Oral health, dental treatment, and medication related osteonecrosis of the jaw in multiple myeloma - a longitudinal cohort study.

OBJECTIVE: The objective of the present study was to investigate oral health status, oral health related quality of life, and identify risk factors associated with invasive dental treatment and medication related osteonecrosis of the jaw in patients with multiple myeloma. MATERIAL AND METHODS: Patients newly diagnosed with multiple myeloma (n = 144) referred between January 2015 and September 2022 were retrospectively included. The patients underwent a thorough clinical and radiological oral examination and odontogenic infections were treated before the start of bisphosphonate treatment. The patients were followed annually, including clinical and radiological examinations. The oral health related quality of life was investigated by the OHIP-14 questionnaire. RESULTS: Dental treatment (RR = 7.75), receiving combination antineoplastic therapy≥3 (RR =4.13), periodontitis (RR = 4.21), and reduced number of teeth (RR = 2.87) were associated with an increased risk of medication related osteonecrosis of the jaw. The response rate of the OHIP-14 questionnaire was 70.2%. Oral pain or discomfort in the mouth related to the medical treatment was reported by 30.5%. CONCLUSION: Dental screening and treatment planning in patients with Multiple Myeloma may result in fewer oral infections and fewer interruptions of the medical treatment of myeloma.

Salivary levels of Osteoprotegerin and receptor activator of nuclear factor-kappa ligand during orthodontic tooth movement-A prospective pilot study.

OBJECTIVES: The aim of this study was to monitor changes in Osteoprotegerin (OPG) and receptor activator of nuclear factor-kappa ligand (RANKL) levels in the saliva during orthodontic tooth movement (OTM). MATERIALS AND METHODS: Nine healthy females (15-20 y of age) with four pre-molar extractions and fixed appliance were included. In total, 134 stimulated and 134 unstimulated saliva samples were collected: at baseline and then every 6-8 weeks at follow-up appointments during the whole orthodontic treatment. Twelve age-matched females with no active orthodontic treatment served as a control group. Saliva samples were analysed by enzyme-linked immunosorbent assay (Elisa). The mean levels of OPG and RANKL were calculated according to the different orthodontic treatment stages: alignment, space closure and finishing. A mixed model analysis was used to compare the means of treatment stages. Baseline OPG levels were compared with the control group using an independent t-test. OPG levels were measured in stimulated saliva due to low levels in unstimulated saliva. RESULTS: No significant difference was observed between baseline OPG values and the control group. OPG increased significantly at all treatment stages: alignment, space closure and finishing compared with baseline (P = 0.002, P = 0.039, P ≤ 0.001, respectively). The salivary levels of OPG increased gradually, except during space closure, reaching peak levels at finishing. RANKL was undetectable in stimulated and unstimulated saliva by sandwich Elisa during OTM. CONCLUSIONS: This novel approach shows the changes in the levels of OPG in OTM and indicates how and when to sample saliva during orthodontic treatment to analyse bone remodelling.

The effect of reconstructive techniques as treatment modality for peri-implant osseous defects - a systematic review and meta-analysis.

OBJECTIVES: The aim of this systematic review is to compare conventional peri-implant flap surgery and reconstructive surgical techniques regarding evidence of remission from peri-implantitis. MATERIAL AND METHODS: Searches were made among randomized controlled trials evaluating clinical aspects and the changes in marginal bone level before and after surgical treatment of peri-implantitis, with and without bone substitute. RESULTS: Nine published articles and 442 patients were eligible for inclusion in the study. Reconstructive techniques exhibited a greater extent of defect fill than conventional surgical techniques alone. No significant differences could be found for clinical measures of peri-implant disease (bleeding on probing and reduction of probing depth) from baseline to the 12-month follow-up. CONCLUSIONS: With regards to the clinical measures of disease, our review shows that there are no differences between open flap debridement and regenerative surgery. From an esthetic standpoint, it may however be that regenerative measures may lead to improvement but further publications with this focus will be necessary to verify this.

Soluble LPS receptor CD14 is increased in saliva of patients with geographic tongue.

