The Dutch Version of the Orthognathic Quality of Life Questionnaire (OQLQ-NL): Validation for Cleft Patients.

OBJECTIVE: The aim of this study is to validate the Dutch version of the Orthognathic Quality of Life Questionnaire (OQLQ-NL) for cleft patients who received orthognathic surgery. METHODS: To compare the OQLQ-NL with the CLEFT-Q, we used a convenience sample of thirty-two cleft patients. Using the Cronbach's alpha coefficient for multiple item scales, internal reliabilities of the OQLQ-NL were evaluated. The OQLQ-NL was repeated at a two-week interval and the intraclass correlation coefficient was calculated, to establish of the test-retest reliability. The construct validity of the OQLQ-NL was evaluated by using Spearman's correlation to test its correlation with the CLEFT-Q. RESULTS: Thirty-two patients filled in the OQLQ-NL and CLEFT-Q. The OQLQ-NL had excellent results in internal reliability and test-retest reliability. The vast majority of the correlations between the domains and scales of the questionnaires were as expected. Data from this study and previous studies confirm the construct validity of the OQLQ-NL. CONCLUSION: Our results suggest the OQLQ-NL is a valid and reliable instrument for measuring quality of life in cleft patients who have received orthognathic surgery in the Netherlands.

Anatomical position of the mandibular condyle after open versus closed treatment of unilateral fractures: A three-dimensional analysis.

This study aimed to compare open and closed treatment for unilateral mandibular condyle neck and base fractures by final three-dimensional (3D) condylar position at 6 months follow-up. 3D position was associated with mandibular functioning and pain. A total of 21 patients received open (n = 11) or closed (n = 10) treatment. 3D positions were assessed on cone-beam computed tomography scans. Volume differences, root mean square, translations, and rotations were obtained related to the pursued anatomical position and compared between treatment groups by the Mann-Whitney U test. The 3D position parameters were associated with the maximum interincisal opening (MIO), mixing ability test (MAT), Mandibular Function Impairment Questionnaire (MFIQ), and pain based on Spearman correlation coefficients (rs). Translation in the medial-lateral direction was smaller after open treatment (P = 0.014). 3D position was not associated with the MAT; however, worse position was associated with a smaller MIO. A larger pitch rotation was associated with a worse MFIQ (rs = 0.499, P = 0.025). Volume reduction of the affected condyle was associated with more pain (rs = -0.503, P = 0.020). In conclusion, after unilateral condylar fractures, worse 3D position is associated with a smaller mouth opening and worse patient-reported outcomes. This is independent of the chosen treatment, despite a better anatomical reduction after open treatment.

Postoperative Daycare as a Safe and Cost-Effective Option for Secondary Alveolar Bone Graft (SABG) Surgery: A Retrospective Comparative Cohort Study.

OBJECTIVE: To evaluate the outcomes of Secondary Alveolar Bone Grafting (SABG) in patients treated either in daycare or with multiple day hospitalization (MDH) in relation to costs and complication rates. DESIGN: Retrospective comparative cohort study. SETTING: The data was collected from two settings: Postoperative daycare or MDH after oral cleft surgery in an Academic Medical Center in The Netherlands. PATIENTS: Data of 137 patients with unilateral Cleft lip, alveolus, and palate (CLAP) treated between 2006-2018 were evaluated. Registered clinical variables: age, gender, cleft subtype, bone donor site, type of hospitalization, length of stay, additional surgery, complications, surgeons, and costs. INTERVENTIONS: Closure of the alveolar cleft with/without closure of the anterior palate. MAIN OUTCOME MEASURES: Univariate analyses. RESULTS: Of the 137 patients, 46.7% were treated in MDH, and 53.3% in daycare. Total costs for daycare were significantly lower (P < .001). All patients treated in daycare received mandibular symphysis bone, whereas in MDH, 46.9% received iliac crest bone instead. Bone donor site was associated with postoperative care type. Complication rates were slightly but not significantly higher in daycare (26%) vs. MDH (14.1%) (P = .09). Most were Grade I (minor) according to Clavien Dindo classification. CONCLUSIONS: Daycare after alveolar cleft surgery is about as safe as MDH, but significantly cheaper.

Mapping of DNA methylation-sensitive cellular processes in gingival and periodontal ligament fibroblasts in the context of periodontal tissue homeostasis.

