RESUMEN
CASE: A 15-year-old girl known with osteogenesis imperfecta presented with left femoral pain. She had been treated with multiple Fassier-Duval intramedullary nails, which were still in situ. Radiographic imaging demonstrated focal osteolysis and periosteal reaction at the telescopic junction of the rod in the distal femur. She underwent implant removal. Intraoperative sampling demonstrating acute sterile inflammation and presence of brownish colored particles consistent with metal debris and osteolysis. Explant analysis confirmed corrosion of the stainless-steel telescopic nail as the underlying cause. CONCLUSION: Osteolysis and periosteal reaction because of corrosion should be considered in conjunction with other more common causes of pain, such as fracture or infection, in patients treated with telescopic intramedullary nails.
Asunto(s)
Osteólisis , Femenino , Humanos , Adolescente , Osteólisis/diagnóstico por imagen , Osteólisis/etiología , Corrosión , Remoción de Dispositivos , Fémur , DolorRESUMEN
Case: We present a case of acute unstable valgus slipped capital femoral epiphysis (SCFE) in an 8-year-old female who presented after a trip and fall. The patient was managed with emergent closed reduction and percutaneous screw fixation and prophylactic fixation of contralateral side after 6 weeks. At 18-month follow-up, the patient was symptom free with a good range of movement and no evidence of slip progression, chondrolysis or avascular necrosis of the femoral head. Conclusion: We demonstrate that, in this case, closed reduction and percutaneous fixation provided satisfactory outcome at 18-month follow-up. This case highlights the need for both anteroposterior and lateral radiographs.
RESUMEN
AIMS: We investigated the prevalence of late developmental dysplasia of the hip (DDH), abduction bracing treatment, and surgical procedures performed following the implementation of universal ultrasound screening versus selective ultrasound screening programmes. METHODS: A systematic search of PubMed, Embase, The Cochrane Library, OrthoSearch, and Web of Science from the date of inception of each database until 27 March 2022 was performed. The primary outcome of interest was the prevalence of late detection of DDH, diagnosed after three months. Secondary outcomes of interest were the prevalence of abduction bracing treatment and surgical procedures performed in childhood for dysplasia. Only studies describing the primary outcome of interest were included. RESULTS: A total of 31 studies were identified, of which 13 described universal screening and 20 described selective screening. Two studies described both. The prevalence of late DDH was 0.10 per 1,000 live births (95% confidence interval (CI) 0.00 to 0.39) in the universal screening group and 0.45 per 1,000 live births (95% CI 0.31 to 0.61) in the selective screening group. Abduction bracing treatment was performed on 55.54 per 1,000 live births (95% CI 24.46 to 98.15) in the universal screening group versus 0.48 per 1,000 live births (95% CI 0.07 to 1.13) in the selective screening group. Both the universal and selective screening groups had a similar prevalence of surgical procedures in childhood for dysplasia being performed (0.48 (95% CI 0.32 to 0.63) vs 0.49 (95% CI 0.31 to 0.71) per 1,000 live births, respectively). CONCLUSION: Universal screening showed a trend towards lower prevalence of late DDH compared to selective screening. However, it was also associated with a significant increase in the prevalence of abduction bracing without a significant reduction in the prevalence of surgical procedures in childhood for dysplasia being performed. High-quality studies comparing both treatment methods are required, in addition to studies into the natural history of missed DDH.Cite this article: Bone Joint J 2023;105-B(2):198-208.
Asunto(s)
Diagnóstico Tardío , Displasia del Desarrollo de la Cadera , Humanos , Diagnóstico Tardío/prevención & control , Incidencia , Tirantes , Bases de Datos FactualesRESUMEN
Purpose: The management of moderate and severe slipped capital femoral epiphysis is controversial. While in situ fixation is commonly used, the modified Dunn's procedure is increasingly popular within high-volume centers. We compared the clinical and radiological outcomes, as well as the rates of femoral head avascular necrosis or chondrolysis in patients managed with either modified Dunn's procedure or in situ fixation. Methods: A systematic search of the PubMed, Embase, The Cochrane Library, Science Direct, and Web of Science was performed in August 2021. Studies comparing outcomes and complications of modified Dunn's procedure versus in situ fixation in patients with moderate or severe slipped capital femoral epiphysis were included. Results: A total of four studies were included in the final analysis. Modified Dunn's procedure did not result in improved clinical outcomes. However, radiological outcomes as measured using Southwick angles and Alpha angles were significantly improved in the modified Dunn's procedure group, with a mean difference of -14.68 (p < 0.00001) and -34.26 degrees (p < 0.00001), respectively, compared to in situ fixation. There was no difference in the odds of femoral head avascular necrosis or chondrolysis, with odds ratio of 0.99 (p = 0.97). Conclusion: Within the limits of our study, modified Dunn's procedure did not improve clinical outcomes. There were significantly improved radiological outcomes without higher odds of femoral head avascular necrosis or chondrolysis. Further long-term studies are required to better guide management of moderate and severe slipped capital femoral epiphysis, especially in unstable slips. In the meantime, we recommend that the modified Dunn's procedure, if done, be restricted to high-volume centers with low complication rates. Level of evidence: Level III-Systematic review of Level III studies. Prospero Registration No: CRD42021279503.