OBJECTIVES: The soluble bacterial pattern recognition receptor, sCD14 augments inflammatory responses in oral cavity. The aim of the study was to investigate whether patients with geographic tongue (GT) with and without fissured tongue (FT) have impaired inflammatory regulation, manifesting as increased levels of sCD14 in the saliva. MATERIAL AND METHODS: An enzyme-linked immunosorbent assay was used to measure the amount of sCD14 in whole and parotid saliva of patients diagnosed with GT (GT whole, n = 21; GT parotid, n = 23) and control subjects (GT whole, n = 25; GT parotid, n = 18). The levels of sCD14 were also evaluated according to our previous clinical assessment of GT based on the number of lesions detected on the tongue, as 'mild' (a single lesion), 'moderate' (2-5 lesions), or 'severe' (≥6 lesions). Diagnosis of FT was established when multiple grooves or fissures were observed on the dorsal and lateral surfaces of the tongue. RESULTS: GT patients had significantly higher sCD14 levels in whole (p<.05) and parotid saliva (p<.001), compared with controls. GT patients with FT had significantly increased sCD14 levels only in parotid saliva. A gradual increase in sCD14 levels in parotid and unstimulated saliva was seen in GT patients with multiple tongue lesions compared with single lesions. CONCLUSIONS: GT patients had increased sCD14 in both parotid and unstimulated saliva. sCD14 seems to increase local inflammatory responses, which suggests its involvement in the pathophysiology of GT.

Prevalence of dry mouth in adult patients in primary health care.

OBJECTIVES: To determine the prevalence and severity of dry mouth by age, gender, presence of disease, and medication intake for patients aged 18 years and over, seeking primary health care on the west coast of Sweden (Region of Västra Götaland, VGR). MATERIALS AND METHODS: Cross-sectional study conducted among patients (n = 374, age ≥ 18) visiting primary health care providers (n = 4) in VGR for any medical reasons. Patients were invited to participate by answering a single-item question, 'Have you experienced dry mouth in the last six months?' Patients giving positive answers (n = 163) were asked to fill in the 11-item Xerostomia Inventory (XI) questionnaire to determine the variability and severity of xerostomia. Patients replying 'No' (n = 211) to the single-item question were considered not to have xerostomia and included in the non-xerostomia group. RESULTS: The overall prevalence of xerostomia was 43.6% with a female dominance (61.2%). The prevalence in different age groups among females and males was similar. The number of medications and/or diseases are positively associated with xerostomia. Medication was a significant predictor of the prevalence of xerostomia, regardless of age and gender (p < .001). Patients with five or more medications had the highest prevalence of xerostomia (71.2%). CONCLUSION: Patients seeking primary care on the west coast of Sweden have a high prevalence of xerostomia. Factors associated with xerostomia were female gender and medications and/or diseases. Awareness is required to manage patients with xerostomia in medical and dental care.

Stimulated saliva composition in patients with cancer of the head and neck region.

BACKGROUND: To analyse over time changes in stimulated whole saliva regarding total protein, Immunoglobulin A (IgA), and mucin type O-glycans (mostly MUC5B and MUC7) in head and neck cancer patients. METHODS: 29 dentate patients (20 men and 9 women, 59 ± 8 years) treated with curative radiation therapy and chemotherapy for cancer of the head and neck region were included. The stimulated whole salivary secretion rate was determined and saliva collected at four time-points: at pretreatment, and at 6 months, 1 and 2 years post treatment. The total protein concentration was determined spectrophotometrically by using Bicinchoninic Acid assay and Immunoglobulin A (IgA) by using ELISA technique. Glycosylation pattern of salivary mucins was determined in samples collected pre- and post treatment by using LC/MS electrospray and mucin content quantified using SDS-AgPAGE gels and PAS staining. RESULTS: Compared with pretreatment, the total protein concentration was increased already at 6 months post treatment (p < 0.01), and continued to increase up to 2 years post treatment (p < 0.001). During that period no significant changes in IgA concentration was detected. At pretreatment, the output/min of both total protein and IgA was significantly higher than at all time-points post treatment. Saliva from the cancer patients showed a low abundance/no detectable MUC7, while the MUC5B level remained, compared to saliva from a healthy control. The glycomic analysis showed that the percentage of core 2 O-glycans was increased as core 1, 3 and 4 O-glycans were decreased. The level of sialylation was higher at 6 months post treatment, while sulfation was lower. CONCLUSION: A decreased output per minute of proteins at decreased salivary secretion rate, as well as reduced sulfation of MUC5B at 6 months post treatment tended to correlate with the patients' experience of sticky saliva and oral dryness. At 2 years post treatment, the decreased amount of IgA combined with a lowered salivary secretion rate indicate a reduced oral defense with increased risk of oral infections.

Monitoring Salivary Levels of Interleukin 1 Beta (IL-1ß) and Vascular Endothelial Growth Factor (VEGF) for Two Years of Orthodontic Treatment: A Prospective Pilot Study.

