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This study aimed to analyse the growth plate fusion and secondary ossification centres of the hind limbs in maned wolves (Chrysocyon brachyurus) using radiographs. Data from three maned wolves estimated to be 3-4 months old were utilised. The right and left hind limbs were radiographed in the mediolateral and craniocaudal views once a month until 11-12 months of age and then every 2-3 months until 18-19 months of age. The growth plates identified in the hind limbs and their closure times were as follows: proximal femur (13-15 months), distal femur (13-15 months), proximal tibia (17-19 months), tibial tuberosity (17-19 months), distal tibia (11-13 months), proximal fibula (13-15 months) and calcaneal tuber (8-9 months). Measurements of the areas of the secondary ossification centres of the proximal epiphysis of the femur, distal epiphysis of the tibia, patella and fibular tarsal bone epiphysis showed a significant difference between the first assessment and 6-7 months. The distal femoral epiphysis, proximal tibial epiphysis and tibial tuberosity showed a statistically significant difference between the first assessment and 7-8 months. The difference in the proximal epiphysis of the fibula was observed between 4 to 5 months and 7 to 8 months. In conclusion, the information obtained regarding the growth plates and secondary ossification centres of the maned wolves may support other studies and help understand the normal patterns of the species., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Introduction: The perfect knee lateral radiograph visualizes anatomic landmarks on the distal femur for clinical and scientific purposes. However, radiographic imaging is a two-dimensional (2D) representation of a three-dimensional (3D) physis. The aim of this study was to characterize the perceived radiographic projection of the femoral physis using perfect lateral digitally reconstructed radiographs (DRRs) and to evaluate discrepancies from this projection to the physis at the lateral and medial cortices., Methods: Pediatric patients from a cohort of CT scans were analyzed. Inclusion criteria were an open physis; exclusion criteria were any implant or pathology affecting the physis. CT scans were imported into 3D imaging software and transformed into lateral DRRs and 3D renderings of the femur. The physis was divided into four equal segments, with fiducial markers placed at the "anterior," "midpoint," and "posterior" points. Lines extended from these points in the lateral and medial direction. The vertical distance from these lines, representing the radiographic projection of the physis, was measured relative to the physis at the lateral and medial cortex of the femur on coronal CT slices., Results: Thirty-one patients were included. On the perfect lateral radiograph DRR, the physis on the medial cortex was located proximal to the visualized physis by 6.64 ± 1.74 mm, 11.95 ± 1.67 mm, and 14.30 ± 1.75 mm at the anterior (25%), midpoint (50%), and posterior (75%) locations, respectively. On the lateral side, the physis on the lateral cortex was proximal to the visualized physis by 2.19 ± 1.13 mm, 3.71 ± 1.19 mm, and 6.74 ± 1.25 mm at the anterior, midpoint, and posterior locations, respectively., Discussion: In this cohort of pediatric patients, the location of the cortical physis was, in all areas measured, proximal to the projection of the visualized physis as seen on the perfect knee lateral DRR. The distance from radiographic physis to cortical physis was greater at the medial cortex compared with the lateral cortex., Study Design: Descriptive laboratory study., Level of Evidence: III, observational radiographic anatomic study., (Copyright © 2024 by the American Academy of Orthopaedic Surgeons.)

This study aimed to assess the fusion of growth plates and the development of secondary ossification centres in the forelimb bones of maned wolves (Chrysocyon brachyurus), contrasting the findings with established data from domestic dogs. Three maned wolves, comprising one male and two females, initially aged between 3 and 4 months, were subjected to monthly radiographic evaluations until 10-11 months of age, followed by bimonthly assessments until 18-19 months of age, encompassing both forelimbs. The closure times of growth plates were observed as follows: supraglenoid tubercle (7-8 months), proximal humerus (17-19 months), distal humerus (8-9 months), medial epicondyle of the humerus (8-9 months), proximal ulna (9-10 months), proximal radius (13-15 months), distal ulna (13-15 months) and distal radius (17-19 months). Statistical analysis revealed significant differences in the areas of secondary ossification centres in the proximal epiphyses of the humerus and radius, respectively, observed from the initial evaluation at 8-9 months and 6-7 months. Conversely, the epiphyses of the supraglenoid tubercle, distal humerus, proximal ulna, distal ulna, medial epicondyle of the humerus and distal radius did not exhibit significant area differences between 3-4 months and 4-5 months, yet notable distinctions emerged at 5-6 months. In summary, while the radiographic appearance of epiphyseal growth plates and secondary ossification centres in maned wolves resembles that of domestic dogs, closure times vary. These findings contribute to understanding the dynamics of epiphyseal growth plates in this species., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Objectives: Salter-Harris type 1 (SH1) fractures of the distal fibula are acute orthopedic injuries with tenderness over the physis without radiographic evidence of fracture. Our primary objective was to establish the accuracy of the physical examination performed by pediatric emergency medicine (PEM) physicians in determining the location of the distal fibular physis compared to a criterion standard of ultrasound., Methods: This was a prospective, observational study at an urban academic pediatric emergency department of a convenience sample of children aged 4 to 10 years old between March 2019 and March 2020. A PEM physician or fellow examined the patient's distal fibula and marked the location of the physis with a marker. A study investigator scanned the distal fibula to establish the location of the physis on ultrasound and measured the distance between the clinician's estimated position and the actual sonographic position. We a priori defined a clinically accurate position as a distance of ≤5 mm. We compared the accuracy rate of physical examination to ultrasound landmarking using proportions with 95% confidence intervals (CI)., Results: We enrolled 71 patients, of whom 52 (73%) were male. The mean age was 6.7 years and the mean weight was 25.5 kg. Participating PEM physicians included 18 attending physicians and 2 fellows. The distal fibular physis was correctly identified in 24 patients, yielding an accuracy rate of 34% (95% CI 23%-46%). The mean distance between the physician's estimated position and the sonographic position was 7.4 mm (95% CI 6.4-8.4 mm)., Conclusions: PEM physicians were unable to accurately identify the distal fibular physis on physical examination., Competing Interests: Declaration of Competing Interest VD, VS, JSA, and SE do not report any conflicts of interest. DJK is on the medical advisory board of Clarius Mobile Health., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Bones in the vertebrate cranial base and limb skeleton grow by endochondral ossification, under the control of growth plates. Mechanisms of endochondral ossification are conserved across growth plates, which increases covariation in size and shape among bones, and in turn may lead to correlated changes in skeletal traits not under direct selection. We used micro-CT and geometric morphometrics to characterize shape changes in the cranium of the Longshanks mouse, which was selectively bred for longer tibiae. We show that Longshanks skulls became longer, flatter, and narrower in a stepwise process. Moreover, we show that these morphological changes likely resulted from developmental changes in the growth plates of the Longshanks cranial base, mirroring changes observed in its tibia. Thus, indirect and non-adaptive morphological changes can occur due to developmental overlap among distant skeletal elements, with important implications for interpreting the evolutionary history of vertebrate skeletal form., Competing Interests: CU, JD, BH, CR No competing interests declared, (© 2021, Unger et al.)