RESUMEN
Growth plate cartilage injuries often result in bony repair at the injury site and premature mineralisation at the uninjured region causing bone growth defects, for which underlying mechanisms are unclear. With the prior microarray study showing upregulated bone morphogenetic protein (BMP) signalling during the injury site bony repair and with the known roles of BMP signalling in bone healing and growth plate endochondral ossification, this study used a rat tibial growth plate drill-hole injury model with or without systemic infusion of BMP antagonist noggin to investigate roles of BMP signalling in injury repair responses within the injury site and in the adjacent "uninjured" cartilage. At days 8, 14 and 35 post-injury, increased expression of BMP members and receptors and enhanced BMP signalling (increased levels of phosphorylated (p)-Smad1/5/8) were found during injury site bony repair. After noggin treatment, injury site bony repair at days 8 and 14 was reduced as shown by micro-CT and histological analyses and lower mRNA expression of osteogenesis-related genes Runx2 and osteocalcin (by RT-PCR). At the adjacent uninjured cartilage, the injury caused increases in the hypertrophic zone/proliferative zone height ratio and in mRNA expression of hypertrophy marker collagen-10, but a decrease in chondrogenesis marker Sox9 at days 14 and/or 35, which were accompanied by increased BMP signalling (increased levels of pSmad1/5/8 protein and BMP7, BMPR1a and target gene Dlx5 mRNA). Noggin treatment reduced the hypertrophic zone/proliferative zone height ratio and collagen-10 mRNA expression, but increased collagen-2 mRNA levels at the adjacent growth plate. This study has identified critical roles of BMP signalling in the injury site bony repair and in the hypertrophic degeneration of the adjacent growth plate in a growth plate drill-hole repair model. Moreover, suppressing BMP signalling can potentially attenuate the undesirable bony repair at injury site and suppress the premature hypertrophy but potentially rescue chondrogenesis at the adjacent growth plate.
Asunto(s)
Placa de Crecimiento , Fracturas de Salter-Harris , Animales , Cartílago , Osteogénesis , Ratas , Ratas Sprague-DawleyRESUMEN
INTRODUCTION: Research is needed to examine trajectories of tobacco use beyond cigarette smoking, particularly during emerging middle young adulthood, and to identify distinct multilevel influences of use trajectories. AIMS AND METHODS: We examined (1) tobacco use trajectories over a 2-year period among 2592 young adult college students in a longitudinal cohort study and (2) predictors of these trajectories using variables from a socioecological framework, including intrapersonal-level factors (eg, sociodemographics, psychosocial factors [eg, adverse childhood experiences, depressive symptoms, and attention-deficit hyperactivity disorder symptoms], early-onset substance use), interpersonal factors (eg, social support, parental substance use), and community-level factors (eg, college type, rural vs. urban). RESULTS: About 64.5% were female and 65.0% were white. From age 18 to 26, 27%-31% of participants reported past 30-day use of any tobacco product. We identified four trajectory classes: Abstainers/Dabblers who never or infrequently used (89.2%); Adult users who began using frequently around age 20 and continued thereafter (5.9%); College Smokers who began using before 19 but ceased use around 25 (2.5%); and Teenage users who used during their teenage years but ceased use by 22 (1.9%). Multinomial regression showed that, compared to Abstainers/Dabblers, significant predictors (p < .05) of being (1) Adult users included being male, earlier onset marijuana use, attending public universities or technical colleges (vs. private universities), and living in urban areas; (2) College users included being male, earlier onset marijuana use, and parental alcohol or marijuana use; and (3) Teenage users included only earlier onset marijuana use. CONCLUSION: Distinct prevention and intervention efforts may be needed to address the trajectories identified. IMPLICATIONS: Among young adult college students, the largest proportion of tobacco users demonstrate the risk of continued and/or progression of tobacco use beyond college. In addition, specific factors, particularly sex, earlier onset marijuana use, parental use of alcohol and marijuana, and contextual factors such as college setting (type of school, rural vs. urban) may influence tobacco use outcomes. As such, prevention and cessation intervention strategies are needed to address multilevel influences.
