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Polyurethane (PU) is a promising material for addressing challenges in bone grafting. This study was designed to enhance the bone grafting capabilities of PU by integrating hydroxyapatite (HAp), which is known for its osteoconductive and osteoinductive potential. Moreover, a uniform distribution of HAp in the porous structure of PU increased the effectiveness of bone grafts. PEG/APTES-modified scaffolds were prepared through self-foaming reactions. A uniform pore structure was generated during the spontaneous foaming reaction, and HAp was uniformly distributed in the PU structure (PU15HAp and PU30HAp) during foaming. Compared with the PU scaffolds, the HAp-modified PU scaffolds exhibited significantly greater protein absorption. Importantly, the effect of the HAp-modified PU scaffold on bone repair was tested in a rat calvarial defect model. The microstructure of the newly formed bone was analyzed with microcomputed tomography (µ-CT). Bone regeneration at the defect site was significantly greater in the HAp-modified PU scaffold group than in the PU group. This innovative HAp-modified PU scaffold improves current bone graft materials, providing a promising avenue for improved bone regeneration.
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Regeneração Óssea , Durapatita , Poliuretanos , Crânio , Alicerces Teciduais , Poliuretanos/química , Animais , Durapatita/química , Alicerces Teciduais/química , Ratos , Regeneração Óssea/efeitos dos fármacos , Crânio/efeitos dos fármacos , Crânio/lesões , Crânio/patologia , Crânio/metabolismo , Ratos Sprague-Dawley , Microtomografia por Raio-X , Masculino , Porosidade , Transplante Ósseo/métodosRESUMO
AIMS: Type 2 diabetes mellitus (T2DM) frequently co-exists with osteoporosis and dyslipidemia. Statins have been commonly used in the treatment of dyslipidemia. Recent studies have indicated a therapeutic role of statins in decreasing the risk of osteoporosis and fractures, but conflicting results have been reported. This study investigated the association between statin use and hip fracture (HFx) risk among T2DM patients. MATERIALS AND METHODS: A retrospective Taiwan population-based propensity-matched cohort study was performed using the Diabetes Mellitus Health Database from Taiwan National Health Insurance Research Database. Patients with newly diagnosed with T2DM between 2010 and 2014 were identified. Patients who previously used statins and had ever suffered HFx before the index date were excluded. HFx that occurred from 2010 to 2019 was collected to compute the cumulative rate of HFx. Hazard ratios (HRs) were calculated for the HFx risk according to the use or non-use of statins. To evaluate the dose-effect relationship of statins, sensitivity analyses were conducted. RESULTS: After propensity score matching for age and sex, 188,588 patients were identified as statin users and non-statin users. Statin use after T2DM diagnosis was associated with a decreased HFx risk with an adjusted HR (aHR) of 0.69 (P < 0.001). A dose-effect relationship was identified. The aHRs for developing HFx were 1.29, 0.67, and 0.36 for patients who used 28-174, 175-447, and >447 cumulative defined daily doses of statins, respectively (P < 0.001). CONCLUSIONS: Statin use in adults with T2DM showed a lower risk of HFx by demonstrating a dose-response relationship.
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Diabetes Mellitus Tipo 2 , Dislipidemias , Fraturas do Quadril , Inibidores de Hidroximetilglutaril-CoA Redutases , Osteoporose , Adulto , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/induzido quimicamente , Estudos Retrospectivos , Estudos de Coortes , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Taiwan/epidemiologia , Osteoporose/induzido quimicamente , Osteoporose/complicações , Osteoporose/tratamento farmacológico , Dislipidemias/complicações , Dislipidemias/tratamento farmacológico , Dislipidemias/epidemiologia , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/etiologia , Fraturas do Quadril/prevenção & controle , Fatores de RiscoRESUMO
MicroRNAs (miRNAs) could serve as ideal entry points to the deregulated pathways in osteoporosis due to their relatively simple upstream and downstream relationships with other molecules in the signaling cascades. Our study aimed to give a comprehensive review of the already identified miRNAs in osteoporosis from human blood samples and provide useful information for their clinical application. A systematic literature search for relevant studies was conducted in the Pubmed database from inception to December 2020. We set two essential inclusion criteria: human blood sampling and design of controlled studies. We sorted the results of analysis on human blood samples according to the study settings and compiled the most promising miRNAs with analyzed diagnostic values. Furthermore, in vitro and in vivo evidence for the mechanisms of the identified miRNAs was also illustrated. Based on both diagnostic value and evidence of mechanism from in vitro and in vivo experiments, miR-23b-3p, miR-140-3p, miR-300, miR-155-5p, miR-208a-3p, and miR-637 were preferred candidates in diagnostic panels and as therapeutic agents. Further studies are needed to build sound foundations for the clinical usage of miRNAs in osteoporosis.
