Femoral Growth Plate Research Articles

Anterior cruciate ligament reconstruction in adolescents (Tanner stages 2 and 3).

Management of anterior cruciate ligament injuries in skeletally immature patients (in Tanner stages 2 and 3) is controversial. Conventional reconstruction used in adults can cause iatrogenic growth disturbance due to physeal damage, and studies that report long-term results using a specific technique are scarce. The aim of this study is to evaluate in a large series the mid- and long-term results of a partial transphyseal technique and define the safe percentage of lesions of the femoral growth plate. Between 1989 and 2012, 42 adolescents at risk of growth disturbances (growth prediction of lower limbs >5 cm-Tanner 2, 3) underwent reconstruction of the anterior cruciate ligament using the semitendinosus and gracilis tendons. Growth characteristics of all the patients were assessed preoperatively, and the percentage of damage that would be produced in the femoral physis by the drilling of a 6-mm-diameter tunnel was determined. The technique used achieved graft fixation at both insertion sites, drilling the femoral physis and avoiding the tibial physis. We distinguished two groups: (a) long-term follow-up (mean 13 years 7 months, min 10.9, max 16.2) and (b) medium follow-up (mean 6 years 3 months, min 3.7, max 9.9). All knees were evaluated subjectively by history and objectively by KT2000 testing, and X-rays of both knees were compared for osteoarthritis using the Kellgren-Lawrence classification. In group A (12 patients) one osteoarthritis grade 2, one instability, and ten good stability and function were observed. The mean KT2000 arthrometer values at 30 lb showed a difference of +2.4 mm (range 1-4 mm) between the operated and non-operated sides (p < 0.05). In group B (21 patients) no growth disturbance of the lower limbs, two failures (reinjury while participating in pivoting sports), and 19 good stability and function were observed. The mean KT2000 arthrometer values at 30 lb showed a difference of +1.9 mm (range 1-5 mm) between the operated and non-operated sides (p < 0.05). The average IKDC score of all the patients was 90 (min: 68, max: 97). None of the adolescents had consequences on growth after an eccentric damage passing tendons less than 7% on the frontal plane and of 1% on cross-sectional area of the femoral physis, and after an oblique tunnel passing 6-mm-diameter tendons of the tibial epiphyseal nucleus. This study defines the possibility to perform a partial transphyseal intra-articular ACL reconstruction in patients in Tanner stages 2 and 3 that avoids tibial physis, involves the distal femoral physis, and produces good results at mid- and long-term follow-up without causing growth disturbances. IV.

Genetically engineered flavonol enriched tomato fruit modulates chondrogenesis to increase bone length in growing animals.

Externally visible body and longitudinal bone growth is a result of proliferation of chondrocytes. In growth disorder, there is delay in the age associated increase in height. The present study evaluates the effect of extract from transgenic tomato fruit expressing AtMYB12 transcription factor on bone health including longitudinal growth. Constitutive expression of AtMYB12 in tomato led to a significantly enhanced biosynthesis of flavonoids in general and the flavonol biosynthesis in particular. Pre-pubertal ovary intact BALB/c mice received daily oral administration of vehicle and ethanolic extract of wild type (WT-TOM) and transgenic AtMYB12-tomato (MYB12-TOM) fruits for six weeks. Animal fed with MYB12-TOM showed no inflammation in hepatic tissues and normal sinusoidal Kupffer cell morphology. MYB12-TOM extract significantly increased tibial and femoral growth and subsequently improved the bone length as compared to vehicle and WT-TOM. Histomorphometry exhibited significantly wider distal femoral and proximal tibial growth plate, increased number and size of hypertrophic chondrocytes in MYB12-TOM which corroborated with micro-CT and expression of BMP-2 and COL-10, marker genes for hypertrophic cells. We conclude that metabolic reprogramming of tomato by AtMYB12 has the potential to improve longitudinal bone growth thus helping in achievement of greater peak bone mass during adolescence.

