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1.
J Arthroplasty ; 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38336307

RESUMO

BACKGROUND: Leaving the patella unresurfaced in total knee arthroplasty (TKA) has increased significantly over the past decade in the United States, likely due to modern patella-friendly implants, complications with resurfacing, and the knowledge that historical studies were scientifically confounded. This study evaluated revision-free survivorship out to 8.5 years in a cohort of contemporary primary TKAs with patella-friendly femoral components and unresurfaced patellae. METHODS: A total of 1,053 consecutive primary TKAs with unresurfaced patellae were retrospectively reviewed. A selective patellar nonresurfacing protocol was used for all cases. Kaplan-Meier survivorship estimates were calculated based on patellar revision and the latest follow-up. An aggressive lateral patellar facetectomy was performed in 78% (823 of 1,053) of cases. The cohort was 62% women and 43% American Society of Anesthesiologists physical status classification I or II with a mean age and body mass index of 65 years (range, 35 to 94) and 35 kg/m2 (range, 18 to 65), respectively. RESULTS: A total of 4 (0.4%, 4 of 1,053) unresurfaced patellae were revised. Three were resurfaced as part of other procedures: 2 for global instability and one for aseptic loosening at a mean of 1.6 years; and one patella was resurfaced by an outside surgeon for unexplained pain. The all-cause revision-free survivorship estimate specifically related to the patella was 98.9% (95% confidence interval, 98 to 100) out to 8.5 years. No significant difference in survivorship was related to patellae with or without a lateral patellar facetectomy (99.5 versus 98.1%, P ≥ .191); however, 3 of 4 patellar revisions occurred in TKAs without a lateral patellar facetectomy (P = .035). CONCLUSIONS: The results of this study demonstrate excellent revision-free survivorship related to unresurfaced patellae, particularly when a lateral facetectomy was performed. These early to midterm results using modern patella-friendly femoral components are promising and comparable to resurfaced patellae in the literature. LEVEL OF EVIDENCE: IV.

2.
Children (Basel) ; 10(9)2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37761517

RESUMO

Idiopathic slipped capital femoral epiphysis (SCFE) is a known disorder in pre/adolescent children with vague hip/knee pain. We wished to study the demographic differences between stable varus, unstable varus, and valgus idiopathic SCFEs using a retrospective review over a 10-year period of SCFE children seen at a tertiary children's hospital. Standard demographic data was collected, and radiographs were measured to determine the Southwick angle and status of the tri-radiate cartilage. There were 190 patients; 138 had stable varus SCFEs, 45 unstable varus SCFEs, and 7 valgus SCFEs. All unstable SCFEs were varus, and all valgus SCFEs were stable. There were significant differences between the three groups by age at diagnosis, sex, race, SCFE severity, weight percentile, and duration of symptoms. The average age at diagnosis was 11.0 ± 1.2, 11.8 ± 1.8, and 12.3 ± 1.7 years for the valgus, unstable varus, and stable varus groups (p = 0.019), and similarly, SCFE severity was 25° ± 15°, 48° ± 18°, and 35° ± 19° (p = 0.0002) for the three same groups. Patients with valgus SCFEs were mostly female (86%) compared to the stable varus (39.9%) and unstable (47%) groups (p = 0.05) and mostly non-White (86%) (0.011). The duration of symptoms was 4.1 ± 4.1, 2.3 ± 5.0, and 4.5 ± 5.0 months for the valgus, unstable varus, and stable varus groups (p = 0.00005). These three types of idiopathic SCFEs demonstrated differences by age at diagnosis, sex, race, weight percentile, and duration of symptoms.