Introduction: Trochlear dysplasia is a known risk factor for patellar dislocations yet normal trochlea development is not well described. This study will define the articular cartilage (AC) and subchondral trochlear morphology development in pediatric patients using magnetic resonance imaging (MRI) evaluation., Methods: A retrospective knee MRI review included patients aged 3 to 16 years with nonpatellofemoral-related diagnoses. International classification of diseases-9/International classification of diseases-10 codes were used to identify eligible study patients. Measurements of the trochlea were made on the basis of previously established methods using the axial MRI just distal to the physis at the deepest portion of the trochlear groove. Three linear [lateral trochlear height (LTH), medial trochlear height (MTH), and central trochlear height (CTH)] and 3 angular [sulcus angle (SA), lateral trochlear slope (LTS), and medial trochlear slope (MTS)] were made at AC and subchondral bone (SCB). The 12 measurements were made independently by 2 study authors. Inter-rater reliability was assessed using an interclass correlation coefficient for absolute agreement to the average of the scores. Trochlea measurements were summarized across age quartiles defined as first quartile (age, 5.1 to 8.3 y), second quartile (8.3 to 11.5 y), third quartile (11.5 to 14.3 y), fourth quartile (14.3to 16.9 y). Associations between age and trochlea measures were assessed using linear regression with Huber-White-adjusted SEs to account for clustering from a small number of patients (N=16) with >1 MRI., Results: In total, 246 knee MRIs from 230 patients were included in this study; 113 patients (51%) were female, whereas 117 (49%) were male. A total of 116 MRIs (47%) were of the left knee and 130 (53%) were right knee. The average patient age was 11.4±3.4 years. Inter-rater agreement was high across all measures with interclass correlation coefficient values >0.7. Mean values for measurements are presented by age quartiles. LTH, MTH, and CTH showed a linear increase with age (range, 2 to 2.6 cm/y; P<0.001). SA, LTS, MTS measured at AC showed no change with age (P>0.05); however, LTS and MTS measured at SCB showed significant increases with age (0.6 and 0.9 degrees/y; P<0.001), whereas SA showed a decrease with age (-1.4 degrees/y; P<0.001). There were no significant differences found in the age associations by laterality, left versus right. There were no sex differences in the age associations for SA, LTS (P>0.05); however, for MTH, LTH, and CTH, males were found to have a significantly greater growth rate (P<0.001)., Conclusions: This study found an increase in AC and SCB MTH, LTH, and CTH over time, as well as an increase in SCB LTS and MTS, with a decrease in SA. However, AC of the LTS and SA remained constant, with no significant change throughout growth. This normative data indicate that the LTS and SA of AC are predictors of final trochlea shape in normal development. Final trochlear morphologic development is nearly complete around age 12 years, with no significant changes occurring thereafter., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The relationship between the medial patellofemoral ligament (MPFL) and the distal femoral physis has been reported in multiple studies., Purpose: To determine the distance from the MPFL central origin on the distal femur to the medial distal femoral physis in skeletally immature participants., Study Design: Systematic review., Methods: A systematic review was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Multiple databases were searched for studies investigating the anatomic origin of the MPFL on the distal femur and its relationship to the medial distal femoral physis in skeletally immature participants. Study methodological quality was analyzed with the Anatomical Quality Assessment tool, with studies categorized as low risk, high risk, or unclear risk of bias. Continuous variable data were reported as mean ± SD. Categorical variable data were reported as frequency with percentage., Results: Seven articles were analyzed (298 femurs, 53.7% male patients; mean age, 11.7 ± 3.4 years). There was low risk of bias based on the Anatomical Quality Assessment tool. The distance from the MPFL origin to the distal femoral physis ranged from 3.7 mm proximal to the physis to 10.0 mm distal to the physis in individual studies. Six of 7 studies reported that the MPFL origin on the distal femur lies distal to the medial distal femoral physis in the majority of specimens. The MPFL originated distal to the medial distal femoral physis in 92.8% of participants at a mean distance of 6.9 ± 2.4 mm., Conclusion: The medial patellofemoral ligament originates distal to the medial distal femoral physis in the majority of cases at a mean proximal-to-distal distance of 7 mm distal to the physis. However, this is variable in the literature owing to study design and patient age and sex.

The usefulness of serum alkaline phosphatase (ALP) and phosphorous in screening and monitoring of metabolic bone disease of prematurity (MBDP) still has some limitations, especially in preterm infants with concomitant conditions such as cholestasis. We aimed to assess a modification of serum ALP (M-ALP) as a biomarker for MBDP in preterm infants, and the use of ultrasound monitoring for the apparition of knee ossification centers as marker of bone mineralization. Biochemical and clinical registers were taken from 94 preterm newborns <32 weeks. A significant correlation existed between serum ALP and direct bilirubin (DB), expressed by the regression equation: M-ALP (IU/L) = 302.1 + 96.9 (DB (mg/dL)). The ratio ALP/M-ALP > 1 was demonstrated to be more specific (87.5%) in the diagnosis of MBDP than the cut-off value of serum ALP > 500 IU/L (62.5%). ALP/M-ALP > 1 showed 100% sensitivity and specificity for the diagnosis of MBDP, and a good correlation with specific bone ALP (B-ALP). Patients with the knee nucleus by post-menstrual week 37 had lower B-ALP compared to patients with no nucleus, and no patients with MBDP presented the nucleus by the 40th week. In the absence of reliable specific B-ALP, reinterpreting serum ALP values by M-ALP plus monitoring of knee ossification centers contribute to better management of MBDP in preterm infants with cholestasis.

Rationale: Explore the MRI-appearance of the healthy distal radial physis and the distribution of stress-related changes in physeal thickness in young gymnasts to aid in the understanding of the pathophysiological process of stress-related physeal injury. Methods: Symptomatic gymnasts with clinically suspected overuse injury of the distal radial physis and age and gender-matched asymptomatic gymnasts and healthy non-gymnasts underwent an MRI-scan of the wrist. A cartilage-specific sequence was used to obtain three-dimensional reconstructions of the distal radial physis. Heat maps and line charts of these reconstructions visualised distribution of physeal thickness per study group and were used to explore differences between study groups. Symptomatic gymnasts displaying the most profound physeal widening ( n  = 10) were analysed separately. Results: Twenty-seven symptomatic - (skeletal age 12.9 ± 1.5 years), 16 asymptomatic - (skeletal age 12.8 ± 1.9 years) and 23 non-gymnasts (skeletal age 13.6 ± 1.9 years) were included for analysis. Physes of healthy non-gymnasts had a thin centre and increased in thickness towards the borders. Gymnasts demonstrated an increase in thickness of the entire physeal surface. In symptomatic gymnasts increase in physeal thickness was most prominent at the volar side when compared to asymptomatic gymnasts and non-gymnasts. Conclusion: The healthy distal radial physis is characterised by a thin centre surrounded by thicker borders. Stress applied to the wrist during gymnastics causes an overall increase in physeal thickness. Profound thickness increase is present at the volar side of the physis mainly in symptomatic gymnasts. These results can help unravel the pathophysiological mechanism of stress-related physeal injury in gymnasts and aid early injury identification.