Sorcin Expression in the Epiphyseal Growth Plates of Mice

Sorcin is a small calcium-binding protein that is widely expressed in many tissues. Sorcin regulates cardiac myocyte apoptosis by modulating mitochondrial Ca2+ cycling and regulates fibroblast cell cycling and apoptosis via Ca2+ signaling through the endoplasmic reticulum (ER). During endochondral ossification, some chondrocytes undergo apoptosis after their terminal differentiation; however, Sorcin’s expression in these cells has not been characterized. Here we examined Sorcin’s gene expression in the chondrocytes derived from mouse growth plate by reverse transcription PCR (RT-PCR), and its protein localization in the chondrocytes of femoral growth plate using immunohistochemistry. Sorcin protein was detected in the chondrocytes, and was particularly abundant in the cytoplasm and nuclei of proliferative zone chondrocytes and in the nuclei of hypertrophic chondrocytes. Apoptotic analysis of the growth plate revealed that many of the hypertrophic chondrocytes undergo the DNA fragmentation. We report for the first time the localization of Sorcin in the epiphyseal growth plate in which one of the apoptotic phenomenon was detected.

Comparison of Growth Plate Violations for Transtibial and Anteromedial Surgical Techniques in Simulated Adolescent Anterior Cruciate Ligament Reconstruction

Background: Increases in the rates and intensity of youth sports participation have led to an elevated incidence of anterior cruciate ligament (ACL) injuries and reconstruction in adolescents. Traditional reconstruction techniques in the skeletally immature patient may violate the growth plates and potentially lead to deformities. Hypothesis/Purpose: The purpose of this study was to compare the volume and location of femoral growth plate violations resulting from anteromedial (AM) and transtibial (TT) techniques in ACL reconstruction. The hypothesis was that the more oblique angle used in femoral tunnels drilled with the AM portal technique would produce larger and more lateral violations compared with those resulting from TT tunnels. Study Design: Controlled laboratory study. Methods: Growth plate disturbances were quantified by performing simulated reconstructions in computer models created from magnetic resonance imaging scans of the knees of 17 adolescent participants. Locations of tunnels drilled with simulated AM and TT portal techniques were specified by an orthopaedic surgeon blinded to the locations of the femoral physes in the knee models. Tunnels with lengths of 20, 25, and 30 mm were placed in each model using simulated drill diameters of 7, 8, and 9 mm in addition to a 4.5-mm tunnel breaching the lateral cortex. Normalized measures of the volume and laterality of violations were computed. Results: Tunnels drilled with the AM portal technique disrupted a significantly larger percentage of the physis (P = .007), but the difference was not substantial. Tunnels drilled with the AM portal technique produced violations that were more lateral in the physis than those drilled with the TT technique (P < .001). Tunnels drilled with the AM portal technique resulted in mean violations that were 5.1% ± 2.1% of the physis as compared with 4.7% ± 2.0% for TT tunnels. The mean value for a normalized measure of the laterality of the violation (L score) was 0.590 ± 0.115 for tunnels drilled with the AM portal technique and 0.290 ± 0.104 for TT tunnels. The AM approach produced 16 of 153 simulated reconstructions with growth plate violations greater than 8% compared with only 10 with the TT approach. Conclusion: Results suggest that the AM approach produces growth plate violations that are larger and more lateral than the violations generated using the TT technique. AM approaches were more likely to remove more than 8% of the physeal volume, a level previously identified as posing a greater risk of growth disturbances. While the difference in the mean physeal volume removed between the approaches was small, the violations for the AM approach were much more lateral, a finding of potentially greater clinical significance. Clinical Relevance: As progressively younger patients are considered candidates for ACL reconstruction, knowledge of how variations in technique affect the developing knee is critical to preventing iatrogenic injuries.

Effects of electromagnetic field (1.8/0.9 GHz) exposure on growth plate in growing rats

The purpose of this study was to determine the effects of whole-body electromagnetic field (EMF) exposure on growth plates in growing male rats. Two groups of rats were exposed to either 900MHz EMF or 1800MHz EMF 2h/day for 90days. Sham control rats were kept under similar conditions without exposure to the EMF. The rats in the EMF group experienced a more rapid weight gain and increase in length (p<0.05). Calcium, growth hormone, estradiol and testosterone levels in the EMF groups were higher (p<0.05). The Safranin O staining density of femoral growth plate was lowest in the reserve zone of rats exposed to 1800MHz and was increased in the proliferative zone of the control group (p<0.05). The trabecular zone was thinnest among all zones and the reserve and proliferative zones were thicker (p<0.05) than other zones in 1800MHz group.In conclusion, 1800MHz and 900MHz EMF may cause prolong the growth phase in growing rats.

