Risk factors for osteonecrosis of the jaws: a case-control study from the CONDOR Dental PBRN.

Case reports and cohort studies have linked bisphosphonate therapy and osteonecrosis of the jaws (ONJ), but neither causality nor specific risks for lesion development have been clearly established. We conducted a 1:3 case-control study with 3 dental practice-based research networks, using dentist questionnaires and patient interviews for collection of data on bisphosphonate therapy, demographics, co-morbidities, and dental and medical treatments. Multivariable logistic regression analyses tested associations between bisphosphonate use and other risk factors with ONJ. We enrolled 191 ONJ cases and 573 controls in 119 dental practices. Bisphosphonate use was strongly associated with ONJ (odds ratios [OR] 299.5 {95% CI 70.0-1282.7} for intravenous [IV] use and OR = 12.2 {4.3-35.0} for oral use). Risk markers included local suppuration (OR = 7.8 {1.8-34.1}), dental extraction (OR = 7.6 {2.4-24.7}), and radiation therapy (OR = 24.1 {4.9-118.4}). When cancer patients (n = 143) were excluded, bisphosphonate use (OR = 7.2 {2.1-24.7}), suppuration (OR = 11.9 {2.0-69.5}), and extractions (OR = 6.6 {1.6-26.6}) remained associated with ONJ. Higher risk of ONJ began within 2 years of bisphosphonate initiation and increased 4-fold after 2 years. Both IV and oral bisphosphonate use were strongly associated with ONJ. Duration of treatment >2 years; suppuration and dental extractions were independent risk factors for ONJ.

ONJ in two dental practice-based research network regions.

The incidence of osteonecrosis of the jaw (ONJ) in the population is low, but specifics are unknown. Potential risk factors include bisphosphonate treatment, steroid treatment, osteoporosis, and head/neck radiation. This Dental Practice-Based Research Network study estimated ONJ incidence and odds ratios from bisphosphonate exposure and other risk factors using a key word search and manual chart reviews of electronic records for adults aged > or = 35 years enrolled during 1995-2006 in 2 large health care organizations. We found 16 ONJ cases among 572,606 cohort members; 7 additional cases were identified through dental plan resources. Among 23 cases (0.63 per 100,000 patient years), 20 (87%) had at least 1 risk factor, and 6 (26%) had received oral bisphosphonates. Patients with oral bisphosphonates were 15.5 (CI, 6.0-38.7) more likely to have ONJ than non-exposed patients; however, the sparse number of ONJ cases limits firm conclusions and suggests that the absolute risks for ONJ from oral bisphosphonates is low.

Dental risk factors for osteonecrosis of the jaws: a CONDOR case-control study.

BACKGROUND: Reports of osteonecrosis of the jaw (ONJ) have associated this lesion to treatment with bisphosphonates (BPs) and dental procedures. In this study, we investigated the association of specific dental diagnoses and procedures with ONJ among patients with past BP use. METHODS: Dentists from three practice-based research networks provided ONJ cases and controls (1:3). Data gathered from patients and dental offices with two respective standard questionnaires included demographic, medical, pharmaceutical, and dental information. Diagnoses and procedures up to 3 years prior to ONJ (prior to interview for controls) were analyzed within risk strata, defined by BP use and cancer status, using interaction terms within conditional logistic regression models. RESULTS: We enrolled 191 ONJ cases and 573 controls from 119 dental offices. Among participants who had used only oral BP, extraction was the only dental risk factor for ONJ (odds ratio (OR) = 12, p = 0.01). Suppuration was also more prevalent in cases (18 %) than in controls (9 %), but not statistically significant (OR = 9, p = 0.06). Among participants who had not used either oral or IV BP (a majority of whom received radiation therapy to the head and neck), suppuration was the only dental risk factor for ONJ (prevalence = 34 % for cases and 8 % for controls; OR = 7, p = 0.01). The prevalence of extractions in this group was also higher, but not statistically significant (44 vs 10 %; OR = 3). Limited power precludes definitive findings among participants exposed to IV BP. CONCLUSIONS: Among patients taking oral BP, extraction was the only dental procedure associated with subsequent ONJ development CLINICAL RELEVANCE: Results of this study suggest that routine dental procedures are not associated with development of ONJ in patients exposed to BPs.

