Complex interplay of oral health, muscle and bone metabolism, and frailty in older individuals.

OBJECTIVES: To investigate molecular and clinical background of associations among oral health, muscle and bone metabolism, and frailty incidence in patients with fall and fracture history. MATERIALS AND METHODS: In total, 88 elderly participants (mean age 71.9 ± 5.8 years) with the distal radius fractures were included. Participants were divided into three groups based on an Oral Health Assessment Tool score. Fried criteria and Mini-nutritional assessments were adopted to diagnose frailty and malnutrition, respectively. Blood samples were collected and analyzed for serum levels of bone turnover markers, proteins, insulin-like growth factor-1, 25-hydroxyvitamin D, and inflammatory cytokines. The mRNA levels of markers of inflammation, muscle synthesis and wasting, and muscle homeostasis regulator in the pronator quadratus muscle were analyzed. RESULTS: Patients with deteriorated oral health demonstrated a higher prevalence of frailty and malnutrition. Significantly lower serum levels of total protein and higher concentrations of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were detected in patients with poor oral health. Significant interaction effects between oral health and frailty level in gait speed, serum TNF-α, IL-1ß, and total protein levels were exhibited. Significantly different mRNA expression levels in the pronator quadratus muscle of TNF-α, IL-1ß, NF kB, MYOG, and FOXO1 following the oral health were detected. CONCLUSION: This study highlights relationship between oral health, nutritional uptake, systemic inflammation, and their combined impact on muscle and bone metabolism, ultimately affecting frailty development in the aging populations. CLINICAL RELEVANCE: A comprehensive understanding of mutual interactions among oral health, nutrition, and inflammation is essential for managing frailty.

Association between joint effusions and concomitant structural injuries (tendinitis and structural injury) on MRI in ankle trauma without fracture.

BACKGROUND: The evaluation of correlations among joint effusion, ligament injuries, tenosynovitis and osteochondral lesion of talus (OLT) in the ankle joint is important for developing a treatment plan and predicting prognosis. PURPOSE: To evaluate correlations among tibiotalar (anterior) and talocalcaneal (posterior) joint effusion, tenosynovitis of major flexor tendons, ligaments, and OLT in a group of patients with ankle trauma. MATERIAL AND METHODS: This retrospective study included 101 patients with ankle trauma who underwent magnetic resonance imaging. Two radiologists assessed the presence and amount of effusion in the tibiotalar and talocalcaneal joints from grade 0 to 2, according to the amount of capsular distension. Concomitant structural injuries were assessed in the tibialis posterior (TP), flexor digitorum longus, flexor hallucis longus, and peroneus tendons, and the anterior talofibular ligament, calcaneofibular ligament, anteroinferior tibiofibular ligament, posteroinferior tibiofibular ligament, and OLT. RESULTS: The proportion of anterior and posterior joint effusion according to grade was 67.3% for anterior joint effusion grade 0, 22.8% for grade 1, and 9.9% for grade 2; for posterior joint effusion, grade 0 was 74.2%, grade 1 was 22.8%, and grade 2 was 3.0%. We found statistically significant correlations between posterior joint effusion and tenosynovitis of TP (P < 0.05) and between posterior joint effusion and OLT (P < 0.05). CONCLUSION: Posterior joint effusion is correlated with TP injury and OLT; however, tendon injuries have no correlation with other structural injuries of the ankle joint in a general population with ankle trauma.

Relationship between skeletal bone mineral density and subjective masticatory difficulty.

