Relationships between cystatin C- and creatinine-based eGFR in Japanese rural community- dwelling older adults with sarcopenia.

BACKGROUND: Sarcopenia is prevalent in patients with chronic kidney disease (CKD). The indices of physical function, such as grip power and gait speed, decreased according to the decline in the estimated glomerular filtration rate (eGFR). METHODS: We examined the relationships between cystatin C-based GFR (eGFRcys), creatinine-based GFR (eGFRcre), their ratio (eGFRcys/eGFRcre) and sarcopenia in community-dwelling older adults in Japan. This cross-sectional study included 302 men aged 73.9 ± 6.2 years and 647 women aged 72.9 ± 5.8 years from a rural area in Hyogo Prefecture, Japan. eGFRcys and eGFRcre were simultaneously measured, and sarcopenia based on the Asia Working Group for Sarcopenia (AWGS) 2019 criteria was evaluated. RESULTS: eGFRcys and the eGFRcys/eGFRcre ratio were significantly correlated with grip power and gait speed (p < 0.001). The eGFRcys/eGFRcre ratio was also correlated with skeletal muscle mass index (SMI) (p < 0.01). Univariate logistic regression analysis showed eGFRcys and eGFRcys/eGFRcre ratio but not eGFRcre were associated with sarcopenia (p < 0.01). The presence of low eGFRcys (CKDcys) and low eGFRcys/eGFRcre ratio (< 1.0) but not that of low eGFRcre (CKDcre) were associated with sarcopenia (p < 0.01). In the multivariate logistic regression analysis, when the eGFRcys/eGFRcre ratio was added as a covariate to the basic model, it was significantly associated with sarcopenia in women (p < 0.05). Moreover, low eGFRcys/eGFRcre ratio (< 1.0) was associated with a higher risk of sarcopenia in men (p < 0.01). CONCLUSION: In conclusion, CKDcys but not CKDcre is associated with sarcopenia. A lower eGFRcys/eGFRcre ratio may be a practical screening marker of sarcopenia in community-dwelling older adults.

The relationship between bone density and the oral function in older adults: a cross-sectional observational study.

BACKGROUND: Falls among older adults with a low bone density can lead to a bedridden state. Declining bone density increases the risk of falls resulting fractures in older adults. A person's physical performance is known to be closely related to bone density, and a relationship between the physical performance and the oral function is also known to exist. However, there currently is a lack of evidence regarding the relationship between bone density and the oral function. We assessed the relationship between the bone density and the both the oral function and physical performance among older adults. PATIENTS AND METHODS: 754 older adults aged 65 years or older who independently lived in rural regions and who were not taking any medications for osteoporosis participated. We checked all participants for osteoporosis using an ultrasonic bone density measuring device. Regarding the oral function, we evaluated the following factors: remaining teeth, occlusal support, masticatory performance, occlusal force, and tongue pressure. We also evaluated body mass index (BMI) and skeletal muscle mass Index as clinical characteristics. The normal walking speed, knee extension force and one-leg standing test were evaluated as physical performance. For the statistical analyses, we used the Mann-Whitney U test, chi-square test, the Kruskal-Wallis, and a multiple regression analysis. RESULTS: Eighty-one percent of the females and 58% of the males had osteoporosis or a decreased bone mass. The occlusal force, masticatory performance and the tongue pressure showed significant association with the bone density. The participants physical performance showed a significant association with their bone states except for walking speed. According to a multiple regression analysis, clinical characteristics (sex, age, BMI), one-leg standing and occlusal force showed independent associations with the bone density. It was suggested that the bone density tends to increase if the occlusal force is high and/or the one-leg standing test results are good. CONCLUSIONS: The bone density in the older adults showed a significant relationship not only with clinical characteristics or physical performance, but also with occlusal force. It may also be effective to confirm a good oral function in order to maintain healthy living for older adults.

Antimicrobial susceptibility surveillance of bacterial isolates recovered in Japan from odontogenic infections in 2013.