3.
J Orthop Res ; 41(9): 1890-1901, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36924069

RESUMO

Composite tissue injuries (CTIs) in extremities include segmental bone defects (SBDs) and volumetric muscle loss. The objective of this study was to determine if skeletal muscle autografting with minced muscle grafts (MMGs) could improve healing in an SBD and improve muscle function in a porcine CTI model that includes an SBD and adjacent volumetric muscle loss injury. Adult Yucatan Minipigs were stratified into three groups including specimens with an isolated SBD, an SBD with volumetric muscle loss (CTI), and an SBD with volumetric muscle loss treated with MMG (CTI + MMG). Bone healing was quantified with serial x-rays and postmortem computed tomography scanning. Muscle function was quantified with a custom in vivo force transducer. Muscle tissue content was determined by biochemical analyses and histology. Anterior cortex-modified Radiographic Union Score for Tibia fractures (mRUSTs) decreased from 2.7 to 1.9 (p = 0.003) in CTI versus SBD animals. MMG improved anterior mRUST scores to 2.5 in CTI + MMG specimens (p = 0.030 compared to CTI specimens) and overall mRUST scores increased from 9.4 in CTI specimens to 11.1 in CTI + MMG specimens (p = 0.049). Residual strength deficits at euthanasia were 42% in SBD (p < 0.001), 44% in CTI (p < 0.001), and 48% in CTI + MMG (p < 0.001) compared to preoperative values. There were no differences in strength deficits between the three groups. Biochemical and histologic analyses demonstrated scattered differences between the three groups compared to contralateral muscle. MMG improved bone healing. However, the primary cause of muscle dysfunction and biochemical changes was the presence of an SBD. Clinical significance: Early mitigation of SBDs may be necessary to prevent muscle damage and weakness in patients sustaining composite extremity trauma.


Assuntos
Músculo Esquelético , Fraturas da Tíbia , Animais , Suínos , Transplante Autólogo , Porco Miniatura , Músculo Esquelético/fisiologia , Fraturas da Tíbia/patologia , Força Muscular , Consolidação da Fratura
4.
J Pediatr Orthop ; 43(3): e230-e235, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36730127

RESUMO

BACKGROUND: Childhood obesity is increased in food deserts, a community with little to no access to healthy food. As obesity is associated with slipped capital femoral epiphysis (SCFE), it was the purpose of this study to analyze the prevalence of SCFE patients by food desert location and its interaction with rural/urban location. METHODS: A retrospective review of all consecutive patients with idiopathic SCFE treated at our institution over 11 years was performed. From the patient's address, the US Census Bureau tract in which the patient resided was determined. Using the census tract code, it was ascertained if the patient lived in a food desert and urban or rural location. Standard statistical analyses were performed; a P <0.05 was considered statistically significant. RESULTS: There were 177 SCFE patients: 79 girls, 98 boys, 106, White, and 69 nonWhite. The average age at diagnosis was 12.1±1.7 years, the average symptom duration 4.1±5.1 months, and the average weight percentile 94±10. Of these 177 patients, 26.5% lived in a food desert, which was higher than the expected 17.5% ( P =0.023). Those living in a food desert were more commonly nonWhite (60% vs. 32%, P =0.0014). There were 25% from rural areas and 75% from urban areas. No rural SCFE patients lived in food deserts whereas 34% of urban patients lived in food deserts. The average poverty rate of the SCFE patient census tracts was 19%, no greater than the expected 15% ( P =0.32). SCFE patients living in rural census tracts had a lower poverty rate ( P <10 -6 ). CONCLUSIONS: There is a correlation with the prevalence of SCFE patients by residence in a "food desert", but not with rural/urban locale or poverty status in Indiana. Further research will be needed to see if these findings apply to other states within the United States and other parts of the world. LEVEL OF EVIDENCE: III.