Low Risk of Physeal Damage from a Medial Patellofemoral Ligament (MPFL) Reconstruction Technique that Uses an Epiphyseal Socket in Children

Objectives:The purpose of this study was to assess short-term distal femoral growth plate safety associated with femoral sockets for hamstring autograft fixation in pediatric MPFL reconstruction.Methods:We retrospectively reviewed a consecutive series of 31 patients (22 females, 9 males) that underwent MPFL reconstruction by one surgeon at a tertiary care academic medical center between 2008 and 2014. Study inclusion criteria consisted of patients who were skeletally immature at the time of surgery, who had greater than 1 year radiographic follow-up and who had a femoral socket introduced during their procedure. Femoral socket location was verified by intraoperative fluoroscopy. All patients received a post-operative x-ray and a clinical follow-up. For the 12 patients that obtained post-operative MRI, growth plate safety was assessed by examining the location of the femoral socket relative to the physis to rule out growth plate injury (Figure 1). Development of lower limb angular deformities or limb length discrepancies was evaluated by examining post-operative standing hip-to-ankle anteroposterior radiographs, patient records, and clinical assessments.Results:The average age at surgery of 13.0 years. The average length of radiographic follow-up was 1.5 years and the average length of clinical follow-up was 1.78 years. At most recent clinical follow-up, 90% (28/31) of patients reported no subsequent patellar dislocations in the treated knee. No patients showed evidence of an angular deformity or limb length discrepancy. Of the 12 patients with postoperative MRI, all showed femoral sockets positioned distal to the physis without growth plate disturbance.Conclusion:The use of an epiphyseal femoral socket for graft fixation presents minimal risk of physeal violation and ensures patellar stability in the majority of pediatric patients. We have demonstrated that using fluoroscopic assistance to place the femoral socket distal to the distal femoral physis is a reliable and safe method for avoiding physeal injury in children with patellar instability.

Dietary Vitamin D during Pregnancy Has Dose-Dependent Effects on Long Bone Density and Architecture in Guinea Pig Offspring but Not the Sows

Background: The effects of vitamin D during pregnancy on maternal and neonatal bone health remain unclear.Objective: This study was designed to test whether dietary vitamin D dose-dependently affects maternal and neonatal bone health.Methods: Female guinea pigs (n = 45; 4 mo old) were randomly assigned at mating to receive 1 of 5 doses of vitamin D3 (cholecalciferol; 0, 0.25, 0.5, 1, or 2 IU/g diet) throughout pregnancy. Plasma vitamin D metabolites, mineral homeostasis, bone biomarkers, and bone mass were tested in sows throughout pregnancy and in 2-d-old pups. Microarchitecture and histology of excised bone were conducted postpartum.Results: By 3 wk of pregnancy, plasma 25-hydroxyvitamin D [25(OH)D] followed a positive dose-response, whereas 1,25-dihydroxyvitamin D [1,25(OH)2D] reached a plateau if vitamin D was ≥0.5 IU/g diet. Weight gain, areal bone mineral density (aBMD), volumetic bone mineral density (vBMD), and bone biomarkers did not differ among maternal groups. A positive dose-response was observed for mean ± SEM pup plasma concentrations of 25(OH)D (10.5 ± 1.50 to 113 ±11.6 nmol/L) and 1,25(OH)2D (123 ± 13.8 to 544 ± 53.3 pmol/L). Pup weight, plasma minerals, and osteocalcin were not different; plasma deoxypyridinoline was lower in the 1- and 0.25-IU/g groups than in all other groups. Pup femur aBMD was higher (9.2–13%; P =0.04) in the 2-IU/g group than in all other groups except for the 0-IU/g group. Tibia and femur vBMD of pups responded to maternal diet in a U-shaped pattern. The femoral growth plate was 7.9% wider in the 0-IU/g group than in the 1-IU/g group.Conclusions: Maternal vitamin D supplementation dose-dependently altered pup long bone architecture and mineral density in a manner similar to vitamin D deficient rickets whereas maternal bone was stable. These data reinforce that inadequate maternal vitamin D intake may compromise neonatal bone health and that exceeding recommendations is not advantageous.