We report on the findings of the first antimicrobial susceptibility surveillance study in Japan of isolates recovered from odontogenic infections. Of the 38 facilities where patients representing the 4 groups of odontogenic infections were seen, 102 samples were collected from cases of periodontitis (group 1), 6 samples from pericoronitis (group 2), 84 samples from jaw inflammation (group 3) and 54 samples from phlegmon of the jaw bone area (group 4) for a total of 246 samples. The positivity rates of bacterial growth on culture were 85.3%, 100%, 84% and 88.9%, respectively, for groups 1, 2, 3 and 4. Streptococcus spp. isolation rates according to odontogenic infection group were 22% (group 1), 17.7% (group 3) and 20.7% (group 4). Anaerobic isolation rates were 66.9% (group 1), 71.8% (group 3) and 68.2% (group 4). Drug susceptibility tests were performed on 726 strains excluding 121 strains that were undergrown. The breakdown of the strains subjected to testing was 186 Streptococcus spp., 179 anaerobic gram-positive cocci, 246 Prevotella spp., 27 Porphyromonas spp., and 88 Fusobacterium spp. The isolates were tested against 30 antimicrobial agents. Sensitivities to penicillins and cephems were good except for Prevotella spp. The low sensitivities of Prevotella spp is due to ß-lactamase production. Prevotella strains resistant to macrolides, quinolones, and clindamycin were found. No strains resistant to carbapenems or penems were found among all strains tested. No anaerobic bacterial strain was resistant to metronidazole. Antimicrobial susceptibility testing performed on the S. anginosus group and anaerobic bacteria, which are the major pathogens associated with odontogenic infections, showed low MIC90 values to the penicillins which are the first-line antimicrobial agents for odontogenic infections; however, for Prevotella spp., penicillins combined with ß-lactamase inhibitor showed low MIC90 values.

Basic survey for the prevention of intraoral residual medication in older adults: A pilot study.

OBJECTIVE: This study aimed to assess the relationship between oral hygiene/stomatognathic function and residual intraoral medication in older adults and to identify the oral factors associated with residual oral medication. METHODS: The study included 309 older adults (77 men, 232 women, mean age: 74.1 ± 7.4 years) who were prescribed medications at regular intervals. The following survey items were assessed: overall physical condition, intraoral condition and oral function. Participants prescribed oral medication were classified into groups with and without residual medication in the oral cavity. Statistical analysis was performed using univariate analysis for each of the factors contributing to the presence of residual medication. RESULTS: Only 1.9% of all patients had residual medication, which suggests that older adults in this survey had a low risk of residual intraoral medication. However, greater attention should be given to residual intraoral medication in older adults receiving long-term care. Powdered-form oral medications were more likely to remain in the oral cavity. Older adults with residual medication had a tendency to have less occlusal support, poor tongue hygiene and poor tongue movement. Oral function, particularly functions that are closely related to swallowing, was significantly lower in the residual intraoral medication group when compared to those of the group without residual intraoral medication. CONCLUSIONS: Reduced oral function and powered medication were associated with greater residual intraoral medication in this sample of older Japanese adults.

Relationship between oral environment and frailty among older adults dwelling in a rural Japanese community: a cross-sectional observational study.

BACKGROUND: Oral functions are known to decline with aging. However, there is limited evidence that supports the relationship between oral health and frailty. This study aimed to clarify the relationship between oral hygiene conditions, measured by remaining teeth and mucosa, and frailty among elderly people dwelling in a Japanese rural community. METHODS: We surveyed self-reliant elderly individuals aged ≥65 years who were dwelling in the Sasayama-Tamba area of Hyogo, Japan. Frailty was evaluated according to the total score of the Kihon Checklist (KCL). Based on the KCL score, elderly participants were divided into three groups: robust, pre-frail, and frail. The items measured to evaluate oral environment included the number of remaining teeth, denture usage condition, oral hygiene status, dry mouth condition, and salivary bacterial count. For statistical analysis, Fisher's exact test, one-way analysis of variance, and multiple comparison technique were used. RESULTS: Of 308 elderly participants, 203 (65.9%), 85 (27.6%), and 20 (6.5%) belonged to the robust, pre-frail, and frail groups, respectively. The proportion of participants who were judged to have poor hygiene was significantly higher in the frail group than in the other two groups. The bacterial count was significantly smaller in the frail group than in the robust group, and the frail group had fewer number of remaining teeth than the other two groups, suggesting that the number of remaining teeth may be associated with bacterial count. CONCLUSION: In elderly adults, physical frailty may affect the oral hygiene status and condition of the remaining teeth.