Mammals have remarkably diverse limb proportions hypothesized to have evolved adaptively in the context of locomotion and other behaviors. Mechanistically, evolutionary diversity in limb proportions is the result of differential limb bone growth. Longitudinal limb bone growth is driven by the process of endochondral ossification, under the control of the growth plates. In growth plates, chondrocytes undergo a tightly orchestrated life cycle of proliferation, matrix production, hypertrophy, and cell death/transdifferentiation. This life cycle is highly conserved, both among the long bones of an individual, and among homologous bones of distantly related taxa, leading to a finite number of complementary cell mechanisms that can generate heritable phenotype variation in limb bone size and shape. The most important of these mechanisms are chondrocyte population size in chondrogenesis and in individual growth plates, proliferation rates, and hypertrophic chondrocyte size. Comparative evidence in mammals and birds suggests the existence of developmental biases that favor evolutionary changes in some of these cellular mechanisms over others in driving limb allometry. Specifically, chondrocyte population size may evolve more readily in response to selection than hypertrophic chondrocyte size, and extreme hypertrophy may be a rarer evolutionary phenomenon associated with highly specialized modes of locomotion in mammals (e.g., powered flight, ricochetal bipedal hopping). Physical and physiological constraints at multiple levels of biological organization may also have influenced the cell developmental mechanisms that have evolved to produce the highly diverse limb proportions in extant mammals. This article is categorized under: Establishment of Spatial and Temporal Patterns > Regulation of Size, Proportion, and Timing Comparative Development and Evolution > Regulation of Organ Diversity Comparative Development and Evolution > Organ System Comparisons Between Species., (© 2020 Wiley Periodicals, Inc.)

Objective: Distal femoral metaphyseal surface morphology is highly variable in extant mammals. This variation has previously been linked to differences in locomotor behavior. We perform the first systematic survey and description of the development of this morphology in extant hominoids., Materials and Methods: We collected 3D surface laser scans of the femora of 179 human and great ape individuals throughout all subadult stages of development. We qualitatively and quantitatively describe metaphyseal surface morphology., Results: We find that the metaphysis is topographically simple in all hominoids during the fetal and infant periods relative to later developmental periods, and in apes it develops significant complexity throughout development. Humans, by contrast, retain relatively flat metaphyseal surfaces throughout ontogeny., Discussion: Major shifts in morphology appear to coincide with major shifts in locomotor behavior, suggesting that metaphyseal morphology is developmentally plastic and highly dependent on the biomechanical loadings at the knee joint. This is consistent with a large body of biomedical research, which demonstrates the primacy of mechanical forces in determining growth plate ossification patterns. Additionally, specific metaphyseal morphology appears highly correlated with specific locomotor modes, suggesting that metaphyseal surface morphology will be useful for reconstructing the locomotor behavior of fossil primate taxa., (© 2020 Wiley Periodicals, Inc.)

Background: Anterior cruciate ligament (ACL) and medial collateral ligament (MCL) injuries in skeletally immature patients are increasingly recognized and surgically treated. However, the relationship between the footprint anatomy and the physes are not clearly defined. The purpose of this study was to identify the origin and insertion of the ACL and MCL, and define the footprint anatomy in relation to the physes in skeletally immature knees., Methods: Twenty-nine skeletally immature knees from 16 human cadaver specimens were dissected and divided into 2 groups: group A (aged 2 to 5 y), and group B (aged 7 to 11 y). Metallic markers were placed to mark the femoral and tibial attachments of the ACL and MCL. Computed tomography scans were obtained for each specimen used to measure the distance from the center of the ligament footprints to the respective distal femoral and proximal tibial physes., Results: The median distance from the ACL femoral epiphyseal origin to the distal femoral physis was 0.30 cm (interquartile range, 0.20 to 0.50 cm) and 0.70 cm (interquartile range, 0.45 to 0.90 cm) for groups A and B, respectively. The median distance from the ACL epiphyseal tibial insertion to the proximal tibial physis for groups A and B were 1.50 cm (interquartile range, 1.40 to 1.60 cm) and 1.80 cm (interquartile range, 1.60 to 1.85 cm), respectively. The median distance from the MCL femoral origin on the epiphysis to the distal femoral physis was 1.20 cm (interquartile range, 1.00 to 1.20 cm) and 0.85 cm (interquartile range, 0.63 to 1.00 cm) for groups A and B, respectively. The median distance from the MCL insertion on the tibial metaphysis to the tibial physis was 3.05 cm (interquartile range, 2.63 to 3.30 cm) and 4.80 cm (interquartile range, 3.90 to 5.10 cm) for groups A and B, respectively., Conclusion: Surgical reconstruction is a common treatment for ACL injury. Computed tomography scanning of pediatric tissue clearly defines the location of the ACL and MCL with respect to the femoral and tibial physes, and may guide surgeons for physeal respecting procedures., Clinical Relevance: In addition to ACL reconstruction, recent basic science and clinical research suggest that ACL repair may be more commonly performed in the future. MCL repair and reconstruction is also occasionally required in skeletally immature patients. This information may be useful to help surgeons avoid or minimize physeal injury during ACL/MCL reconstructions and/or repair in skeletally immature patients.

Growth impairment in mucopolysaccharidoses (MPSs) is an unresolved issue as it is resistant to enzyme replacement therapy (ERT) and growth hormone therapy. C-type natriuretic peptide (CNP) is a promising agent that has growth-promoting effects. Here we investigate the effects of CNP on growth impairment of MPSs using Gusbmps-2J mice, a model for MPS type VII, with combination therapy of CNP and ERT by hydrodynamic gene delivery. Although monotherapies were not sufficient to restore short statures of treated mice, combination therapy resulted in successful restoration. The synergistic effects of CNP and ERT were not only observed in skeletal growth but also in growth plates. ERT reduced cell swelling in the resting zone and increased cell number by accelerating proliferation or inhibiting apoptosis. CNP thickened the proliferative and hypertrophic zones. Regarding changes in the bone, ERT restored bone sclerosis through decreased bone formation and increased bone resorption, and CNP did not adversely affect this process. In addition, improvement of joint deformation by ERT was suggested by analyses of joint spaces and articular cartilage. CNP additively provided restoration of the short stature of MPS VII mice in combination with ERT, which improved abnormalities of growth plates and bone metabolism., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Cam morphology is not completely understood. The aim of this study was threefold: (1) to investigate if cam morphology development is associated with growth plate status; (2) to examine whether cam morphology continues to develop after growth plate closure; and (3) to qualitatively describe cam morphology development over 5-year follow-up., Methods: Academy male football players (n=49) participated in this prospective 5-year follow-up study (baseline 12-19 years old). Anteroposterior and frog-leg lateral views were obtained at baseline (142 hips), 2.5-year (126 hips) and 5-year follow-up (98 hips). Cam morphology on these time points was defined as: (A) visual scores of the anterior head-neck junction, classified as: (1) normal, (2) flattening, and (3) prominence; and (B) alpha angle ≥60°. Proximal femoral growth plates were classified as open or closed. Cam morphology development was defined as every increase in visual score and/or increase in alpha angle from <60° to ≥60°, between two time points. This resulted in 224 measurements for cam morphology development analysis., Results: Cam morphology development was significantly associated with open growth plates based on visual score (OR: 10.03, 95% CI 3.49 to 28.84, p<0.001) and alpha angle (OR: 2.85, 95% CI 1.18 to 6.88, p=0.020). With both definitions combined, cam developed in 104 of 142 hips during follow-up. Of these 104 hips, cam developed in 86 hips (82.7%) with open growth plate and in 18 hips (17.3%) with a closed growth plate. Cam morphology developed from 12 to 13 years of age until growth plate closure around 18 years., Conclusion: Cam morphology of the hip is more likely to develop with an open growth plate., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Obese children grow faster than their normal-weight peers. Insulin resistance and hyperinsulinemia have been associated with obesity-related growth acceleration. To determine whether obesity-associated hyperinsulinemia promotes bone growth by activating the insulin receptor in the growth plate, we generated TamCart IR flox/flox mice. The injection of 4 doses of tamoxifen in these mice (beginning at postnatal day 5th with 2 days interval between injections) resulted in the Insulin Receptor (IR) gene excision exclusively in the cartilage. TamCart IR flox/flox tamoxifen-treated mice (KO mice) and their IR flox/flox control littermates (C mice) at 3 weeks of age were exposed to a standard or hypercaloric (high-fat) diet for 4 weeks. At the end of study, C and KO mice fed with a high-fat diet exhibited greater weight gain than the respective strains fed with a standard diet. Body and tibial growth and growth plate height of C mice fed with high-fat diet were greater than those of standard-diet-fed C mice; however, no difference was observed between KO mice fed with standard or high-fat diet with respect to body and tibial growth and growth plate height. Circulating levels of insulin, IGF-1 and leptin were significantly higher in C and KO mice exposed to high-fat diet compared to those in the same strain exposed to standard diet. Increased phosphorylation of Akt (one of the intracellular mediators of insulin action in bone) in the growth plate of C mice on high-fat diet (compared to those on standard diet) suggests that high-fat-mediated increased circulating insulin levels may directly affect growth plate function and bone growth. High-fat diet was not associated with any change of Akt phosphorylation in KO mice. In addition, in vitro studies in cultured primary chondrocytes revealed that Akt mediates the stimulatory effects of insulin on chondrocyte proliferation and differentiation. In conclusion, the activation of the insulin receptor in the growth plate of mice fed with a hypercaloric diet stimulates skeletal growth and growth plate chondrogenesis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Growth plate cartilage contributes to the generation of a large variety of shapes and sizes of skeletal elements in the mammalian system. The removal of cartilage and how this process regulates bone shape are not well understood. Here we identify a non-bone-resorbing osteoclast subtype termed vessel-associated osteoclast (VAO). Endothelial cells at the bone/cartilage interface support VAOs through a RANKL-RANK signalling mechanism. In contrast to classical bone-associated osteoclasts, VAOs are dispensable for cartilage resorption and regulate anastomoses of type H vessels. Remarkably, proteinases including matrix metalloproteinase-9 (Mmp9) released from endothelial cells, not osteoclasts, are essential for resorbing cartilage to lead directional bone growth. Importantly, disrupting the orientation of angiogenic blood vessels by misdirecting them results in contorted bone shape. This study identifies proteolytic functions of endothelial cells in cartilage and provides a framework to explore tissue-lytic features of blood vessels in fracture healing, arthritis and cancer.

