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1.
J Clin Invest ; 134(15)2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38885336

RESUMO

Osteogenesis imperfecta (OI) type V is the second most common form of OI, distinguished by hyperplastic callus formation and calcification of the interosseous membranes, in addition to the bone fragility. It is caused by a recurrent, dominant pathogenic variant (c.-14C>T) in interferon-induced transmembrane protein 5 (IFITM5). Here, we generated a conditional Rosa26-knockin mouse model to study the mechanistic consequences of the recurrent mutation. Expression of the mutant Ifitm5 in osteo-chondroprogenitor or chondrogenic cells resulted in low bone mass and growth retardation. Mutant limbs showed impaired endochondral ossification, cartilage overgrowth, and abnormal growth plate architecture. The cartilage phenotype correlates with the pathology reported in patients with OI type V. Surprisingly, expression of mutant Ifitm5 in mature osteoblasts caused no obvious skeletal abnormalities. In contrast, earlier expression in osteo-chondroprogenitors was associated with an increase in the skeletal progenitor cell population within the periosteum. Lineage tracing showed that chondrogenic cells expressing the mutant Ifitm5 had decreased differentiation into osteoblastic cells in diaphyseal bone. Moreover, mutant IFITM5 disrupted early skeletal homeostasis in part by activating ERK signaling and downstream SOX9 protein, and inhibition of these pathways partially rescued the phenotype in mutant animals. These data identify the contribution of a signaling defect altering osteo-chondroprogenitor differentiation as a driver in the pathogenesis of OI type V.


Assuntos
Diferenciação Celular , Sistema de Sinalização das MAP Quinases , Osteoblastos , Osteogênese Imperfeita , Fatores de Transcrição SOX9 , Animais , Feminino , Masculino , Camundongos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos Transgênicos , Mutação , Osteoblastos/metabolismo , Osteoblastos/patologia , Osteogênese/genética , Osteogênese Imperfeita/genética , Osteogênese Imperfeita/patologia , Osteogênese Imperfeita/metabolismo , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOX9/metabolismo , Células-Tronco/metabolismo , Células-Tronco/patologia , MAP Quinases Reguladas por Sinal Extracelular
2.
J Biol Chem ; 300(8): 107494, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38925326

RESUMO

The commitment of stem cells to differentiate into osteoblasts is a highly regulated and complex process that involves the coordination of extrinsic signals and intrinsic transcriptional machinery. While rodent osteoblastic differentiation has been extensively studied, research on human osteogenesis has been limited by cell sources and existing models. Here, we systematically dissect human pluripotent stem cell-derived osteoblasts to identify functional membrane proteins and their downstream transcriptional networks involved in human osteogenesis. Our results reveal an enrichment of type II transmembrane serine protease CORIN in humans but not rodent osteoblasts. Functional analyses demonstrated that CORIN depletion significantly impairs osteogenesis. Genome-wide chromatin immunoprecipitation enrichment and mechanistic studies show that p38 MAPK-mediated CCAAT enhancer binding protein delta (CEBPD) upregulation is required for CORIN-modulated osteogenesis. Contrastingly, the type I transmembrane heparan sulfate proteoglycan SDC1 enriched in mesenchymal stem cells exerts a negative regulatory effect on osteogenesis through a similar mechanism. Chromatin immunoprecipitation-seq, bulk and single-cell transcriptomes, and functional validations indicated that CEBPD plays a critical role in controlling osteogenesis. In summary, our findings uncover previously unrecognized CORIN-mediated CEBPD transcriptomic networks in driving human osteoblast lineage commitment.


Assuntos
Proteína delta de Ligação ao Facilitador CCAAT , Osteoblastos , Osteogênese , Serina Endopeptidases , Humanos , Osteoblastos/metabolismo , Osteoblastos/citologia , Serina Endopeptidases/metabolismo , Serina Endopeptidases/genética , Proteína delta de Ligação ao Facilitador CCAAT/metabolismo , Proteína delta de Ligação ao Facilitador CCAAT/genética , Perfilação da Expressão Gênica , Diferenciação Celular , Animais , Células-Tronco Pluripotentes/metabolismo , Células-Tronco Pluripotentes/citologia , Transcriptoma , Camundongos
3.
Calcif Tissue Int ; 115(1): 14-22, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38744723