BACKGROUND: Masticatory ability is an essential factor for sustaining quality of life and social and systemic well-being, particularly in elderly. This study aimed to reveal the association between subjective masticatory difficulty and skeletal bone mineral density (BMD). METHODS: Data from the Korean National Health and Nutrition Examination Survey, which was conducted from 2008 to 2011 were analyzed. This study included 13,092 Koreans (5656 males, 7436 females) over 50 years of age. Masticatory difficulty was evaluated based on a self-reported questionnaire. Areal BMD of the total hip, femoral neck, and lumbar spine as well as lean body mass were determined using dual-energy X-ray absorptiometry. Data about the sociodemographic characteristics, physical activity, number of teeth present, sum of decayed, missing, and filled permanent teeth (DMFT) index and Community Periodontal Index (CPI) were collected. Multivariate logistic regression analysis was conducted to analyze associations between subjective masticatory difficulty and BMD, adjusting for the confounding covariates. RESULTS: Significant differences were observed in the areal BMD of the total hip, femoral neck, and lumbar spine as well as lean body mass accordance with the presence of subjective masticatory difficulty in both males and females. The number of teeth, DMFT, and CPI score did not show significant differences based on the presence of self-reported satisfaction of chewing performance in both males and females. Results from multivariate logistic regression demonstrated that the subjective masticatory difficulty showed significant interactions with skeletal BMD and the associations between masticatory satisfaction and BMD of the total hip and femoral neck were more prominent in females compared to those in males. CONCLUSIONS: The skeletal BMD, particularly areal BMD of the femoral neck was significantly associated with subjective masticatory difficulty in elderly, especially in elder females.

Bone mineral density, bone microstructure, and bone turnover markers in females with temporomandibular joint osteoarthritis.

OBJECTIVE: The pathogenesis of the temporomandibular joint osteoarthritis (TMJ OA) has not been clearly revealed. This study aimed to investigate the pathogenesis of TMJ OA based on bone metabolism. METHODS: Fifty-nine young (mean age 23.4 ± 3.4 years) and 41 post-menopausal females (mean age 57.2 ± 4.6 years) were enrolled. Areal bone mineral density (aBMD) was measured via dual-energy X-ray absorptiometry of the lumbar spine, femoral neck, total hip, and ultradistal radius. Levels of four bone resorption markers, serum ionized calcium and C-telopeptide of type I collagen (CTx) and urinary N-telopeptide of type I collagen and deoxypyridinoline, two bone formation markers, serum bone alkaline phosphatase and osteocalcin, and serum 25-dihydroxyvitamin D were analyzed at baseline and after 12 months. Condylar bone quality was assessed by 3D reconstructed CT images. RESULTS: Significant differences in condylar bone quality and aBMDs of the lumbar spine in accordance with TMJ OA stages were observed in young and post-menopausal females. The level of CTx was significantly associated with the development and progression of TMJ OA only in young females, whereas 25-dihydroxyvitamine D demonstrated significant associations in young and post-menopausal females. Progression of TMJ OA was accompanied by reduced condylar bone quality and concomitant with lower lumbar spine aBMDs in young and post-menopausal females. CONCLUSION: Bone metabolism and condylar quality might be involved in the development and progression of TMJ OA. CLINICAL RELEVANCE: CTx could be considered as a potential diagnostic and monitoring marker in young females, and vitamin D showed a therapeutic potential for TMJ OA.

Metformin, resveratrol, and exendin-4 inhibit high phosphate-induced vascular calcification via AMPK-RANKL signaling.

Vascular calcification increases the risk of developing cardiovascular disease, and it is closely associated with metabolic disorders such as diabetes mellitus and non-alcoholic fatty liver disease. We investigated whether the activators of AMP-activated protein kinase (AMPK), metformin, resveratrol, and exendin-4, improved inorganic phosphate (Pi)-induced vascular calcification in rat vascular smooth muscle cells (VSMCs) and whether these effects were via AMPK. Pi increased calcium deposition in a dose-dependent manner, and metformin, resveratrol, and exendin-4 significantly decreased calcium deposition in the Pi-treated VSMCs. Moreover, metformin and exendin-4 increased the expression of a SMC marker gene, α-smooth muscle actin, and Ampk and reduced the receptor activator of nuclear factor kappa-Β ligand (Rankl)/osteoprotegerin ratio. Metformin, resveratrol, and exendin-4 reduced the expression of osteoblast differentiation-associated factors, such as runt-related transcription factor 2, bone morphogenic protein-2, p-small mothers against decapentaplegic 1/5/8, and Rankl. Inhibition of AMPK by siRNA adversely affected the anti-calcification effects of metformin, resveratrol, and exendin-4 and reversed the reduction of the expression of Rankl by metformin and exendin-4 in the Pi-treated VSMCs. These data suggest that metformin, resveratrol, and exendin-4 ameliorate Pi-induced vascular calcification by inhibiting osteoblast differentiation of VSMCs, which is mediated by AMPK.