Asunto(s)
Estudiantes/psicología , Trastornos Relacionados con Sustancias/epidemiología , Uso de Tabaco/epidemiología , Adolescente , Adulto , Femenino , Georgia/epidemiología , Humanos , Estudios Longitudinales , Masculino , Trastornos Relacionados con Sustancias/psicología , Uso de Tabaco/psicología , Universidades , Adulto JovenRESUMEN
Faulty bony repair causes dysrepair of injured growth plate cartilage and bone growth defects in children; however, the underlying mechanisms are unclear. Recently, we observed the prominent induction of neurotrophin3 (NT-3) and its important roles as an osteogenic and angiogenic factor promoting the bony repair. The current study investigated its roles in regulating injury site remodelling. In a rat tibial growth plate drill-hole injury repair model, NT-3 was expressed prominently in osteoblasts at the injury site. Recombinant NT-3 (rhNT-3) systemic treatment enhanced, but NT-3 immunoneutralization attenuated, expression of cartilage-removal proteases (MMP-9 and MMP-13), presence of bone-resorbing osteoclasts and expression of osteoclast protease cathepsin K, and remodelling at the injury site. NT-3 was also highly induced in cultured mineralizing rat bone marrow stromal cells, and the conditioned medium augmented osteoclast formation and resorptive activity, an ability that was blocked by presence of anti-NT-3 antibody. Moreover, NT-3 and receptor TrkC were induced during osteoclastogenesis, and rhNT-3 treatment activated TrkC downstream kinase Erk1/2 in differentiating osteoclasts although rhNT-3 alone did not affect activation of osteoclastogenic transcription factors NF-κB or NFAT in RAW264.7 osteoclast precursor cells. Furthermore, rhNT-3 treatment increased, but NT-3 neutralization reduced, expression of osteoclastogenic cytokines (RANKL, TNF-α, and IL-1) in mineralizing osteoblasts and in growth plate injury site, and rhNT-3 augmented the induction of these cytokines caused by RANKL treatment in RAW264.7 cells. Thus, injury site osteoblast-derived NT-3 is important in promoting growth plate injury site remodelling, as it induces cartilage proteases for cartilage removal and augments osteoclastogenesis and resorption both directly (involving activing Erk1/2 and substantiating RANKL-induced increased expression of osteoclastogenic signals in differentiating osteoclasts) and indirectly (inducing osteoclastogenic signals in osteoblasts).
Asunto(s)
Cartílago Articular/patología , Placa de Crecimiento/metabolismo , Placa de Crecimiento/patología , Neurotrofina 3/metabolismo , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Péptido Hidrolasas/metabolismo , Animales , Callo Óseo/metabolismo , Callo Óseo/patología , Citocinas/metabolismo , Activación Enzimática/efectos de los fármacos , Placa de Crecimiento/efectos de los fármacos , Humanos , Masculino , Ratones , FN-kappa B/metabolismo , Factores de Transcripción NFATC/metabolismo , Osteoblastos/efectos de los fármacos , Osteoblastos/patología , Osteoclastos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Ligando RANK/farmacología , Células RAW 264.7 , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas Sprague-Dawley , Receptor trkC/metabolismoRESUMEN
Neurotrophins and their receptors are key molecules that are known to be critical in regulating nervous system development and maintenance and have been recognized to be also involved in regulating tissue formation and healing in skeletal tissues. Studies have shown that neurotrophins and their receptors are widely expressed in skeletal tissues, implicated in chondrogenesis, osteoblastogenesis, and osteoclastogenesis, and are also involved in regulating tissue formation and healing events in skeletal tissue. Increased mRNA expression for neurotrophins NGF, BDNF, NT-3, and NT-4, and their Trk receptors has been observed in injured bone tissues, and NT-3 and its receptor, TrkC, have been identified to have the highest induction at the injury site in a drill-hole injury repair model in both bone and the growth plate. In addition, NT-3 has also recently been shown to be both an osteogenic and angiogenic factor, and this neurotrophin can also enhance expression of the key osteogenic factor, BMP-2, as well as the major angiogenic factor, VEGF, to promote bone formation, vascularization, and healing of the injury site. Further studies, however, are needed to investigate if different neurotrophins have differential roles in skeletal repair, and if NT-3 can be a potential target of intervention for promoting bone fracture healing.