New paste for severe stomatitis in patients undergoing head-and-neck cancer radiotherapy and/or chemotherapy with oral appliance.

BACKGROUND: The aim of the present study was to evaluate the physical properties of "admixture paste", which is a commercially available gel containing hinokitiol for use against severe stomatitis, and its characteristics as a moisturizing gel and denture adhesive. METHODS: The admixture paste, which contained dexamethasone (Dexaltin®), gel for oral care (Refrecare H®) and petrolatum, and its 3 components, either alone or in different combinations, were subjected to viscosity, adhesiveness and elution testing to compare their physical properties. Viscosity was measured with a stress-controlled rheometer. Adhesive force was measured by tension test. Elution under a simulated oral environment was evaluated by monitoring with a fixed-point camera and absorbance. Both adhesiveness and elution were evaluated every hour for 6 h. A linear mixed-effects model was used to assess differences in the time course of elution between samples. In 3 og-rank test was used to compare time to elution into saliva among samples. RESULTS: The results of viscosity testing demonstrated that the admixture paste had similar viscosity to cream-type denture adhesives and this was temperature independent. In the adhesiveness tests, the admixture paste showed stronger adhesiveness than that of cream-type denture adhesives. In the elution test, the admixture paste demonstrated gradual dissolution and apparent temporal changes for 6 h in a simulated oral environment. CONCLUSIONS: The results of the present study demonstrated that the admixture paste has adhesive force similar to those of denture adhesives and good local retention in saliva, and that it might be suitable for therapeutic use in patients with severe stomatitis derived from radiotherapy and/or chemotherapy for cancer.

National Survey on Bisphosphonate-Related Osteonecrosis of the Jaws in Japan.

PURPOSE: From 2011 to 2013, a nationwide retrospective cohort study was conducted by the Japanese Society of Oral and Maxillofacial Surgeons and the Japanese Society of Dentistry for Medically Compromised Patients to assess the development of bisphosphonate (BP)-related osteonecrosis of the jaws (BRONJ) and to elucidate the outcomes and factors associated with remission. MATERIALS AND METHODS: A written questionnaire, including clinical characteristics, management, and outcomes of patients with BRONJ, was sent to 501 institutions. RESULTS: This large-scale study included 4,797 cases with a female preponderance. BRONJ occurred twice as often in the mandible as in the maxilla. Most patients had BRONJ stage 2 (61.4%), followed by stage 1 (20.7%) and stage 3 (16.8%); stage 0 was excluded. The most common primary disease was malignant neoplasm (46.5%), followed by osteoporosis (including prevention; 45.3%). The proportion of patients on oral BPs increased, with the incidence approaching that of patients receiving parenteral BP. Surgical therapy rates of patients with BRONJ stages 1, 2, and 3 were 14.0, 37.6, and 53.5%, respectively. Outcome assessment for 936 patients with BRONJ stage 2 who underwent surgical therapy indicated remission in 46.3% of cases, improvement in 30.6%, disease progression in 5.4%, and no change in 6.1%. Good prognosis (remission or improvement) was seen in 76.9% of cases and poor prognosis (disease progression or no change) was seen in 11.5%. Analysis showed that risk factors for onset of BRONJ (P = .031), surgical procedure (P < .024), condition of the wound (P = .017), and discontinuation of BP (P < .001) were factors affecting prognosis. CONCLUSION: The number of patients with BRONJ has increased in Japan. Attention to oral BP and proper treatment is required to minimize the number of cases. Surgical therapy seems to be effective for BRONJ stage 2.