The patterns of longitudinal and peripheral growth were analyzed in human autopod cartilage anlagen (fetal developmental stage 20th-22nd week) through morphometric assessment of chondrocyte parameter size, shape, alignment and orientation between peripheral and central sectors of the anlage transition zone defined by primary ossification center and the epiphyseal basis. The aim was to correlate the chondrocyte dynamics with the longitudinal and peripheral growth. A further comparison was carried out between the corresponding sectors of the postnatal (3-5 months old) growth plate cartilage documenting: (1) the different chondrocyte framework and the new peripheral mechanism; (2) the opposite direction of fetal periosteal ossification versus the Lacroix bone bark. Measurement of multiple parameters (% lac area, % total matrix area, total lac density and mean single lac area), which characterize the cartilage Anlage growth, suggested the following correlations with chondrocyte duplication rate: (a) slow duplication rate ≈ coupled, intralacunar chondrocytes (in central epiphysis); (b) repeated/frequent cell duplications ≈ clusters (in the basal epiphyseal layer); (c) clusters of chondrocytes before becoming hypertrophic were stacked up on the top of each other (both in the Anlage transition zone or in the columns of metaphyseal growth plate); (d) enhanced osteoclastic resorption of the Lacroix bone bark lower end, extended to the more external metaphyseal trabeculae counterbalancing the discrepancy between the epiphyseal and the diaphyseal circumferential growth., (© 2018 Wiley Periodicals, Inc.)

Background: Controversy exists with regard to the amount of fracture displacement that warrants surgical fixation of medial epicondyle fractures. Inaccurate determination of degree of displacement on plain radiographs may account for the disputed management. Recently, a novel distal humerus axial radiograph technique has been developed to improve the accuracy of radiographs. The purposes of the study are 2-fold; to identify the anatomic orientation of the medial elbow epicondyle physis in children and to compare the accuracy of determining fracture displacement between axial radiographs and standard anterior-posterior (AP) radiographs in a cadaveric medial epicondyle fracture model., Methods: Twelve pediatric elbow computed tomographic scans and 19 pediatric elbow magnetic resonance imaging scans were analyzed for the orientation of the medial elbow physis. After determining the correct orientation, 15 adult cadaveric medial epicondyle fracture models were created at displacements of 2, 5, 10 mm, and maximum displacement with elbow at 90 degrees of flexion. A linear mixed model regression analysis was used to compare displacement based on the axial versus the AP radiographic methods., Results: The medial epicondyle physis was found to be a posterior structure angled distally at ~36 degrees (range, 10.7 to 49.6) and angled posteriorly at 45 degrees (range, 32.2 to 59). The AP radiograph significantly underestimated displacement relative to the axial radiograph at 5 mm [mean difference, -1.6; 95% confidence interval (CI), -2.9 to -0.3], at 10 mm (mean difference, -4.5; 95% CI, -5.8 to -3.2 mm), and at maximal displacement (mean, 15 mm; range, 13 to 20 mm) (mean difference, -7.1; 95% CI, -8.3 to -5.8)., Conclusions: The medial epicondyle physis of the distal humerus is a posterior structure angled distally and posteriorly. When displacement was >5 mm, the distal humerus axial radiograph technique was significantly more accurate than the AP radiograph technique at determining actual fracture displacement in our adult cadaveric fracture models. Therefore, we recommend clinicians to include the axial radiograph view during the evaluation of patients with medial epicondyle fractures., Clinical Relevance: This study provides further insight into the location and orientation of the medial humeral epicondyle physis, and further supports the improved accuracy of the distal humerus axial radiograph at detecting displacement in medial epicondyle fractures.