Assuntos
Obesidade Infantil , Escorregamento das Epífises Proximais do Fêmur , Masculino , Feminino , Humanos , Criança , Estados Unidos , Escorregamento das Epífises Proximais do Fêmur/diagnóstico , População Rural , Fatores de Risco , Estudos Retrospectivos
5.
Sports Health ; 15(3): 422-426, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-35502132

RESUMO

BACKGROUND: Little data exist regarding the association of slipped capital femoral epiphysis (SCFE) and sporting activities. HYPOTHESIS: There is no association between SCFE and sporting activities. STUDY DESIGN: Retrospective review of all SCFE cases at our institution from 2010 through March 2021. LEVEL OF EVIDENCE: Level 3. METHODS: All patients with idiopathic SCFE were reviewed looking for the presence/absence of sporting activities and symptom onset. Also collected were the age, symptom duration, and weight/height of the patient, sex, race, and stable/unstable nature of the SCFE. The severity of the SCFE was measured using the lateral epiphyseal-shaft angle. RESULTS: There were 193 children (110 boys, 83 girls) with idiopathic SCFEs. The SCFE was stable in 147, unstable in 45, and unknown in 1. The average age was 12.1 ± 1.8 years, average SCFE angle 38° ± 20° and symptom duration 4.0 ± 5.1 months. An association with a sporting activity was present in 64 (33%). The sporting activity was basketball (18), football (11), baseball/softball (10), and others (23). Football, basketball, and soccer predominated in boys, baseball and running sports were equal between boys and girls, and cheerleading/gymnastics/dancing predominated in girls. Differences showed that those involved in sports had a slightly lower body mass index (BMI) (88th percentile vs 95th percentile, P = 0.00). There were no differences between those involved and those not those involved in sporting activities for symptom duration, SCFE severity, sex, race, or stable/unstable SCFE type. CONCLUSION: Sporting activities are associated with the onset of symptoms in 1 of 3 of patients with SCFE, refuting the null hypothesis. CLINICAL RELEVANCE: A high level of suspicion for SCFE should be given when any peripubertal athlete presents with hip or knee pain regardless of BMI/obesity status, and appropriate imaging performed.


Assuntos
Escorregamento das Epífises Proximais do Fêmur , Esportes , Masculino , Feminino , Criança , Humanos , Adolescente , Escorregamento das Epífises Proximais do Fêmur/complicações , Escorregamento das Epífises Proximais do Fêmur/diagnóstico , Estudos Retrospectivos , Índice de Massa Corporal
6.
J Pediatr Orthop B ; 32(1): 8-14, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35635534

RESUMO

Talipes equinovarus (TEV) can be an isolated idiopathic deformity or associated with various syndromes. The purpose of our study was to examine the demographics of TEV in Indiana. All TEV patients from 2010 to 2019 from our institution were reviewed, recording standard demographic variables. The socioeconomic level of the family was determined using the 2018 Area Deprivation Index (ADI). There were 568 patients; 456 had idiopathic TEV and 112 syndromic. Within the idiopathic group, 69.1% were male, 92.1% were typical and 7.9% were atypical. Medical issues during the pregnancy occurred in 19.5%, maternal smoking in 2.9%, hypertension in 3.9% and diabetes in 5.3%. The most common syndromic patients were myelomeningocele (29%) and arthrogryposis (17%). Patients with syndromic TEV had more bilateral involvement (68.2% vs. 45.2%) and other associated congenital deformities (67.0% vs. 11.4%). TEV was less common in Hispanics and Asians but more common in Whites and Blacks ( P = 0.003). Complex TEVs were less frequent in White (6.9%) and Black (5.0%) and more common in Hispanic (30%) children ( P = 0.0002). The ADI demonstrated no difference in prevalence across socioeconomic levels. There were no differences by state ADI levels for TEV type (syndromic/idiopathic), sex, maternal smoking or illicit drug use, or typical/complex TEV. This study is the first to describe the demographics of TEV in Indiana, demographic differences between typical and complex types of clubfeet, and TEV patients using the ADI. TEV did not show any difference in prevalence by socioeconomic level.