Interactions between gingival fibroblasts (GFs) and oral pathogens contribute to the chronicity of inflammation in periodontitis. Epigenetic changes in DNA methylation are involved in periodontitis pathogenesis, and recent studies indicate that DNA methyltransferase (DNMT) inhibitors may protect against epithelial barrier disruption and bone resorption. To assess the impact of DNMT inhibition on GFs, cells were cultured with decitabine (5-aza-2'-deoxycytidine, DAC) for 12 days to induce DNA hypomethylation. We observed several potentially detrimental effects of DAC on GF biological functions. First, extended treatment with DAC reduced GF proliferation and induced necrotic cell death. Second, DAC amplified Porphyromonas gingivalis- and cytokine-induced expression and secretion of the chemokine CCL20 and several matrix metalloproteinases (MMPs), including MMP1, MMP9, and MMP13. Similar pro-inflammatory effects of DAC were observed in periodontal ligament fibroblasts. Third, DAC upregulated intercellular adhesion molecule-1 (ICAM-1), which was associated with increased P. gingivalis adherence to GFs and may contribute to bacterial dissemination. Finally, analysis of DAC-induced genes identified by RNA sequencing revealed increased expression of CCL20, CCL5, CCL8, CCL13, TNF, IL1A, IL18, IL33, and CSF3, and showed that the most affected processes were related to immune and inflammatory responses. In contrast, the genes downregulated by DAC were associated with extracellular matrix and collagen fibril organization. Our observations demonstrate that studies of DNMT inhibitors provide important insights into the role of DNA methylation in cells involved in periodontitis pathogenesis. However, the therapeutic potential of hypomethylating agents in periodontal disease may be limited due to their cytotoxic effects on fibroblast populations and stimulation of pro-inflammatory pathways.

Oral functioning after open versus closed treatment of unilateral condylar neck or base fractures: A two-centre controlled clinical trial.

BACKGROUND: Oral functioning and rehabilitation in patients after condylar trauma can be measured by objective functional outcomes and patient-reported outcomes. The similarities or differences between these outcomes may contribute to the decision if open treatment (OT) or closed treatment (CT) will obtain the most advantageous results. OBJECTIVES: The aim of this study was to compare OT versus CT for unilateral condylar mandibular neck or base fractures in a two-centre controlled clinical trial by objective functional outcomes and patient-reported outcomes measured at 6 weeks and 6 months follow-up. Additionally, these outcomes were compared within each group. METHODS: Patients were enrolled between January 2017 and November 2019. In one centre, patients received OT by extra-oral open reduction and internal fixation. In another centre, patients received CT by maxillomandibular fixation. Objective measurements included the mixing ability test (MAT) and mandibular active range of motion (ROM). Patient-reported outcomes included the mandibular function impairment questionnaire (MFIQ) and visual analogue scale (VAS) for pain. Independent t-tests and Mann-Whitney U-tests were used to determine differences between the treatment groups at 6 weeks and 6 months follow-up. Paired t-tests and Wilcoxon signed rank tests were used to determine differences within each group. RESULTS: Thirty-three patients were enrolled. No differences were found between the groups treated with OT or CT for MAT, ROM, MFIQ and VAS. Both groups showed functional improvement. CONCLUSION: Good objective functional outcomes and patient-reported outcomes were achieved with both OT and CT in patients with unilateral condylar mandibular neck or base fractures.

Limitations of Jaw Movement in Fibrodysplasia Ossificans Progressiva: A Review.

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder characterized by heterotopic ossification (HO) of the skeletal muscles, fascia, tendons and ligaments. Patients often experience limitations in jaw function due to HO formation in the maxillofacial region. However, no studies have yet analyzed the age of onset and location of HO and the type of restrictions it may yield in the maxillofacial region. The aim of this study was to evaluate all existing literature on the site of onset of HO and associated functional restrictions of the jaw. To this end, a scoping review was performed focusing on limitations of jaw movement in FOP patients. The literature search resulted in 725 articles, of which 30 articles were included for full study after applying the exclusion criteria. From these articles 94 FOP patients were evaluated for gender, age, presence and age at which HO started in the maxillofacial region, location of HO, whether HO was caused spontaneous or traumatic and maximum mouth opening. Formation of HO is slightly more common in female patients compared to male patients, but the age of HO onset or the maximum mouth opening does not differ between genders. Trauma-induced HO occurred at a significantly younger age than spontaneous HO. Interestingly, a difference in maximum mouth opening was observed between the different ossified locations in the maxillofacial region, with ossification of the masseter muscle resulting in the smallest and ossification of the zygomatic arch resulting in the largest maximum mouth opening. This review revealed that the location of the maxillofacial region affected by HO determines the degree of limitations of the maximum mouth opening. This finding may be important for establishing clinical guidelines for the dental management of FOP patients.

Although Anatomically Micrometers Apart: Human Periodontal Ligament Cells Are Slightly More Active in Bone Remodeling Than Alveolar Bone Derived Cells.