Asunto(s)
Remodelación Ósea/fisiología , Huesos/embriología , Condrogénesis/fisiología , Factores de Crecimiento Nervioso/metabolismo , Osteogénesis/fisiología , Receptor trkC/metabolismo , Proteína Morfogenética Ósea 2/biosíntesis , Huesos/irrigación sanguínea , Neovascularización Fisiológica/fisiología , Factores de Crecimiento Nervioso/genética , Neurotrofina 3 , Osteoblastos/fisiología , Receptor trkC/genética , Factor A de Crecimiento Endotelial Vascular/biosíntesisRESUMEN
OBJECTIVE: This study investigated associations between the use of alternative tobacco products (e.g., cigarettes, little cigars/cigarillos, hookah, e-cigarettes), alcohol, and marijuana among college students and use by their parents, siblings, and friends. A large literature exists for social influences on adolescent substance use, but few studies have focused on college samples. PARTICIPANTS: 3,418 college students from seven universities in the state of Georgia participated in this study. METHODS: Web-based surveys were completed by students (45-60 minutes) during the fall semester, 2014. RESULTS: Findings largely indicated specificity of associations between college student use and use by social influences for similar tobacco products and other substances. For each tobacco product or substance, the highest associations were for friends' use. Structural equation analyses further supported the specificity of associations and highlighted the relative strength of friends' use on student use. CONCLUSION: Similar to findings with adolescents, the use of alternative tobacco products, alcohol, and marijuana by parents, siblings, and friends is associated with higher levels of use among college students, and friends' use was the most potent correlate for this phase of the lifespan.
Asunto(s)
Consumo de Alcohol en la Universidad/psicología , Fumar Marihuana/psicología , Grupo Paritario , Fumar/psicología , Conducta Social , Adolescente , Adulto , Femenino , Amigos/psicología , Georgia , Humanos , Estudios Longitudinales , Masculino , Estudiantes/psicología , Encuestas y Cuestionarios , Universidades , Adulto JovenRESUMEN
Limited public health research has used psychographic profiling to segment young adults and examine their substance use behaviors. We aimed to conduct market research to identify young adult market segments at risk for alternative tobacco products (ATPs), alcohol, and marijuana use. Substance use; psychographics per the Values, Attitudes, and Lifestyle Scale (VALS); and other key variables were assessed at baseline in a longitudinal study of 3,418 students aged 18-25 from seven colleges/universities in the state of Georgia. Cluster analysis was conducted on VALS factors to identify distinct segments. Regression examined segments in relation to substance use risk. Past 30-day use prevalence for each substance was as follows: cigarettes, 13.3%; little cigars/cigarillos (LCCs), 11.2%; smokeless tobacco (SLT), 3.6%; e-cigarettes, 10.9%; hookah, 12.2%; alcohol, 63.1%; and marijuana, 19.0%. Five segments were identified, created, and named: Conventionals, Simple Lifes, Open Minds, Confident Novelty-seekers, and Stoic Individualists. Controlling for sociodemographics, Open Minds, Confident Novelty-seekers, and Stoic Individualists (vs. Conventionals [referent]) were more likely to smoke cigarettes. Confident Novelty-seekers were more likely to use LCCs. Simple Lifes were less likely to use SLT. Open Minds and Confident Novelty-seekers were more likely to use e-cigarettes. Open Minds were more likely and Simple Lifes were less likely to use hookah. Open Minds were more likely to use alcohol; Simple Lifes and Stoic Individualists were less likely to use alcohol. Open Minds were more likely to use marijuana. Market research is an effective strategy for identifying young adults at risk for using distinct ATPs and can inform targeted health campaigns and cessation interventions.
RESUMEN
INTRODUCTION: Perthes disease (PD) is an idiopathic disorder presenting with avascular necrosis to the femoral head, which frequently results in flattening. Long-term function is directly related to the subsequent femoral head sphericity. Current treatment includes mechanical modalities and surgical procedures, which are therapeutic but are not uniformly able to prevent collapse. The use of the nitrogen-containing bisphosphonate zoledronic acid (ZA) to inhibit osteoclastic bone resorption is aimed at preserving femoral head strength, reducing collapse and thus maintaining shape. The proposed multicentre, prospective, randomised controlled trial intends to evaluate the efficacy of ZA treatment in PD. METHODS AND ANALYSIS: An open-label randomised control trial recruiting 100 children (50 each treatment arm) 5 to 16 years old with unilateral PD. Subjects are randomly assigned to either (a) ZA and standard care or (b) Standard care. The primary outcome measure is deformity index (DI), a radiographic parameter of femoral head roundness assessed at 24 months, following 12 months of ZA treatment (3-monthly doses of ZA 0.025 mg/kg at baseline, 3, 6, 9 and 12 months) plus 12 months observation (group A) or 24 months of observation (group B). Secondary outcome measures are femoral head subluxation, Faces Pain scale, Harris hip score and quality of life. Assessments are made at baseline, 3 monthly during the first year of follow-up and then 6 monthly, until the 24th month. ETHICS AND DISSEMINATION: The study commenced following the written approval from the Human Research Ethics Committee. Safety considerations regarding the effects of ZA are monitored which include the subject's symptomatology, mineral status, bone mass and turnover activity, and metaphyseal modelling. Data handling plan requires that all documents, clinical information, biological samples and investigation results will be held in strict confidence by study investigators to preserve its safety and confidentiality. TRIAL REGISTRATION NUMBER: Australian and New Zealand Clinical Trials ACTRN12610000407099, pre-results.