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MicroRNAs/sangue , MicroRNAs/genética , Osteoporose/genética , Fraturas por Osteoporose/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estrogênios/sangue , Feminino , Idoso Fragilizado , Humanos , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Osteoporose/complicações , Osteoporose/metabolismo , Via de Sinalização Wnt/genéticaRESUMO
The fragile nature of porous bioceramic substitutes cannot match the toughness of bone, which limits the use of these materials in clinical load-bearing applications. Statins can enhance bone healing, but it could show rhabdomyolysis/inflammatory response after overdosing. In this study, the drug-containing bone grafts were developed from poly(lactic acid-co-glycolic acid)-polyethylene glycol (PLGA-PEG) nanoparticles encapsulating simvastatin (SIM) (SIM-PP NPs) loaded within an appropriately mechanical bioceramic scaffold (BC). The combination bone graft provides dual functions of osteoconduction and osteoinduction. The mechanical properties of the bioceramic are enhanced mainly based on the admixture of a combustible reverse-negative thermoresponsive hydrogel (poly(N-isopropylacrylamide base). We showed that SIM-PP NPs can increase the activity of alkaline phosphatase and osteogenic differentiation of bone marrow stem cells. To verify the bone-healing efficacy of this drug-containing bone grafts, a nonunion radial endochondral ossification bone defect rabbit model (N = 3/group) and a nonunion calvarial intramembranous defect Sprague Dawley (SD) rat model (N = 5/group) were used. The results indicated that SIM-PP NPs combined with BC can improve the healing of nonunion bone defects of the radial bone and calvarial bone. Therefore, the BC containing SIM-PP NPs may be appropriate for clinical use as a synthetic alternative to autologous bone grafting that can overcome the problem of determining the clinical dosage of simvastatin drugs to promote bone healing.
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Transplante Ósseo/métodos , Diferenciação Celular/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Transplante Autólogo/métodos , Resinas Acrílicas/administração & dosagem , Resinas Acrílicas/química , Animais , Regeneração Óssea/efeitos dos fármacos , Cerâmica/química , Cerâmica/farmacologia , Humanos , Hidrogel de Polietilenoglicol-Dimetacrilato , Nanopartículas/administração & dosagem , Nanopartículas/química , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/química , Poliglactina 910/administração & dosagem , Poliglactina 910/química , Coelhos , Ratos , Sinvastatina/administração & dosagem , Sinvastatina/química , Crânio/química , Crânio/efeitos dos fármacos , Alicerces Teciduais/químicaRESUMO
Large bone defects may develop fracture nonunion, leading to disability and psychosocial burdens. Bone grafting with anabolic agents is a good autografting alternative. Simvastatin, as a cholesterol-lowering agent worldwide, is proven to enhance osteogenesis. Considering its dose-dependent adverse effects, we developed a simvastatin derivative, named KMUHC-01, which has bone anabolic capacity and lower cytotoxicity than simvastatin. We hypothesize that KMUHC-01 could help bone formation in bone-defect animal models. We used rat models of critical calvarial and long-bone defects to evaluate the effects of KMUHC-01 and simvastatin on biological changes at the bone defect through histology, immunohistology, and mechanical testing using three-point bending and evaluated the new bone formation microstructure through microcomputed tomography analysis. The newly formed bone microstructure at the calvarial defect site showed a significantly improved trabecular bone volume in the KMUHC-01 1-µM group compared with that in the control and simvastatin groups. The biomechanical study revealed a significantly increased maximal strength in the KMUHC-01 1-µM group compared with that in the control group. KUMHC-01, as a simvastatin derivative, showed a great anabolic effect in promoting bone defect healing. However, further studies will be conducted to prove the bioavailability and bone-forming efficacy of KMUHC-01 via systemic administration.