Idiopathic Avascular Necrosis of Trapezoid in Adolescence: 3-Year Follow-Up.

Avascular necrosis (AVN) is relatively uncommon in the carpal bones, although it most frequently involves the lunate and scaphoid. The trapezoid has abundant vascular channels from a rich network of dorsal and palmar vessels, and only a few cases of AVN have been reported in adults who sustained a traumatic insult. We present a rare case of idiopathic AVN of the trapezoid in an adolescent presenting with refractory pain at the second metacarpal base. Over a period of 36 months, follow-up symptom evaluations and serial magnetic resonance images showed prominent gradual improvement, consistent with spontaneous resolution.

Radiographic Remodeling of the Proximal Phalangeal Head Using a Stretching Exercise in Patients With Camptodactyly.

PURPOSE: The aims of this study were to verify proximal phalangeal head normalization after a stretching exercise in patients with infantile-type camptodactyly and to propose radiographic indices for quantifying bony deformities. METHODS: Forty-eight fingers of 20 patients with camptodactyly were enrolled in this study. All patients and their parents received instruction on how to perform the stretching exercise. The qualitative assessments of proximal phalangeal head remodeling were conducted by consensus of 2 hand surgeons. Two radiographic parameters, head triangle ratio (HTR) and head angle (HA), were measured on finger lateral radiographs taken at the initial visit and at 12-month follow-up. The intra- and interobserver reliability of both parameters was assessed. Those parameters of the patients were compared with those of 177 fingers of 80 children without camptodactyly. The extent of proximal interphalangeal (PIP) joint flexion contracture was used to evaluate clinical outcomes resulting from nonsurgical treatment. RESULTS: Qualitative assessments of proximal phalangeal head remodeling exhibited meaningful improvements. Both radiographic parameters showed significant change between their status before and after intervention and had excellent intra- and interobserver reliability. Average PIP joint flexion contracture significantly improved. In the noncamptodactyly group, neither parameter showed significant differences in accordance with finger types and age ranges. CONCLUSIONS: Stretching improved movement within the proximal phalangeal joint and helped to restore proximal phalangeal head roundness and concentricity in patients with infantile-type camptodactyly. The HTR and HA would be useful indices for objectively assessing the degree of bony deformity in patients with camptodactyly. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Altered gene and protein expressions of vitamin D receptor in skeletal muscle in sarcopenic patients who sustained distal radius fractures.

Despite the presence of vitamin D receptor (VDR) in skeletal muscle cells, the relationship between VDR expressions and muscle mass or function has not been well studied. The purpose of this study was to compare VDR gene and protein expression in the forearm muscle between sarcopenic and non-sarcopenic individuals who have sustained distal radius fractures. Twenty samples of muscle tissue from sarcopenic patients (mean age 63.4 ± 8.1 years) and 20 age- and sex-matched control tissues (62.1 ± 7.9 years) were acquired from the edge of dissected pronator quadratus muscle during surgery for distal radius fractures. The mRNA expression levels of VDR as well as the myokines of interest that may be associated with muscle mass change (myogenin and myostatin) were analyzed with real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). In addition, Western blot assay and immunohistochemistry for VDR were performed. Sarcopenic patients showed a significantly lower level of gene expression for VDR and myogenin, but a greater level of gene expression for myostatin than the controls according to qRT-PCR analysis. The density of VDR protein expressions was 2.1 times greater, while that of myostatin was 2.6 times lower, in the control group than in the sarcopenic group according to Western blot analysis. On immunohistochemical analysis, the density of the cells expressing VDR was significantly decreased in the sarcopenic patients. Sarcopenic patients who sustained distal radius fractures presented lower vitamin D receptor gene and protein expression in skeletal muscles compared to non-sarcopenic individuals.

Prognostic Factors for Nonsurgically Treated Sagittal Band Injuries of the Metacarpophalangeal Joint.