The periodontal ligament (PDL) and the alveolar bone are part of the periodontium, a complex structure that supports the teeth. The alveolar bone is continuously remodeled and is greatly affected by several complex oral events, like tooth extraction, orthodontic movement, and periodontitis. Until now, the role of PDL cells in terms of osteogenesis and osteoclastogenesis has been widely studied, whereas surprisingly little is known about the bone remodeling capacity of alveolar bone. Therefore, the purpose of this study was to compare the biological character of human alveolar bone cells and PDL cells in terms of osteogenesis and osteoclastogenesis in vitro. Paired samples of PDL cells and alveolar bone cells from seven patients with compromised general and oral health were collected and cultured. Bone A (early outgrowth) and bone B (late outgrowth) were included. PDL, bone A, bone B cell cultures all had a fibroblast appearance with similar expression pattern of six mesenchymal markers. These cultures were subjected to osteogenesis and osteoclastogenesis assays. For osteoclastogenesis assays, the cells were co-cultured with peripheral blood mononuclear cells, a source for osteoclast precursor cells. The total duration of the experiments was 21 days. Osteogenesis was slightly favored for PDL compared to bone A and B as shown by stronger Alizarin red staining and higher expression of RUNX2 and Collagen I at day 7 and for ALP at day 21. PDL induced approximately two times more osteoclasts than alveolar bone cells. In line with these findings was the higher expression of cell fusion marker DC-STAMP in PDL-PBMC co-cultures compared to bone B at day 21. In conclusion, alveolar bone contains remodeling activity, but to a different extent compared to PDL cells. We showed that human alveolar bone cells can be used as an in vitro model to study bone remodeling.

Activin-A Induces Early Differential Gene Expression Exclusively in Periodontal Ligament Fibroblasts from Fibrodysplasia Ossificans Progressiva Patients.

Fibrodysplasia Ossificans Progressiva (FOP) is a rare genetic disease characterized by heterotopic ossification (HO). It is caused by mutations in the Activin receptor type 1 (ACVR1) gene, resulting in enhanced responsiveness to ligands, specifically to Activin-A. Though it has been shown that capturing Activin-A protects against heterotopic ossification in animal models, the exact underlying mechanisms at the gene expression level causing ACVR1 R206H-mediated ossifications and progression are thus far unknown. We investigated the early transcriptomic changes induced by Activin-A of healthy control and patient-derived periodontal ligament fibroblasts (PLF) isolated from extracted teeth by RNA sequencing analysis. To study early differences in response to Activin-A, periodontal ligament fibroblasts from six control teeth and from six FOP patient teeth were cultured for 24 h without and with 50 ng/mL Activin-A and analyzed with RNA sequencing. Pathway analysis on genes upregulated by Activin-A in FOP cells showed an association with pathways involved in, among others, Activin, TGFß, and BMP signaling. Differential gene expression induced by Activin-A was exclusively seen in the FOP cells. Median centered supervised gene expression analysis showed distinct clusters of up- and downregulated genes in the FOP cultures after stimulation with Activin-A. The upregulated genes with high fold changes like SHOC2, TTC1, PAPSS2, DOCK7, and LOX are all associated with bone metabolism. Our open-ended approach to investigating the early effect of Activin-A on gene expression in control and FOP PLF shows that the molecule exclusively induces differential gene expression in FOP cells and not in control cells.

Collaboration Around Rare Bone Diseases Leads to the Unique Organizational Incentive of the Amsterdam Bone Center.

In the field of rare bone diseases in particular, a broad care team of specialists embedded in multidisciplinary clinical and research environment is essential to generate new therapeutic solutions and approaches to care. Collaboration among clinical and research departments within a University Medical Center is often difficult to establish, and may be hindered by competition and non-equivalent cooperation inherent in a hierarchical structure. Here we describe the "collaborative organizational model" of the Amsterdam Bone Center (ABC), which emerged from and benefited the rare bone disease team. This team is often confronted with pathologically complex and under-investigated diseases. We describe the benefits of this model that still guarantees the autonomy of each team member, but combines and focuses our collective expertise on a clear shared goal, enabling us to capture synergistic and innovative opportunities for the patient, while avoiding self-interest and possible harmful competition.

Cells Derived from Human Long Bone Appear More Differentiated and More Actively Stimulate Osteoclastogenesis Compared to Alveolar Bone-Derived Cells.