RESUMEN
BACKGROUND: The use of a brace has been shown to be an effective treatment for hip dislocation in infants; however, previous studies of such treatment have been single-center or retrospective. The purpose of the current study was to evaluate the success rate for brace use in the treatment of infant hip dislocation in an international, multicenter, prospective cohort, and to identify the variables associated with brace failure. METHODS: All dislocations were verified with use of ultrasound or radiography prior to the initiation of treatment, and patients were followed prospectively for a minimum of 18 months. Successful treatment was defined as the use of a brace that resulted in a clinically and radiographically reduced hip, without surgical intervention. The Mann-Whitney test, chi-square analysis, and Fisher exact test were used to identify risk factors for brace failure. A multivariate logistic regression model was used to determine the probability of brace failure according to the risk factors identified. RESULTS: Brace treatment was successful in 162 (79%) of the 204 dislocated hips in this series. Six variables were found to be significant risk factors for failure: developing femoral nerve palsy during brace treatment (p = 0.001), treatment with a static brace (p < 0.001), an initially irreducible hip (p < 0.001), treatment initiated after the age of 7 weeks (p = 0.005), a right hip dislocation (p = 0.006), and a Graf-IV hip (p = 0.02). Hips with no risk factors had a 3% probability of failure, whereas hips with 4 or 5 risk factors had a 100% probability of failure. CONCLUSIONS: These data provide valuable information for patient families and their providers regarding the important variables that influence successful brace treatment for dislocated hips in infants. LEVEL OF EVIDENCE: Prognostic Level I. See Instructions for Authors for a complete description of levels of evidence.
Asunto(s)
Tirantes , Luxación Congénita de la Cadera/terapia , Articulación de la Cadera/diagnóstico por imagen , Femenino , Luxación Congénita de la Cadera/diagnóstico por imagen , Humanos , Lactante , Recién Nacido , Masculino , Pronóstico , Estudios Prospectivos , Radiografía , Insuficiencia del Tratamiento , Resultado del Tratamiento , UltrasonografíaRESUMEN
OBJECTIVES: To review evidence for the increased incidence of late diagnosed developmental dysplasia of the hip (DDH) in South Australia; to identify perinatal risk factors associated with late DDH in babies born between 2003 and 2009 in SA. DESIGN: Linkage study of data collected prospectively by the South Australian Birth Defects Register (SABDR) and the Pregnancy Outcome Statistics Unit (SA Department of Health), supplemented by medical records review. PARTICIPANTS: All children born 2003-2009 in whom DDH was diagnosed between 3 months and 5 years of age and notified to the SABDR (data inclusion range, 2003-2014). Children with teratological hip dislocations and other major congenital abnormalities were excluded. MAIN OUTCOME MEASURES: Uni- and multivariable analyses were performed to identify perinatal risk factors for late diagnosed DDH. RESULTS: The incidence of late diagnosed DDH in babies born 2003-2009 was 0.77 per 1000 live births, contrasting with the figure of 0.22 per 1000 live births during 1988-2003. Significant perinatal risk factors were birth in a rural hospital (v metropolitan public hospital: odds ratio [OR], 2.47; CI, 1.37-4.46; P = 0.003), and being the second child (v being the first-born: OR, 1.69; CI, 1.08-2.66; P = 0.023). Breech presentation was highly significant as a protective factor when compared with cephalic presentation (OR, 0.25; CI, 0.12-0.54; P < 0.001). CONCLUSIONS: The incidence of late DDH has increased in SA despite an ongoing clinical screening program. Increased awareness, education, and avoidance of inappropriate lower limb swaddling are necessary to reverse this trend.