RESULTS: A gradual increase in IL-1ß and VEGF was observed at alignment, reaching significance at space closure (p = 0.002 and p = 0.025, respectively). At finishing, both IL-1ß and VEGF declined, however, without reverting to baseline values (p = 0.172 and p = 0.207, respectively). Bland-Altman analysis showed the agreement between IL-1ß and VEGF in terms of a systematic increase, with a higher percentage difference for VEGF. CONCLUSIONS: The salivary levels of both IL-1ß and VEGF increased following orthodontic treatment and reached their peaks during the treatment stage of space closure. This novel approach provides a hint on how and when to sample saliva during orthodontic treatment to analyse bone remodelling.

Expression of tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) in minor salivary glands and saliva.

OBJECTIVE: The aim of this study was to characterize the baseline expression of tumor necrosis factor (tnf)-related apoptosis inducing ligand (TRAIL) in minor salivary glands, gingiva and saliva from healthy individuals. DESIGN: Minor salivary gland and gingival tissues were used in the study for immunohistochemical staining. An enzyme-linked immunosorbent assay was used to measure the levels of TRAIL in unstimulated saliva and parotid saliva collected from non-smoking individuals. The salivary levels of TRAIL are presented as secretory output. RESULTS: Parotid saliva showed higher secretory output (327.8 ±â€¯41.6 pg/min) for TRAIL compared to unstimulated saliva (212.3 ±â€¯32.1 pg/min; p =0.041). For unstimulated saliva, the young female subjects had the lowest secretory output (119 ±â€¯17.2 pg/min) compared to elderly females (275 ±â€¯62.18 pg/min; p =0.046) and young males (294.4 ±â€¯50.2 pg/min; p =0.021). The ductal cells of salivary glands exhibited the strongest positivity for TRAIL, whereas mucous cells showed no staining for TRAIL. Serous cells displayed an intermediate staining. Gingival tissues showed gradually decreasing staining towards the basal layer. CONCLUSIONS: The current study shows that TRAIL is not only expressed by immune cells, but also by the epithelial cells of salivary glands. Saliva contains high concentrations of soluble TRAIL that suggest roles of this protein in the apoptosis of tumor cells.

Increased levels of calprotectin in the saliva of patients with geographic tongue.

OBJECTIVE: We investigated whether patients with geographic tongue have increased salivary levels of calprotectin and whether there is a correlation between the salivary levels of calprotectin and interleukin 8 (IL-8), which is another marker of inflammation. METHODS: Twenty-three patients diagnosed with geographic tongue and 32 control subjects without oral mucosal lesions were included in the study. The patients with geographic tongue were classified based on clinical appearance and number of oral lesions. ELISAs were used to determine the levels of calprotectin and IL-8 in whole saliva samples. RESULTS: There was a statistically significant increase in the salivary output of calprotectin in patients with geographic tongue compared with the healthy controls (62 ± 9,1 vs. 37,5 ± 4,7 µg/min; p = .0134). Furthermore, the levels of calprotectin correlated positively with the number of oral lesions in patients with geographic tongue. There was also a significant and positive correlation between the salivary levels of calprotectin and IL-8, both for the patients with geographic tongue and the controls. CONCLUSION: This study supports the notion that GT is an inflammatory disease, in which the activation of neutrophils and production of calprotectin in the saliva may play roles in its pathogenesis.

Lingual microbiota profiles of patients with geographic tongue.

Geographic tongue (GT) is an oral mucosal lesion that affects the tongue. The association between GT and the bacterial colonization profiles of the tongue is not clear. Lingual swabs were collected from lesion sites and healthy sites of 35 patients with GT (19 males and 16 females; Mage = 54.3 ± 16.1 years) and 22 controls (12 males and 10 females; Mage = 56.3 ± 15.8 years). Bacterial DNA was extracted and sequenced by next-generation sequencing. At the phylum level, Fusobacteria were significantly less abundant, while Spirochaetes were significantly more abundant in GT patients compared to controls. At the operational taxonomic units level, multivariate analysis revealed distinct clusters for the three groups based on the lingual microbiota composition. Acinetobacter and Delftia were significantly associated with GT lesion and healthy sites. However, Microbacterium, Leptospira, Methylotenera, and Lactococcus were significantly associated with GT lesion sites. Additionally, Mogibacterium and Simonsiella were significantly associated with GT healthy sites and controls. The changes in the lingual microbiota profiles of patients with GT imply a shift in the lingual bacterial ecology. However, it remains unknown if this shift is a consequence of the lesions or of factors associated with the initiation and progression of the disease.