PURPOSE: The aim of this study was to evaluate the factors that influence the prognosis for patients with sagittal band injuries who were treated nonsurgically. METHODS: A total of 94 patients who had been diagnosed with traumatic sagittal band injury and initially treated with 7 weeks of metacarpophalangeal (MCP) joint extension orthosis wear (5 weeks of full-time followed by 2 weeks of part-time use) were studied. The response to treatment, including finger range of motion (ROM), extensor tendon instability, grip strength, and functional outcome measured as Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score were assessed at 24-week follow-up. The factors that were assessed for their influence on the outcomes were age, sex, occupation, hand dominance, type of injury, injury severity, time to treatment, and the duration of orthosis wear. Potential predictor variables in bivariate analyses were entered into multivariable analyses to determine prognostic indicators of the outcomes. RESULTS: After 24 weeks' follow-up, 67 patients (71%) achieved resolution of symptomatic tendon translocation with 83% of grip strength and 90% of ROM compared with the unaffected hand. The final mean QuickDASH scores was 15. Twenty-seven patients (29%) had persistently symptomatic tendon subluxation, and of those, 18 (19%) underwent surgical repair. There were significantly more manual laborers in the failure group than in the success group. Subjects in the treatment failure group were older, had longer symptom durations, and were more likely to have grade III injuries than were those in the success group. Multivariable analysis revealed that manual labor, longer symptom duration, and grade III injury were associated with a higher likelihood of treatment failure. CONCLUSIONS: An MCP extension orthosis for sagittal band injury (5 weeks of full-time followed by 2 weeks of part-time use) led to mostly satisfactory results with 71% of patients achieving resolution of symptomatic tendon translocation, but manual labor, longer symptom duration, and grade III injury were associated with a higher likelihood of treatment failure. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

Skeletal maturation and predicted adult height in adolescents with temporomandibular joint osteoarthritis.

BACKGROUND: The occurrence of osteoarthritis (OA) of the temporomandibular joint (TMJ) in juveniles could be associated with fluctuating levels of oestrogen and growth hormone (GH) during adolescence. OBJECTIVE: To investigate extent of skeletal maturation and predicted adult height in adolescents with TMJ OA. METHOD: In total, 155 adolescents (54 males, 101 females; mean age, 14.1 ± 2.0 years) were enrolled. Among them, 19 adolescents (CON) showed no sign of TMD, 50 adolescents exhibited signs of disc displacement but did not have TMJ OA (TMDnoOA), 23 adolescents exhibited the initial stage of TMJ OA (TMJOAini) and 63 adolescents exhibited the severe stage of TMJ OA (TMJOApro). TMJ OA was diagnosed based on the Research Diagnostic Criteria axis I and bone age was estimated using the Greulich-Pyle method. The height, weight and body mass index of participated adolescents were measured and statistically converted to z-scores. The predicted adult height and age of peak height velocity (APHV) were calculated using the BoneXpert® software. RESULTS: In female adolescents, the differences between the chronological and bone ages were significantly higher and the z-score for height was significantly lower in the TMJOApro. Female adolescents with TMJOA exhibited a significantly shorter predicted adult height and earlier APHV than those in the CON and TMDnoOA. CONCLUSION: The adolescents with TMJ OA exhibited premature skeletal maturations and short predicted adult stature, particularly the female adolescents.

Prognostic Factors of Arthroscopic Debridement for Central Triangular Fibrocartilage Complex Tears in Adults Younger Than 45 Years: A Retrospective Case Series Analysis.

PURPOSE: The purpose of this study was to analyze factors that affect the treatment outcomes of arthroscopic debridement for central triangular fibrocartilage complex (TFCC) lesions in adults <45 years of age. METHODS: A total of 71 patients (mean age, 39 years; range, 20-44 years) who had been arthroscopically diagnosed with central TFCC tears were treated with arthroscopic debridement. Demographic, clinical, and arthroscopic findings were examined and analyzed. The response to treatment, including pain numeric rating scale on an ulnar provocation test; Disability of the Arm, Shoulder, and Hand score; and satisfaction with treatment, was assessed at 12-month follow-up. RESULTS: The mean pain numeric rating scale (6.6 ± 3.6 to 2.4 ± 2.0, P < .01) and Disability of the Arm, Shoulder, and Hand (59.3 ± 15.0 to 33.7 ± 14.1, P < .01) scores exhibited significant clinical improvement at 12-month follow-up. In terms of satisfaction, 43 patients (70.5%) were satisfied (enthusiastic or satisfied) and 18 (29.5%) were dissatisfied (noncommittal or disappointed). In the satisfied group, there were 24 flap and 19 wearing tears, whereas in the dissatisfied group, there were 4 flap and 14 wearing tears (P = .02). The extent of ulnar plus variance on preoperative radiographs also differed between the 2 groups (0.5 ± 1.2 vs 1.7 ± 1.1, P < .01). There were no significant differences in age, gender, hand dominance, or work level between the groups. After controlling for confounding variables, the wearing type tears (odds ratio, 3.4) and greater ulnar plus variance (odds ratio, 2.0) were associated with a higher likelihood of dissatisfaction after arthroscopic TFCC debridement. CONCLUSIONS: Although clinical outcome scores showed significant improvement after arthroscopic debridement for central TFCC tears, wearing type tears and greater ulnar plus variance were associated with dissatisfaction and poorer postoperative outcomes after the procedure. LEVEL OF EVIDENCE: Level IV, case series.