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Denosumab is approved for osteoporosis treatment in subjects with and without chronic kidney disease (CKD). Confirmation is required for its safety, treatment adherence, renal function effect, and mortality in patients with CKD. A retrospective cohort study was conducted to compare new users of denosumab in terms of their two-year drug adherence in all participants (overall cohort) and CKD participants (CKD subcohort), which was defined as baseline estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2. The eGFR was calculated using the 2021 CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation. We defined high adherence (HA) users as receiving three or four doses and low adherence (LA) users as receiving one or two doses. All-cause mortality was analyzed using Kaplan-Meier curves and Cox regression models. In total, there were 1142 subjects in the overall cohort and 500 subjects in the CKD subcohort. HA users had better renal function status at baseline than LD users in the overall cohort. A decline in renal function was only observed among LD users in the overall cohort. In the CKD subcohort, no baseline renal function difference or renal function decline was demonstrated. The all-cause mortality rate of HA users was lower than LA users in both the overall cohort and CKD. A randomized control trial is warranted to target this unique population to confirm our observations.
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Anatomical reduction is the fundamental principle of hip function restoration after posterior acetabular wall fractures (PWFs). Some patients exhibit poor outcomes despite anatomical reduction, and the prognostic factors leading to poor outcomes remain elusive. This study aimed to investigate the clinical and radiographic outcomes in patients with PWFs who had undergone anatomical reduction and internal fixation and to identify the predictors that impair clinical and radiologic outcomes. The clinical records of 60 patients with elementary PWFs who had undergone anatomical reduction and internal fixation between January 2005 and July 2015 were reviewed retrospectively. The Harris hip score (HHS) and modified Merle d'Aubigné clinical hip scores (MMAS) were used to evaluate the clinical outcome. Preoperative and final follow-up radiographs were cross checked to identify poor radiographic outcomes that included the presence of advanced osteoarthritis and osteonecrosis, as well as the need for conversion to total hip arthroplasty. Acetabular dome comminution was assessed from computerized tomography, and the outcomes were further evaluated according to the involvement of fragment comminution. The fracture comminution and age were negatively correlated with functional outcomes (correlation coefficients were -0.41 and -0.39 in HHS and MMAS, respectively) and were significantly related to the severity of osteoarthritis and osteonecrosis as well as the need for total hip arthroplasty. Regarding the radiographic factors, significantly worse post-operative HHS and MMAS were found in the fracture comminution group. In the subanalysis of the status of fracture comminution, patients with fragment comminution involving the acetabular dome had significantly lower functional scores than those with other fracture patterns. In conclusion, age, fracture comminution, and dome comminution were the prognostic indicators of advanced osteoarthritis and poor functional scores after the anatomical reduction and internal fixation of PWFs. We emphasized the relevance of acetabular dome comminution as an important contributing factor to clinical and radiographic outcomes.
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Osteoarthritis (OA) is one of the most common diseases leading to physical disability, with age being the main risk factor, and degeneration of articular cartilage is the main focus for the pathogenesis of OA. Autophagy is a crucial intracellular homeostasis system recycling flawed macromolecules and cellular organelles to sustain the metabolism of cells. Growing evidences have revealed that autophagy is chondroprotective by regulating apoptosis and repairing the function of damaged chondrocytes. Then, OA is related to autophagy depending on different stages and models. In this review, we discuss the character of autophagy in OA and the process of the autophagy pathway, which can be modulated by some drugs, key molecules and non-coding RNAs (microRNAs, long non-coding RNAs and circular RNAs). More in-depth investigations of autophagy are needed to find therapeutic targets or diagnostic biomarkers through in vitro and in vivo situations, making autophagy a more effective way for OA treatment in the future. The aim of this review is to introduce the concept of autophagy and make readers realize its impact on OA. The database we searched in is PubMed and we used the keywords listed below to find appropriate article resources.