RESUMO

Increased ß-adrenergic receptor activity has been hypothesized to cause bone loss in those with dementia. We investigated the effect of long-term ß-blocker use on rate of bone loss in older adults with dementia. We used a linear mixed-effects model to estimate the relationship between long-term ß-blocker use and rate of bone loss in participants from the Health Aging and Body Composition study. Records of 1198 participants were analyzed, 44.7% were men. Among the men, 25.2% had dementia and 20.2% were on ß-blockers, while in the women, 22.5% had dementia and 16.6% received ß-blockers. In the 135 men with dementia, 23 were taking ß-blockers, while 15 of 149 women with dementia were using ß-blockers. In men with dementia, ß-blocker users had 0.00491 g/cm2 less bone mineral density (BMD) loss per year at the femoral neck (i.e., 0.63% less loss per year) than non-users (p < 0.05). No differences were detected in women with or without dementia and men without dementia. ß-blockers may be protective by slowing down bone loss in older men with dementia.


Assuntos
Antagonistas Adrenérgicos beta , Densidade Óssea , Demência , Humanos , Masculino , Feminino , Antagonistas Adrenérgicos beta/uso terapêutico , Antagonistas Adrenérgicos beta/farmacologia , Idoso , Densidade Óssea/efeitos dos fármacos , Demência/tratamento farmacológico , Idoso de 80 Anos ou mais , Osteoporose/tratamento farmacológico , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo
4.
Artigo em Inglês | MEDLINE | ID: mdl-38188189

RESUMO

Background: The study aims to develop a data-driven methodology to assess bone drilling in preparation for future clinical trials in residency training. The existing assessment methods are either subjective or do not consider the interdependence among individual skill factors, such as time and accuracy. This study uses quantitative data and radar plots to visualize the balance of the selected skill factors. Methods: In the experiment, straight vertical drilling was assessed across 3 skill levels: expert surgeons (N = 10), intermediate residents (postgraduate year-2-5, N = 5), and novice residents (postgraduate year-1, N = 10). Motion and force were measured for each drilling trial, and data from multiple trials were then converted into 5 performance indicators, including overshoot, drilling time, overshoot consistency, time consistency, and force fluctuation. Each indicator was then scored between 0 and 10, with 10 being the best, and plotted into a radar plot. Results: Statistical difference (p < 0.05) was confirmed among 3 skill levels in force, time, and overshoot data. The radar plots revealed that the novice group exhibited the most distorted pentagons compared with the well-formed pentagons observed in the case of expert participants. The intermediate group showed slight distortion that was between the expert and novice groups. Conclusion/Clinical Relevance: This research shows the utility of radar plots in drilling assessment in a comprehensive manner and lays the groundwork for a data-driven training scheme to prepare novice residents for clinical practice.

5.
J Orthop Res ; 42(1): 223-229, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37448149

RESUMO

In this study, we sought to synthesize chitosan nanoparticles (CS-NPs) and characterize their morphology, efficacy in inhibiting bacterial attachment, and efficacy in eradicating bacteria established on implantable hardware. CS-NPs possess desirable properties, including antibacterial properties in biofilm-mediated infections. CS-NPs were produced using ionic gelation and characterized via scanning electron microscope imaging. Staphylococcus aureus was incubated with CS-NPs at various concentrations and compared to a 1% povidone-iodine with 1% H2 O2 control in 24-well plates. Stainless steel bone screws were placed in six-well plates and inoculated with S. aureus. After 24 h, the screws were transferred to one of three solutions (saline, 40 mg/mL CS-NP, or 1% povidone-iodine with 1% H2 O2 ). Four screws from each group were vortexed in saline and plated. The remaining screw from each group was prepped and imaged to map the location of persistent bacteria. Synthesized CS-NPs had a mean diameter of 0.39 ± 0.13 µm and circularity of 0.87 ± 0.05. The percent inhibition of bacterial attachment was 73% at 20 mg/mL, 73% at 30 mg/mL, 75% at 40 mg/mL, 79% at 50 mg/mL, and 78% at 60 mg/mL. When compared to saline, the 40 mg/mL CS-NP solution reduced bacteria on the screws by 76%. No bacteria were retrieved from the 1% povidone-iodine with 1% H2 O2 group. This study demonstrated that CS-NP solution effectively inhibited S. aureus bacterial attachment and was more effective than saline in eradicating bacteria from orthopedic hardware, suggesting that CS-NPs have the potential for prevention and treatment of musculoskeletal infections as a component of an intraoperative surgical irrigation solution.