Spondyloepiphyseal dysplasia (SED) exemplifies a group of heritable diseases caused by mutations in collagenous proteins of the skeletal system. Its main feature is altered skeletal growth. Pathomechanisms of SED include: changes in the stability of collagen II molecules, inability to form proper collagen fibrils, excessive intracellular retention of mutant molecules, and endoplasmic reticulum stress. The complexity of this pathomechanism presents a challenge for designing therapies for SED. Our earlier research tested whether such therapies only succeed when applied during a limited window of development. Here, employing an inducible mouse model of SED caused by the R992C mutation in collagen II, we corroborate our earlier observations that a therapy must be applied at the prenatal or early postnatal stages of skeletal growth in order to be successful. Moreover, we demonstrate that blocking the expression of the R992C collagen II mutant at the early prenatal stages leads to long-term positive effects. Although, we could not precisely mark the start of the expression of the mutant, these effects are not significantly changed by switching on the mutant production at the early postnatal stages. By demonstrating the need for early therapeutic interventions, our study provides, for the first time, empirically-based directions for designing effective therapies for SED and, quite likely, for other skeletal dysplasias caused by mutations in key macromolecules of the skeletal system., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The medial patellofemoral ligament (MPFL) is frequently reconstructed to treat recurrent patellar instability. The femoral origin of the MPFL is well described in adults but not in the skeletally immature knee., Purpose: To identify a radiographic landmark for the femoral MPFL attachment in the skeletally immature knee and study its relationship to the distal femoral physis., Study Design: Descriptive laboratory study., Methods: Thirty-six cadaveric specimens between 2 and 11 years old were dissected and examined (29 male and 7 female). Metallic markers were placed at the proximal and distal borders of the MPFL femoral origin footprint. Computed tomography scans with 0.625-mm slices in the axial, coronal, and sagittal planes were used to measure the maximum ossified height and ossified depth. The measurements were used to describe the position of the midpoint MPFL attachment with respect to the posterior-anterior and distal-proximal dimensions of the femoral condyle on the sagittal view and to describe the distance from the physis to the femoral origin of the MPFL., Results: In 23 of 36 specimens, the femoral origin of the MPFL was distal to the physis. Thirteen of the 36 specimens had an MPFL origin at or proximal to the physis, with a more proximal MPFL origin consistently seen in older specimens. The distance of the MPFL origin to the physis ranged from 15.1 mm distal to the physis to 8.3 mm proximal to the physis. The mean midpoint of the MPFL femoral origin was located 3.0 ± 5.5 mm distal to the physis for all specimens. For specimens aged <7 years, the mean MPFL origin was 4.7 mm distal to the physis, and for specimens aged ≥7 years, the mean MPFL origin was 0.8 mm proximal to the femoral physis. The MPFL origin was more proximal and anterior for those aged ≥7 years and more distal and posterior for those aged <7 years., Conclusion: Surgical reconstruction of the MPFL is a common treatment to restore patellar stability. There appears to be significant variability in the origin of the MPFL in skeletally immature specimens. This study demonstrated that the MPFL origin was more proximal and anterior with respect to the physis in the older age group. The MPFL origin footprint may be customized for different age groups., Clinical Relevance: This information shows anatomic variation of the MPFL origin with age, with older specimens having a footprint that was more proximal and anterior than younger specimens. Customization of the surgical technique might be considered based on patient age.

Mg-based biodegradable materials are considered promising candidates in the paediatric field due to their favourable mechanical and biological properties and their biodegrading potential that makes a second surgery for implant removal unnecessary. In many cases the surgical fixation technique requires a crossing of the growth plate by the implant in order to achieve an adequate fragment replacement or fracture stabilisation. This study investigates the kinetics of slowly and rapidly degrading Mg alloys in a transphyseal rat model, and also reports on their dynamics in the context of the physis and consecutive bone growth. Twenty-six male Sprague-Dawley rats received either a rapidly degrading (ZX50; n = 13) or a slowly degrading (WZ21; n = 13) Mg alloy, implanted transphyseal into the distal femur. The contralateral leg was drilled in the same manner and served as a direct sham specimen. Degradation behaviour, gas formation, and leg length were measured by continuous in vivo micro CT for up to 52 weeks, and additional high-resolution µCT (HRS) scans and histomorphological analyses of the growth plate were performed. The growth plate was locally destroyed and bone growth was significantly diminished by the fast degradation of ZX50 implants and the accompanying release of large amounts of hydrogen gas. In contrast, WZ21 implants showed homogenous and moderate degradation performance, and the effect on bone growth did not differ significantly from a single drill-hole defect., Statement of Significance: This study is the first that reports on the effects of degrading magnesium implants on the growth plate in a living animal model. The results show that high evolution of hydrogen gas due to rapid Mg degradation can damage the growth plate substantially. Slow degradation, however, such as seen for WZ21 alloys, does not affect the growth plate more than drilling alone, thus meeting one important prerequisite for deployment in paediatric osteosynthesis., (Copyright © 2017. Published by Elsevier Ltd.)

Background: Restoration of the natural joint line is a cornerstone for kinematically aligned total knee arthroplasty (TKA). The purpose of this study was to investigate the relative orientation of the tibial growth plate (GP) with respect to the tibial plateau (TP) for possible application in predicting natural joint line for knees with highly advanced osteoarthritis patient at the time of kinematically aligned TKA., Methods: Images from computed tomography (CT) of 27 normal knees (9 males, 18 females; mean age, 31.6 years) were studied. Geometry of the GP was extracted from CT images, and its moment-of-inertia axes were calculated for the whole GP and the medial and lateral halves. Angular orientations of each GP axis with respect to the TP plane were measured in anatomical coordinates., Results: The TP and GP planes were oriented in 2.3 ± 1.8° of varus and 1.1 ± 1.9° of valgus relative to the tibial mechanical axis, respectively. With respect to the TP plane, the whole GP plane was inclined in 3.4 ± 1.5° of valgus. Orientation of the GP plane differed drastically between medial and lateral halves. The medial GP was in 4.9 ± 2.9° of varus and 1.8 ± 2.5° of anterior inclination, and the lateral half was in 10.4 ± 2.4° of valgus and 18.6 ± 4.0° of anterior inclination relative to the TP., Conclusions: Angular orientation of the original TP plane can be predicted in reference to the GP plane and may provide reasonable guidance for the target bone resection angle of the tibia in kinematically aligned TKA.

Background: Anterior cruciate ligament (ACL) reconstruction failure rates are highest in youth athletes. The role of the anterolateral ligament in rotational knee stability is of increasing interest, and several centers are exploring combined ACL and anterolateral ligament reconstruction for these young patients. Literature on the anterolateral ligament of the knee is sparse in regard to the pediatric population. A single study on specimens younger than age 5 years demonstrated the presence of the anterolateral ligament in only one of eight specimens; therefore, much about the prevalence and anatomy of the anterolateral ligament in pediatric specimens remains unknown., Questions/purposes: We sought to (1) investigate the presence or absence of the anterolateral ligament in prepubescent anatomic specimens; (2) describe the anatomic relationship of the anterolateral ligament to the lateral collateral ligament; and (3) describe the anatomic relationship between the anterolateral ligament and the physis., Methods: Fourteen skeletally immature knee specimens (median age, 8 years; range, 7-11 years) were dissected (12 male, two female specimens). The posterolateral structures were identified in all specimens, including the lateral collateral ligament and popliteus tendon. The presence or absence of the anterolateral ligament was documented in each specimen, along with origin, insertion, and dimensions, when applicable. The relationship of the anterolateral ligament origin to the lateral collateral ligament origin was recorded., Results: The anterolateral ligament was identified in nine of 14 specimens. The tibial attachment point was consistently located in the same region on the proximal tibia, between the fibular head and Gerdy's tubercle; however, the femoral origin of the anterolateral ligament showed considerable variation with respect to the lateral collateral ligament origin. The median femoral origin of the anterolateral ligament was 10 mm (first interquartile 6 mm, third interquartile 13) distal to the distal femoral physis, whereas its median insertion was 9 mm (first interquartile 5 mm, third interquartile 11 mm) proximal to the proximal tibial physis., Conclusions: The frequency of the anterolateral ligament in pediatric specimens we observed was much lower than other studies on adult specimens; future studies might further investigate the prevalence, development, and functional role of the anterolateral ligament of the knee., Clinical Relevance: This study expands our understanding of the anterolateral ligament and provides important anatomic information to surgeons considering anterolateral ligament reconstruction concomitantly with primary or revision ACL reconstruction in pediatric athletes.

