Idiopathic Slipped Capital Femoral Epiphysis: Demographic Differences and Similarities between Stable, Unstable, and Valgus Types.

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.

Minced muscle autografting improves bone healing but not muscle function in a porcine composite injury model.

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.

Slipped Capital Femoral Epiphysis, Food Deserts, Poverty, and Urban/Rural Residence: Is There a Link?

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.

Slipped Capital Femoral Epiphysis Associated With Athletic Activity.

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.

The demographics of talipes equinovarus in Indiana, with a particular emphasis on comparisons between clubfoot types.

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.

Association of Socioeconomic Status With Relapse After Ponseti Method Treatment of Idiopathic Clubfeet.

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.

Do Patient Demographics and Socioeconomic Status Influence Severity and Time to Diagnosis in Children With Stable Slipped Capital Femoral Epiphysis?

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.

The Effects of SRT1720 Treatment on Endothelial Cells Derived from the Lung and Bone Marrow of Young and Aged, Male and Female Mice.

Angiogenesis is critical for successful fracture healing. Age-related alterations in endothelial cells (ECs) may cause impaired bone healing. Therefore, examining therapeutic treatments to improve angiogenesis in aging may enhance bone healing. Sirtuin 1 (SIRT1) is highly expressed in ECs and its activation is known to counteract aging. Here, we examined the effects of SRT1720 treatment (SIRT1 activator) on the growth and function of bone marrow and lung ECs (BMECs and LECs, respectively), derived from young (3-4 month) and old (20-24 month) mice. While aging did not alter EC proliferation, treatment with SRT1720 significantly increased proliferation of all LECs. However, SRT1720 only increased proliferation of old female BMECs. Vessel-like tube assays showed similar vessel-like structures between young and old LECs and BMECs from both male and female mice. SRT1720 significantly improved vessel-like structures in all LECs. No age, sex, or treatment differences were found in migration related parameters of LECs. In males, old BMECs had greater migration rates than young BMECs, whereas in females, old BMECs had lower migration rates than young BMECs. Collectively, our data suggest that treatment with SRT1720 appears to enhance the angiogenic potential of LECs irrespective of age or sex. However, its role in BMECs is sex- and age-dependent.

The effects of bone morphogenetic protein 2 and thrombopoietin treatment on angiogenic properties of endothelial cells derived from the lung and bone marrow of young and aged, male and female mice.

With an aging world population, there is an increased risk of fracture and impaired healing. One contributing factor may be aging-associated decreases in vascular function; thus, enhancing angiogenesis could improve fracture healing. Both bone morphogenetic protein 2 (BMP-2) and thrombopoietin (TPO) have pro-angiogenic effects. The aim of this study was to investigate the effects of treatment with BMP-2 or TPO on the in vitro angiogenic and proliferative potential of endothelial cells (ECs) isolated from lungs (LECs) or bone marrow (BMECs) of young (3-4 months) and old (22-24 months), male and female, C57BL/6J mice. Cell proliferation, vessel-like structure formation, migration, and gene expression were used to evaluate angiogenic properties. In vitro characterization of ECs generally showed impaired vessel-like structure formation and proliferation in old ECs compared to young ECs, but improved migration characteristics in old BMECs. Differential sex-based angiogenic responses were observed, especially with respect to drug treatments and gene expression. Importantly, these studies suggest that NTN1, ROBO2, and SLIT3, along with angiogenic markers (CD31, FLT-1, ANGPT1, and ANGP2) differentially regulate EC proliferation and functional outcomes based on treatment, sex, and age. Furthermore, treatment of old ECs with TPO typically improved vessel-like structure parameters, but impaired migration. Thus, TPO may serve as an alternative treatment to BMP-2 for fracture healing in aging owing to improved angiogenesis and fracture healing, and the lack of side effects associated with BMP-2.

The effects of high fat diet, bone healing, and BMP-2 treatment on endothelial cell growth and function.

Angiogenesis is a vital process during the regeneration of bone tissue. The aim of this study was to investigate angiogenesis at the fracture site as well as at distal locations from obesity-induced type 2 diabetic mice that were treated with bone morphogenetic protein-2 (BMP-2, local administration at the time of surgery) to heal a femoral critical sized defect (CSD) or saline as a control. Mice were fed a high fat diet (HFD) to induce a type 2 diabetic-like phenotype while low fat diet (LFD) animals served as controls. Endothelial cells (ECs) were isolated from the lungs (LECs) and bone marrow (BMECs) 3 weeks post-surgery, and the fractured femurs were also examined. Our studies demonstrate that local administration of BMP-2 at the fracture site in a CSD model results in complete bone healing within 3 weeks for all HFD mice and 66.7% of LFD mice, whereas those treated with saline remain unhealed. At the fracture site, vessel parameters and adipocyte numbers were significantly increased in BMP-2 treated femurs, irrespective of diet. At distal sites, LEC and BMEC proliferation was not altered by diet or BMP-2 treatment. HFD increased the tube formation ability of both LECs and BMECs. Interestingly, BMP-2 treatment at the time of surgery reduced tube formation in LECs and humeri BMECs. However, migration of BMECs from HFD mice treated with BMP-2 was increased compared to BMECs from HFD mice treated with saline. BMP-2 treatment significantly increased the expression of CD31, FLT-1, and ANGPT2 in LECs and BMECs in LFD mice, but reduced the expression of these same genes in HFD mice. To date, this is the first study that depicts the systemic influence of fracture surgery and local BMP-2 treatment on the proliferation and angiogenic potential of ECs derived from the bone marrow and lungs.

No pain, no gain? The effects of pain-promoting neuropeptides and neurotrophins on fracture healing.

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.