Validity, Reliability and Responsiveness of the Korean Version of Quick Disabilities of the Arm, Shoulder, and Hand Questionnaire in Patients with Carpal Tunnel Syndrome.

BACKGROUND: The Quick Disabilities of the Arm, Shoulder, and Hand questionnaire (QuickDASH) is one of the most widely used questionnaires for assessing functional ability of the patients with upper extremity diseases. Carpal tunnel syndrome (CTS) is the most common neuropathic disease in the upper extremities. The aim of this study was to verify the validity, reliability, and responsiveness of Korean version of QuickDASH questionnaire (K-QuickDASH) in the patients with CTS. METHODS: In total, 83 subjects who underwent open carpal tunnel release (CTR) operation were selected. They fulfilled Korean version of Disabilities of the Arm, Shoulder and Hand questionnaire (K-DASH) and K-QuickDASH at two different time points: before and six months after the surgery. Both criterion-related and construct validities were evaluated using Pearson's correlation coefficient and factor analysis. Internal consistency was estimated using Cronbach's alpha, and test-retest reliability was assessed to verify the reliability of K-QuickDASH using intraclass correlation coefficient (ICC). The standardized response mean and the effect size were analyzed to confirm the responsiveness of the K-QuickDASH in CTS patients. RESULTS: Significant positive correlation was found between K-QuickDASH and K-DASH. All the questionnaire items were categorized into three factors. Acceptable internal consistency was confirmed in three categories of K-QuickDASH. A high test-retest reliability and responsiveness of K-QuickDASH were detected. CONCLUSION: K-QuickDASH in Korean patients with CTS was confirmed to have high degree of validity and reliability, and responsiveness after CTR. Therefore, the K-QuickDASH would be a good evaluation tool for evaluating clinical symptoms and determination of treatment outcomes in the patients with CTS.

Transcriptional Profiling of Muscle in Females With Distal Radius Fracture and Functional Sarcopenia.

Skeletal muscle and bone interact with each other in mechanical and biochemical ways. This study aimed to investigate the molecular mechanisms of interaction between muscle and bone by analyzing the transcriptional profiles of total RNA from the muscle tissue of females with distal radius fractures. A total of 30 female participants (mean age 71.1 ±â€…8.9 years) with distal radius fractures were recruited. Participants were categorized into 2 groups: the NORM group consisted of participants with T score of the areal bone mineral density (aBMD) of the femoral neck higher than -1.0, handgrip strength greater than 18 kg, and gait speed faster than 1.0 m/s (n = 10). Otherwise, participants with T score of the aBMD of the femoral neck equal to or less than -1.0, handgrip strength lower than 18 kg, and gait speed slower than 1.0 m/s (n = 20) were categorized into EXP group. Pronator quadratus muscle samples were obtained from all participants. Total RNA was extracted from frozen muscle samples and sequenced. The gene ontology analysis demonstrated that the potential interactions between attached muscle function and the density of the associated bone would be linked with collagen biosynthetic activity and maintenance of extracellular matrix structures. The analysis of the pathway, network, and protein class exhibited that integrin signaling, inflammatory reactions, matrix metalloproteinase (MMP) activity, and extracellular matrix protein structure had possible associations with the molecular background of muscle-bone interaction. Through integrin signaling, MMP activity, inflammatory reactions, and collagen biosynthesis, muscle and bone may mutually interact with one another.

