Expression of osteogenic markers after administration of selective estrogen receptor modulators during implant placement in the osteoporotic rat maxilla.

PURPOSE: This study examined the effects of raloxifene during bone formation around the dental implant in the ovariectomy-induced osteoporotic rat maxilla. METHODS: Fifty-four female 10-week-old Sprague-Dawley rats were divided into three groups (n = 18 each); sham-operated (control), ovariectomized (OVX), and ovariectomized and raloxifene-administered (RAL). Eight weeks after ovariectomy, both upper first molars were extracted, and implants were placed 4 weeks post-extraction. The RAL group was given 1 mg/kg of raloxifene per day while the other groups received a vehicle. Six rats in each group were sacrificed at days 4, 7, and 14 and submitted for quantitative reverse transcription polymerase chain reaction and immunohistochemical staining, for evaluation of osteogenic genes expressions. RESULTS: The alkaline phosphatase expression was upregulated in the RAL group compared to the OVX group at day 4. The osteocalcin expression was significantly higher between the RAL group and the OVX group at day 7. Immunohistochemical staining revealed increased expression during the initial bone-forming process and indicated more active bone formation in the RAL group than in the OVX group. CONCLUSION: Raloxifene administration enhanced the osteogenic genes and proteins expression in the bone around the implant. Further studies are required to establish the long-term clinical effects of raloxifene administration.

High prevalence of stress and suicidal ideation in women with temporomandibular disorder: A population-based cross-sectional survey.

Objective: To investigate the association between temporomandibular disorders (TMD) and psychological factors according to gender in a large representative sample.Methods: Participants provided demographic, socio-economic, and behavioral information and responded to questionnaires assessing mental health status regarding perceived stress, mood disturbance, suicidal ideation, and diagnosis of depression. The association between TMD and its risk factors by gender and the association between psychological factors and TMD were statistically analyzed.Results: In men, perceived stress was highly associated with TMD. However, in women, not only perceived stress but suicidal ideation showed significantly high rates of TMD. The suicidal ideation was significantly associated with TMD in women after controlling confounders.Discussion: Current results provide evidence that TMD is associated with stress in both genders and with suicidal ideation, especially in women. This study has important implications for intense screening and evaluation of suicidal ideation among patients with TMD according to gender.

Enhancement of peri-implant bone formation via parathyroid hormone administration in a rat model at risk for medication-related osteonecrosis of the jaw.

PURPOSE: Dental implant-associated medication-related osteonecrosis of the jaw has been frequently reported in patients administered bisphosphonates (BPs) to prevent osteoporosis. The aim of this study was to investigate the effect of intermittent administration of parathyroid hormone (PTH) on peri-implant bone in the maxillae of ovariectomized rats systemically administered BPs. METHODS: Thirty 8-week-old female Sprague-Dawley rats were randomly divided into 3 groups. The OVX-ZP group included ovariectomized rats administered 60 µg/kg of zoledronate once a week for 6 weeks and 30 µg/kg PTH after implant installation. The OVX-Z group included ovariectomized rats administered 60 µg/kg of zoledronate once a week for 6 weeks and saline after implant installation, and the control group included rats that underwent a sham operation and were then administered saline. Rats were sacrificed 4 weeks after implant placement for histomorphometric and micro-computed tomography (CT) analyses. RESULTS: The average bone area percentage was greater in the OVX-ZP group than in the OVX-Z group (53.4%±4.0% vs. 28.9%±9.5%, P=0.01). The bone-to-implant contact ratio was 50.8%±1.4% in the OVX-ZP group and 16.9%±2.4% in the OVX-Z group (P=0.012). The average bone volume ratio as shown on micro-CT was 31.3%±19.8% in the OVX-ZP group and 19.4%±9.3% in the OVX-Z group (P=0.045). The OVX-ZP and OVX-Z groups displayed similar trabecular thickness (0.06±0.004 mm vs. 0.06±0.002 mm) (P>0.05) and trabecular separation (0.21±0.02 mm vs. 0.29±0.13 mm) (P>0.05). However, the number of trabeculae in the OVX-ZP group was significantly higher than that in the OVX-Z group (4.3±1.33/mm3 vs. 2.2±0.19/mm3) (P=0.024). CONCLUSIONS: The present findings indicate that intermittently-administered PTH can promote peri-implant bone formation and suggest that PTH administration may aid in effective treatment for medication-related osteonecrosis of the jaw after dental implantation.

Effect of Raloxifene on Bone Formation Around Implants in the Osteoporotic Rat Maxilla: Histomorphometric and Microcomputed Tomographic Analysis.