Assuntos
Quitosana , Nanopartículas , Povidona-Iodo/farmacologia , Quitosana/farmacologia , Staphylococcus aureus , Antibacterianos/farmacologia
6.
Injury ; 54(7): 110795, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37183090

RESUMO

Many studies have evaluated splint strength at maturity with multiple splint materials, methods, and configurations but none have analyzed splints as they cure. The purpose of this study is to evaluate the properties of different splint materials immediately following activation and as they mature. Splints were dipped for three seconds in two temperatures of water and an additional group of fiberglass with no water was tested as well. Splint weight was taken as an additional measurement to assure homogenous groups. All splints were tested in three-point bending at a constant displacement. The generalized linear model (GLM) including all time frames showed differences in yield load and ultimate loads after three minutes. All ultimate loads occurred at greater than 20° of angulation. Plaster had a much lower displacement at its yield load at all times after 3 min. Plaster had a higher stiffness at 1° of angulation at all time points after six minutes. The GLM that excluded the three-day time showed that the higher temperature increased initial stiffness in the splints at three and six minutes. Fiberglass has a higher yield point and ultimate load when compared to plaster. However, these loads were measured at significant splint angulation for the fiberglass, suggesting that plaster is acting as a true splint. Fiberglass is stronger and faster to cure than plaster. In situations where the surgeon desires the strongest splint, fiberglass may be preferable. However, the initial stiffness of plaster is superior to fiberglass.


Assuntos
Exostose , Contenções , Humanos , Moldes Cirúrgicos , Temperatura , Fáscia
7.
J Orthop Res ; 41(2): 378-385, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35578977

RESUMO

The purpose of this study is to propose a quantitative assessment scheme to help with surgical bone drilling training. This pilot study gathered and compared motion and force data from expert surgeons (n = 3) and novice residents (n = 6). The experiment used three-dimensional printed bone simulants of young bone (YB) and osteoporotic bone (OB), and drilling overshoot, time, and force were measured. There was no statistically significant difference in overshoot between the two groups (p = 0.217 for YB and 0.215 for OB). The results, however, show that the experts took less time (mean = 4.01 s) than the novices (mean = 9.98 s), with a statistical difference (p = 0.003 for YB and 0.0001 for OB). In addition, the expert group performed more consistently than the novices. The force analysis further revealed that experts used a higher force to drill the first cortical section and a noticeably lower force in the second cortex to control the overshoot (approximate reduction of 5.5 N). Finally, when drilling time and overshoot distance were combined, the motion data distinguished the skill gap between expert and novice drilling; the force data provided insight into the drilling mechanism and performance outcomes. This study lays the groundwork for a data-driven training scheme to prepare novice residents for clinical practice.


Assuntos
Osso e Ossos , Projetos Piloto , Osso e Ossos/cirurgia
8.
J Spine Surg ; 9(4): 380-389, 2023 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-38196722

RESUMO

Background: Proper vascular injury risk stratification (VIRS) methods for L4-L5 lateral lumbar interbody fusion (LLIF) surgery have not been well-described. The objective of this study was to propose a novel VIRS method for L4-L5 LLIF surgery via the transpsoas approach. Methods: Axial magnetic resonance imaging (MRI) of adult patients were obtained and analyzed. The VIRS scores were assessed using anterior disc line to posterior vessel wall distance, the disc vessel angle (DVA), and the disc edge to vessel distance at the level of L4-L5 disc space. Results: Ninety-one consecutive adult patients were included in the study. The right common iliac vein (CIV) had a high risk of injury with both right- and left-sided approaches. The left CIV had a moderate risk with a left-sided approach when the iliocaval confluence was above the L4-L5 disc space but had a high risk when the confluence was at the L4-L5 disc space. The left CIV had a high risk with a right-sided approach when the confluence was above the L4-L5 disc space but had a moderate risk when the confluence was at the L4-L5 disc space. The inferior vena cava (IVC) had a high risk with both right- and left-sided approaches. The aorta had a moderate risk regardless of the right or left-sided approaches. The left common iliac artery (CIA) had a moderate risk with a right-sided approach and a low risk with a left-sided approach. The right CIA had a low risk with both right- and left-sided approaches. Conclusions: There are significant vascular anatomic variations at the L4-L5 disc level and a proper VIRS can be performed utilizing a combination of anterior disc line to posterior vessel wall distance, DVA, and disc edge to vessel distance, on the axial MRI.