Change in tongue pressure in patients with head and neck cancer after surgical resection.

Tongue pressure is reportedly associated with dysphagia. This study investigated relationships among characteristics of head and neck cancer, tongue pressure and dysphagia screening tests performed in patients with head and neck cancer during the acute phase after surgical resection. Fifty-seven patients (36 men, 21 women; age range 26-95 years) underwent surgical resection and dysphagia screening tests (Repetitive Saliva Swallowing Test, Water Swallowing Test, Modified Water Swallowing Test and Food Test) and pre- and postoperative measurement of tongue pressure at 5 time points (preoperatively, and 1-2 weeks and 1, 2, and 3 months postoperatively). Progression of cancer (stage), tracheotomy, surgical reconstruction, chemotherapy, radiotherapy and neck dissection were factors associated with postoperative tongue pressure. Data were analyzed by linear mixed-effect model, Spearman correlation coefficient and receiver operating characteristic (ROC) curve. Tongue pressure was significantly reduced 1-2 weeks after surgery, and recovered over time. Changes in tongue pressure were significantly associated with stage, radiotherapy and reconstruction. All screening tests showed a significant relationship with tongue pressure. Analysis of ROC and area under the effect curve suggested that a tongue pressure of 15 kPa can be used as a cut-off value to detect dysphagia after surgery for head and neck cancer. Our results suggest that tongue pressure evaluation might offer a safe, useful and objective tool to assess dysphagia immediately postoperatively in patients with head and neck cancer.

[Oral management for perioperative patients.]

During perioperative period, several oral-related complications happen to occur, including not only postoperative pneumonia and surgical site infection, but also damage to teeth. Furthermore, in case of surgeries where the materials such as prosthetic valves and artificial joints are installed inside the body, there is a potential risk of developing foreign material infections due to bacteremia from the oral cavity as the periodontitis remains there. There is a possibility that a necessary treatment during perioperative period is not performed with only the oral cleaning which is narrowly defined as oral care, without an assessment of potential problems for oral. The oral-related perioperative complications can be prevented by putting the oral management into practice, which include a necessary dental treatment, rehabilitation for mastication and swallowing, and education of patients and medical staff, based on accurate oral assessment.

Utility of intraoral stents in external beam radiotherapy for head and neck cancer.

AIM: This study aimed to assess the utility and stability of intraoral stent during intensity-modulated radiation therapy (IMRT). BACKGROUND: The benefits of intraoral stents in radiotherapy are unclear. MATERIALS AND METHODS: We analyzed 386 setup errors in 12 patients who received IMRT for head and neck cancers without intraoral stents (intraoral stent [-]) and 183 setup errors in 6 patients who received IMRT with intraoral stents (intraoral stent [+]). All patients were matched according to the immobilization method (masks and boards). Setup errors were measured as the distance from the initial setup based on the marking on the skin and mask to the corrected position based on bone matching on cone beam computed tomography. RESULTS: The mean interfractional setup errors in the right-left, craniocaudal, anterior-posterior (AP), and three-dimensional (3D) directions were -0.33, 0.08, -0.25, and 2.75 mm in the intraoral stent (-) group and -0.37, 0.24, -0.63, and 2.42 mm in the intraoral stent (+) group, respectively (P = 0.50, 0.65, 0.01, and 0.02, respectively). The systematic errors for the same directions were 0.89, 1.46, 1.15, and 0.88 mm in the intraoral stent (-) group and 0.62, 1.69, 0.68, and 0.56 mm in the intraoral stents (+) group, respectively. The random errors were 1.43, 1.43, 1.44, and 1.22 mm in the intraoral stent (-) group and 1.06, 1.11, 1.05, and 0.92 mm in the intraoral stents (+) group, respectively. CONCLUSION: Setup errors can be significantly reduced in the AP and 3D-directions by using intraoral stents.