Osteoclasts and chondroclasts are necessary, during endochondral ossification, for the resorption of primary bone and calcified cartilage septa, respectively. The bisphosphonates inhibit mineralized tissue resorption by various mechanisms according to the different types of this drug, which can affect bone remodeling during skeletal growth. The objective of the present study is to analyze the way that alendronate (ALN) and etidronate (ETN) can affect osteoclastogenesis and bone formation during endochondral ossification of the long bones of growing rats. Newborn Wistar rats were treated daily with ETN, ALN, or sterile saline solution (control) for 21 days. Their femur and tibiae epiphyses were radiographed and analyzed by light, scanning and transmission electron microscopy. The expression of genes related to osteogenesis and to osteoclast differentiation and activity were analyzed by real-time quantitative polymerase chain reaction. The ETN group presented reduced body weight, disorganized growth plate and an extended area of cartilage in the ossification zone with little bone matrix; in the ALN group, this area was not altered. The ALN presented latent TRAP-positive cells, whereas in the ETN group, they were activated. The expression of NFκB1 and 2, OPG, Spp1 and Runx2 in the ossification zone was reduced by both bisphosphonates. RANKL expression was reduced by ETN, whereas ALN decreased the expression of RANK. The results also indicated that, in addition to the anti-resorptive effect of the drugs, disturbances in bone deposition occurred concomitantly with the reduced expression of osteogenesis-related genes.

Background: Young athletes sustain patellar dislocations in a variety of sports. The medial patellofemoral ligament (MPFL) is a critical structure that functions as an anatomic checkrein to help prevent lateral patellar dislocation. Reconstruction of this ligament is challenging in patients with open physes because of concerns about iatrogenic damage to the femoral physis., Purpose: To evaluate the relationship of the distal femoral physis and the MPFL., Study Design: Descriptive laboratory study., Methods: In 15 cadaveric, pediatric knees (age, 7-11 years), markers were placed at the proximal/distal limits of the MPFL femoral attachment and were evaluated with computed tomography. The distance from the MPFL attachment midpoint to the most medial aspect of the distal femoral physis was measured., Results: The mean femoral width of the MPFL was 8.1 mm (range, 4.3-13.8 mm). The femoral MPFL midpoint was distal to the femoral physis in 11 specimens and proximal to the physis in 4 specimens. The most proximal portion of the MPFL femoral attachment extended above the medial physis in 7, was at the physis in 5, and was below the physis in 3 specimens. One specimen had the entire MPFL femoral attachment above the physis. For knees with the MPFL midpoint above the medial physis, the distance between the center of the MPFL and physis was 3.3 mm (range, 0.3-7.1 mm). For knees with the MPFL below the medial physis, the distance between the center of the MPFL and physis was -6.8 mm (range, -0.7 to -22.0 mm)., Conclusion: The relationship of the femoral attachment of the MPFL and the medial femoral physis shows some anatomic variation. In all cases, the MPFL is close to the medial femoral physis, but the midpoint of the MPFL is at, slightly above, or slightly below the physis., Clinical Relevance: The relationship of the MPFL femoral attachment footprint to the femoral physis in the skeletally immature patient is not well understood, and access to pediatric cadaveric tissue is very limited. This small series demonstrates that there is considerable variation in the relationship between the MPFL and distal femoral physis. This anatomic information may guide MPFL reconstruction technique in young patients and reduce the risk of iatrogenic physeal arrest on the femur., (© 2016 The Author(s).)

The growth plate (physis) is responsible for enabling and regulating longitudinal growth of upper and lower limbs. This regulation occurs through interaction of the cells in the growth plate with systemic and locally produced factors. This complex interaction leads to precisely controlled changes in chondrocyte size, receptors, and matrix, which ultimately result in endochondral bone formation. With advances in cellular and molecular biology, our knowledge about these complex interactions has increased significantly over the past decade. Deficiency of any of the regulating factors or physeal injury during childhood can alter this well-orchestrated sequence of events and lead to abnormalities in growth. This review highlights the histology of the normal physis, including recent findings at the cellular and molecular levels, mechanics and mechanobiology of the growth plate, pathologies that can affect the physis, and treatment options, including interposition materials.

Mechanical stimuli play a significant role in the process of endochondral growth. Thus far, approaches to understand the endochondral mechanical growth rate have been limited to the use of approximated location and geometry of the growth plate. Furthermore, growth has been simulated based on the average deflection of the growth plate or of the femoral neck. It has also been reported in the literature that the growth plate lies parallel to one of the principal stresses acting on it, to reduce the shear between epiphysis and diaphysis. Hence the current study objectives were (1) to evaluate the significance of a subject-specific finite element model of the femur and growth plate compared to a simplified growth plate model and (2) to explore the different growth direction models to better understand proximal femoral growth mechanisms. A subject-specific finite element model of an able-bodied 7-year old child was developed. The muscle forces and hip contact force were computed for one gait cycle and applied to a finite element model to determine the specific growth rate. Proximal femoral growth was simulated for two different growth direction models: femoral neck deflection direction and principal stress direction. The principal stress direction model captured the expected tendency for decreasing the neck shaft angle and femoral anteversion for both growth plate models. The results of this study suggest that the subject-specific geometry and consideration of the principal stress direction as growth direction may be a more realistic approach for correct prediction of proximal femoral growth morphology., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Heel pain in children and secondary MR imaging (MRI) of the hindfoot have been increasing in incidence. Our purpose is to illustrate the, previously unreported, MRI stages in development of the posterior calcaneal apophysis, with attention to imaging pitfalls. This should aid in distinguishing normal growth from true disease., Material and Methods: Consecutive ankle MRIs in children <18 years, from 2008-2014, were subdivided into 0≤5, 5≤10, 10≤15 and 15≤18 age groups and retrospectively reviewed for development of the calcaneal apophysis., Results: 204 ankle MRI studies in 188 children were identified. 40 studies were excluded with final cohort of 164 studies in 154 patients (82 boys, 72 girls). The calcaneal apophysis was cartilaginous until age 5. Foci of decreased as well as increased signal were embedded in cartilage, prior to ossification. Early, secondary ossification centers appeared in plantar third of the apophysis in 100% of children by age 7. Increased T2 signal in the ossifications was seen in 30% of children. Apohyseal fusion began at 12 and was complete in 78% of 14≤15 year olds and in 88% of 15≤18 year olds. Curvilinear low signal in the ossification centers, paralleling, but distinguished from growth plate, and not be confused with fracture line, was common., Conclusion: Development of the posterior calcaneus follows a unique sequence. Apophyseal fusion occurs earlier than reported in the literature. Familiarity with this maturation pattern, in particular the apophyseal increased T2 signal and the linear low signal paralleling the growth plate, will avoid misinterpreting it for pathology.