9.
J Hand Surg Glob Online ; 4(6): 348-354, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36425373

RESUMO

Purpose: The advent of total wrist arthroplasty has allowed for motion-sparing surgical treatment for wrist arthritis. The Integra Freedom Total Wrist Arthroplasty recently incorporated locking caps into its distal component fixation to minimize implant micromotion and improve osseous integration. The purpose of this study was to assess the kinematic effect of locking caps in a cadaveric model. Methods: The Integra Freedom was implanted in 4 matched-pair cadavers and tested with and without the use of the locking caps, with the testing order randomized. Each specimen was tested on a custom testing system in a position of 15° of radial deviation, neutral position, and 15° of ulnar deviation with 25 N, 50 N, 75 N, and 100 N of compressive force. The rotation of the capitate, trapezoid, and hamate at all positions was measured using a 3-dimensional digitizer. Results: Statistical analysis showed no difference in carpal rotation between the nonlocking cap and locking cap groups at all testing loads and wrist positions. The absolute motion of the distal row was minimal. However, of the total 216 loads/positions tested, only 4 (1.8%) showed a rotation of greater than 2° and only 34 (15.7%) showed a rotation of greater than 1°. Conclusions: This study shows that in a time zero cadaveric model, the initial osseous fixation of the distal component in the Integra Freedom is robust with or without locking caps. The addition of locking caps did not have a kinematic effect on distal carpal row fixation. However, further investigation into its clinical role is necessary. Clinical Relevance: At time zero, there is minimal carpal motion after implantation of the Integra Freedom Total Wrist with functional loading. The addition of locking caps did not lead to any decrease in carpal motion.

10.
Sci Rep ; 12(1): 8117, 2022 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-35581227

RESUMO

High-resolution computed tomography (CT) is widely used to assess bone structure under physiological and pathological conditions. Although the analytic protocols and parameters for micro-CT (µCT) analyses in mice are standardized for long bones, vertebrae, and the palms in aging mice, they have not yet been established for craniofacial bones. In this study, we conducted a morphometric assessment of craniofacial bones, in comparison with long bones, in aging mice. Although age-related changes were observed in the microarchitecture of the femur, tibia, vertebra, and basisphenoid bone, and were more pronounced in females than in males, the microarchitecture of both the interparietal bone and body of the mandible, which develop by intramembranous ossification, was less affected by age and sex. By contrast, the condyle of the mandible was more affected by aging in males compared to females. Taken together, our results indicate that mouse craniofacial bones are uniquely affected by age and sex.


Assuntos
Densidade Óssea , Fêmur , Envelhecimento/fisiologia , Animais , Feminino , Masculino , Camundongos , Crânio , Microtomografia por Raio-X
11.
J Pediatr Orthop ; 42(7): 361-366, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35543603

RESUMO

BACKGROUND: Open pediatric Monteggia fracture-dislocations are a relatively uncommon injury pattern, with limited numbers reported in previous series. Open fracture-dislocations frequently represent more severe injury patterns with potential for contamination. We aim to determine differences in long-term clinical and functional outcomes in the operative management of closed versus open pediatric Monteggia fracture-dislocations. METHODS: A retrospective review of operatively treated pediatric Monteggia fracture-dislocations was performed. Closed versus open injuries were compared in both clinical outcomes, as well as patient-reported outcomes through Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) questionnaire. RESULTS: Of 30 operatively treated injuries, 12/30 (40%) were open fracture-dislocations. Patients were followed clinically for an average of 15.65 months in open injuries and an average of 4.61 months in closed injuries. A trend toward increased time to union was observed, however, significance was not achieved; open injuries averaged 8.0 versus 5.8 weeks for closed injuries ( P =0.07). Two patients (11%) in the closed fracture group experienced postoperative complications; both were minor. Five patients (42%) in the open fracture-dislocation group experienced a total of 6 postoperative complications; 5 of the 6 complications were major. QuickDASH scores were obtained at an average of 5 years postoperatively; mean QuickDASH scores were higher in the open fracture group, 13.1, compared with the closed fracture group, 5.9 ( P =0.038). Increased QuickDASH scores were independently associated with presence of postoperative complications. QuickDASH score could be expected to increase by 12.5 points in those with major complications ( P =0.044). CONCLUSION: We present the largest single cohort of pediatric open Monteggia fracture-dislocation injuries to date. These injuries are predictive of poorer outcomes including trend toward increased time to union, increased risk of major complication, and can independently predict worse long-term patient-reported functional outcomes. LEVEL OF EVIDENCE: Level III-these data represent a retrospective comparative study of clinical and functional outcomes.