Osteonecrosis of the jaw in an AIDS patient: a case report.

We report a rare case of osteonecrosis of the jaw following necrotizing gingivitis in a Japanese AIDS patient. Intraoral examination showed exposed necrotic bone in the left mandible and spontaneous loss of teeth. This patient was successfully treated with highly active anti-retroviral therapy combined with minimally invasive surgical procedures to remove the osteonecrosis of the jaw.

Expression of interleukin-34 and colony stimulating factor-1 in the stimulated periodontal ligament cells with tumor necrosis factor-α.

Tumor necrosis factor-α (TNF-α) directly and indirectly plays a crucial role in osteoclastogenesis. However, the indirect effects of TNF-α on colony-stimulating factor-1 receptor (CSF-1R)-mediated osteoclastogenesis achieved via periodontal ligament (PDL) cells are not fully understood. We herein examined the potency of osteoclast differentiation and maturation induced by fivefold supernatants in the stimulated human PDL cells with a physiologically high concentration (10 ng/mL) of recombinant TNF-α to human peripheral blood monocytes/macrophages in the simultaneous presence of the receptor activator of nuclear factor kappa-B ligand. The number of tartrate-resistant acid phosphatase-positive cells with multiple nuclei, but not those with a single nucleus, was decreased by approximately 50% by neutralization with rabbit IgG against either interleukin-34 (IL-34) or CSF-1. Small and large amounts of IL34 and CSF1 transcripts were measured in the stimulated PDL cells using real-time polymerase chain reaction. The corresponding amounts of proteins to IL34 and CSF1 transcripts were observed in the stimulated PDL cells on immunohistochemical staining or Western blotting. Moreover, 0.13 ng/mL of IL-34 and 5.0 ng/mL of CSF-1 were measured in the supernatants of the stimulated PDL cells using an enzyme-linked immunosorbent assay. IL-34 derived from the stimulated PDL cells with TNF-α appeared to synergistically function with CSF-1 in the CSF-1R-mediated maturation of osteoclastogenesis.

Long-term follow-up of a patient with Parkinson's disease under nursing care after replacement of fixed implant-supported prostheses with an implant overdenture: a case report.

BACKGROUND: In older patients with progressive neurodegeneration, replacing fixed implant-supported prostheses (FIP) with implant overdentures (IOD) has been proposed to prevent future mucosal injury and create an oral environment that is easier for caregivers to clean. However, there have been no reports on the progress after replacing FIP with IOD. In this report, we present the progress of an older patient with Parkinson's disease in whom FIP was replaced with IOD. CASE PRESENTATION: An 81-year-old male patient with Parkinson's disease presented to our outpatient clinic with bruxism and crossbites. FIPs, with five Brånemark system implants, were placed in the bilateral lower molars. The FIP was replaced with an IOD with two locator attachments to create an oral environment that was easier for caregivers to clean and allow easy recovery of masticatory function if residual teeth were fractured in the care environment. As his systemic condition deteriorated, treatment was changed from outpatient to in-home visits. During dental care visits, professional oral cleaning and denture repair were continued, and good nutritional status was maintained. However, the patient developed cholecystitis and was hospitalized. During hospitalization, gastrostomy was performed because he developed aspiration pneumonia. After discharge from the hospital, the patient remained in bed all day and could not wear an IOD, resulting in buccal mucosa ulceration due to abrasion of the locator abutment. We decided to replace the abutment with cover screws; however, not all the implants could sleep submucosally. Although regular oral cleaning was resumed, new ulcers developed even when cover screws were installed. Additionally, swelling and drainage were observed at the peri-implant mucosal site where peri-implantitis had once occurred during an outpatient visit. The patient was readmitted to the hospital for a urinary tract infection, and subsequent visits were abandoned. CONCLUSIONS: By replacing FIP with IOD in an older patient with Parkinson's disease, we addressed a barrier to caregiver-provided oral management. The removable prosthesis facilitated smooth oral care by caregivers and functional recovery in the event of trouble with residual teeth. However, it could not completely avoid the recurrence of buccal mucosal ulcers or peri-implantitis.