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Cartilagem Articular , MicroRNAs , Osteoartrite , Humanos , RNA Circular , Autofagia/fisiologia , Osteoartrite/patologia , Apoptose/fisiologia , MicroRNAs/metabolismo , Biomarcadores/metabolismoRESUMO
AIM: Taiwan's response to the coronavirus disease 2019 (COVID-19) differed in that it successfully prevented the spread without having to shutdown or overburden medical services. Patients' fear regarding the pandemic would be the only reason to reduce surgeries, so Taiwan could be the most suitable place for research on the influence of psychological factors. This study aimed to assess the impact of patients' fear on orthopedic surgeries in Taiwan amid the peak period of the COVID-19 pandemic. PATIENTS AND METHODS: The investigation period included the COVID-19 pandemic (March 2020 to April 2020) and the corresponding period in the previous year. The following data on patients with orthopedic diseases were collected: outpatient visits, hospital admission, and surgical modalities. RESULTS: The COVID-19 pandemic led to a 22%-29% and 20%-26% reduction in outpatients, 22%-27% and 25%-37% reduction in admissions, and 26%-35% and 18%-34% reduction in surgeries, respectively, at both hospitals. The weekly mean number of patients was significantly smaller during the COVID-19 pandemic for all types of surgery and elective surgeries at the university hospital, and for all types of surgery, elective surgeries, and total knee arthroplasties at the community hospital. Further, patients visiting the community hospital during the pandemic were significantly younger, for all types of surgery, elective surgeries, and total knee arthroplasties. CONCLUSIONS: The reduction in orthopedic surgeries in Taiwan's hospitals during COVID-19 could be attributed to patients' fear. Even without restriction, the pandemic inevitably led to a reduction of about 20%-30% of the operation volume.
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Artroplastia do Joelho/psicologia , COVID-19/epidemiologia , Hospitais/estatística & dados numéricos , Pacientes Ambulatoriais , Pandemias , SARS-CoV-2 , Comorbidade , Hospitalização/tendências , Humanos , Masculino , Taiwan/epidemiologiaRESUMO
AIMS: Osteoarthritis (OA) is prevalent among the elderly and incurable. Intra-articular parathyroid hormone (PTH) ameliorated OA in papain-induced and anterior cruciate ligament transection-induced OA models; therefore, we hypothesized that PTH improved OA in a preclinical age-related OA model. METHODS: Guinea pigs aged between six and seven months of age were randomized into control or treatment groups. Three- or four-month-old guinea pigs served as the young control group. The knees were administered 40 µl intra-articular injections of 10 nM PTH or vehicle once a week for three months. Their endurance as determined from time on the treadmill was evaluated before kill. Their tibial plateaus were analyzed using microcalculated tomography (µCT) and histological studies. RESULTS: PTH increased the endurance on the treadmill test, preserved glycosaminoglycans, and reduced Osteoarthritis Research Society International score and chondrocyte apoptosis rate. No difference was observed in the subchondral plate bone density or metaphyseal trabecular bone volume and bone morphogenetic 2 protein staining. CONCLUSION: Subchondral bone is crucial in the initiation and progression of OA. Although previous studies have shown that subcutaneous PTH alleviates knee OA by improving subchondral and metaphyseal bone mass, we demonstrated that intra-articular PTH injections improved spontaneous OA by directly affecting the cartilage rather than the subchondral or metaphyseal bone in a preclinical age-related OA model. Cite this article: Bone Joint Res 2021;10(8):514-525.