Interventions for treating growth plate fractures of the distal femur: a systematic review protocol

REVIEW QUESTION/OBJECTIVE 1.What are safe and effective interventions for the management of distal femoral growth plate fractures in children in terms of rates of growth deformity and rates of growth arrest? More specifically, the objectives are to compare: 1. different methods of surgical treatments in the acute management of distal femoral growth plate fractures in children and adolescents; 2. different methods of non-surgical treatments in the acute management of distal femoral growth plate fractures in children and adolescents; 3. surgical versus non-surgical treatments in the acute management of distal femoral growth plate fractures in children and adolescents; and 4. different outpatient follow-up strategies, in particular, frequency of visits, frequency of radiographic evaluation and longevity of patient follow-up, following treatment of distal femoral growth plate fractures in children. Surgery will be defined as treatment either by incision or physical manipulation by a surgical doctor. INCLUSION CRITERIA Types of participants This review will consider studies which include male and female children, younger than or equal to 18 years of age, with a distal femoral physeal fracture treated either operatively or conservatively, within 72 hours of presentation to hospital. Children may have a single or multiple injuries. The distal femoral physeal fractures considered may be open or closed injuries. Studies which follow-up these patients in the outpatient setting will also be reviewed to evaluate the incidence or detection rates of the later-appearing complications. This review will not consider children with osteochondritis dissecans, Blount’s disease, or children with other comorbidities TRUNCATED AT 250 WORDS

The cn/cn dwarf mouse. Histomorphometric, ultrastructural, and radiographic study in mutants corresponding to human acromesomelic dysplasia Maroteaux type (AMDM).

BackgroundThe cn/cn dwarf mouse is caused by a loss-of-function mutation in the natriuretic peptide receptor 2 (NPR-2) gene which helps positively regulate endochondral longitudinal bone growth. The gene mutation corresponds to that in the human skeletal dysplasia Acromesomelic Dysplasia Maroteaux type (AMDM). This study assesses histomorphometric, ultrastructural and radiographic correlates of the growth abnormality.MethodsTen litters of cn/cn and cn/+littermates at ages ranging from 2.5 to 6.5 weeks were studied by skeletal radiographs, histomorphometry and physeal ultrastructure. Skeletal radiographs were done on 2 cn/cn and 2 cn/+littermates at 5 weeks of age. Humeral, femoral, and tibial lengths were measured from 34 intact bones (17 cn/cn, 17 cn/+) at 2.5 to 6.5 weeks. Growth plate histomorphometry in 50 bones (26 cn/cn and 24 cn/+) determined the hypertrophic zone/entire physeal cartilage ratios in 204 sections (87 cn/+, 117 cn/cn) at 3 time periods (2.5-3, 4–4.5, and 6–6.5 weeks). Electron microscopy assessed 6 cn/cn and 6 cn/+age and site-matched physeal cartilage.ResultsCn/cn mice were two thirds the size of the cn/+. Cn/cn bones were normal in shape or only minimally deformed except for the radius with mid-diaphyseal bowing. Length ratios of cn/cn humeri, femurs, and tibias were a mean of 0.65 (±0.03, n = 34, 17 ratios) compared to cn/+bones. The main physeal abnormality was a markedly shortened hypertrophic zone with the ratio of hypertrophic zone to entire physis 0.17 (±0.063) in the cn/cn and 0.30 (±0.052) in the cn/+mice. Ratio assessments were similar comparing humeral, femoral, and tibial growth plates as were ratios from each of the 3 time periods. Ultrastructural assessments from the resting zone to the lower hypertrophic zone-metaphyseal junction showed no specific individual cell abnormalities in cn/cn compared to cn/+physes.ConclusionsThe disorder causes a shortened physeal hypertrophic zone but normal ultrastructure of cn/cn chondrocytes points to abnormality primarily affecting the hypertrophic zone rather than a structural cell or matrix synthesis problem.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2474-15-347) contains supplementary material, which is available to authorized users.