Assuntos
Fraturas Fechadas , Fraturas Expostas , Luxações Articulares , Fratura de Monteggia , Fraturas da Ulna , Criança , Fixação Interna de Fraturas/efeitos adversos , Fraturas Fechadas/cirurgia , Fraturas Expostas/cirurgia , Humanos , Luxações Articulares/complicações , Luxações Articulares/cirurgia , Fratura de Monteggia/complicações , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Resultado do Tratamento , Fraturas da Ulna/complicações
12.
J Bone Miner Res ; 37(4): 675-686, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34997935

RESUMO

Osteogenesis imperfecta (OI) is a genetically heterogenous disorder most often due to heterozygosity for mutations in the type I procollagen genes, COL1A1 or COL1A2. The disorder is characterized by bone fragility leading to increased fracture incidence and long-bone deformities. Although multiple mechanisms underlie OI, endoplasmic reticulum (ER) stress as a cellular response to defective collagen trafficking is emerging as a contributor to OI pathogenesis. Herein, we used 4-phenylbutiric acid (4-PBA), an established chemical chaperone, to determine if treatment of Aga2+/- mice, a model for moderately severe OI due to a Col1a1 structural mutation, could attenuate the phenotype. In vitro, Aga2+/- osteoblasts show increased protein kinase RNA-like endoplasmic reticulum kinase (PERK) activation protein levels, which improved upon treatment with 4-PBA. The in vivo data demonstrate that a postweaning 5-week 4-PBA treatment increased total body length and weight, decreased fracture incidence, increased femoral bone volume fraction (BV/TV), and increased cortical thickness. These findings were associated with in vivo evidence of decreased bone-derived protein levels of the ER stress markers binding immunoglobulin protein (BiP), CCAAT/-enhancer-binding protein homologous protein (CHOP), and activating transcription factor 4 (ATF4) as well as increased levels of the autophagosome marker light chain 3A/B (LC3A/B). Genetic ablation of CHOP in Aga2+/- mice resulted in increased severity of the Aga2+/- phenotype, suggesting that the reduction in CHOP observed in vitro after treatment is a consequence rather than a cause of reduced ER stress. These findings suggest the potential use of chemical chaperones as an adjunct treatment for forms of OI associated with ER stress. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).


Assuntos
Osteogênese Imperfeita , Animais , Butilaminas , Colágeno Tipo I/metabolismo , Modelos Animais de Doenças , Camundongos , Chaperonas Moleculares/metabolismo , Mutação , Osteoblastos/metabolismo , Osteogênese , Osteogênese Imperfeita/tratamento farmacológico , Osteogênese Imperfeita/genética , Osteogênese Imperfeita/metabolismo , Fenótipo
13.
Nat Commun ; 12(1): 7199, 2021 12 10.
Artigo em Inglês | MEDLINE | ID: mdl-34893625

RESUMO

Type I collagen (Col1) is the most abundant protein in mammals. Col1 contributes to 90% of the total organic component of bone matrix. However, the precise cellular origin and functional contribution of Col1 in embryogenesis and bone formation remain unknown. Single-cell RNA-sequencing analysis identifies Fap+ cells and Fsp1+ cells as the major contributors of Col1 in the bone. We generate transgenic mouse models to genetically delete Col1 in various cell lineages. Complete, whole-body Col1 deletion leads to failed gastrulation and early embryonic lethality. Specific Col1 deletion in Fap+ cells causes severe skeletal defects, with hemorrhage, edema, and prenatal lethality. Specific Col1 deletion in Fsp1+ cells results in Osteogenesis Imperfecta-like phenotypes in adult mice, with spontaneous fractures and compromised bone healing. This study demonstrates specific contributions of mesenchymal cell lineages to Col1 production in organogenesis, skeletal development, and bone formation/repair, with potential insights into cell-based therapy for patients with Osteogenesis Imperfecta.


Assuntos
Colágeno Tipo I/biossíntese , Desenvolvimento Embrionário/fisiologia , Fibroblastos/metabolismo , Osteogênese Imperfeita/metabolismo , Osteogênese/fisiologia , Animais , Medula Óssea/metabolismo , Medula Óssea/patologia , Linhagem da Célula , Colágeno Tipo I/genética , Cadeia alfa 1 do Colágeno Tipo I/biossíntese , Cadeia alfa 1 do Colágeno Tipo I/genética , Desenvolvimento Embrionário/genética , Feminino , Fêmur , Fibroblastos/patologia , Humanos , Masculino , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Osteogênese/genética , Osteogênese Imperfeita/genética , Osteogênese Imperfeita/patologia , Fenótipo , Gravidez
14.
Elife ; 102021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-34036937