Asunto(s)
Luxación Congénita de la Cadera/diagnóstico , Preescolar , Diagnóstico Tardío/estadística & datos numéricos , Femenino , Humanos , Lactante , Masculino , Estudios Prospectivos , Factores de Riesgo , Australia del SurRESUMEN
OBJECTIVES: We examined psychographic characteristics associated with tobacco use among Project DECOY participants. METHODS: Project DECOY is a 2-year longitudinal mixed-methods study examining risk for tobacco use among 3418 young adults across 7 Georgia colleges/universities. Baseline measures included sociodemographics, tobacco use, and psychographics using the Values, Attitudes, and Lifestyle Scale. Bivariate and multivariable analyses were conducted to identify correlates of tobacco use. RESULTS: Past 30-day use prevalence was: 13.3% cigarettes; 11.3% little cigars/cigarillos (LCCs); 3.6% smokeless tobacco; 10.9% e-cigarettes; and 12.2% hookah. Controlling for sociodemographics, correlates of cigarette use included greater novelty seeking (p < .001) and intellectual curiosity (p = .010) and less interest in tangible creation (p = .002) and social conservatism (p < .001). Correlates of LCC use included greater novelty seeking (p < .001) and greater fashion orientation (p = .007). Correlates of smokeless tobacco use included greater novelty seeking (p = .006) and less intellectual curiosity (p < .001). Correlates of e-cigarette use included greater novelty seeking (p < .001) and less social conservatism (p = .002). Correlates of hookah use included greater novelty seeking (p < .001), fashion orientation (p = .044), and self-focused thinking (p = .002), and less social conservatism (p < .001). CONCLUSIONS: Psychographic characteristics distinguish users of different tobacco products.
Asunto(s)
Personalidad , Uso de Tabaco/epidemiología , Uso de Tabaco/psicología , Adulto , Femenino , Georgia/epidemiología , Humanos , Estudios Longitudinales , Masculino , Prevalencia , Factores de Riesgo , Adulto JovenRESUMEN
Injured growth plate is often repaired by bony tissue causing bone growth defects, for which the mechanisms remain unclear. Because neurotrophins have been implicated in bone fracture repair, here we investigated their potential roles in growth plate bony repair in rats. After a drill-hole injury was made in the tibial growth plate and bone, increased injury site mRNA expression was observed for neurotrophins NGF, BDNF, NT-3, and NT-4 and their Trk receptors. NT-3 and its receptor TrkC showed the highest induction. NT-3 was localized to repairing cells, whereas TrkC was observed in stromal cells, osteoblasts, and blood vessel cells at the injury site. Moreover, systemic NT-3 immunoneutralization reduced bone volume at injury sites and also reduced vascularization at the injured growth plate, whereas recombinant NT-3 treatment promoted bony repair with elevated levels of mRNA for osteogenic markers and bone morphogenetic protein (BMP-2) and increased vascularization and mRNA for vascular endothelial growth factor (VEGF) and endothelial cell marker CD31 at the injured growth plate. When examined in vitro, NT-3 promoted osteogenesis in rat bone marrow stromal cells, induced Erk1/2 and Akt phosphorylation, and enhanced expression of BMPs (particularly BMP-2) and VEGF in the mineralizing cells. It also induced CD31 and VEGF mRNA in rat primary endothelial cell culture. BMP activity appears critical for NT-3 osteogenic effect in vitro because it can be almost completely abrogated by co-addition of the BMP inhibitor noggin. Consistent with its angiogenic effect in vivo, NT-3 promoted angiogenesis in metatarsal bone explants, an effect abolished by co-treatment with anti-VEGF. This study suggests that NT-3 may be an osteogenic and angiogenic factor upstream of BMP-2 and VEGF in bony repair, and further studies are required to investigate whether NT-3 may be a potential target for preventing growth plate faulty bony repair or for promoting bone fracture healing. © 2016 American Society for Bone and Mineral Research.