ONJ in two dental practice-based research network regions.

The incidence of osteonecrosis of the jaw (ONJ) in the population is low, but specifics are unknown. Potential risk factors include bisphosphonate treatment, steroid treatment, osteoporosis, and head/neck radiation. This Dental Practice-Based Research Network study estimated ONJ incidence and odds ratios from bisphosphonate exposure and other risk factors using a key word search and manual chart reviews of electronic records for adults aged ≥ 35 yrs enrolled during 1995-2006 in two large health-care organizations. We found 16 ONJ cases among 572,606 cohort members; seven additional cases were identified through dental plan resources. Among 23 cases (0.63 per 100,000 patient years), 20 (87%) had at least one risk factor, and six (26%) had received oral bisphosphonates. Patients with oral bisphosphonates were 15.5 (CI, 6.0-38.7) more likely to have ONJ than non-exposed patients; however, the sparse number of ONJ cases limits firm conclusions and suggests that the absolute risks for ONJ from oral bisphosphonates is low.

Risk factors for osteonecrosis of the jaws: a case-control study from the CONDOR dental PBRN.

Case reports and cohort studies have linked bisphosphonate therapy and osteonecrosis of the jaws (ONJ), but neither causality nor specific risks for lesion development have been clearly established. We conducted a 1:3 case-control study with three dental Practice-based Research Networks, using dentist questionnaires and patient interviews for collection of data on bisphosphonate therapy, demographics, co-morbidities, and dental and medical treatments. Multivariable logistic regression analyses tested associations between bisphosphonate use and other risk factors with ONJ. We enrolled 191 ONJ cases and 573 controls in 119 dental practices. Bisphosphonate use was strongly associated with ONJ (odds ratios [OR] 299.5 {95%CI 70.0-1282.7} for intravenous [IV] use and OR = 12.2 {4.3-35.0} for oral use). Risk markers included local suppuration (OR = 7.8 {1.8-34.1}), dental extraction (OR = 7.6 {2.4-24.7}), and radiation therapy (OR = 24.1 {4.9-118.4}). When cancer patients (n = 143) were excluded, bisphosphonate use (OR = 7.2 {2.1-24.7}), suppuration (OR = 11.9 {2.0-69.5}), and extractions (OR = 6.6 {1.6-26.6}) remained associated with ONJ. Higher risk of ONJ began within 2 years of bisphosphonate initiation and increased four-fold after 2 years. Both IV and oral bisphosphonate use were strongly associated with ONJ. Duration of treatment > 2 years; suppuration and dental extractions were independent risk factors for ONJ.

Long-term adverse effects of hematopoietic stem cell transplantation on dental development in children.

PURPOSE: The purpose of this study was to assess late effects of cytotoxic therapy with hematopoietic stem cell transplantation (HCT) on dental development in survivors of childhood cancer. MATERIALS AND METHODS: Forty children who underwent allogeneic HCT for a variety of hematological malignancies were evaluated at a minimum of 2 years after transplantation. We obtained information on oral symptoms, exposed panoramic radiographs (PRG), and performed an oral examination. PRGs were scored for agenesis and root and/or crown abnormalities. The root-crown ratio was calculated, and dental age was assessed using Demirjian' s method. MAIN RESULTS: The studied group showed a significantly higher prevalence of tooth agenesis compared to normative data for first and second premolars in both the maxilla and mandible, as well as the second molars in the mandible (all p values <0.001). Children who were <3 years old at the time of cancer treatment had significantly more missing teeth than older children, F(2,37) = 7.58, p < 0.002. Root-crown ratios were lower in the study sample than those from normative data. In addition, the mean dental age was higher (as a result of earlier apical root closure) than the mean chronological age, t(28) = 2.47, p < 0.020. CONCLUSIONS: Nearly all children examined had dental development disturbances, including agenesis, short roots, and arrested root development. An oral/dental evaluation and preventative oral supportive care regimens should be part of programs monitoring late effects in long-term survivors of childhood cancer.