RESUMO

Osteogenesis imperfecta (OI) is characterized by short stature, skeletal deformities, low bone mass, and motor deficits. A subset of OI patients also present with joint hypermobility; however, the role of tendon dysfunction in OI pathogenesis is largely unknown. Using the Crtap-/- mouse model of severe, recessive OI, we found that mutant Achilles and patellar tendons were thinner and weaker with increased collagen cross-links and reduced collagen fibril size at 1- and 4-months compared to wildtype. Patellar tendons from Crtap-/- mice also had altered numbers of CD146+CD200+ and CD146-CD200+ progenitor-like cells at skeletal maturity. RNA-seq analysis of Achilles and patellar tendons from 1-month Crtap-/- mice revealed dysregulation in matrix and tendon marker gene expression concomitant with predicted alterations in TGF-ß, inflammatory, and metabolic signaling. At 4-months, Crtap-/- mice showed increased αSMA, MMP2, and phospho-NFκB staining in the patellar tendon consistent with excess matrix remodeling and tissue inflammation. Finally, a series of behavioral tests showed severe motor impairments and reduced grip strength in 4-month Crtap-/- mice - a phenotype that correlates with the tendon pathology.


Assuntos
Tendão do Calcâneo/patologia , Proteínas da Matriz Extracelular/deficiência , Atividade Motora , Osteogênese Imperfeita/patologia , Osteogênese Imperfeita/fisiopatologia , Ligamento Patelar/patologia , Tendão do Calcâneo/metabolismo , Actinas/metabolismo , Fatores Etários , Animais , Modelos Animais de Doenças , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Proteínas da Matriz Extracelular/genética , Colágenos Fibrilares/genética , Colágenos Fibrilares/metabolismo , Genes Recessivos , Predisposição Genética para Doença , Força da Mão , Metaloproteinase 2 da Matriz/metabolismo , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Chaperonas Moleculares/genética , NF-kappa B/metabolismo , Osteogênese Imperfeita/genética , Osteogênese Imperfeita/metabolismo , Ligamento Patelar/metabolismo , Fenótipo , Fosforilação , Resistência Física , Células-Tronco/metabolismo , Células-Tronco/patologia
15.
J Orthop Trauma ; 34(11): 572-577, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33065656

RESUMO

OBJECTIVES: Multidimensional fluoroscopy is new imaging technology that generates intraoperative cross sectional imaging. Can this technology be used to assess accuracy and safety of percutaneously placed iliosacral screws intraoperatively? DESIGN: Retrospective study. SETTING: Level 1 academic trauma center. PATIENTS/PARTICIPANTS: Fifty-two consecutive patients during a 7-month period with unstable posterior pelvic ring disruptions. INTERVENTION: All patients were treated with percutaneous iliosacral and/or transsacral screw fixation by a single experienced surgeon. Traditional triplanar fluoroscopy was performed during guidepin insertion. Intraoperative multidimensional fluoroscopy was used for all patients after iliosacral screw fixation. MAIN OUTCOME MEASUREMENTS: Intraoperative multidimensional fluoroscopy and postoperative computed tomography (CT) scans for each patient were retrospectively reviewed by the treating surgeon and another trauma surgeon. Screw position in relation to the sacral neuroforamen was assessed using multidimensional fluoroscopy and compared to postoperative CT scan. Screws were classified as extraforaminal, juxtaforaminal, or intraforaminal. RESULTS: No screws were intraforaminally seen on intraoperative multidimensional fluoroscopy or postoperative CT scan. All iliosacral and transsacral screws were considered safe. Intraobserver and interobserver variability existed between reviewers when grading screws as extraforaminal versus juxtaforaminal. This was not clinically significant because both agreed that extraforaminal and juxtaforaminal screw positions are safe. Multidimensional fluoroscopy was used in 3 patients to assess guidepin placement before definitive screw fixation. Two patients underwent a change of fixation after reviewing multidimensional fluoroscopy. No postoperative neurological examination changes occurred. CONCLUSIONS: Multidimensional fluoroscopy is a novel imaging technology that can safely be used intraoperatively to accurately determine iliosacral and transsacral screw placement. LEVELS OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Fraturas Ósseas , Ossos Pélvicos , Parafusos Ósseos , Fluoroscopia , Fixação Interna de Fraturas , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Humanos , Ílio/diagnóstico por imagem , Ílio/cirurgia , Ossos Pélvicos/diagnóstico por imagem , Ossos Pélvicos/cirurgia , Estudos Retrospectivos , Sacro/diagnóstico por imagem , Sacro/cirurgia
16.
J Orthop Trauma ; 34(4): e109-e113, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32195891