Effect of Surgical Technique on Growth-Plate Violation in Simulated Adolescent ACL Reconstruction

Objectives:Increases in rates of participation and intensity of youth sports have led to elevated incidences of anterior cruciate ligament (ACL) injury and ACL reconstruction in adolescents. When applied to the skeletally immature patient, traditional reconstruction techniques lead to violations of the growth plates that carry with them the potential for disturbed growth and deformity. The purpose of this study was to compare the volume and location of the femoral growth plate violations that follow from the use of anteromedial (AM) and transtibial (TT) techniques. Growth plate disturbances were quantified by performing simulated reconstructions on computer models created from magnetic resonance (MR) images of adolescent knees.Methods:MR scans were made of the right knees of 17 adolescent participants (10 M; 7 F; mean age 11.4 ± 2.0 y) positioned in both extension and in flexion. These scans were used to construct three dimensional computer models using Simpleware imaging software. An orthopedic surgeon, who was blinded to the location of the femoral physis in the models, specified the locations of simulated AM and TT tunnels. Tunnels with lengths of 20 mm, 25 mm, and 30 mm were placed for each subject with simulated drill diameters of 7 mm, 8 mm, and 9 mm (Figure 1). Normalized measures of both violation volume and the laterality of the violation were computed using routines custom written in MATLAB.Results:For the AM approach, the mean normalized violation volumes for the 7 mm, 8 mm, and 9 mm drills were 4.14%, 5.02%, 6.01%, respectively, and 3.84%, 4.70%, 5.65% for the TT approach. The mean lateral positions of the violation for the AM approach, normalized by physis width for 7 mm, 8 mm, and 9 mm drills were 0.579, 0.590, 0.600, respectively, and 0.293, 0.290, 0.286 for the TT approach (with 0.000 corresponding to the femoral midline and 1.000 to the lateral cortex). Tunnels created using an AM approach disrupted a significantly larger percentage of the physis (p = 0.007) and produced a violation that was significantly more lateral (p < 0.001) when compared to the TT approach. Sixteen out of 153 (9 conditions x 17 subjects) simulated reconstructions for the AM approach and ten (out of 153) for the TT approach produced growth-plate violations greater than 8%.Conclusion:Use of an AM approach produced growth plate violations that were larger and more lateral than the violations generated using a TT technique. It has been suggested that more lateral violations are more likely to result in growth limitation and valgus deformity. In addition, violations accounting for more than 8% of the total physeal volume have been identified as posing a greater risk of growth disturbance. In the present study, younger subjects in general had larger physis violations, and violations of 8% or greater tended to occur when using a larger diameter drill to create a longer tunnel, regardless of the approach. Caution should be taken when using larger diameter drills and tunnel lengths 25mm or greater, especially in younger subjects for whom growth-plate violations may be greater than 8% for the AM approach.

Age-specific bone tumour incidence rates are governed by stem cell exhaustion influencing the supply and demand of progenitor cells

Knudson's carcinogenic model, which simulates incidence rates for retinoblastoma, provides compelling evidence for a two-stage mutational process. However, for more complex cancers, existing multistage models are less convincing. To fill this gap, I hypothesize that neoplasms preferentially arise when stem cell exhaustion creates a short supply of progenitor cells at ages of high proliferative demand. To test this hypothesis, published datasets were employed to model the age distribution of osteochondroma, a benign lesion, and osteosarcoma, a malignant one. The supply of chondrogenic stem-like cells in femur growth plates of children and adolescents was evaluated and compared with the progenitor cell demand of longitudinal bone growth. Similarly, the supply of osteoprogenitor cells from birth to old age was compared with the demands of bone formation. Results show that progenitor cell demand-to-supply ratios are a good risk indicator, exhibiting similar trends to the unimodal and bimodal age distributions of osteochondroma and osteosarcoma, respectively. The hypothesis also helps explain Peto's paradox and the finding that taller individuals are more prone to cancers and have shorter lifespans. The hypothesis was tested, in the manner of Knudson, by its ability to convincingly explain and demonstrate, for the first time, a bone tumour's bimodal age-incidence curve.

The origin points of the knee collateral ligaments: an MRI study on paediatric patients during growth.