Prevalence of oral soft tissue lesions in HIV-infected minority children treated with highly active antiretroviral therapies.

PURPOSE: This project studied the prevalence of oral soft tissue disease in HIV-infected children treated with highly active antiretroviral therapy (HAART). METHODS: Thirty-eight HIV-infected children participated in the study. Twenty-three of these patients were treated with HAART while 14 received exclusively reverse transcriptase inhibitors (RTI) and served as controls. The children were examined three times at approximately one-month intervals while their health history and laboratory data were abstracted from medical charts. Analyses were performed to determine differences in lesion prevalence between treatment groups as well as between lesion and no lesion groups with regard to immune differences. RESULTS: Thirty patients (79%) had oral lesions detected in at least one visit. There were no differences in specific lesion prevalence between HAART compared with RTI-treated children. However, a trend for more oral candidiasis in the latter group was observed. Subjects with oral soft tissue lesions had lower CD4 counts (P = 0.04) and percentage (P = 0.01) but similar viral loads when compared to patients without oral soft tissue disease. CONCLUSIONS: HAART does not appear to significantly affect oral soft tissue disease prevalence in HIV-infected children. Presence of lesions was associated with decreased immunity and may signal advancing disease.

Oral soft tissue manifestations in HIV-positive vs. HIV-negative children from an inner city population: a two-year observational study.

PURPOSE: Data accrued after two years of longitudinal observation of oral soft tissue lesions in a cohort of HIV-infected children and comparisons to a group of uninfected controls is presented. SUBJECTS AND METHODS: One hundred and four HIV-positive subjects were enrolled from an inner city pediatric HIV clinic and HIV-negative household peers served as control. Oral exams were performed at six-month intervals while laboratory data of interest were obtained from the children's medical records. RESULTS: HIV-positive children had significantly more oral soft tissue lesions than their HIV-negative peers. In particular, the prevalence of candidiasis, linear gingival erythema and median rhomboid glossitis were high. However, oral lesions were not good predictors of mortality and only candidiasis was associated with a low CD4 count. CONCLUSIONS: Oral soft tissue lesions were common among HIV-positive children. While candidiasis was correlated with advanced disease, oral lesions were not good predictors of mortality.

Oral cancer and oral effects of anticancer therapy.

The term "oral cancer" generally refers to squamous cell carcinoma of oral mucosal origin, which accounts for more than 90% of all malignancies of this location. Although a relatively uncommon disease in the United States, this malignancy is nonetheless important, as it accounts for significant morbidity and mortality. Approximately half of the estimated 30 thousand cases diagnosed annually in this country have a fatal outcome. Survivors of the surgical and medical management may suffer from sequelae of treatment ranging from pain and infection to partial or total disfigurement and loss of stomatognathic function. Such high morbidity and mortality are truly regrettable, since many of these malignancies are preventable. This article will review recent developments in the epidemiology, treatment and chemoprevention of oral squamous cell carcinoma as they relate to early diagnosis, and management of the oral cancer patient.

Oral verruca vulgaris in a bone marrow transplant patient: a case report and review of literature.

Viral infections can cause severe morbidity in immunosuppressed cancer patients. A case of rapidly enlarging, biopsy-documented oral verruca vulgaris in a patient undergoing conditioning chemotherapy prior to bone marrow transplantation (BMT) is described. Human papillomavirus infections in immunosuppressed patients are discussed.

Helium-neon laser effects on conditioning-induced oral mucositis in bone marrow transplantation patients.