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The impact of diabetes mellitus (DM) on hip fracture (HFx) is still controversial. We used nationwide population-based data in Taiwan to observe postoperative outcomes of HFx in patients with type 2 diabetes mellitus (T2DM) and found that the impact of T2DM may be related to medication of blood glucose control. OBJECTIVE: Published studies evaluating diabetic patients with HFx have shown controversial outcomes. We assessed the impact of T2DM on postoperative outcomes after HFx in elderly patients using the nationwide population database in Taiwan. RESEARCH DESIGN AND METHODS: We used data from the National Health Research Institute in Taiwan to recruit patients who had undergone operations for HFx between 2000 and 2009. The recruited patients with T2DM were divided into the oral antidiabetic drug (OAD) cohort and the insulin cohort according to the use or non-use of insulin. Patients without DM were propensity score matched in a 1:1 ratio by four variables. We used the χ2 test, linear regression and Cox proportional hazards model to assess variables, including length of hospital stay, medical cost, complications, early readmission, and 1-year mortality. RESULTS: We identified 5490 subjects in total. The insulin cohort exhibited prolonged hospital stay (11.8 days), higher medical costs, more complications within 30 and 90 after hip surgery, earlier readmission, and higher 1 year mortality rate (25.8%) than the OAD and non-DM cohorts. The OAD cohort had longer hospital stay (10.1 days) and higher readmission rate but fewer complications and mortality rates (14.9%) than the non-DM cohort. CONCLUSIONS: After matching confounding factors, the T2DM with OAD control groups were not associated with higher complication or mortality rates but were associated with higher readmission rates. However, diabetic patients with insulin control have poor outcome. The impact of T2DM on the postoperative outcomes of patients with HFx may be related to blood glucose control medication.
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Diabetes Mellitus Tipo 2/epidemiologia , Fixação de Fratura , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/cirurgia , Complicações Pós-Operatórias/mortalidade , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Seguimentos , Humanos , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Tempo de Internação , Estudos Longitudinais , Masculino , Mortalidade , Readmissão do Paciente , Complicações Pós-Operatórias/etiologia , Pontuação de Propensão , Taiwan/epidemiologia , Resultado do TratamentoRESUMO
Type 2 diabetes mellitus (T2DM) is associated with a high rate of comorbidity, including osteoporosis and peptic ulcers. Proton pump inhibitors (PPIs) are a group of acid-suppressing drugs commonly used for treating peptic ulcers. However, observational studies have reported an association between PPI therapy and osteoporotic fractures. This study investigated the association between PPI use and hip fracture (HFx) among patients with T2DM. We conducted this population-based propensity-matched retrospective cohort study using the National Health Insurance Research Database in Taiwan. Patients newly diagnosed with T2DM between 2000 and 2008 were identified. After excluding those who previously used PPIs or suffered HFx, 398,885 patients were recruited (44,341 PPI users; 354,544 non-users). HFx risk data from 2000 to 2013 were collected to calculate the cumulative rate of HFx in these two groups. Sensitivity analyses were conducted to evaluate the effects of PPI dose. After propensity score matching of 1:4, 44,431 and 177,364 patients were assigned to the PPI user and non-user groups, respectively. PPI user group showed an increased risk of HFx with an adjusted hazard ratio of 1.41 (95% CI 1.29-1.54) without dose-response relationship. Thus, there is an increased risk of HFx in patients with T2DM receiving long-term PPI treatment.