Factors associated with geographic tongue and fissured tongue.

OBJECTIVES: The primary objective of this study was to investigate the association of systemic diseases, use of medications, allergies and tobacco habits with geographic tongue (GT) and fissured tongue (FT) lesions. The secondary objectives were to evaluate the clinical characteristics of tongue lesions and to compare the overall results for referred and non-referred patients. METHODOLOGY: Non-referred patients with GT (GTgp; n = 130) and FT (FTgp; n = 62) were examined by general practitioners (gp) and compared to a control group without oral mucosal lesions (C; n = 1029). Referred patients with GT (GTs; n = 166) and FT (FTs; n = 15) were examined by oral medicine specialists (s) and compared to GTgp and FTgp. Statistical analyses were performed using unpaired t-test or Fisher's exact test. A multiple logistic regression model was developed to control for age and gender as confounders. RESULTS: Compared to the C group, GTgp patients used more anti-hypertensive medications and Swedish snus (p < 0.01). The GTgp group consisted of older males (p < 0.001) compared to C. Compared to the GTgp group, the GTs group was younger, more likely to have symptomatic lesions (p < 0.0001) and comprised of more females. Among the groups examined, FT patients had the highest mean age. CONCLUSION: This study identified an association between GT and anti-hypertensive medications, as well as the use of Swedish snus. It also found differences in the activities and symptoms of the lesions between referred patients and their counterparts who were seen in general dental practice; these parameters influenced the results when these conditions were taken into account.

Quantitative detection of epidermal growth factor and interleukin-8 in whole saliva of healthy individuals.

OBJECTIVES: This study aims to create consensus concerning the use of a methodology by which the handling of saliva is standardized and quantitative detection of IL-8 and EGF in whole saliva is achieved. Our study involves evaluating the extent to which the pre-treatment of saliva samples with an anionic detergent - sodium dodecyl sulphate (SDS) - improved detection levels for IL-8 and EGF. METHODS: Whole saliva samples (n=28) were collected from healthy individuals and a protease inhibitor cocktail was added immediately. They were treated with either SDS or PBS for 20min and were then applied to a sandwich ELISA. RESULTS AND CONCLUSIONS: Saliva is a complex viscous fluid that requires degrading before the analysis of salivary biomarkers. We found that pre-treatment of samples with SDS significantly increased the detection levels for both EGF (293%) and IL-8 (346%) when compared with PBS-treated pairs (***P<0.001). According to the results we recommend: (i) pre-treatment of whole saliva samples with SDS for quantitative analysis (ii) using secretory output instead of concentration in the presentation of results to avoid individual variations and (iii) taking into consideration gender, age and meal intake since these have an impact on the secretory output of salivary proteins.

A non-peptide receptor inhibitor with selectivity for one of the neutrophil formyl peptide receptors, FPR 1.

The neutrophil formyl peptide receptors (FPR1 and FPR2) are members of the G-protein coupled receptor family. The signals generated by occupied FPRs are both pro-inflammatory and anti-inflammatory. Accordingly, these receptors have become a therapeutic target for the development of novel drugs that may be used to reduce injuries in inflammatory diseases including asthma, rheumatoid arthritis, Alzheimer's disease and cardiovascular diseases. To support the basis for a future pharmacological characterization, we have identified a small molecular non-peptide inhibitor with selectivity for FPR1. We used the FPR1 and FPR2 specific ligands fMLF and WKYMVM, respectively, and an earlier described ratio technique, to determine inhibitory activity combined with selectivity. We show that the compound 3,5-dichloro-N-(2-chloro-5-methyl-phenyl)-2-hydroxy-benzamide (BVT173187) fulfills the criteria for an FPR1 inhibitor selective for FPR1 over FPR2, and it inhibits the same functional repertoire in neutrophils as earlier described peptide antagonists. Accordingly, the new inhibitor reduced neutrophil activation with FPR1 agonists, leading to mobilization of adhesion molecules (CR3) and the generation of superoxide anion from the neutrophil NADPH-oxidase. The effects of a number of structural analogs were determined but these were either without activity or less active/specific than BVT173187. The potency of the new inhibitor for reduction of FPR1 activity was the same as that of the earlier described FPR1 antagonist cyclosporine H, but signaling through the C5aR and CXCR (recognizing IL8) was also affected by BVT173187.

Parasympathetic non-adrenergic, non-cholinergic transmission in rat parotid glands: effects of cholecystokinin-A and -B receptor antagonists on the secretory response.

