites showed CIBD microscopically, while 17.6% showed chronic fibrosing osteomyelitis. Only 11.2% of lesions were easily localized via radiographs. Conclusions: CIBD is seen in one third of cadaver mandibles from individuals who have died in presumably ischemic states. The lesions are typically in the molar/premolar region and often multiple. Radiographs did no help to localize most lesions.
SEVERITY OF HYPOSALIVATION IN THE POLYPHARMACY PATIENT POPULATION ARWA FARAG, MABI SINGH, MATTHEW FINKELMAN, ATHENA PAPAS. TUFTS UNIVERSITY SCHOOL OF DENTAL MEDICINE, USA. Objectives: Hyposalivation due to polypharmacy is among the most common complaints. It receives less attention compared to Sjögren syndrome (SJS) and post-radiation hyposalivation, despite its major effect on the patient’s quality of life. The aim of this study was to evaluate the severity of hyposalivation in patients with polypharmacy compared to those with SJS. Methods: Adult subjects with reported xerostomia due to SJS, medication (MED) and healthy controls were recruited to the Oral Medicine Clinic at Tufts University School of Dental Medicine between October and December of 2014. Demographic data, medical history and information about medications were collected. A five-point questionnaire (DMQ) was given to subjectively evaluate the severity of xerostomia. Oral examination and the Challancomb scale (10-point-scale) were used to
INNOVATIVE APPROACH FOR RISK STRATIFICATION OF PATIENTS ON BISPHOSPHONATES NOAM YAROM, MERAV LEIBA, RAN YAHALOM, AYA PESSING, YAN GONG, NOA DAVIS, NOAM SHOMRON, JOSEPH KATZ. SCHOOL OF DENTAL MEDICINE, TEL AVIV UNIVERSITY, ISRAEL. Objectives: Osteonecrosis of the jaw (ONJ) may affect up to 18% of cancer patients treated with bisphosphonates. In many cases, dento-alveolar surgery is associated with the development of bisphosphonate-related ONJ (BRONJ). To date, there is no reliable assay to predict the risk of developing BRONJ. This reported trial is a multi-center, international study, aiming to unravel SNPs associated with BRONJ and to stratify the risk for ONJ. Methods: We sequenced 125 exomes of subjects receiving bisphosphonates due to multiple myeloma (106 patients) or other cancers (19 patients). Of these, 69 patients had BRONJ and 56 were disease-free for at least two years. Bioinformatics was performed as follows: short reads were mapped to a reference human genome with BWA aligner and variant calling was performed using the FreeBayes pipeline. Samples were divided into Training/Testing sets. We used PLINK to find candidate SNPs in the Training set and then to test them in the Testing set. Results: We found six SNPs that were associated with BRONJ (Thresholds were: P < .05 with False Positive Rate <20% in both sets). Additionally, 13 SNPs located in three genes showed association with the disease in an ethnicity-dependent manner. Some of these SNPs reside in genes with biological functions possibly relevant to the etiology of BRONJ. A statistical model yielded 93% sensitivity among cancer patients who developed BRONJ, and 68% specificity among BRONJ-free cancer patients. Conclusions: The 19 SNPs associated with BRONJ were discovered on a single sample set and tested on an independent set, which strengthens their reliability. Since there is no effective treatment for BRONJ, combining these SNPs into a predicting algorithm is instrumental in stratifying BRONJ risk in patients administrated with bisphosphonates who are candidate for dental surgery. Moreover, a predictive algorithm may be utilized by
OOOO October 2016 oncologists for the management of high-risk patients, and by dentists for personalized treatment plan.
PATTERNS OF MAXILLOFACIAL ISCHEMIC BONE DISEASE – FIRST CADAVER INVESTIGATION JERRY BOUQUOT, WESLEY SHANKLAND, FIROOZEH SAMIM. THE MAXILLOFACIAL CENTER FOR EDUCATION & RESEARCH, USA. Objectives: Chronic ischemic bone disease (CIBD) has very unique histopathologic, imaging and gross anatomic characteristics, including multi-site involvement and bone cavitations. While the gross appearances are well established in long bones, they remain largely unknown for the jaws, despite the fact that jaws are among the most commonly affected bones. The purpose of this investigation was to characterize CIBD in mandibles from a cadaver cohort representing patients with high risk of chronic systemic ischemia. Methods: 66 well-preserved mandibles, 62.2% from females, were harvested from cadavers with death from malignancy, cardiovascular and certain autoimmune diseases. The average age at death was 69.0 years (range: 42-91 years). Radiographs were taken and hemimandibles were sectioned sagittally after formic acid decalcification. Representative samples of cancellous bone were removed for microscopic evaluation from the third molar and premolar regions, as well as all grossly abnormal regions. Results: 24 mandibles (33.4%) had 34 areas of grossly abnormal bone, with an average lesion size of 14x4 mm (range: 5x3 to 31x9 mm.). The typical grossly visible lesion (n ¼ 34) was a soft brown discoloration (79.3%), with ischemic cavitations only in 11.8% & osteosclerosis in 5.9%; 79.4 of lesions were touching or surrounding the inferior mandibular nerve. 40.7% of positive gross sites showed CIBD microscopically, while 17.6% showed chronic fibrosing osteomyelitis. Only 11.2% of lesions were easily localized via radiographs. Conclusions: CIBD is seen in one third of cadaver mandibles from individuals who have died in presumably ischemic states. The lesions are typically in the molar/premolar region and often multiple. Radiographs did no help to localize most lesions.
SEVERITY OF HYPOSALIVATION IN THE POLYPHARMACY PATIENT POPULATION ARWA FARAG, MABI SINGH, MATTHEW FINKELMAN, ATHENA PAPAS. TUFTS UNIVERSITY SCHOOL OF DENTAL MEDICINE, USA. Objectives: Hyposalivation due to polypharmacy is among the most common complaints. It receives less attention compared to Sjögren syndrome (SJS) and post-radiation hyposalivation, despite its major effect on the patient’s quality of life. The aim of this study was to evaluate the severity of hyposalivation in patients with polypharmacy compared to those with SJS. Methods: Adult subjects with reported xerostomia due to SJS, medication (MED) and healthy controls were recruited to the Oral Medicine Clinic at Tufts University School of Dental Medicine between October and December of 2014. Demographic data, medical history and information about medications were collected. A five-point questionnaire (DMQ) was given to subjectively evaluate the severity of xerostomia. Oral examination and the Challancomb scale (10-point-scale) were used to