Assuntos
Pé Torto Equinovaro , Família , Criança , Feminino , Humanos , Masculino
7.
Foot Ankle Orthop ; 7(3): 24730114221119180, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36046551

RESUMO

Background: The Ponseti method is today's standard treatment of idiopathic talipes equinovarus (ITEV). Compliance with foot abduction bracing (FABO) and socioeconomic factors have been shown to impact treatment outcome. We wished to further study socioeconomic factors using the Area Deprivation Index (ADI), a more comprehensive way to evaluate socioeconomic status, which has not been done before. Methods: All TEV patients from 2010 through 2019 treated with the Ponseti method were reviewed. Standard demographic variables, as well as the number of casts to complete initial correction, FABO compliance, and occurrence of relapse were tabulated. Socioeconomic level was quantified with the 2018 ADI. Results: There were 168 children; 151 had typical and 17 complex TEV. Average follow-up was 4.3 ± 1.8 years; relapse occurred in 46%. There were no significant differences in the percentage of relapse by sex, race, or ADI. FABO noncompliance was present in 46%. Relapse increased with increasing time of follow-up and FABO noncompliance (76% vs 21%, P < 10-6). Multivariate logistic regression analysis revealed that only FABO compliance and length of follow-up were associated with relapse. The OR of relapse for FABO noncompliance was 17.9 (7.6, 42.4, P < 10-6) and for follow-up >4 years the OR was 4.97 (2.1, 11.70, P = .0003). Conclusion: The outcome of the Ponseti method for TEV treatment is dependent on local circumstances. In our state, socioeconomic status, as determined by the ADI, was not associated with the occurrence of relapse. Thus, each center needs to assess its results, and analyze its own reasons for relapse. There were no other demographic variables associated with relapse except FABO compliance and length of follow-up. Parents should be strongly advised that FABO compliance and follow-up appears paramount to achieving the best results, and that complex TEV are at greater risk for relapse. Level of Evidence: Level IV, case series.

8.
J Pediatr Orthop ; 42(4): e324-e330, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35132014

RESUMO

BACKGROUND: The time to diagnosis in stable slipped capital femoral epiphysis (SCFE) is often several months because of nebulous history, symptoms of knee/thigh pain, and Medicaid insurance. This study examined the impact of socioeconomic status and demographics on the time to diagnosis and SCFE severity in Indiana children. METHODS: A retrospective review of all patients at a tertiary children's hospital with SCFE from January 2010 through March 2021 was performed. Standard demographic data and type of insurance was collected. Neighborhood Atlas Mapping was used to determine the state decile of the area deprivation index (ADI), a measure of socioeconomic status using 17 variables related to income, employment, education, and housing. Statistical analyses consisted of standard univariate and bivariate analyses; logistic regression analysis was used to determine predictors of a mild SCFE. A P<0.05 was considered statistically significant. RESULTS: There were 142 patients; 81 male and 61 female. The average age was 12.2±1.7 years, lateral epiphyseal shaft angle of 35±19 degrees, and symptom duration of 4.5±5.0 months. There was no correlation between ADI state deciles and lateral epiphyseal shaft angle (r2=0.008) or symptom duration (r2=0.019). Insurance status and race differed by ADI deciles. In the first decile (least disadvantaged), 44% had government insurance and 89% were White; in the 10th decile (most disadvantaged), 95% had government insurance and 38% were White. Predictors of a mild SCFE were female sex [odds ratio (OR): 3.2 [1.5, 7.0]; P=0.004], symptom duration <3 months [OR: 5.3 (2.4, 11.7); P=0.00004], and White race [OR: 2.4 (1.3, 6.2); P=0.01]. Insurance status and ADI were not significant. CONCLUSIONS: Contrary to other studies, neither insurance or socioeconomic status were associated with a delay in diagnosis or SCFE severity. The symptom duration in children with SCFE does not appear to be decreasing over the last several decades. Further investigation is required as to why. LEVEL OF EVIDENCE: Level III-retrospective comparative study.