Recent studies show i.v. administered pentagastrin and cholecystokinin to evoke protein/amylase secretion from the rat parotid gland and to stimulate gland protein synthesis, the two phenomena being abolished by cholecystokinin receptor antagonists. In the rat parotid gland, non-adrenergic, non-cholinergic transmission mechanisms contribute to secretion of fluid and protein/amylase. Since cholecystokinin may act as a neurotransmitter, activation of cholecystokinin receptors of the gland might contribute to the parasympathetic nerve-evoked secretion. In this study, the parasympathetic innervation was stimulated in non-atropinized (in periods of 2 min) or atropinized (in periods of 3 min) pentobarbitone-anaesthetized rats before and after administration of the cholecystokinin-A receptor antagonist lorglumide (48 mg/kg, i.v.) and the cholecystokinin-B receptor antagonist itriglumide (5.5 mg/kg, i.v.). The non-adrenergic, non-cholinergic transmission fatigues rapidly resulting in declining responses. Therefore, atropinized rats, not receiving the cholecystokinin receptor antagonists, had to serve as controls. Neither at a stimulation frequency of 10 Hz nor of 40 Hz were the secretory responses of the atropinized rats affected by the receptor antagonists. After lorglumide, the saliva volume and the amylase output were (expressed as percentage of the response to the stimulation period before the administration of the antagonist) 98.0+/-3.8% (vs. control 91.1+/-4.0%) and 91.9+/-4.9% (vs. 87.7+/-3.7%) at 10 Hz, respectively, and 79.8+/-4.5% (vs. 77.3+/-2.1%) and 73.6+/-5.3% (vs. 71.7+/-2.3%) at 40 Hz, respectively. After itriglumide, the corresponding percentage figures for saliva volume and amylase output were, at 10 Hz, 99.5+/-8.9% (vs. 92.0+/-2.8%) and 95.8+/-11.8% (vs. 89.2+/-6.4%), respectively, and, at 40 Hz, 74.0+/-3.1% (vs. 79.6+/-2.2%) and 66.6+/-3.3% (vs. 63.9+/-6.0%), respectively. Similarly, the antagonists were without effect on the parotid secretory responses of non-atropinized rats subjected to stimulation at 10 Hz. Thus, under physiological conditions, the cholecystokinin receptors of the parotid gland are likely to be stimulated by circulating hormones rather than by nervous activity.

Pentagastrin-induced protein synthesis in the parotid gland of the anaesthetized rat, and its dependence on CCK-A and -B receptors and nitric oxide generation.

In parotid glands of pentobarbitone-anaesthetized rats, the incorporation of [3H]leucine into trichloroacetic acid-insoluble materials, reflecting protein synthesis, increased by 17% (compared to saline-treated rats) in response to infusion of pentagastrin (20 microg kg(-1), i.v. for 1 h) under muscarinic and alpha- and beta-adrenoceptor blockade. Both the CCK-A receptor antagonist lorglumide (48 mg kg(-1), i.v.) and the CCK-B receptor antagonist itriglumide (5.5 mg kg(-1), i.v.), given separately, prevented the expected increase in pentagastrin and, in addition, reduced the glandular protein synthesis by 16 and 12%, respectively, below the level of saline-treated rats. In rats treated with saline only, the glandular protein synthesis was reduced by 22% by the CCK-A receptor antagonist and by 17% by the CCK-B receptor antagonist; combined, the two antagonists caused no further reduction (20%). There was no increase in the glandular protein synthesis of pentagastrin-treated rats compared to that of the saline-treated rats when both groups of rats were exposed to a combination of the two types of CCK receptor antagonists. In pentagastrin-treated rats, the protein synthesis in the parotid glands was 23% less in the presence of the non-selective nitric oxide (NO) synthase inhibitor L-NAME (30 mg kg(-1), i.v.) than in its absence; the result was the same (23%) when the neuronal NO synthase inhibitor Nomega-propyl-L-arginine (N-PLA; 30 mg kg(-1), i.v.) replaced L-NAME. The protein synthesis in rats treated with saline only was not reduced by L-NAME; nor was the protein synthesis of saline-treated rats different from that of pentagastrin- and L-NAME-treated rats. Thus, under 'basal' conditions, a portion of the glandular protein synthesis, as well as the whole increase in synthesis in response to administration of pentagastrin, engaged both types of CCK receptors. Furthermore, NO generation, owing to neuronal NO synthase activity, was required for the increase to occur in response to pentagastrin, whereas a non-NO-dependent pathway was responsible for the protein synthesis under 'basal' conditions.