PURPOSE: Raloxifene, an antiresorptive drug, prevents bone loss and promotes bone formation by secondary anabolic action. The purpose of this study was to investigate the effectiveness of raloxifene on the osseointegration of implants in the rat model of the osteoporotic maxilla. MATERIALS AND METHODS: Thirty Sprague-Dawley female rats aged 10 weeks were randomly assigned to the following groups: (1) raloxifene (RAL) group (n = 10), (2) ovariectomized (OVX) group (n = 10), and (3) control group (sham-operated, n = 10). Both ovaries were removed to induce osteoporosis, and the maxillary right molar was extracted. After 4 weeks, an implant was placed on the same edentulous area. Raloxifene 1 mg/kg/day was administered to the experimental animals in the RAL group, while those in the ovariectomized group and sham-operated group were given the same amount. All experimental animals were sacrificed at 4 weeks after implants were placed. Histomorphometric measurements of the bone area ratio (BA, %) and bone-to-implant contact ratio (BIC, %) around the implant were performed. Three-dimensional (3D) microcomputed tomographic (micro-CT) analysis of peri-implant bone microarchitecture was also performed and statistically analyzed. RESULTS: In the histomorphometric analysis, the BA ratio of the implant in the RAL group was higher than that in the OVX group (53.3% ± 7.2% vs 38.2% ± 11.7%, P = .024). BIC around the implant in the RAL group did not show a statistical difference compared with that in the OVX group (42.7% ± 15.0% vs 34.5% ± 16.2%, P > .05). In microstructural analysis, the RAL group showed a significant increase of trabecular thickness compared with the OVX group (0.09 ± 0.02 mm vs 0.06 ± 0.01 mm, P = .013). However, raloxifene did not show convincing differences between the groups in other micro-CT parameters (P > .05). CONCLUSION: The results show that raloxifene administration demonstrated enhanced new peri-implant bone formation in the osteoporotic rat maxilla. Further research is needed to reveal the effect of raloxifene on the clinical outcome of patients with poor bone quality who undergo dental implant treatment.

Effect of Raloxifene Administration on Bone Response Around Implant in the Maxilla of Osteoporotic Rats.

OBJECTIVES: To determine the effect of raloxifene (RAL) on bone response around implants in the maxilla of osteoporotic rats. MATERIALS AND METHODS: Forty-five female rats at 8 weeks-old were divided into 3 groups: (1) control group, sham-operated rats, (2) ovariectomized group (OVX), and (3) ovariectomized and raloxifene-administered group (RAL). Eight weeks after the ovariectomy, upper right molar was extracted and an implant was placed at 4 weeks post-extraction. The RAL group was administered with 1 mg/kg/d of raloxifene via gavage while the OVX group and the control group received saline only. Three rats in each group were sacrificed at 1, 4, 7, 14, and 28 days and histologic sections were evaluated by hematoxylin and eosin staining and micro-computerized tomography was taken. RESULTS: The RAL group showed faster bone formation around the implant than the OVX group. At 4 weeks after implantation, newly formed bone close to implant threads was mature with considerable quantity of bone marrow in the RAL group. CONCLUSION: Raloxifene showed increased bone formation around implant. This might have clinical implications in prosthetic restoration by dental implants for patients with poor bone quality.

Association of temporomandibular disorder and high frequency of suicide ideation in Korean adolescents: a cross-sectional survey.

BACKGROUND: This study investigated the association between psychological factors and temporomandibular disorder (TMD) in a representative sample using data from the Korean nationwide survey. METHODS: The study included 1337 adolescents. Participants provided demographic, socio-economic and behavioural information, and responses to questionnaires assessing their mental health status including perceived stress, depressed mood and suicidal ideation in the presence of TMD. In univariate analysis, t-test was used to test the association between TMD and risk factors by gender in a complex sampling design. Multivariate logistic regression analyses were used to examine the association between TMD and psychological factors. RESULTS: Male adolescents with TMD were highly engaged with depressed mood and suicidal ideation (p = .0006, p = .0223), however, no psychological factors were significant in female adolescents (p < .05). Male adolescents with both depressed mood and suicidal ideation had significantly high rates of TMD (p = .0024). The risks for experiencing depressed mood (OR: 3.07) and suicidal ideation (OR: 2.564) were significantly associated with TMD in male adolescents after adjusting confounders. CONCLUSIONS: The results provide evidence that the depressed mood and suicidal ideation were associated with TMD in male adolescents. This study has important implications for enhanced screening and evaluation of mental health among patients with TMD according to gender.

Improved Bone Regeneration With Multiporous PLGA Scaffold and BMP-2-Transduced Human Adipose-Derived Stem Cells by Cell-Permeable Peptide.