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Diabetes Mellitus Tipo 2/complicações , Fraturas do Quadril/etiologia , Osteoporose/complicações , Úlcera Péptica/tratamento farmacológico , Inibidores da Bomba de Prótons/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Fraturas do Quadril/induzido quimicamente , Fraturas do Quadril/epidemiologia , Humanos , Seguro Saúde , Masculino , Pessoa de Meia-Idade , Fraturas por Osteoporose/induzido quimicamente , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/etiologia , Úlcera Péptica/complicações , Pontuação de Propensão , Modelos de Riscos Proporcionais , Inibidores da Bomba de Prótons/uso terapêutico , Estudos Retrospectivos , Fatores de RiscoRESUMO
There is no clear evidence how effective the antiresorptive (AR) drugs alendronate and raloxifene are at reducing risk of second hip fracture and mortality in dialysis populations. The purpose of this study was to compare the risk of hospitalization for second hip fracture and risk of mortality between AR user and non-user groups in Taiwanese women on long-term dialysis with hip fractures. We conducted a retrospective cohort study using Taiwan National Health Insurance Research Datasets. Long-term dialysis women older than 50 years with newly diagnosed hip fractures and new to AR therapy from 2005 to 2011 were recruited. The patients were divided into AR users and non-users and matched by propensity score. We used Cox Proportional Hazards models to assess association of AR with risks of second hip fracture and mortality. Totally, 1,079 dialysis patients were included, and after matching, we were left with 74 AR users and 74 non-users. AR users did not show a significant reduction in the incidence of second hip fracture compared with non-users (adjusted Hazard Ratio (HR): 0.91, 95% CI: 0.30-2.76), and alendronate users exhibited higher risk of second hip fracture compared with raloxifene users (adjusted HR: 2.80, 95% CI: 0.42-18.79). In addition, AR users were found to have significantly lower 1- and 2-year mortality rates than the non-users (1- year: adjusted HR 0.25, 95% CI, 0.07-0.90; 2-year: 0.35, 95%CI: 0.17-0.72). AR treatment did not significantly improve the risk of second hip fracture but significantly reduce mortality in older women on dialysis. Further clinical trials on effectiveness of AR medications for dialysis populations should be warranted.
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Alendronato/administração & dosagem , Conservadores da Densidade Óssea/administração & dosagem , Fraturas do Quadril/mortalidade , Cloridrato de Raloxifeno/administração & dosagem , Diálise Renal/mortalidade , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/terapia , Humanos , Incidência , Estudos Longitudinais , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Taiwan/epidemiologiaRESUMO
Thrombomodulin (TM) is a transmembrane glycoprotein that contains five functional domains. Soluble TM (sTM), comprising extracellular domains TMD1 (lectin-like), TMD2 (epidermal growth factor [EGF]-like repeat containing), and TMD3 (serine-threonine rich), can be shed from cells by the intramembrane protease rhomboid-like-2 (RHBDL2). TM is expressed by osteoblasts, yet its role there has not been determined. Herein we aimed to investigate the properties of TM and its domains in osteoblast function and bone repair following injury in diabetes. In response to a scratch injury of cultured osteoblast-like MG63 cells, expression of TM and RHBDL2 was enhanced, with increased release of sTM. Conditioned media from the injured cells promoted osteoblast migration, an effect that was lacking with conditioned media from MG63 cells in which TM was silenced by shRNA. Exogenous recombinant TMD1 had no effect on osteoblast activities or on bone repair in vivo. However, TM domains 2 and 3 (TMD2/3), induced MG63 cell migration, proliferation and mineralization in vitro, and when locally administered in mice, improved in vivo healing of injured calvarium. This beneficial effect of TMD2/3, mediated via fibroblast growth factor receptor (FGFR)/ERK signaling pathways, was also observed in vitro under high glucose conditions where endogenous TM expression was reduced, and in vivo in diabetic mice following tibia fracture or calvarium injury, where the osteoblastic response and healing were otherwise dampened. Taken together, osteoblast TM participates in bone healing, and recombinant TMD2/3 holds promise as a novel therapy for diabetic bone defect healing. © 2020 American Society for Bone and Mineral Research.