Bacterial Lipopolysaccharide Induces PD-L1 Expression and an Invasive Phenotype of Oral Squamous Cell Carcinoma Cells.

BACKGROUND: Expression of programmed death ligand-1 (PD-L1) is related to the prognosis of many solid malignancies, including oral squamous cell carcinoma (OSCC), but the mechanism of PD-L1 induction remains obscure. In this study, we examined the expression of PD-L1 and partial epithelial-mesenchymal transition (pEMT) induced by bacterial lipopolysaccharide (LPS) in OSCC. METHODS: The expression of Toll-like receptor 4 (TLR4) recognizing LPS in OSCC cell lines was analyzed. Moreover, the induction of PD-L1 expression by Porphyromonas gingivalis (P.g) or Escherichia coli (E. coli) LPS and EMT was analyzed by western blotting and RT-PCR. Morphology, proliferation, migration, and invasion capacities were examined upon addition of LPS. PD-L1 within EXOs was examined. RESULTS: PD-L1 expression and pEMT induced by LPS of P.g or E. coli in TLR4-expressing OSCC cell lines were observed. Addition of LPS did not change migration, proliferation, or cell morphology, but increased invasive ability. Moreover, higher expression of PD-L1 was observed in OSCC EXOs with LPS. CONCLUSION: Oral bacterial LPS is involved in enhanced invasive potential in OSCC cells, causing PD-L1 expression and induction of pEMT. The enhancement of PD-L1 expression after addition of LPS may be mediated by EXOs.

[Assessment of oral health using the general oral health assessment index in patients with overactive bladder].

Patients administered anti-cholinergic agents, as first-line therapy for an overactive bladder (OAB) are often unable to continue medical treatment because of dry mouth. We assessed oral health in patients with OAB using the General Oral Health Assessment Index (GOHAI), an oral health-related quality of life questionnaire. We investigated 75 patients with OAB who were receiving continuous administration of anti-cholinergic agents. The OAB symptom score, as well as GOHAI and our original dry mouse score were determined by self-administered questionnaires. The mean age of the subjects was 70.9±10.2 years, the median period of anti-cholinergic agent use was 20 (1-116) months and the mean OAB symptom score was 6.3±3.1. The GOHAI score for all patients was 51.9±8.4 and not significantly different from the national normal value (p＝0.22). On the other hand, the score in patients with a severely dry mouth was 49.2±8.6, which was worse than the national normal value (p＝0.04). The psychosocial functioning score in patients with a severely dry mouth was significantly lower than in those with a slightly dry mouth (p＝0.02). Our results indicate that dry mouth in patients with OAB is significantly associated with worsening of oral health. GOHAI is useful as a screening test to assess the quality of life in patients with OAB.

[Oral management for cancer patients].

Chemotherapy and radiotherapy administered to cancer patients can be harmful because of their effect on normal cells as well as cancer cells, and cause many adverse events. The oral cavity is one of the sites most vulnerable to the direct and indirect effects of cancer therapy. Severe adverse events of the oral cavity can not only reduce a patient's QOL, but also disrupt cancer treatment. We discuss the concept of oral management by maintenance of the oral environment.

Usefulness of quantitative bone SPECT/CT for evaluating medication-related osteonecrosis of the jaw treatment response.