Purpose: The purpose of this study was to investigate the effects of transplantation of an in vitro-generated, scaffold-free, tissue-engineered cartilage tissue analogue (CTA) using a suspension chondrocyte culture in a rabbit growth-arrest model., Materials and Methods: We harvested cartilage cells from the articular cartilage of the joints of white rabbits and made a CTA using a suspension culture of 2×10⁷ cells/mL. An animal growth plate defect model was made on the medial side of the proximal tibial growth plate of both tibias of 6-week-old New Zealand white rabbits (n=10). The allogenic CTA was then transplanted onto the right proximal tibial defect. As a control, no implantation was performed on the left-side defect. Plain radiographs and the medial proximal tibial angle were obtained at 1-week intervals for evaluation of bone bridge formation and the degree of angular deformity until postoperative week 6. We performed a histological evaluation using hematoxylin-eosin and Alcian blue staining at postoperative weeks 4 and 6., Results: Radiologic study revealed a median medial proximal tibial angle of 59.0° in the control group and 80.0° in the CTA group at 6 weeks. In the control group, statistically significant angular deformities were seen 3 weeks after transplantation (p<0.05). On histological examination, the transplanted CTA was maintained in the CTA group at 4 and 6 weeks postoperative. Bone bridge formation was observed in the control group., Conclusion: In this study, CTA transplantation minimized deformity in the rabbit growth plate injury model, probably via the attenuation of bone bridge formation.

Apophyses are growth zones attached to the shaft (corpus) of larger bones. They vary in size and develop their own ossification centres or form as part of an usually fibrocartilaginous tendon or ligament insertion. The structure of the cartilaginous apophyseal plate is very similar to that of an epiphyseal growth plate and like these they are adapted to withstand perpendicular compressive forces without becoming harmed. This is best highlighted by the fact that their mineralized borders always orient themselves perpendicular to the overall resulting force vector. The edges of the apophyseal plates are characteristically bent which allows them to resist moderate shear forces. Like the epiphyseal plates the apophyseal plates exhibit a zonal organization which is not very well adapted to permanently withstand shear forces, especially if they occur under dynamic conditions. In these situations the tendinous insertions with their collagen fibre anchoring system have to provide compensation when balancing the load transmitted across the system.

Background: The structure of apophyses and apophyseal growth plates is not substantially different from those of epiphyses and epiphyseal growth plates. In contrast to epiphyseal growth plates, apophyses and apophyseal growth plates do not contribute to the longitudinal growth of the extremity. They are associated with their adjacent joints, triggering the lengths of their lever arms and influencing their external shape and internal architecture. The formative stimulus on apophyses is given by muscles and tendons inserting at the apophysis or canopying the apophsis., Apophysis of the Greater Trochanter: The apophysis of the greater trochanter significantly contributes to the lever arm length of the hip joint. Its growth activity triggers the neck-shaft angle and finally the centration of the hip joint., Tibial Apophysis: The tibial apophysis interacts with the slope of the proximal tibia and hereby influences the sagittal stability of the knee joint. A damage to the growth plate of the tibial tubercle leads to an anteverted tibial slope and a genu recurvatum difficult to treat., Calcaneal Apophysis: The calcaneal apophysis determines the length and position of the calcaneus and herewith influences the torque of the ankle joint. In a nutshell you may regard the apophyses as adjusting screws acting on their adjacent joints and influencing their growth, form and structure.

Purpose: 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)., Methods: 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., Results: 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)., Conclusions: 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.

Cartilage canals have been shown to contain discontinuous blood vessels that enable circulating bacteria to bind to cartilage matrix, leading to vascular occlusion and associated pathological changes in pigs and chickens. It is also inconsistently reported that cartilage canals are surrounded by a cellular or acellular wall that may influence whether bacterial binding can occur. It is not known whether equine cartilage canals contain discontinuous endothelium or are surrounded by a wall. This study aimed to examine whether there were discontinuities in the endothelium of cartilage canal vessels, and whether canals had a cellular or acellular wall, in the epiphyseal growth cartilage of foals. Epiphyseal growth cartilage from the proximal third of the medial trochlear ridge of the distal femur from six healthy foals that were 1, 24, 35, 47, 118 and 122 days old and of different breeds and sexes was examined by light microscopy (LM), transmission electron microscopy (TEM) and immunohistochemistry. The majority of patent cartilage canals contained blood vessels that were lined by a thin layer of continuous endothelium. Fenestrations were found in two locations in one venule in a patent cartilage canal located deep in the growth cartilage and close to the ossification front in the 118-day-old foal. Chondrifying cartilage canals in all TEM-examined foals contained degenerated endothelial cells that were detached from the basement membrane, resulting in gap formation. Thirty-three percent of all canals were surrounded by a hypercellular rim that was interpreted as contribution of chondrocytes to growth cartilage. On LM, 69% of all cartilage canals were surrounded by a ring of matrix that stained intensely eosinophilic and consisted of collagen fibres on TEM that were confirmed to be collagen type I by immunohistochemistry. In summary, two types of discontinuity were observed in the endothelium of equine epiphyseal cartilage canal vessels: fenestrations were observed in a patent cartilage canal in the 118-day-old foal; and gaps were observed in chondrifying cartilage canals in all TEM-examined foals. Canals were not surrounded by any cellular wall, but a large proportion was surrounded by an acellular wall consisting of collagen type I. Bacterial binding can therefore probably occur in horses by mechanisms that are similar to those previously demonstrated in pigs and chickens., (© 2015 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of the Anatomical Society.)

Background: A child's knee undergoes significant morphologic changes during development. Age-specific normal parameters have not been previously described. The purpose of this study was to delineate knee morphology changes that occur with maturation utilizing magnetic resonance imaging (MRI)., Methods: A retrospective review of knee MRIs, ages 4 to 18 years, was performed using "normal" diagnosis codes, including: knee pain, plicae, septic arthritis, jumper's knee, growing pains, benign neoplasm, and osteomyelitis. Seventeen osseous parameters were measured, plus their cartilaginous counterparts, if different. Spearman ρ correlations were calculated between age and MRI measures., Results: A total of 132 MR images were reviewed. Significant correlation with age was observed in all osseous measurements, except medial patellofemoral ligament (MPFL) insertion (P<0.05). Similarly, the cartilage measures demonstrated significant correlation with age, except the notch width index, MPFL insertion, and trochlear morphology. The magnitude of correlation was significantly different between the osseous and cartilage measures for all but 4 of the variables: anterior cruciate ligament (ACL) length and width, intercondylar width and tibial tubercle-trochlear groove (TT-TG) interval. Sex seems to affect ACL length, Insall-Salvati ratio, intercondylar width, and sulcus angle.The MPFL origin starts distal to the physis and moves proximal with age (ρ=0.33, P<0.001), when at age 7 years, it is located at or above the femoral physis. The mean ACL diameter grows from 6.5 to 9.8 mm. Cartilage sulcus angle remains consistently 150 degrees, and the TT-TG interval shifts from 6 to 12 mm with maturity., Conclusions: The normative data presented here demonstrates that maturity correlates well with the morphologic changes seen in most of the studied parameters. These data not only aid in the identification of the abnormal findings by sex and age, but also provides normal sizes of the ACL and location of insertion for the MPFL which can benefit surgical planning.

Slipped capital femoral epiphysis (SCFE) is an orthopedic pathology in which damage of the growth plate leads to the anterosuperior displacement of the femoral body in respect to the femoral head. Despite being a widely studied disease, its etiology is still unknown. This study was carried out to determine the influence of the physeal-diaphysis angle, body mass, the presence of the perichondrial ring, the type of physical activity, and physeal thickness on SCFE. For this purpose, a finite element analysis of the hip joint and the femur-physis interface was carried out. With the computational model, the Von Mises stresses along the growth plate were calculated and subsequently analyzed statistically to find their correlation with the studied factors. It was found that body mass, the type of physical activity, and the presence of the perichondrial ring had more statistical relevance for the physeal stresses than the physeal-diaphysis angle and the physeal thickness. Thus, our work suggests that changes in growth plate inclination and thickness do not influence the etiology of SCFE.