Asunto(s)
Proteína Morfogenética Ósea 2/metabolismo , Regeneración Ósea/fisiología , Cartílago/metabolismo , Placa de Crecimiento/metabolismo , Neurotrofina 3/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Animales , Sistema de Señalización de MAP Quinasas/fisiología , Masculino , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Osteogénesis/fisiología , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
Chemotherapy-induced bone damage is a frequent side effect which causes diminished bone mineral density and fracture in childhood cancer sufferers and survivors. The intensified use of anti-metabolite methotrexate (MTX) and other cytotoxic drugs has led to the need for a mechanistic understanding of chemotherapy-induced bone loss and for the development of protective treatments. Using a young rat MTX-induced bone loss model, we investigated potential bone protective effects of phytoestrogen genistein. Oral gavages of genistein (20 mg/kg) were administered daily, for seven days before, five days during, and three days after five once-daily injections (sc) of MTX (0.75 mg/kg). MTX treatment reduced body weight gain and tibial metaphyseal trabecular bone volume (p < 0.001), increased osteoclast density on the trabecular bone surface (p < 0.05), and increased the bone marrow adipocyte number in lower metaphyseal bone (p < 0.001). Genistein supplementation preserved body weight gain (p < 0.05) and inhibited ex vivo osteoclast formation of bone marrow cells from MTX-treated rats (p < 0.001). However, MTX-induced changes in bone volume, trabecular architecture, metaphyseal mRNA expression of pro-osteoclastogenic cytokines, and marrow adiposity were not significantly affected by the co-administration of genistein. This study suggests that genistein may suppress MTX-induced osteoclastogenesis; however, further studies are required to examine its potential in protecting against MTX chemotherapy-induced bone damage.
Asunto(s)
Antimetabolitos Antineoplásicos/efectos adversos , Resorción Ósea/inducido químicamente , Resorción Ósea/prevención & control , Huesos/efectos de los fármacos , Genisteína/uso terapéutico , Metotrexato/efectos adversos , Fitoestrógenos/uso terapéutico , Adipocitos/efectos de los fármacos , Adipocitos/patología , Animales , Peso Corporal/efectos de los fármacos , Densidad Ósea/efectos de los fármacos , Médula Ósea/efectos de los fármacos , Médula Ósea/patología , Resorción Ósea/genética , Resorción Ósea/patología , Huesos/metabolismo , Huesos/patología , Regulación de la Expresión Génica/efectos de los fármacos , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: We compared fruit and vegetable (FV) intake, physical activity (PA), and overweight/ obesity among Black and White females attending two- and four-year colleges. METHODS: We recruited 24,055 students at six colleges in the Southeast to complete an online survey, yielding 4840 responses (20.1% response rate). The current analyses focused on the 2276 Black and White females. RESULTS: Binary logistic regression analyses indicated that recommended FV intake among White females was associated with greater extraversion (Odds Ratio [OR] = 1.05, 95% Confidence Interval [CI] 1.00, 1.11, p = 0.05) and greater conscientiousness (OR = 1.08, CI 1.02, 1.14, p = 0.01), whereas among Black females correlates included greater openness to experience (OR = 1.08, CI 1.01, 1.15, p = 0.03). Ordinal logistic regression analyses indicated that, among White females, greater PA was associated with attending a four-year college (Beta = 0.27, CI 0.01, 0.53, p = 0.04), whereas among Black females, correlates were with younger age (Beta = 0.01, CI 0.17, 0.03, p = 0.003) and greater emotional stability (Beta = 0.07, CI 0.01, 0.13, p = 0.02). Binary logistic regression analyses indicated that, among White females, being overweight or obese was associated with older age (OR = 1.08, CI 1.01, 1.16, p = 0.03), attending a two-year college (OR = 1.62, CI 1.22, 2.16, p = 0.001), and lower satisfaction with life (OR = 0.96, CI 0.94, 0.98, p = 0.002), whereas among Black females, being overweight or obese was associated with older age (OR = 1.87, CI 1.10, 1.28, p < 0.001). CONCLUSIONS: Identifying factors related to obesity-related factors is critical in developing interventions targeting factors associated with overweight and obesity among Black and White females attending two- and four-year colleges. Moreover, understanding different college settings and the contextual factors associated with overweight/obesity is critical.
RESUMEN
OBJECTIVES: We examined correlates of 1) being a virgin; 2) drug or alcohol use prior to the last intercourse; and 3) condom use during the last intercourse in a sample of college students. METHODS: We recruited 24,055 students at six colleges in the Southeast to complete an online survey, yielding 4840 responses (20.1% response rate), with complete data from 4514. RESULTS: Logistic regression indicated that correlates of virginity included being younger (p < 0.001), male (p = 0.01), being White or other ethnicity (p < 0.001), attending a four-vs. two-year school (p < 0.001), being single/never married (p < 0.001), lower sensation seeking (p < 0.001), more regular religious service attendance (p < 0.001), lower likelihood of smoking (p < 0.001) and marijuana use (p = 0.002), and less frequentdrinking (p < 0.001). Correlates of alcohol or drug use prior to most recent intercourse including being older (p = 0.03), being White (p < 0.01), attending a four-year college (p < 0.001), being homosexual (p = 0.041) or bisexual (p = 0.011), having more lifetime sexual partners (p = 0.005), lower satisfaction with life (p = 0.004), greater likelihood of smoking (p < 0.001) and marijuana use (p < 0.001), and more frequent drinking (p < 0.001). Correlates of condom use during the last sexual intercourse including being older (p = 0.003), being female (p < 0.001), being White (p < 0.001), attending a two-year school (p = 0.04), being single/never married (p = 0.005), being homosexual or bisexual (p = 0.04), and a more frequent drinking (p = 0.001). CONCLUSIONS: Four-year college attendees were more likely to be a virgin but, if sexually active, reported higher sexual risk behaviors. These nuances regarding sexual risk may provide targets for sexual health promotion programs and interventions.