OBJECTIVE: For assessment of therapeutic response in medication-related osteonecrosis of the jaw (MRONJ) cases, the clinical usefulness of quantitative bone single-photon computed tomography-computed tomography (SPECT/CT) results was investigated. MATERIALS AND METHODS: Sixteen patients (18 lesions) with a clinical diagnosis of MRONJ underwent bone SPECT/CT scanning before and during/after anti-inflammatory therapy given for 3 or more months. The GI-BONE software package was used to determine standard uptake values (SUVs), including maximum (SUVmax), peak (SUVpeak), and mean (SUVmean), and metabolic bone volume (MBV) and also total bone uptake (TBU). In both responders (downstage) and non-responders (upstage or no change), differences in quantitative values between the first and second SPECT/CT examinations were analyzed using a Wilcoxon test. RESULTS: Following therapy, significant reductions in SUVmax, SUVpeak, SUVmean, MBV and TBU values for 11 lesions were noted in the responders after therapy (p = 0.003, p = 0.006, p = 0.004, p = 0.003, and p = 0.002, respectively). On the other hand, those for the seven lesions in the non-responder group were not significantly different (p = 0.17, p = 0.16, p = 0.26, p = 0.96, and p = 0.12, respectively). Results for SUVmax change showed sensitivity and specificity values of 45.5% and 85.7%, respectively, for differentiating responders from non-responders, with - 37.3% the optimal cutoff value. Those for MBV change were 72.7 and 85.7%, respectively, with - 29.4% the optimal cutoff value. Those for TBU change were 81.8% and 85.7%, respectively, with - 36.3% the optimal cutoff value. CONCLUSION: The present findings showed that therapeutic response in MRONJ cases could be determined by use of quantitative SUV, MBV, and TBU values based on bone SPECT/CT findings.

G­CSF delays tooth extraction socket bone healing via the inhibition of bone turnover in mice.

Granulocyte colony-stimulating factor (G-CSF) regulates the survival, proliferation and differentiation of all cells in the neutrophil lineage, and is consequently used for neutropenic conditions. Upon G-CSF administration, osteoblasts and osteocytes are suppressed, and the support system allowing hematopoietic stem cells to remain in the microenvironment is diminished. The present study focused on and investigated G-CSF as a regulatory factor of bone remodeling. The aim of the present study was to investigate the effect of G-CSF administration on the bone healing of tooth extraction sockets. Significant differences in the bone volume fraction, and trabecular separation of the proximal femurs and alveolar septa were observed between the G-CSF and control (saline-treated) groups. The trabecular bone of the femur and alveolar septa was reduced in the G-CSF group compared with that in the control group. In addition, serum procollagen type 1 N-terminal propeptide levels, a marker of bone formation, were lower in the G-CSF group compared with in the control group. Fibrous connective tissues and immature bone were observed in the extraction socket, and bone healing was delayed in the G-CSF group compared with that in the control group. The bone area in the extraction socket 6 days after tooth extraction was significantly smaller in the G-CSF group (23.6%) than that in the control group (45.1%). Furthermore, G-CSF administration reduced the number of canaliculi per osteocyte and inhibited the connection of osteocyte networks. Consequently, osteoblast activation was inhibited and bone remodeling changed to a state of low bone turnover in the G-CSG group. Analysis of bone formation parameters revealed that the G-CSF group exhibited a lower mineral apposition rate compared with in the control group. In conclusion, these findings indicated that G-CSF may delay bone healing of the socket after tooth extraction.

Incidence of antiresorptive agent-related osteonecrosis of the jaw: A multicenter retrospective epidemiological study in Hyogo Prefecture, Japan.

