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.

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.

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.

Detection of hemizygosity in Hermansky-Pudlak syndrome by quantitative real-time PCR.

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by oculocutaneous albinism, a bleeding diathesis and, in some patients, pulmonary fibrosis or granulomatous colitis. HPS is associated with biosynthesis defects of melanosomes, platelet-dense bodies, and lysosomes. There are seven genetic HPS subtypes; HPS-1 is the most common. We used a real-time quantitative PCR (qPCR) approach to investigate six HPS-1 patients, previously assigned as having homozygous mutations in the HPS1 gene. HPS1 gene copy numbers, calculated by use of a comparative Ct method, revealed that one patient was in fact hemizygous for her c.1189delC (S396delC) HPS1 mutation. The causative deletion/insertion was 13,966 bp in size, with defined breakpoints, and involved an adjacent gene (C10orf33). A mechanism of formation is proposed for the deletion/insertion, and both multiplex and qPCR indicated that the deletion/insertion was present in the patient, her brother, and her father. qPCR amplification is valuable for detecting deletions too small to be identified by fluorescence in situ hybridization. This demonstration of hemizygosity, performed using genomic DNA, can eliminate concerns about non-paternity and can verify the diagnosis of an autosomal recessive disorder when a DNA alteration appears to be homozygous by standard PCR and sequencing methods, and its pathogenicity is in doubt.