Docosahexanoic Acid Attenuates Palmitate-Induced Apoptosis by Autophagy Upregulation via GPR120/mTOR Axis in Insulin-Secreting Cells.

BACKGRUOUND: Polyunsaturated fatty acids (PUFAs) reportedly have protective effects on pancreatic ß-cells; however, the underlying mechanisms are unknown. METHODS: To investigate the cellular mechanism of PUFA-induced cell protection, mouse insulinoma 6 (MIN6) cells were cultured with palmitic acid (PA) and/or docosahexaenoic acid (DHA), and alterations in cellular signaling and apoptosis were examined. RESULTS: DHA treatment remarkably repressed caspase-3 cleavage and terminal deoxynucleotidyl transferase-mediated UTP nick end labeling (TUNEL)-positive red dot signals in PA-treated MIN6 cells, with upregulation of autophagy, an increase in microtubule- associated protein 1-light chain 3 (LC3)-II, autophagy-related 5 (Atg5), and decreased p62. Upstream factors involved in autophagy regulation (Beclin-1, unc51 like autophagy activating kinase 1 [ULK1], phosphorylated mammalian target of rapamycin [mTOR], and protein kinase B) were also altered by DHA treatment. DHA specifically induced phosphorylation on S2448 in mTOR; however, phosphorylation on S2481 decreased. The role of G protein-coupled receptor 120 (GPR120) in the effect of DHA was demonstrated using a GPR120 agonist and antagonist. Additional treatment with AH7614, a GPR120 antagonist, significantly attenuated DHA-induced autophagy and protection. Taken together, DHA-induced autophagy activation with protection against PA-induced apoptosis mediated by the GPR120/mTOR axis. CONCLUSION: These findings indicate that DHA has therapeutic effects on PA-induced pancreatic ß-cells, and that the cellular mechanism of ß-cell protection by DHA may be a new research target with potential pharmacotherapeutic implications in ß-cell protection.

Glucagon-Like Peptide Receptor Agonist Inhibits Angiotensin II-Induced Proliferation and Migration in Vascular Smooth Muscle Cells and Ameliorates Phosphate-Induced Vascular Smooth Muscle Cells Calcification.

BACKGRUOUND: Glucagon-like peptide-1 receptor agonist (GLP-1RA), which is a therapeutic agent for the treatment of type 2 diabetes mellitus, has a beneficial effect on the cardiovascular system. METHODS: To examine the protective effects of GLP-1RAs on proliferation and migration of vascular smooth muscle cells (VSMCs), A-10 cells exposed to angiotensin II (Ang II) were treated with either exendin-4, liraglutide, or dulaglutide. To examine the effects of GLP-1RAs on vascular calcification, cells exposed to high concentration of inorganic phosphate (Pi) were treated with exendin-4, liraglutide, or dulaglutide. RESULTS: Ang II increased proliferation and migration of VSMCs, gene expression levels of Ang II receptors AT1 and AT2, proliferation marker of proliferation Ki-67 (Mki-67), proliferating cell nuclear antigen (Pcna), and cyclin D1 (Ccnd1), and the protein expression levels of phospho-extracellular signal-regulated kinase (p-Erk), phospho-c-JUN N-terminal kinase (p-JNK), and phospho-phosphatidylinositol 3-kinase (p-Pi3k). Exendin-4, liraglutide, and dulaglutide significantly decreased the proliferation and migration of VSMCs, the gene expression levels of Pcna, and the protein expression levels of p-Erk and p-JNK in the Ang II-treated VSMCs. Erk inhibitor PD98059 and JNK inhibitor SP600125 decreased the protein expression levels of Pcna and Ccnd1 and proliferation of VSMCs. Inhibition of GLP-1R by siRNA reversed the reduction of the protein expression levels of p-Erk and p-JNK by exendin-4, liraglutide, and dulaglutide in the Ang II-treated VSMCs. Moreover, GLP-1 (9-36) amide also decreased the proliferation and migration of the Ang II-treated VSMCs. In addition, these GLP-1RAs decreased calcium deposition by inhibiting activating transcription factor 4 (Atf4) in Pi-treated VSMCs. CONCLUSION: These data show that GLP-1RAs ameliorate aberrant proliferation and migration in VSMCs through both GLP-1Rdependent and independent pathways and inhibit Pi-induced vascular calcification.