OBJECTIVE: Currently, much work has focused on the engineering of bone using adipose-derived stem cells (ADSCs), which differentiate into osteogenic cells. This study was conducted to assess the bone-regenerating capacity of ADSCs with genetic modification. MATERIALS AND METHODS: ADSCs were cultured and transduced with recombinant adenovirus-expressing bone morphogenetic protein-2 (rAd/BMP-2). Two 5-mm full-thickness bone defects were created on the parietal bones of 24 rats. The defects were left empty (n = 12), restored with a scaffold alone (n = 12), transplanted with ADSCs in osteogenic media (n = 12), or transplanted with rAd/BMP-2-transduced ADSCs (n = 12). Six defects from each group were assessed by histologic observation, histomorphometric analysis, and microcomputed tomography (micro-CT) imaging at 4 and 8 weeks after transplantation. RESULTS: Increased new bone formation was observed in the rAd/BMP-2-transduced ADSC groups, compared with the other groups. On micro-CT, significant differences were noted in bone volume-to-tissue volume ratios between rAd/BMP-2-transduced ADSCs group and the other groups at both time points (P < 0.05). CONCLUSION: The result demonstrates that transferring BMP-2 promotes the osteogenic differentiation of ADSCs and enhances bone regeneration. Under limitation of this study, genetic modification of ADSCs with BMP-2 could be adopted in clinical application.

Intermittent Parathyroid Hormone Improves Bone Formation Around Titanium Implants in Osteoporotic Rat Maxillae.

PURPOSE: Parathyroid hormone (PTH) plays an important role in the treatment of osteoporosis due to its anabolic effect. In this study, PTH was administered intermittently to rats with ovariectomy-induced osteoporosis, titanium implants were placed into the rat maxillae, and the response of surrounding bone was evaluated. MATERIALS AND METHODS: A total of 30 female 8-week-old Sprague-Dawley rats were either ovariectomized to induce osteoporosis or sham operated. After 8 weeks, the upper right first molar was extracted and after a 4-week healing period an implant was placed. The animals were then divided into three groups: the PTH group (n = 10), which had been ovariectomized and received postimplant PTH; the OVX group (n = 10), which had been ovariectomized but did not receive postimplant PTH; and the control group (n = 10), which had been sham operated only (n = 10). Following implant placement, the rats in the PTH group received intermittent doses (three times a week) of PTH (30 µg/kg) subcutaneously in the dorsum. All the rats were sacrificed 4 weeks after implantation and specimens of the peri-implant maxillary bone were harvested, including the implant. Samples were evaluated by histomorphometric analysis and three-dimensional microcomputed tomography. RESULTS: Histomorphometric results showed that the mean bone area per tissue area (BA/TA) was 54.16% ± 2.2% in the PTH group and 45.24% ± 6.3% in the OVX group. The percentage of bone-to-implant contact (BIC) was 45.58% ± 9.4% in the PTH group and 32.00% ± 10.9% in the OVX group. Mean BA/TA and mean BIC values in the PTH group were higher than those in the OVX group; however, the differences were not statistically significant (P > .05). Microstructural data also showed differences between the groups. Bone volume was greater and trabecular bone was thicker in the PTH group than in the OVX group and more trabeculae were found in the PTH group. Bone mineral density was also higher in the PTH group. However, statistical analysis failed to show a significant difference between these two groups in any parameters other than trabecular thickness (P = .023). CONCLUSION: Despite the limitations of this study, intermittent PTH administration in humans may be helpful in accelerating new bone formation around implants. PTH treatment could improve clinical outcomes when dental implants are placed in jaws with low-quality bone.

Ascending Facial Necrotizing Fasciitis in a Patient Taking a Bisphosphonate.

Facial necrotizing fasciitis (NF) is a rare fulminant infection of the soft and connective tissues that spreads along the fascial planes of the face. Its origins most commonly involve odontogenic infection and it is usually associated with a history of dentoalveolar surgery, such as tooth extraction or implant placement. We present a case of ascending facial NF with odontogenic origin in a patient taking a bisphosphonate.

Enhancing Effect of Intermittent Parathyroid Hormone Administration on Bone Formation After Titanium Implant Placement in an Ovariectomized Rat Maxilla.

OBJECTIVE: This study examined the effect of intermittent parathyroid hormone (PTH) administration on the bone response around implant on the maxilla of rats with ovariectomy-induced osteoporosis. MATERIAL AND METHODS: A total of 27 female Sprague-Dawley rats were divided into 3 groups (n = 9) and were ovariectomized (OVX). Eight weeks after, upper right molar was extracted and an implant was placed at 4 weeks after extraction. The PTH group received PTH, and the OVX group and the control group received vehicle only. Beginning after implant placement, 30 µg/kg of PTH was subcutaneously administered in the dorsum 3 times a week. Three rats in each group were killed at 1, 2, and 4 weeks and histologic sections were evaluated. RESULTS: After 4 weeks, the amount of newly formed bone around implants in the PTH group was comparable with the control group, with bone covering the implant surface in both groups. However, the OVX group displayed relatively small amount of new bone. CONCLUSION: Intermittent PTH has the potential to increase new bone formation around implant. These findings have clinical implications in prosthetic restoration by implants with poor bone quality.