Different femoral origins for both the medial collateral ligament (MCL) and the lateral collateral ligament (LCL) have been reported in the growing skeleton (epiphyseal and metaphyseal). Knowledge about the exact attachment sites is mandatory for anatomically correct reconstruction. This study assesses the femoral origins of the knee collateral ligaments in skeletally immature individuals using magnetic resonance imaging (MRI). MRIs of 336 knee joints (median age 15 years (range 2-18 years), m = 209 and f = 127) were retrospectively analysed to assess the distances between the femoral origins of the MCL and LCL to the distal femoral growth plate. In 175 patients, the body sizes were additionally retrieved from medical records. Both MCL and LCL ligament origins were invariably located on the epiphysis. Mean MCL origin-growth plate distance was 9.6 mm (SD 2.1 mm; range 2.2-13.6 mm) in boys and 8.6 mm (SD 1.5 mm; range 3.4-12.0 mm) in girls. Mean LCL origin-growth plate distance was 9.3 mm (SD 1.8 mm; range 4.3-13.0 mm) in boys and 8.2 mm (SD 1.5 mm; range 3.4-11.8 mm) in girls. The distance between the growth plate and both collateral ligaments as well as the length of the LCL correlated positively with patients' age and body size (MCL R(2) = 0.673 and 0.556, LCL R (2) = 0.734 and 0.645, LCL length R(2) = 0.589 and 0.741; all p < 0.001). During growth, the femoral origins of the MCL and the LCL are constantly located on the distal femoral epiphysis. There is a linear increase in the distances from the ligaments' origins to the growth plate according to age and body size. This new information may be of clinical importance for reconstructive surgery of the knee's collateral ligaments.

A Cam Deformity Is Gradually Acquired During Skeletal Maturation in Adolescent and Young Male Soccer Players

Background: A cam deformity is a major risk factor for hip osteoarthritis, and its formation is thought to be influenced by high-impact sporting activities during growth. Purpose: To (1) prospectively study whether a cam deformity can evolve over time in adolescents and whether its formation only occurs during skeletal maturation and (2) examine whether clinical or radiographic features can predict the formation of a cam deformity. Study Design: Cohort study (prognosis); Level of evidence, 2. Methods: Preprofessional soccer players (N = 63; mean age, 14.43 years; range, 12-19 years) participated both at baseline and follow-up (mean follow-up, 2.4 ± 0.06 years). At both time points, standardized anteroposterior and frog-leg lateral radiographs were obtained. For each hip, the α angle was measured, and the anterosuperior head-neck junction was classified by a 3-point visual system as normal, flattened, or having a prominence. Differences between baseline and follow-up values for the α angle and the prevalence of each visual hip classification were calculated. Additionally, the amount of internal hip rotation, growth plate extension into the neck, and neck shaft angle were determined. Results: Overall, there was a significant increase in the prevalence of a cam deformity during follow-up. In boys aged 12 and 13 years at baseline, the prevalence of a flattened head-neck junction increased significantly during follow-up (13.6% to 50.0%; P = .002). In all hips with an open growth plate at baseline, the prevalence of a prominence increased from 2.1% to 17.7% (P = .002). After closure of the proximal femoral growth plate, there was no significant increase in the prevalence or increase in severity of a cam deformity. The α angle increased significantly from 59.4° at baseline to 61.3° at follow-up (P = .018). The amount of growth plate extension was significantly associated with the α angle and hip classification (P = .001). A small neck shaft angle and limited internal rotation were associated with cam deformities and could also significantly predict the formation of cam deformities (α angle >60°) at follow-up. Conclusion: In youth soccer players, cam deformities gradually develop during skeletal maturation and are probably stable from the time of growth plate closure. The formation of a cam deformity might be prevented by adjusting athletic activities during a small period of skeletal growth, which will have a major effect on the prevalence of hip osteoarthritis.