RESUMEN
Growth plate injuries often result in undesirable bony repair causing bone growth defects, for which the underlying mechanisms are unclear. Whilst the key importance of pro-angiogenic vascular endothelial growth factor (VEGF) is well-known in bone development and fracture repair, its role during growth plate bony repair remains unexplored. Using a rat tibial growth plate injury repair model with anti-VEGF antibody, Bevacizumab, as a single i.p. injection (2.5âmg/kg) after injury, this study examined the roles of VEGF-driven angiogenesis during growth plate bony repair. Histology analyses observed isolectin-B4-positive endothelial cells and blood vessel-like structures within the injury site on days 6 and 14, with anti-VEGF treatment significantly decreasing blood-vessel-like structures within the injury site (P<0.05). Compared with untreated controls, anti-VEGF treatment resulted in an increase in undifferentiated mesenchymal repair tissue, but decreased bony tissue at the injury site at day 14 (P<0.01). Consistently, microcomputed tomography analysis of the injury site showed significantly decreased bony repair tissue after treatment (P<0.01). RT-PCR analyses revealed a significant decrease in osteocalcin (P<0.01) and a decreasing trend in Runx2 expression at the injury site following treatment. Furthermore, growth plate injury-induced reduced tibial lengthening was more pronounced in anti-VEGF-treated injured rats on day 60, consistent with the observation of a significantly increased height of the hypertrophic zone adjacent to the growth plate injury site (P<0.05). These results indicate that VEGF is important for angiogenesis and formation of bony repair tissue at the growth plate injury site as well as for endochondral bone lengthening function of the uninjured growth plate.
Asunto(s)
Cartílago/irrigación sanguínea , Cartílago/metabolismo , Placa de Crecimiento/irrigación sanguínea , Placa de Crecimiento/metabolismo , Tibia/fisiopatología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Animales , Cartílago/lesiones , Cartílago/fisiopatología , Placa de Crecimiento/fisiopatología , Masculino , Neovascularización Patológica , Ratas , Ratas Sprague-Dawley , Fracturas de Salter-Harris , Tibia/irrigación sanguínea , Tibia/lesiones , Tibia/metabolismo , Cicatrización de HeridasRESUMEN
INTRODUCTION: Injured growth plate cartilage is often repaired by bony tissue, causing bone growth defects in children. Currently, mechanisms for the undesirable repair remain unclear and there are no biological treatments available to prevent the associated bone growth defects. Osterix is known as a vital transcription factor for osteoblast differentiation which is critical for normal bone formation and bone repair, and osterix is known to be regulated by protein kinase-D; however it is unknown whether protein kinase-D-osterix signalling plays any roles in the bony repair of injured growth plate. METHODS: Using a rat model, this study investigated potential roles of protein kinase-D (PKD) in regulating expression of osteogenic transcription factor osterix and the growth plate bony repair. 4 days post injury at the proximal tibial growth plate, rats received four once-daily injections of vehicle or 2.35 mg/kg gö6976 (a PKD inhibitor), and growth plate tissues collected at day 10 were examined histologically and molecularly. In addition, effects of PKD inhibition on osteogenic and chondrogenic differentiation were examined in vitro using rat bone marrow mesenchymal stromal cells. RESULTS: Compared to vehicle control, PKD inhibition caused a decrease in bone volume (p<0.05), an increase in % of mesenchymal tissue (p<0.01), and an increase in cartilaginous tissue within the injury site. Consistently, gö6976 treatment tended to decrease expression of bone-related genes (osterix, osteocalcin) and increase levels of cartilage-related genes (Sox9, collagen-2a, collagen-10a1). In support, in vitro experiments showed that gö6976 presence in the primary rat marrow stromal cell culture resulted in a decrease of alkaline phosphatase(+) CFU-f colonies formed (p<0.05) and an increase in collagen-2a expression in chondrogenic pellet culture (p<0.05). CONCLUSION: These studies suggest that PKD is important for growth plate bony repair and its inhibition after growth plate injury may result in less bone formation and potentially more cartilage repair.