Assuntos
Escorregamento das Epífises Proximais do Fêmur , Adolescente , Criança , Demografia , Epífises , Feminino , Humanos , Masculino , Estudos Retrospectivos , Escorregamento das Epífises Proximais do Fêmur/diagnóstico , Escorregamento das Epífises Proximais do Fêmur/epidemiologia , Classe Social
9.
Data Brief ; 37: 107244, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34258338

RESUMO

In this article we report data collected to evaluate the pathomechanistic effect of acute anaerobic metabolism in the polytraumatized patient and its subsequent effect on fracture nonunion; see "Base Deficit ≥6 within 24 Hours of Injury is a Risk Factor for Fracture Nonunion in the Polytraumatized Patient" (Sardesai et al., 2021) [1]. Data was collected on patients age ≥16 with an Injury Severity Score (ISS) >16 that presented between 2013-2018 who sustained a fracture of the tibia or femur distal to the femoral neck. Patients presenting to our institution greater than 24 hours post-injury and those with less than three months follow-up were excluded. Medical charts were reviewed to collect patient demographic information and known nonunion risk-factors, including smoking, alcohol use, and diabetes. In addition, detailed injury characteristics to quantify injury magnitude including ISS, Glasgow Coma Scale (GCS) at admission, and ICU length of stay were recorded. ISS values were obtained from our institutional trauma database where they are entered by individuals trained in ISS calculations. Associated fracture-related features including fracture location, soft-tissue injury (open vs. closed fracture), vascular injury, and compartment syndrome were recorded. Finally, vital signs, base deficit (BD), and blood transfusions over 24 hours from admission were recorded. We routinely measure BD and less consistently measure serum lactate in trauma patients at the time of presentation or during resuscitation. BD values are automatically produced by our laboratory with any arterial blood gas order, and we recorded BD values from the medical record. Clinical notes and radiographs were reviewed to confirm fracture union versus nonunion and assess for deep infection at the fracture site. Patients were categorized as having a deep infection if they were treated operatively for the infection prior to fracture healing or classification as a nonunion. Nonunion was defined by failure of progressive healing on sequential radiographs and/or surgical treatment for nonunion repair at least six months post-injury.

10.
ScientificWorldJournal ; 2021: 5548481, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33994881

RESUMO

Publication and authorship are important in academia for career advancement, obtaining grants, and improved patient care. There has been a recent interest in bibliometric changes over time, especially regarding the gender gap. The purpose of this study was to explore bibliometric changes in the musculoskeletal literature. Bibliometric variables (number of authors, institutions, countries, pages, references, corresponding author position, author gender, geographic region of origin, and editorial board makeup) were analyzed for 5 basic science and 12 clinically oriented musculoskeletal journals from 1985 through 2016. Statistical analyses comprised bivariate analyses, multifactorial ANOVAs, and logistic regression analyses. A p < 0.005 was considered significant. Nearly, all variables increased over time. Asia had the highest number of authors and corresponding author positions, Australia/New Zealand the highest number of institutions and references, North America the highest number of pages, and Europe the highest number of countries. Those with a female first author had more authors, institutions, countries, references, and pages. Likewise, those with a female corresponding author had more authors, institutions, countries, references, and pages. Single-authored manuscripts decreased over time. The percentage of female first authors rose from 10.8% in 1985-1987 to 23.7% in 2015-2016. There were more female 1st authors in the basic science journals compared to the clinical journals (33.2% vs. 12.7%). Single-authored manuscripts were more likely to be written by males (5.1 vs. 2.4%) and decreased over time. The many differences by geographic region of origin likely reflect different socio/cultural attitudes regarding academia and research, as well as the gender composition of the disciplines by geographic region. Overall, there has been an increase in the number of female 1st and corresponding authors, editorial board members, and chief editors, indicating a slow but progressive narrowing of the gender gap.