Bilateral growth plate fractures of the distal femur

Growth plate fractures represent about 18-30% of the total amount of fractures in a pediatric age. From these, about 2% to 7% happens in the distal growth plate of the femur, with Salter-Harris type II fractures, observed in about half of the cases. A single case report of a 12-year-old girl with bilateral femoral Salter-Harris type II distal growth plate fractures, who underwent closed reduction, followed by internal fixation with crossed smooth Kirschner wires in our hospital. Report on her 15-month follow-up. Bilateral femoral distal growth plate fractures are extremely rare. To our knowledge, this is the third case described in the literature for the ambulating child, the first studied in detail and also and the first that focuses on the short and medium term recovery.

Reslip of a Previously Fixed Slipped Upper Femoral Epiphysis with an Associated Vitamin D Deficiency

Slipped upper femoral epiphysis (SUFE) is a relatively common adolescent hip disorder that represents a biomechanical instability of the proximal femoral growth plate. A link between vitamin D deficiency and SUFE has emerged in recent years; however, we present a unique case of a 10-year-old girl who presented with a reslip of a previously fixed SUFE with an associated vitamin D deficiency.

Idiopathic Cam Morphology Is Not Caused by Subclinical Slipped Capital Femoral Epiphysis: An MRI and CT Study.

Background:Cam impingement as a known sequelae of slipped capital femoral epiphysis (SCFE) has led to speculation that subclinical SCFEs may be the causative factor in idiopathic cam morphology; alternatively, others have implicated an abnormal extension of the growth plate as a causative factor.Hypothesis/Purpose:To investigate the growth plate tilt angle in 4 patient cohorts: normal patients, patients with idiopathic cam morphology (CamIP), patients with cam morphology secondary to known SCFE (CamSCFE), and patients with incidental findings of an asymptomatic cam (Camasymp).Study Design:Case-control study; Level of evidence, 3.Methods:A database of 192 computed tomography scans of abdomens/pelvises of patients (ages, 5-19 years) with no known orthopaedic issues, reformatted to neutral tilt, inclination, and rotation, were utilized for the normal cohort, the Camasymp cohort, and to create an age- and sex-matched control cohort. In addition, a retrospective review of all patients treated for femoroacetabular impingement (FAI) with preoperative advance imaging was conducted, and patients were separated to CamIP and CamSCFE cohorts. The alpha angle and tilt angle were measured on each hip. Statistical analysis was performed.Results:The mean tilt angle among the normal patients was 12.1°, with 1.9% of the variation in tilt angle being explained by age; each additional year of age decreased the tilt angle by 0.27° (P = .008). The tilt angle for the CamSCFE cohort (mean, 44.5°) was found to be significantly greater than both the CamIP cohort (mean, 5.9°; P < .001) and the control cohort (mean, 12.8°; P < .001). The tilt angle for the CamIP cohort was found to be significantly less than the control cohort (P = .003). The alpha angle and tilt angle were positively correlated in the CamIP cohort, but no correlation was found in the other cohorts. The mean tilt angle of the 18 hips in the Camasymp cohort was 13.9° ± 11.5° (range, –12° to 37°), with 12 hips (67%) in the tilt angle range of CamIP cohort and 6 in the tilt angle range of CamSCFE.Conclusion: The proximal femoral growth plate normally has a posterior tilt that becomes more anterior through maturation. Idiopathic cam morphology has a drastically different growth plate tilt angle than cam morphology secondary to SCFE, suggesting that a majority of idiopathic cam morphology is not the result of subclinical SCFEs.

Modulation of endochondral ossification by MEK inhibitors PD0325901 and AZD6244 (Selumetinib)