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Osteogênese , Animais , Diferenciação Celular , Diabetes Mellitus Experimental , Camundongos , Osteoblastos , TrombomodulinaRESUMO
Green tea drinking can ameliorate postmenopausal osteoporosis by increasing the bone mineral density. (-)-Epigallocatechin-3-gallate (EGCG), the abundant and active compound of tea catechin, was proven to be able to reduce bone loss and ameliorate microarchitecture in female ovariectomized rats. EGCG can also enhance the osteogenic differentiation of murine bone marrow mesenchymal stem cells and inhibit the osteoclastogenesis in RAW264.7 cells by modulation of the receptor activator of nuclear factor-kB (RANK)/RANK ligand (RANKL)/osteoprotegrin (OPG) (RANK/RANKL/OPG) pathway. Our previous study also found that EGCG can promote bone defect healing in the distal femur partially via bone morphogenetic protein-2 (BMP-2). Considering the osteoinduction property of BMP-2, we hypothesized that EGCG could accelerate the bone healing process with an increased expression of BMP-2. In this manuscript, we studied whether the local use of EGCG can facilitate tibial fracture healing. Fifty-six 4-month-old rats were randomly assigned to two groups after being weight-matched: a control group with vehicle treatment (Ctrl) and a study group with 10 µmol/L, 40 µL, EGCG treatment (EGCG). Two days after the operation, the rats were treated daily with EGCG or vehicle by percutaneous local injection for 2 weeks. The application of EGCG enhanced callus formation by increasing the bone volume and subsequently improved the mechanical properties of the tibial bone, including the maximal load, break load, stiffness, and Young's modulus. The results of the histology and BMP-2 immunohistochemistry staining showed that EGCG treatment accelerated the bone matrix formation and produced a stronger expression of BMP-2. Taken together, this study for the first time demonstrated that local treatment of EGCG can accelerate the fracture healing process at least partly via BMP-2.
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Catequina/análogos & derivados , Consolidação da Fratura/efeitos dos fármacos , Chá/química , Animais , Fenômenos Biomecânicos , Calo Ósseo/diagnóstico por imagem , Calo Ósseo/fisiopatologia , Catequina/farmacologia , Catequina/uso terapêutico , Masculino , Ratos Sprague-Dawley , Tíbia/diagnóstico por imagem , Tíbia/efeitos dos fármacos , Tíbia/patologia , Tíbia/fisiopatologia , Fraturas da Tíbia/diagnóstico por imagem , Fraturas da Tíbia/tratamento farmacológico , Fraturas da Tíbia/patologia , Fraturas da Tíbia/fisiopatologia , Microtomografia por Raio-XRESUMO
(-)-Epigallocatechin 3-gallate (EGCG) is the main active green tea catechin and has a wide variety of benefits for health. Post-traumatic osteoarthritis (PTOA) occurs as a consequence of joint injuries that commonly happen in the young population. In this study, we investigated the effects of EGCG on PTOA prevention by using the anterior cruciate ligament transection (ACLT)-OA model and further investigated the roles of autophagy in OA treatment. Our results showed that intra-articular injection of EGCG significantly improved the functional performances and decreased cartilage degradation. EGCG treatment attenuated the inflammation on synovial tissue and cartilage through less immunostained cyclooxygenase-2 and matrix metalloproteinase-13. We further noted EGCG may modulate the chondrocyte apoptosis by activation of the cytoprotective autophagy through reducing the expression of the mTOR and enhancing the expression of microtubule-associated protein light chain 3, beclin-1, and p62. In conclusion, intra-articular injection of EGCG after ACL injury inhibited the joint inflammation and cartilage degradation, thereby increasing joint function. EGCG treatment also reduced the chondrocyte apoptosis, possibly by activating autophagy. These findings suggested that EGCG may be a potential disease-modifying drug for preventing OA progression.