Osteoblasts derived from mouse skulls have increased osteoclastogenic potential compared to long bone osteoblasts when stimulated with 1,25(OH)2 vitamin D3 (vitD3). This indicates that bone cells from specific sites can react differently to biochemical signals, e.g., during inflammation or as emitted by bioactive bone tissue-engineering constructs. Given the high turn-over of alveolar bone, we hypothesized that human alveolar bone-derived osteoblasts have an increased osteogenic and osteoclastogenic potential compared to the osteoblasts derived from long bone. The osteogenic and osteoclastogenic capacity of alveolar bone cells and long bone cells were assessed in the presence and absence of osteotropic agent vitD3. Both cell types were studied in osteogenesis experiments, using an osteogenic medium, and in osteoclastogenesis experiments by co-culturing osteoblasts with peripheral blood mononuclear cells (PBMCs). Both osteogenic and osteoclastic markers were measured. At day 0, long bones seem to have a more late-osteoblastic/preosteocyte-like phenotype compared to the alveolar bone cells as shown by slower proliferation, the higher expression of the matrix molecule Osteopontin (OPN) and the osteocyte-enriched cytoskeletal component Actin alpha 1 (ACTA1). This phenotype was maintained during the osteogenesis assays, where long bone-derived cells still expressed more OPN and ACTA1. Under co-culture conditions with PBMCs, long bone cells also had a higher Tumor necrose factor-alfa (TNF-α) expression and induced the formation of osteoclasts more than alveolar bone cells. Correspondingly, the expression of osteoclast genes dendritic cell specific transmembrane protein (DC-STAMP) and Receptor activator of nuclear factor kappa-Β ligand (RankL) was higher in long bone co-cultures. Together, our results indicate that long bone-derived osteoblasts are more active in bone-remodeling processes, especially in osteoclastogenesis, than alveolar bone-derived cells. This indicates that tissue-engineering solutions need to be specifically designed for the site of application, such as defects in long bones vs. the regeneration of alveolar bone after severe periodontitis.

Tooth autotransplantation in the anterior maxilla and mandible: retrospective results in young patients.

OBJECTIVE: This retrospective study evaluated survival rates, prognosis, and overall success of autotransplanted teeth in young patients missing anterior teeth as a result of trauma, agenesis, or developmental disturbances. STUDY DESIGN: Retrospective data were collected from the medical records of patients who had undergone tooth autotransplantations to anterior sites between January 2001 and December 2012. Clinical variables, such as gender, age, surgical indications, donor and recipient sites, type of anesthetics, bone augmentation, and complications during follow-up, were assessed. RESULTS: A total of 59 donor teeth in 46 patients (30 boys and 16 girls; average age 12.15 years) were autotransplanted to the anterior region of the maxilla and mandible. After a mean follow-up period of 17.35 months (range 10-61 months), all of the transplanted teeth remained in situ with no complications. CONCLUSIONS: This study supports the autotransplantation of teeth to the anterior alveolus as a viable option suitable in growing patients with missing anterior teeth.

Systemic diseases and the risk of developing salivary stones: a case control study.

OBJECTIVE: To investigate the possible relationship between the presence of salivary stones and systemic diseases, medication, smoking, and alcohol consumption. STUDY DESIGN: A retrospective, case control study. Medical records of patients with salivary stones and those of control patients without salivary stones were retrospectively reviewed. Data regarding the affected salivary gland, the presence of systemic disease, and the use of medication, tobacco, and alcohol were recorded. Statistical analysis was performed using the Fisher Exact tests. RESULTS: Medical records of 208 patients with salivary stones and those of 208 control patients were reviewed. Of the patients diagnosed with salivary stones, the submandibular gland was affected in 85.6% of the patients, the parotid gland in 9.6%, and the sublingual gland in 2.4% of the patients. None of the recorded systemic diseases was more prevalent in patients with salivary stones. Patients with salivary stones used significantly more antibiotics compared with the control group (P = .037). No significant differences were observed for other types of medication. There was no correlation between salivary stone formation, smoking, and alcohol consumption. CONCLUSIONS: The present study suggested that systemic diseases, medication, smoking, and alcohol consumption play no or only a limited role in the onset of salivary stones.

Evaluation of temporomandibular function after high partial condylectomy because of unilateral condylar hyperactivity.

PURPOSE: The purpose of this study was to assess temporomandibular function after condylectomy because of unilateral condylar hyperactivity (UCH) by means of standardized diagnostic criteria. The results were compared with those obtained in a control group. PATIENTS AND METHODS: In this study, 33 patients with UCH who underwent condylectomy and 31 controls matched for age and gender filled out a history questionnaire and underwent a clinical examination as part of the research diagnostic criteria for temporomandibular disorders. Data analysis was performed by use of the Fisher exact test for 2-by-2 tables. RESULTS: Patients and controls did not differ significantly regarding myofacial pain (P = .131), disc displacement (P = .516), and depression (P = .34). The groups differed significantly concerning arthralgia, osteoarthritis, and osteoarthrosis (P = .003), as well as pain with low disability (P = .022). CONCLUSIONS: In patients with UCH who underwent condylectomy because of progressive mandibular asymmetry, more joint-related temporomandibular problems as well as more postoperative pain developed when compared with age- and gender-matched controls. However, these problems did not lead to more severe disabilities in daily life.