RESUMO

OBJECTIVES: Prefabrication and storage of antibiotic beads may decrease surgical time and allow for use in other settings. This study investigated the effects of sterilization technique and storage time on the bioactivity of antibiotic polymethyl methacrylate (PMMA) beads. METHODS: Uniform beads of PMMA containing 1 g each of tobramycin and vancomycin were sterilized using autoclave, ethylene oxide (ETO), or ultraviolet (UV) light. Beads were made in a sterile fashion as a control. Disks containing eluted antibiotics from each of the 4 groups were placed onto agar plates inoculated with Staphylococcus aureus. Zones of inhibition, a measure of bioactivity for antibiotic eluted, were determined for the experimental groups and control. Repeat testing was performed for beads stored for 1 week, 1, 3, and 6 months. RESULTS: Beads sterilized using autoclave, ETO, and UV light showed similar ZOIs after 24 hours of and 1 week of elution compared with the control group. Beads stored for up to 6 months demonstrated similar bioactivity to beads made sterile and tested immediately. CONCLUSION: PMMA beads containing vancomycin and tobramycin made in a sterile fashion and stored for up to 6 months have the same efficacy as the current standard of beads made sterile and used immediately. The elution and bioactivity of vancomycin-tobramycin antibiotic beads are not negatively impacted by the sterilization methods of autoclaving, ETO gas, or UV light. Furthermore, nonsterile beads can be sterilized and stored up to 6 months with an expected efficacy comparable with beads made in a standard sterile fashion.


Assuntos
Tobramicina , Vancomicina , Antibacterianos/uso terapêutico , Cimentos Ósseos , Humanos , Polimetil Metacrilato , Esterilização
17.
J Bone Miner Res ; 35(6): 1132-1148, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32053224

RESUMO

Osteogenesis imperfecta (OI) is a genetic bone dysplasia characterized by bone deformities and fractures caused by low bone mass and impaired bone quality. OI is a genetically heterogeneous disorder that most commonly arises from dominant mutations in genes encoding type I collagen (COL1A1 and COL1A2). In addition, OI is recessively inherited with the majority of cases resulting from mutations in prolyl-3-hydroxylation complex members, which includes cartilage-associated protein (CRTAP). OI patients are at an increased risk of fracture throughout their lifetimes. However, non-union or delayed healing has been reported in 24% of fractures and 52% of osteotomies. Additionally, refractures typically go unreported, making the frequency of refractures in OI patients unknown. Thus, there is an unmet need to better understand the mechanisms by which OI affects fracture healing. Using an open tibial fracture model, our study demonstrates delayed healing in both Col1a2 G610c/+ and Crtap -/- OI mouse models (dominant and recessive OI, respectively) that is associated with reduced callus size and predicted strength. Callus cartilage distribution and chondrocyte maturation were altered in OI, suggesting accelerated cartilage differentiation. Importantly, we determined that healed fractured tibia in female OI mice are biomechanically weaker when compared with the contralateral unfractured bone, suggesting that abnormal OI fracture healing OI may prime future refracture at the same location. We have previously shown upregulated TGF-ß signaling in OI and we confirm this in the context of fracture healing. Interestingly, treatment of Crtap -/- mice with the anti-TGF-ß antibody 1D11 resulted in further reduced callus size and predicted strength, highlighting the importance of investigating dose response in treatment strategies. These data provide valuable insight into the effect of the extracellular matrix (ECM) on fracture healing, a poorly understood mechanism, and support the need for prevention of primary fractures to decrease incidence of refracture and deformity in OI patients. © 2020 American Society for Bone and Mineral Research.


Assuntos
Osteogênese Imperfeita , Animais , Colágeno , Colágeno Tipo I/genética , Proteínas da Matriz Extracelular , Feminino , Consolidação da Fratura , Humanos , Camundongos , Chaperonas Moleculares , Osteogênese Imperfeita/genética
18.
J Orthop Trauma ; 33(11): 564-568, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31356448

RESUMO

OBJECTIVE: To determine whether a position screw will maintain the interfragmentary compression force obtained by a reduction clamp across an anatomically reduced cortical bone fracture and determine whether this compressive force is equivalent to that generated by a lag screw (LS). METHODS: Oblique fractures were created in 6 composite cortical bone models. Interfragmentary compression was measured using force sensors within the fracture after reduction with a clamp. A position screw was then placed perpendicular to the fracture, and force measurements were repeated with both the clamp and the screw. Finally, the clamp was removed, and force measurements were taken with the screw only to measure maintenance of initial compression. After these measurements, the screw was removed, and the near fragment was overdrilled to allow LS placement by technique. Compression force measurements were repeated for clamp only, clamp + screw, and screw only. RESULTS: The mean force of clamp alone across all 12 trials was 139.77 N. Application of an LS increased the compression across the fracture (P = 0.01) which was unchanged when the clamp was removed. The position screw had the opposite effect, reducing compression, and the removal of the clamp further reduced the compression (P = 0.013). CONCLUSIONS: A reduction clamp will initially compress a fracture to an average of 139 N. An LS will significantly increase this interfragmentary compression. A position screw will not maintain the compression created by the clamp and in fact will significantly decrease interfragmentary compression.