MEK inhibitors (MEKi) PD0325901 and AZD6244 (Selumetinib) are drugs currently under clinical investigation for cancer treatment, however the Ras–MAPK pathway is also an important mediator of normal bone cell differentiation and function. In this study we examined the effects of these compounds on endochondral processes using both in vitro and in vivo models. Treatment with PD0325901 or AZD6244 significantly increased Runx2 and Alkaline phosphate gene expression in calvarial osteoblasts and decreased TRAP+ cells in induced osteoclast cultures. To test the effects of these drugs on bone healing, C57/Bl6 mice underwent a closed tibial fracture and were treated with PD0325901 or AZD6244 at 10mg/kg/day. Animals were culled at day 10 and at day 21 post-fracture for analysis of the fracture callus and the femoral growth plate in the contralateral leg. MEKi treatment markedly increased cartilage volume in the soft callus at day 10 post-fracture (+60% PD0325901, +20% AZD6244) and continued treatment led to a delay in cartilage remodeling. At the growth plate, we observed an increase in the height of the hypertrophic zone relative to the proliferative zone of +78% in PD0325901 treated mice. Osteoclast surface was significantly decreased both at the terminal end of the growth plate and within the fracture calluses of MEKi treated animals. The mechanistic effects of MEKi on genes encoding cartilage matrix proteins and catabolic enzymes were examined in articular chondrocyte cultures. PD0325901 or AZD6244 led to increased matrix protein expression (Col2a1 and Acan) and decreased expression of catabolic factors (Mmp13 and Adamts-5). Taken together, these data support the hypothesis that MEKi treatment can impact chondrocyte hypertrophy, matrix resorption, and fracture healing. These compounds can also affect bone architecture by expanding the hypertrophic zone of the growth plate and reducing osteoclast surface systemically.

Resveratrol treatment delays growth plate fusion and improves bone growth in female rabbits.

Trans-resveratrol (RES), naturally produced by many plants, has a structure similar to synthetic estrogen diethylstilbestrol, but any effect on bone growth has not yet been clarified. Pre-pubertal ovary-intact New Zealand white rabbits received daily oral administration of either vehicle (control) or RES (200 mg/kg) until growth plate fusion occurred. Bone growth and growth plate size were longitudinally monitored by X-ray imaging, while at the endpoint, bone length was assessed by a digital caliper. In addition, pubertal ovariectomized (OVX) rabbits were treated with vehicle, RES or estradiol cypionate (positive control) for 7 or 10 weeks and fetal rat metatarsal bones were cultured in vitro with RES (0.03 µM–50 µM) and followed for up to 19 days. In ovary-intact rabbits, sixteen-week treatment with RES increased tibiae and vertebrae bone growth and subsequently improved final length. In OVX rabbits, RES delayed fusion of the distal tibia, distal femur and proximal tibia epiphyses and femur length and vertebral bone growth increased when compared with controls. Histomorphometrical analysis showed that RES-treated OVX rabbits had a wider distal femur growth plate, enlarged resting zone, increased number/size of hypertrophic chondrocytes, increased height of the hypertrophic zone, and suppressed chondrocyte expression of VEGF and laminin. In cultured fetal rat metatarsal bones, RES stimulated growth at 0.3 µM while at higher concentrations (10 μM and 50 μM) growth was inhibited. We conclude that RES has the potential to improve longitudinal bone growth. The effect was associated with a delay of growth plate fusion resulting in increased final length. These effects were accompanied by a profound suppression of VEGF and laminin expression suggesting that impairment of growth plate vascularization might be an underlying mechanism.

Ipsilateral distal femoral and proximal tibial epiphyseal growth plate injury: a case report

IntroductionBoth the isolated distal femoral epiphysiolysis and the isolated proximal tibial epiphysiolysis are the least common epiphyseal injuries. Even though they are uncommon, they have a high incidence rate of complications.Case presentationWe present a case with Gustilo-Anderson grade 3b open and Salter-Harris type 1 epiphysiolysis of the distal femur and proximal tibia caused by a farm machinery accident. The patient was a 10-year-old boy, treated by open reduction and internal fixation.ConclusionAlthough distal femoral and proximal tibial growth plate injuries are rarely seen benign fractures, their management requires meticulous care. Anatomic reduction is important, especially to minimize the risk of growth arrest and the development of degenerative arthritis. However, there is a high incidence of growth arrest and neurovascular injury with these type of fractures.

P.His165Pro: A novel SOX9 missense mutation of campomelic dysplasia

Campomelic dysplasia (CD) is a rare skeletal dysplasia caused by mutation in the SOX9 gene located on chromosome 17q24.3-q25.1, which regulates testis and chondrocyte development. Severe bowing of the long bones was seen at second-trimester scan. DNA analysis demonstrated a previously unreported de novo missense mutation in p.His165Pro. Ultrasound-based, molecular biology diagnosis led to early therapeutic termination of pregnancy. Histologic examination of the femoral epyphyseal growth plate confirmed scanty proliferation zone and maturation zone with degenerated chondrocytes.