Assuntos
Autoria , Bibliometria , Papel de Gênero , Doenças Musculoesqueléticas/fisiopatologia , Publicações Periódicas como Assunto/tendências , Análise de Variância , Ásia , Austrália , Pesquisa Biomédica/ética , Pesquisa Biomédica/organização & administração , Europa (Continente) , Feminino , Humanos , Masculino , Doenças Musculoesqueléticas/cirurgia , Doenças Musculoesqueléticas/terapia , Nova Zelândia , América do Norte , Fatores Sexuais
11.
Injury ; 52(11): 3271-3276, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34053772

RESUMO

BACKGROUND: Polytrauma patients are at risk for fracture nonunion, but the reasons are poorly understood. Increased base deficit (BD) is associated with hypovolemic shock. Although shock delays bone healing in animal models, there have been no clinical studies evaluating the impact of BD on nonunion risk. MATERIALS AND METHODS: Patients age ≥ 16 with injury severity score > 16 that presented to an academic Level One trauma center with an operative femur or tibia fracture were reviewed. Clinical notes and radiographs were assessed to determine fracture healing status. Patient demographics, injury characteristics, BD, and number of packed red blood cell transfusions were recorded. Bivariate and multivariate analyses of multiple risk factors associated with nonunion were conducted to investigate the association of BD with nonunion. RESULTS: The union group was comprised of 243 fractures; there were 36 fractures in the nonunion group. The following predictors were associated with nonunion: smoking (p = 0.009), alcohol use (p < 0.001), open fracture (p < 0.001), and treatment for deep infection at fracture site (p = 0.016). Additionally, worst BD over 24 h ≥ 6 (p = 0.031) was significant for nonunion development. A multivariate logistic regression analysis revealed worst BD ≥6 over 24 h remained significantly associated with the development of nonunion (odds ratio 3.02, p = 0.011) when adjusting for other risk factors. CONCLUSIONS: A BD ≥ 6 within 24 h of admission was associated with a significantly increased risk of developing lower extremity fracture nonunion in polytrauma patients, even after adjusting for multiple other risk factors. Acute post-traumatic acidosis may have effects on long-term fracture healing.


Assuntos
Fraturas não Consolidadas , Fraturas da Tíbia , Consolidação da Fratura , Fraturas não Consolidadas/diagnóstico por imagem , Humanos , Estudos Retrospectivos , Fatores de Risco , Fraturas da Tíbia/complicações , Fraturas da Tíbia/diagnóstico por imagem , Fraturas da Tíbia/cirurgia , Resultado do Tratamento
12.
Ann Med Surg (Lond) ; 55: 200-206, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32518641

RESUMO

BACKGROUND: The purpose of this study was to better understand the authorship publishing trends in the field of hand surgery. To accomplish this, a comparative analysis was completed between the European and American volumes of the Journal of Hand Surgery (JHSE and JHSA) over the past three decades. Well-established bibliometric methods were used to examine one representative year from each of the past three decades. The focus of the study was to examine changes in author gender over time as well as to compare authorship trends across the two volumes. MATERIALS AND METHODS: All JHSA and JHSE publications from 1985, 1995, 2005, and 2015 were placed into a Microsoft Excel spreadsheet. Data was collected for each publication including the gender of first and corresponding authors, corresponding author position, corresponding author country of origin, number of credited institutions, authors, printed pages, and references. Countries were grouped by regions. RESULTS: A total of 450 and 763 manuscripts from JHSE and JHSA, respectively, met inclusion criteria. JHSE and JHSA both showed increases in most variables analyzed over time. Both journals showed an increase in female first and corresponding authors. JHSE and JHSA displayed a rise in collaboration between institutions and countries. CONCLUSIONS: Both JHSE and JHSA display increasing female inclusion in the hand surgery literature, which has traditionally been a male dominated field. The observed increase in collaboration between institutions and countries is likely linked to advances in technology that allow sharing of information more conveniently and reliably than was previously possible. As further advances are made socially and technologically, hopefully these trends will continue, leading to faster and higher quality research being generated in the field of hand surgery.