Inhibition of Sodium-Glucose Cotransporter-2 during Serum Deprivation Increases Hepatic Gluconeogenesis via the AMPK/AKT/FOXO Signaling Pathway.

BACKGRUOUND: Sodium-dependent glucose cotransporter 2 (SGLT2) mediates glucose reabsorption in the renal proximal tubules, and SGLT2 inhibitors are used as therapeutic agents for treating type 2 diabetes mellitus. This study aimed to elucidate the effects and mechanisms of SGLT2 inhibition on hepatic glucose metabolism in both serum deprivation and serum supplementation states. METHODS: Huh7 cells were treated with the SGLT2 inhibitors empagliflozin and dapagliflozin to examine the effect of SGLT2 on hepatic glucose uptake. To examine the modulation of glucose metabolism by SGLT2 inhibition under serum deprivation and serum supplementation conditions, HepG2 cells were transfected with SGLT2 small interfering RNA (siRNA), cultured in serum-free Dulbecco's modified Eagle's medium for 16 hours, and then cultured in media supplemented with or without 10% fetal bovine serum for 8 hours. RESULTS: SGLT2 inhibitors dose-dependently decreased hepatic glucose uptake. Serum deprivation increased the expression levels of the gluconeogenesis genes peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1α), glucose 6-phosphatase (G6pase), and phosphoenolpyruvate carboxykinase (PEPCK), and their expression levels during serum deprivation were further increased in cells transfected with SGLT2 siRNA. SGLT2 inhibition by siRNA during serum deprivation induces nuclear localization of the transcription factor forkhead box class O 1 (FOXO1), decreases nuclear phosphorylated-AKT (p-AKT), and p-FOXO1 protein expression, and increases phosphorylated-adenosine monophosphate-activated protein kinase (p-AMPK) protein expression. However, treatment with the AMPK inhibitor, compound C, reversed the reduction in the protein expression levels of nuclear p- AKT and p-FOXO1 and decreased the protein expression levels of p-AMPK and PEPCK in cells transfected with SGLT2 siRNA during serum deprivation. CONCLUSION: These data show that SGLT2 mediates glucose uptake in hepatocytes and that SGLT2 inhibition during serum deprivation increases gluconeogenesis via the AMPK/AKT/FOXO1 signaling pathway.

Knowledge on osteoporosis in guardians of hip fracture patients.

Treatment gap between the treatment guideline and real clinical practice of osteoporosis has been found to be worldwide. Although insufficient knowledge of guardians on osteoporosis might be one important obstacle to diagnose and treatment of osteoporotic patients, there was not a study on the knowledge of guardians. We evaluated the guardians' knowledge on osteoporosis compared with the knowledge of orthopedic doctors, using a self-administered questionnaire, a modified Facts on Osteoporosis Quiz (FOOQ). In March and April 2012, the knowledge of osteoporosis was measured in 40 guardians of hip fracture patients and 40 orthopedic surgeons using, a modified FOOQ. In terms of treatment and prevention of osteoporosis, the modified FOOQ score of the guardians have inadequate knowledge and understanding about the osteoporosis, compared with orthopedic doctors (p < 0.001). The level of guardians' knowledge on osteoporosis should be considered and improved to achieve satisfactory osteoporosis treatment in hip fracture patients.

Associations between oral health status and risk of fractures in elder adults.

Oral health condition, bone mineral density, skeletal muscle mass, fall, fracture, and frailty seem to be strongly interconnected. This study aimed to investigate associations between probability of osteoporotic fractures and oral health in the elderly. In total, 2322 Korean subjects from the 2008-2009 Korea National Health and Nutritional Examination Survey aged over 65 years were included. The 10-year probabilities of major and hip fractures were calculated using the Fracture Risk Assessment (FRAX) tool. Data on anthropometry, skeletal bone mineral density, sociodemographic characteristics, physical activity, individual history of fractures and falls, parental history of osteoporosis, number of teeth, metabolic syndrome, the Decayed, Missing, and Filled permanent Teeth index, and Community Periodontal Index (CPI), were collected. Participants were classified into three groups based on FRAX score for major osteoporotic fractures. A multivariate linear regression analysis was conducted to analyze associations between FRAX scores and oral health-related factors, adjusting for confounding factors. BMI, presence of metabolic syndrome, number of teeth, dental patterns, and CPI score showed significant differences among three groups in males and females. Results from multivariate linear regression analysis demonstrated significant relationships between total tooth number and probabilities of fracture in male and female elderly. The interdisciplinary approach for handling osteoporosis and sarcopenia including dentists, physicians is necessary to facilitate a better quality of life in the elderly.