BACKGROUND: Oral mucositis is a common complication of bone marrow transplantation (BMT) conditioning therapy. Sequelae consist of increased risk for infection, moderate to severe pain, compromised oral function, and bleeding. This study investigated helium-neon laser treatment for prevention of conditioning-induced oral mucositis in BMT patients. Patterns and severity of mucositis for specific conditioning drug regimens also were analyzed. METHODS: Twenty patients received laser radiation to their oral mucosa, either left or right of midline. The contralateral side was sham-treated and served as a control. Mucositis severity was scored independently by two modified versions of the Oral Mucositis Index Scale (OMI-A and OMI-B) and the Eastern Cooperative Oncology Group (ECOG) Oral Toxicity Scale; pain severity was scored by subjects on a visual analogue scale (VAS). Cumulative scores were analyzed for differences between the laser-treated and sham-treated sides. RESULTS: Oral mucositis and pain scores were significantly lower for the treated versus the untreated side by OMI-A and B (P < 0.005) and VAS (P = 0.027) criteria, respectively. Ulcerative lesions occurred in all patients bilaterally; severity increased until Day +6, and lesions resolved by Day +21. Mucositis was more severe for patients conditioned with busulfan/carboplatin/thiotepa than for patients conditioned with busulfan/cyclophosphamide/etoposide. CONCLUSIONS: Helium-neon laser treatment was well-tolerated and reduced the severity of conditioning-induced oral mucositis in BMT patients.

Squamous cell carcinoma of the gingiva. A case series analysis.

Recent studies suggest that patients with carcinoma of the gingiva exhibit demographic features that differ from those of persons with squamous carcinoma at other intraoral sites. In this study, we sought to explore this hypothesis in greater detail. Records from the University of Connecticut Oral Biopsy Service from 1975 through 1992 inclusive were surveyed for cases of oral carcinoma. A total of 577 cases were retrieved and analyzed with respect to prevalence, gender distribution, and age at diagnosis. We found that the gingiva (alveolar ridge included) was the third most common site for oral squamous carcinoma after carcinoma of the floor of the mouth and tongue. Further, the relative proportion of gingival cancer versus carcinoma at other intraoral subsites remained essentially constant throughout the study period. Male-to-female ratios were significantly greater for cancer of the floor of the mouth as compared with both cancer of the tongue and cancer of the gingiva (ridge included). Age was not a significant predictor of oral cancer subsite, and there were no apparent differences between carcinoma of the dentate gingiva and that of the edentulous ridge. Results of this study indicate that gender-specific predilections exist for squamous cell carcinoma at different intraoral subsites. These differences suggest the possibility of different etiologic factors and pathogenetic mechanisms involved in carcinoma of the gingiva compared with surface carcinoma at other intraoral sites.

Smoking, gender, and age as risk factors for site-specific intraoral squamous cell carcinoma. A case-series analysis.

BACKGROUND: Studies assessing risk factors for oral cancer do not generally report results for specific oral sites. The purpose of the current study was to examine differences in the distribution of age, gender, and tobacco use by intraoral site in a series of oral cancer cases. METHODS: Information on gender, age at diagnosis, and lesion location was obtained for all incident cases of oral squamous cell carcinoma diagnosed through the University of Connecticut Oral Pathology Biopsy Service during the period 1987-1991 (N = 150). Information on tobacco use was obtained through a telephone interview or from medical or dental records. RESULTS: The tongue, floor of the mouth (FOM), and gingiva, respectively, were the most commonly affected sites. The male-to-female ratio was greatest for FOM cancer (3.4) and lowest for gingival cancer (0.5). The mean age at diagnosis did not differ significantly by site. The percentage of smokers among cases of FOM, tongue, and gingival cancer was 97%, 64%, and 50%, respectively. When multiple logistic regression was used to compare FOM and gingival cancer, gender and smoking remained significant predictors. The odds of smoking among patients with FOM cancer were 32 times the odds of smoking among patients with gingival cancer (odds ratio for age, gender adjusted = 32.6, 3.3-323.5). CONCLUSIONS: The findings suggest that cancer of the FOM is more strongly associated with smoking than is cancer of the gingiva and, perhaps, the tongue. The reported results should be interpreted cautiously in light of study limitations, which include the absence of information on alcohol consumption and lack of a noncancer control group.

Management of oral pain in patients with malignant diseases.

Painful oral complications are common in patients undergoing treatment for malignant diseases. Correct diagnosis of painful oral lesions, as well as identification of etiological factors and appropriate therapy, are imperative for this group of patients. Oral mucosites, infections, and graft-versus-host disease and their respective current and prospective methods of management are reviewed.