13.
Injury ; 51(7): 1439-1447, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32362447

RESUMO

Complications related to treatment of long bone fractures still stand as a major challenge for orthopaedic surgeons. Elucidation of the mechanisms of bone healing and development, and the subsequent alteration of these mechanisms to improve outcomes, typically requires animal models as an intermediary between in vitro and human clinical studies. Murine models are some of the most commonly used in translational research, and mouse fracture models are particularly diverse, offering a wide variety of customization with distinct benefits and limitations depending on the study. This review critically examines three common femur fracture models in the mouse, namely cortical hole, 3-point fracture (Einhorn), and segmental bone defect. We lay out the general procedure for execution of each model, evaluate the practical implications and important advantages/disadvantages of each and describe recent innovations. Furthermore, we explore the applications that each model is best adapted for in the context of the current state of murine orthopaedic research.


Assuntos
Modelos Animais de Doenças , Fraturas do Fêmur/fisiopatologia , Fraturas do Fêmur/cirurgia , Consolidação da Fratura/fisiologia , Animais , Camundongos
14.
Bone ; 131: 115109, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31715336

RESUMO

Neuropeptides and neurotrophins are key regulators of peripheral nociceptive nerves and contribute to the induction, sensitization, and maintenance of pain. It is now known that these peptides also regulate non-neuronal tissues, including bone. Here, we review the effects of numerous neuropeptides and neurotrophins on fracture healing. The neuropeptides calcitonin-gene related peptide (CGRP), substance P (SP), vasoactive intestinal peptide (VIP), and pituitary adenylate cyclase-activating peptide (PACAP) have varying effects on osteoclastic and osteoblastic activity. Ultimately, CGRP and SP both accelerate fracture healing, while VIP and PACAP seem to negatively impact healing. Unlike the aforementioned neuropeptides, the neurotrophins nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) have more uniform effects. Both factors upregulate osteoblastic activity, osteoclastic activity, and, in vivo, stimulate osteogenesis to promote fracture healing. Future research will need to clarify the exact mechanism by which the neuropeptides and neurotrophins influence fracture healing. Specifically, understanding the optimal expression patterns for these proteins in the fracture healing process may lead to therapies that can maximize their bone-healing capabilities and minimize their pain-promoting effects. Finally, further examination of protein-sequestering antibodies and/or small molecule agonists and antagonists may lead to new therapies that can decrease the rate of delayed union/nonunion outcomes and fracture-associated pain.


Assuntos
Consolidação da Fratura , Fatores de Crescimento Neural , Humanos , Dor , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Peptídeo Intestinal Vasoativo
15.
World J Stem Cells ; 11(6): 281-296, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31293713

RESUMO

Successful fracture healing requires the simultaneous regeneration of both the bone and vasculature; mesenchymal stem cells (MSCs) are directed to replace the bone tissue, while endothelial progenitor cells (EPCs) form the new vasculature that supplies blood to the fracture site. In the elderly, the healing process is slowed, partly due to decreased regenerative function of these stem and progenitor cells. MSCs from older individuals are impaired with regard to cell number, proliferative capacity, ability to migrate, and osteochondrogenic differentiation potential. The proliferation, migration and function of EPCs are also compromised with advanced age. Although the reasons for cellular dysfunction with age are complex and multidimensional, reduced expression of growth factors, accumulation of oxidative damage from reactive oxygen species, and altered signaling of the Sirtuin-1 pathway are contributing factors to aging at the cellular level of both MSCs and EPCs. Because of these geriatric-specific issues, effective treatment for fracture repair may require new therapeutic techniques to restore cellular function. Some suggested directions for potential treatments include cellular therapies, pharmacological agents, treatments targeting age-related molecular mechanisms, and physical therapeutics. Advanced age is the primary risk factor for a fracture, due to the low bone mass and inferior bone quality associated with aging; a better understanding of the dysfunctional behavior of the aging cell will provide a foundation for new treatments to decrease healing time and reduce the development of complications during the extended recovery from fracture healing in the elderly.

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