Biomechanical comparative finite element analysis between a conventional proximal interphalangeal joint flexible hinge implant and a novel implant design using a rolling contact joint mechanism.

BACKGROUND: The rolling contact joint (RCJ) mechanism is a system of constraint that allows two circular bodies connected with flexible straps to roll relative to one another without slipping. This study aims to compare the biomechanical characteristics between the conventional proximal interphalangeal joint (PIPJ) flexible hinge (FH) implant and the novel PIPJ implant adopting a RCJ mechanism during PIPJ range of motion using finite element (FE) analysis. METHODS: The three-dimensional (3D) surface shape of a conventional PIPJ FH implant was obtained using a 3D laser surface scanning system. The configuration and parameters of the novel PIPJ implant were adapted from a previous study. The two implants were assumed to have the same material characteristics and each implant was composed of a hyperelastic material, silicone elastomers. The configuration data for both implants were imported to a computer-aided design program to generate 3D geometrical surface and hyperelastic models of both implants. The hyperelastic models of both implants were imported into a structural engineering software to produce the FE mesh and to perform FE analysis. The FE analysis modeled the changes of mechanics during flexion-extension motion between 0° and 90° of two PIPJ implants. The mean and maximum values of von-Mises stress and strain as well as the total moment reaction based on the range of motion of the PIPJs were calculated. The mean values within the PIPJ's functional range of motion of the mean and maxinum von-Mises stress and strain and the total moment reaction were also determined. RESULTS: The maximum values for the von-Mises stress, and strain, as well as the total moment reactions of the conventional PIPJ FH and novel PIPJ implants were all at 90° of PIPJ flexion. The maximum value of each biomechanical property for the novel PIPJ implant was considerably lower compared with that of the conventional PIPJ FH implant. The mean values within the PIPJ's functional range of motion of the maximum von-Mises stress and strain for the novel PIPJ implant was approximately 6.43- and 6.46-fold lower compared with that of the conventional PIPJ FH implant, respectively. The mean value within a PIPJ's functional range of motion of the total moment reaction of the novel PIPJ implant was approximately 49.6-fold lower compared with that of the conventional PIPJ FH implant. CONCLUSIONS: The novel PIPJ implant with an RCJ mechanism may offer improved biomechanical performance compared with conventional PIPJ FH implant.

Quality and readability of online information on hand osteoarthritis.

Objectives: This study aimed to evaluate the quality and readability of web pages providing information about hand osteoarthritis using several authorized methods.Methods: A web page exploration was performed using the Google internet search engine. The three search terms, "hand osteoarthritis," "finger osteoarthritis," and "hand OA," were used and the top 100 ranked websites were selected and divided into six categories. The Health on the Net Foundation (HON) grade scale, an instrument for judging the quality of written consumer health information on treatment choice (DISCERN instrument), and the Ensuring Quality Information for Patients (EQIP) score were used to evaluate the quality of each website. The Flesch-Kincaid reading ease (FRE) score, Flesch-Kincaid grade (FKG) level, Gunning-Fog index, and Simple Measure of Gobbledygook grade level were used to evaluate website readability.Results: Among 300 websites, 57 websites were selected following exclusion criteria. News portal websites, including the online version of newspapers and periodicals, showed the highest score in all three quality evaluation tools. Only four websites were regarded as high-quality websites based on the HON grade scale (n = 3) and the EQIP score (n = 1). Each type of website showed an average FKG level higher than 7th grade and obtained an average FRE score of less than 80 points, indicating an inappropriate level for a layperson to read.Conclusions: The online information about hand osteoarthritis is low quality and difficult to read for the general public. There is a need to enhance the quality and readability of web-based information related to hand osteoarthritis for patients to obtain credible information and receive proper treatment for the disease.