Bone formation on biomimetic calcium phosphate-coated and zoledronate-immobilized titanium implants in osteoporotic rat tibiae.

PURPOSE: Coating prostheses with calcium phosphate (CaP) can boost ossification and provide an appropriate vehicle for drug delivery. In this study, CaP coating was performed using a biomimetic method, and zoledronate (ZOL) was incorporated to promote peri-implant bone formation in an osteoporotic environment. MATERIALS AND METHODS: Twenty female 8-week-old rats were ovariectomized to induce osteoporosis. Twelve weeks later, the animals were randomly separated into four groups representing different ZOL concentrations in the immersion solution: 0 (control), 8, 80, and 800 µg/mL. Surface-treated implants were inserted in both tibiae, and the rats were sacrificed 8 weeks after implantation. Specimens were retrieved for histomorphometric and microcomputed tomographic analyses. RESULTS: A thin CaP coating was formed on the surface of the titanium implants, and ZOL was successfully incorporated into the structure of the biomimetic CaP coating. There were significant differences between the groups with regard to bone volume, whereas bone-implant contact comparisons did not yield any significant differences. The microstructural results clearly illustrated the positive effect of ZOL loading on the implants, as compared to the controls. CONCLUSIONS: The data suggest that biomimetic CaP coating followed by bisphosphonate immobilization is effective in improving bone quality and preserving bone volume around dental implants; therefore, this technique may be beneficial for osteoporosis patients.

Association between insulin resistance and periodontitis in Korean adults.

OBJECTIVE: Recent studies have proposed an association between periodontitis and metabolic abnormalities. We investigated the association between insulin resistance and periodontitis among Korean adults. METHODS: A cross-sectional analysis was conducted using the Korea National Health and Nutrition Examination Survey 2008-2010. A total of 16,720 non-diabetic subjects over 18 years old were evaluated (7060 men and 9660 women). Periodontal status was assessed by the Community Periodontal Index. Insulin resistance was measured using the homeostasis model assessment of insulin resistance (HOMA-IR). Participants in the highest and lowest quartile of HOMA-IR were defined as insulin-resistant and insulin-sensitive respectively. RESULTS: The prevalence of periodontitis increased significantly with higher HOMA-IR quartiles in post-menopausal women (p for linear association = 0.019). Among post-menopausal women, participants in the highest quartile of HOMA-IR were significantly more likely to have periodontitis compared to those in the lowest quartile [adjusted odds ratio (OR), 1.47; 95% confidence interval (CI), 1.07-2.01]. Moreover, obese post-menopausal women showed an increased association between insulin resistance and periodontitis (adjusted OR, 1.92; 95% CI,1.29-2.87). However, this association was not found in men or pre-menopausal women. CONCLUSIONS: Our results suggest that insulin resistance may be associated with periodontitis, especially when combined with obesity, among post-menopausal women in Korea.

Expression of E-cadherin, P-cadherin and N-cadherin in oral squamous cell carcinoma: correlation with the clinicopathologic features and patient outcome.

PURPOSE: Alteration of cadherin expression is associated with the loss of cellular differentiation, the acquisition of an invasive phenotype and a poor prognosis in many types of cancer. This study aimed to evaluate the immunoreactivity of E-, P- and N-cadherins (cad) in oral squamous cell carcinoma and to correlate their expression with clinicopathological features and clinical outcome. The interaction between the cadherins was also investigated. METHODS: A total of 71 tissue samples were examined by immunohistochemical methods on paraffin sections using specific antibodies. RESULTS: In the primary lesions and lymph node metastases, the immunoreactivity of E-cad was reduced and P-cad was over-expressed, but the expression of N-cad was negative (p<0.001, 0.01 and 0.05, respectively). The reduced primary E-cad expression was related to the invasion pattern and lymph node metastasis (p=0.046 and 0.037, respectively). However, the expression of cadherins did not appear to differ significantly in relation to the histological grade, invasion, tumour size, stage of oral SCC or tumour recurrence. A much greater reduction in the expression of E-cad was found in the positive N-cadherin group (p=0.008). Nonetheless, cadherin expression was not significantly associated with failure-free survival or overall survival in this experiment subset. CONCLUSION: The reduced E-cad expression and the aberrant N-cad expression are closely associated with each other in oral cancer cases, and this suggests that cadherin switching from E. cad to N. cad may play a critical role in cancer development and metastasis.