Narcotic receptor blockade and its effect on the analgesic response to placebo and ibuprofen after oral surgery.

The purpose of this study was to evaluate the contribution of endogenous opiates to the analgesic response after treatment with placebo, codeine, and ibuprofen after oral surgery. Eighty-one patients undergoing complicated dental extractions were pretreated with either a placebo or the narcotic antagonist naltrexone 50 mg, 30 minutes before surgery. After surgery, patients self administered one of three possible postsurgical medications, which included placebo, codeine 60 mg, and ibuprofen 400 mg, when their pain reached a moderate or severe intensity. The study was double-blind with the three postsurgical treatments being randomly allocated within each presurgical treatment block. Pain intensity, pain relief, pain half gone, and overall evaluations were assessed for up to 6 hours. Ibuprofen was significantly more efficacious (p < .05) than codeine or placebo for most analgesic measures. The administration of naltrexone before surgery reduced the analgesic response to both placebo and codeine. Pretreatment with naltrexone did not diminish the peak analgesic response to ibuprofen, but surprisingly prolonged (p < .05) the duration of its action. The results suggest that a blockade of endogenous opiates by naltrexone diminished the placebo response, but that naltrexone may prolong ibuprofen analgesia by some unknown mechanism.

Postextraction osteomyelitis in a bone marrow transplant recipient.

This report describes a case of mandibular osteomyelitis after a dental extraction in a patient who subsequently underwent bone marrow transplantation (BMT) for lymphoblastic lymphoma. Surgical guidelines consistent with National Cancer Institute recommendations were followed for the extraction, which was performed before initiation of the myelosuppressive conditioning regimen. However, moderate tenderness developed at the extraction site beginning 10 days after marrow infusion. On day 26 the patient became febrile and blood culture-positive for Staphylococcus epidermidis. Radiographs exposed on day 28 demonstrated changes consistent with low-grade osteomyelitis, including diffuse loss of lamina dura and an irregular osseous rarefaction extending 1 cm posterior to the extraction site. Although the indwelling Hickman catheter was the presumed source for bacteremia, clinical and radiographic data led to consideration of mandibular osteomyelitis as an alternative cause. Characteristics of this infection in BMT recipients are reviewed. Recommendations for dental extractions and prophylactic antibiotic regimens for catheterized BMT recipients are also discussed. Although mandibular osteomyelitic lesions are not common in profoundly immunosuppressed BMT recipients, prompt recognition and treatment are essential when the disease occurs.

Symptoms of schizotypal personality disorder.

The authors examined the symptoms of 35 patients with schizotypal personality disorder. In contrast to the suggestion, based on studies of nonclinical, familial samples, that patients with schizotypal disorder are best characterized by the negative symptoms of social isolation and impaired functioning, they found that the positive symptoms of odd communication, ideas of reference, magical thinking, and illusions were equally valid discriminators of their clinically based group of patients. The findings argue against the idea that schizotypal personality disorder be redefined in the revision of DSM-III (DSM-III-R) to emphasize negative symptoms and suggest that clinical samples of schizotypal patients may differ from familial samples.

Serum prolactin correlates with depressed mood during alcohol withdrawal.

Alterations in central dopamine function have been identified in depression and in alcohol withdrawal. Attempts to determine the magnitude and direction of the central dopamine alteration in alcohol withdrawal have produced conflicting results. In this study serum prolactin (PRL) was used as an indicator of central dopamine activity since dopamine is the most important factor in the control of prolactin secretion from the pituitary. Increased serum PRL levels were found during alcohol withdrawal and they correlated significantly with high scores on the Hamilton Depression Rating Scale (HDRS). No significant correlations were identified with The Brief Psychiatric Rating Scale (BPRS), the 'Mini-Mental State' of Folstein (MMS), The Beck Depression Inventory (BDI) or The Modified Gross Alcohol Withdrawal Selective Severity Assessment Scale (GAWSSA). The authors concluded that the transient depressive symptomatology typically found in detoxifying alcoholic patients may be, in part, the result of a central hypodopaminergic state.