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PURPOSE: To evaluate the effect of timing of arthroscopic release and manipulation under anesthesia for frozen shoulder in patients with diabetes and non-diabetes. METHODS: One hundred and twenty-seven patients with frozen shoulder were included in the study. Each patient was assigned to: 1) one of four groups according to the duration from symptom onset to surgery (group A: ≤3 months; group B: 3-6 months; group C: 6-12 months; group D: >12 months), 2) diabetic or nondiabetic group. The outcomes were measured by shoulder range of motion (ROM), Disabilities of the Arm, Shoulder, and Hand (DASH) score, American Shoulder and Elbow Surgeons (ASES) Shoulder score, the period of pain relief, overall duration of disease, and satisfaction. RESULTS: All the patients got great improvement in shoulder ROM (P < .0001) after arthroscopic surgery, but there was no statistical difference in the pre-operative and post-operative shoulder ROM between the four groups and between diabetic and nondiabetic groups. The overall duration of disease was mean 55.4~68.7 weeks, which demonstrated much shorter disease course compared with nature course. Improvement were also seen in shoulder ROM at one week to one month, and the period of total pain relief was at a mean time of 3.7 to 3.8 weeks. There were higher ASES Shoulder score in group B than in group C (P = 0.02) and higher DASH score in diabetic group in short term follow-up. CONCLUSIONS: Arthroscopic release provides effective and rapid improvements to shoulder motion and function, unrelated to the timing of surgery, in patients with frozen shoulder. The diabetic patients do not have functional outcomes as good as the nondiabetic patient at short-term follow-up.
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Artroscopia , Bursite/cirurgia , Diabetes Mellitus/patologia , Adulto , Idoso , Bursite/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Complicações Pós-Operatórias/etiologia , Amplitude de Movimento Articular , Fatores de Tempo , Resultado do TratamentoRESUMO
After acute hip surgery, the 1-year mortality rate is high. Therefore, this study evaluated the risk factors for 1-year mortality. The purposes of this study was first to examine the effect of integrated care on 1-year mortality in surgical patients and secondly to explore magnitude of comorbidity and complication on mortality.This retrospective cohort study included 313 patients received surgery for hip fragility fracture. Patients with multiple fractures or combined trauma were excluded. The patients were grouping into integrated (nâ=â106) and non-integrated care group (nâ=â207) models. Univariate and multiple Cox regression were used to examine effect of care model, comorbidity, and complication event.One-year mortality in integrated and non-integrated patients was 4.7% and 14.0% respectively. After adjustments, patients in non-integrated care, have 2.89 times (95% confidence interval [CI] 1.07-7.81) likely to die 1-year after discharged.Patients had elevated comorbidity or postoperative complications contributed to the mortality. Our study found the effect of patients treated by integrated care models, compared with usual model, significantly reduced 1-year mortality rate. Appropriated treatment of comorbidities during hospitalization and after discharge is critical to post-surgical survival. The findings imply that the co-care for hip fracture of hip surgical patients with orthogeriatricians is strongly recommended, particularly for those with >3 comorbidities.
Assuntos
Fraturas do Quadril/mortalidade , Fraturas do Quadril/cirurgia , Complicações Pós-Operatórias/mortalidade , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Fraturas do Quadril/complicações , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Fatores de TempoRESUMO
Early readmission following hip fracture (HFx) is associated with high morbidity and mortality. We conducted a survival analysis of patients with readmission within 1 year after HFx to elucidate the trend and predictors for readmission. We used Taiwan National Health Insurance Database to recruit HFx patients who underwent operations between 2000 and 2009. Patients < 60 years; with pathological fractures; involved in major traffic accidents; with previous pelvis, femur, and hip operations; or who died during the index admission were excluded. We used the Chi-square test, logistic regression, Kaplan-Meier method, and Cox proportional hazards model to analyze variables, including age, gender, hospital stay duration, index admission time, and comorbidity on readmission. 5,442 subjects (61.2% female) met the criteria with mean age of 78.8 years. Approximately 15% and 43% HFx patients were readmitted within 30 days (early) and between 30 days and 1 year (late) after discharge, respectively. Highest readmission incidence was observed within the first 30 days. Most common causes of readmission in early and late groups were respiratory system diseases and injuries, respectively. Cox model showed male, old age, hospital stay > 9 days, Charlson Comorbidity Index ≥ 1, index admission during 2000-2003, and internal fixation of HFx were independent predictors of readmission. One-year mortality of the early and the late readmission groups was 44.9% and 32.3%, much higher than overall mortality which was 16.8%. Predictive factors for readmission within 1 year included male, old age, comorbidities, and longer hospital stay. One-year mortality in readmitted patients was significantly higher. HFx patients with these factors need careful follow-up, especially within 30 days after discharge.