Assuntos
Parafusos Ósseos , Força Compressiva , Fixação Interna de Fraturas/instrumentação , Fraturas Ósseas/cirurgia , Cadáver , Desenho de Equipamento , Fêmur/cirurgia , Fixação Interna de Fraturas/métodos , Humanos , Úmero/cirurgia , Sensibilidade e Especificidade
19.
J Am Geriatr Soc ; 67(6): 1132-1137, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30830698

RESUMO

OBJECTIVES: Patients with dementia are at high risk for hip fractures and often have poor outcomes when a fracture is sustained. Despite this poor prognosis, little data are available on what factors should be prioritized to guide surgical decision making in these cases. We aimed to understand the decision-making process for older dementia patients hospitalized after hip fractures. DESIGN: We performed a qualitative analysis of in-depth elite interviews conducted with a clinical care team involved in management of patients with dementia after hospitalization for hip fractures. SETTING: Interviews were conducted with an interprofessional team involved in the care of patients with dementia after being hospitalized for hip fractures. PARTICIPANTS: Interviewees included nine orthopaedic surgeons, three hospitalists, three geriatricians, five nurses, three occupational therapists, three physical therapists, and two clinical ethicists. MEASUREMENTS: Verbatim transcripts of the interviews were analyzed and coded using QSR International's NVivo 10 qualitative database management software. RESULTS: The three main themes that most interviewees discussed were pain control, functional status, and medical comorbidities. Interviewees brought up many factors related to restoring functional status including baseline functional status, rehabilitation potential, social support, and the importance of mobility. Dementia and its impact on rehabilitation potential were mentioned by all geriatricians. CONCLUSION: Although frailty, prognosis, and life expectancy were largely absent from the responses, the emphasis on dementia, advanced directives, and involving family or caregivers by the three geriatricians indicates the importance of including geriatricians in the decision-making team for these patients.


Assuntos
Comorbidade , Tomada de Decisões , Demência/psicologia , Fraturas do Quadril/cirurgia , Equipe de Assistência ao Paciente , Diretivas Antecipadas , Idoso , Idoso de 80 Anos ou mais , Feminino , Fraturas do Quadril/reabilitação , Hospitalização , Humanos , Masculino , Manejo da Dor
20.
Women Health ; 59(8): 845-853, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30721115

RESUMO

Coronary artery disease (CAD) and osteoporosis, the two most frequently occurring chronic diseases of aging populations, share many risk factors including lack of estrogen, smoking, and low physical activity. CAD and low bone mineral density (BMD) are strongly associated. Statins, (3-hydroxy-3-methylglutaryl coenzyme A [HMG-CoA] reductase inhibitors), are used to prevent and treat CAD and have been associated with high BMD. This cross-sectional study examined associations of BMD with statin use and nonuse in elderly women with or without CAD. Multivariate regression analyses were conducted on 185 women aged ≥60 years who were referred between October 2010 and March 2015 to a geriatric osteoporosis clinic in Houston, Texas, for compromised skeletal health. Compared to the control group (without CAD and without statin use), patients with CAD and no statin use were more likely to have lower femoral neck BMD (ß: -0.46, 95% confidence interval: -0.75 to -0.18). The BMD of patients taking statins, regardless of presence of CAD, was similar to that of the control group. Statins may be protective in preventing bone loss in elderly women suffering from CAD. Prospective trials are warranted to determine if continued use of statins in them would help prevent both CAD and bone loss.


Assuntos
Densidade Óssea/efeitos dos fármacos , Doença da Artéria Coronariana/tratamento farmacológico , Fraturas do Colo Femoral/prevenção & controle , Colo do Fêmur/efeitos dos fármacos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Osteoporose/etiologia , Idoso , Idoso de 80 Anos ou mais , Doença da Artéria Coronariana/epidemiologia , Estudos Transversais , Fêmur/diagnóstico por imagem , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Pessoa de Meia-Idade , Osteoporose/epidemiologia , Fatores de Proteção , Estudos Retrospectivos
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