Background/purpose: The incidence of medication-related osteonecrosis of the jaw is increasing worldwide, mostly due to the use of antiresorptive agents (ARAs) such as bisphosphonate (BP) and denosumab (Dmab). However, the proportion of BP-related osteonecrosis of the jaw (BRONJ) and Dmab-related osteonecrosis of the jaw (DRONJ) among all ARA-related osteonecrosis of the jaw (ARONJ) cases is not clear; this hinders appropriate treatment, recurrence-prevention planning, and avoidance of unnecessary Dmab withdrawal. Moreover, the causative drug administered at each disease stage remains unknown. Therefore, we conducted a retrospective study of patients with ARONJ who visited oral and maxillofacial surgery departments at hospitals in Hyogo Prefecture, Japan, over 3 years to classify and compare patient characteristics with those having BRONJ and DRONJ. We sought to identify the proportion of DRONJ in ARONJ. Materials and methods: After excluding stage 0 patients, 1021 patients were included (471 high-dose; 560 low-dose). ARA treatment for bone metastases of malignant tumors and multiple myeloma was considered high dose, while that for cancer treatment-induced bone loss and osteoporosis was low dose. Results: Low doses of BP and Dmab accounted for >50% patients; the results differed from those in other countries. DRONJ accounted for 58% and 35% of high-dose and low-dose cases, respectively. Stage 3 ARONJ cases comprised 92 (19.5%) low-dose BRONJ, 39 (20.1%) high-dose BRONJ, 24 (30%) low-dose DRONJ, and 68 (24.5%) high-dose DRONJ. Eighty-nine patients who received switch therapy were divided into BRONJ or DRONJ, but there was no difference in the ratio of each stage compared to the non-switch therapy. Conclusion: To the best of our knowledge, this is the first study to clarify the proportion of BRONJ and DRONJ cases, causative drug, and its doses by disease stages. DRONJ accounted for approximately 30% of the ARONJ, approximately 60% of which was due to high doses.

Usefulness of quantitative bone SPECT/CT for medication-related osteonecrosis of the jaw in clinical settings.

OBJECTIVE: This study was conducted to investigate the clinical utility of quantitative bone single-photon computed tomography-computed tomography (SPECT/CT) for detection and classification for medication-related osteonecrosis of the jaw (MRONJ). MATERIALS AND METHODS: Fifty-nine patients (69 lesions) clinically diagnosed as MRONJ by four specialists of Japanese Society of Oral Surgery according to the AAOMS diagnostic criteria and who underwent bone SPECT/CT were enrolled. One reader determined standard uptake values (SUVs), including maximum (SUVmax), peak (SUVpeak), and mean (SUVmean), as well as metabolic bone volume (MBV), representing total volume above threshold, and total bone uptake (TBU), calculated as MBV × SUVmean, using the GI-BONE software package. One-way repeated-measures analysis of variance and subsequent post hoc analysis were employed to compare quantitative values between clinical stages. To check reproducibility of values, another reader calculated these quantitative values. RESULTS: Mean SUVmax values for stage 0 (n = 21), 1 (n = 13), 2 (n = 25), and 3 (n = 10) were 5.82 ± 3.20, 5.46 ± 3.79, 8.16 ± 3.93, and 10.57 ± 8.43, respectively, while values for MBV were 9.52 ± 6.33, 11.36 ± 7.32, 12.4 ± 8.21, and 17.84 ± 16.94, respectively, and for TBU were 40.60 ± 46.97, 53.70 ± 77.26, 62.37 ± 42.91, and 102.01 ± 74.52, respectively. There were significant differences for SUVmax, SUVpeak, and SUVmean between clinical stages (p = 0.024, p = 0.027, p = 0.039, respectively). Subsequent post hoc analysis showed that SUVmax and SUVpeak of stage 3 were significantly higher than those of stage 0 (p = 0.046, 0.045, respectively). MBV and TBU showed a tendency to increase with increased stage, though differences between stages were not significant (p = 0.15, p = 0.053, respectively). Little differences of mean SUVmax, SUVpeak, SUVmean, MBV, and TBU between two readers were observed (- 3.10%, - 0.26%, - 4.24%%, 0.69%, and - 3.42%, respectively). The intraclass correlation coefficients (ICCs) of SUVmax, SUVpeak, SUVmean, MBV, and TBU were 0.985, 0.990, 0.980, 0.994, and 0.994, respectively (almost perfect for all values). CONCLUSION: As objective and reliable indicators, SUVmax and SUVpeak derived from quantitative bone SPECT/CT results are useful for detection of early status disease, as well as staging in MRONJ patients.