The subchondral bone plate (SBP), a dynamic component of the osteochondral unit, shows functional adaptation to long-term loading by distribution of the mineral content in a manner best serving the mechanical demands. Since the received joint-load is transmitted into the trabecular system, the spongy bone also exhibits differences in strain energy density which models it for optimal support. To evaluate the regional variations in trabecular architecture, in accordance with the density distribution of the SBP revealing its long-term load intake, CT- and μCT-datasets of ten physiologic patellae were analysed for defined parameters of bony structure. For the SBP, the density distributions as well as area measurements were used. The trabecular architecture was described using parameters of bone morphology comprising the first 5mm (examined in 1mm steps) below the SBP. The obtained measurements are: Bone volume fraction (BV/TV); Bone surface density (BS/TV); Trabecular number (Tb.N); Trabecular separation (Tb.Sp); Trabecular thickness (Tb.Th); structure model index (SMI); and the Degree of anisotropy (DA). The evaluated architectural parameters varied within the trabecular system and showed an inhomogeneous distribution pattern. It proved to be distinctive with maxima of material and stability situated below areas of the highest long-term load intake. With increasing depth, the pattern of distribution was persistent but lessened in intensity. The parameters significantly correlated with the density distribution of the SBP within the first and second millimetres. With increasing depth down to the fifth millimetre, the coefficients of correlation decreased for all values. The trabecular network adapts to its mechanical needs and is therefore not homogenously built. Dependent upon the long-term load intake, the trabecular model optimizes the support with significant correlation to the density distribution of the SBP., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

Introduction: In forensic practice, there is a growing need for accurate methods of age estimation, especially in the cases of young individuals of unknown age. Age can be estimated through somatic features that are universally considered associated with chronological age. Unfortunately, these features do not always coincide with the real chronological age: for these reasons that age determination is often very difficult. Our aim is to evaluate accuracy of skeletal age estimation using Tomei's MRI method in subjects between 12 and 19 years old for forensic purposes., Material and Methods: Two investigators analyzed MRI images of the left hand and wrist of 77 male and 74 female caucasian subjects, without chronic diseases or developmental disorders, whose age ranged from 12 to 19 years. Skeletal maturation was determined by two operators, who analyzed all MRI images separately, in blinded fashion to the chronological age. Inter-rater agreement was measured with Pearson (R (2)) coefficient. One of the examiners repeated the evaluation after 6 months, and intraobserver variation was analyzed. Bland-Altman plots were used to determine mean differences between skeletal and chronological age., Results: Inter-rater agreement Pearson coefficient showed a good linear correlation, respectively, 0.98 and 0.97 in males and females. Bland-Altman analysis demonstrated that the differences between chronological and skeletal age are not significant. Spearman's correlation coefficient showed good correlation between skeletal and chronological age both in females (R (2) = 0.96) and in males (R (2) = 0.94)., Conclusions: Our results show that MRI skeletal age is a reproducible method and has good correlation with chronological age.

Purpose: To quantitatively evaluate growth plates around the knees in adolescent soccer players utilizing the diffusion-weighted MR imaging (DWI)., Methods: The knees and adjacent growth plates of eleven 14-year-old male soccer players were evaluated by MRI before (end of season's summer break) and after two months of intense soccer training. MRI evaluation was conducted in coronal plane by PD-FSE and DWI. All images were screened for any major pathological changes. Later, central growth plate surface area (CGPSA) was measured and the apparent diffusion coefficient (ADC) values were calculated in two most central coronal slices divided into four regions: distal femur medial (DFM), distal femur lateral (DFL), proximal tibia medial (PTM), and proximal tibia lateral (PTL)., Results: No gross pathology was diagnosed on MRI. CGPSA was not significantly reduced: DFM 278 versus 272, DFL 265 versus 261, PTM 193 versus 192, and PTL 214 versus 210. ADC decrease was statistically significant only for PTM: DFM 1.27 versus 1.22, DFL 1.37 versus 1.34, PTM 1.13 versus 1.03 (p = 0.003), and PTL 1.28 versus 1.22., Conclusions: DWI measurements indicate increased cellularity in growth plates around knees in footballers most prominent in PTM after intense training. No detectable differences on a standard PD-FSE sequence were observed.

Mountain biking (MB), unlike road cycling (RC) involves exposure to ground impact bone strain and requires upper-body muscle forces to maintain stability over uneven terrain and therefore may have differential effects on radial bone structure and strength. This study aimed to compare serum bone turnover marker concentration, 1-repetition maximum muscle strength and the radial proximal (diaphysis) and distal (metaphysis) bone structure [bone mineral content, total and cortical area (CoA), density and thickness, diameter and circumference], strength strain indices and muscle cross-sectional area (MCSA) using peripheral quantitative computed tomography (pQCT) between 30 male cyclists (18-34 years) MB (n = 10), RC (n = 10) and non-athletes controls (CON, n = 10). Differences were assessed by ANOVA and an ANCOVA (adjusting for body mass and height) where appropriate. MB radii were characterised by significantly stronger (14-16%), denser (9-27%) and larger (10%) metaphyses and stronger (22-23%) and larger (11-13%) diaphyses compared to RC and CON. RC had significantly 7% higher strength indices and 4% greater CoA and thickness than CON at the diaphysis, with no differences for other bone measurements. Serum C-terminal telopeptides of type-1 collagen concentration (bone resorption marker) was higher in RC than MB (p < 0.05) and above the age-reference range. MCSA and strength were greater in MB than RC (p < 0.05). Muscle forces generated during RC appear to produce an osteogenic stimulus to increase radial bone strength indices with minimal improvement in bone structure. However greater resorptive activity in RC suggests inadequate loading to support bone maintenance. In conclusion, bone loading, muscle size and strength of MB are superior to RC.

Background: Patellar dislocations are common in skeletally immature athletes, and the medial patellofemoral ligament (MPFL) is an important primary restraint to lateral patellar translation. The relationship between the MPFL femoral origin footprint and femoral physis is unclear. The purpose of this study was to evaluate the MPFL femoral origin footprint and its relationship to the femoral physis in skeletally immature anatomic specimens., Methods: Six skeletally immature cadaver knee specimens were examined through gross dissection (group A: 1, 11, and 11 mo; and group B: 8, 10, and 11 y). Metallic markers were placed at the center of the MPFL femoral origin footprint. Computed tomography scans for each specimen were analyzed. The MPFL footprint width, and the vertical distances from the center and proximal extent of the MPFL footprint to the medial aspect of the physis were measured., Results: The mean width of the MPFL femoral origin footprint was 0.70 cm (0.48 to 1.09 cm) and 1.12 cm (1.03 to 1.29 cm) for groups A and B, respectively. The mean distance from the center of the MPFL origin footprint to medial aspect of the distal femoral physis was 0.90 cm (0.52 to 1.30 cm) and 0.40 cm (0.00 to 0.86 cm) distal to the physis for groups A and B, respectively. The mean distance from the proximal extent of the MPFL origin footprint to the medial aspect of the femoral physis was -0.55 cm (-0.28 to -1.03 cm) and 0.16 cm (-0.34 to 0.64 cm) for groups A and B, respectively., Conclusions: All subjects were found to have a center of the MPFL origin footprint at or below the physis. The proximal extent of the MPFL origin footprint was found to extend above the physis in the 2 older specimens., Clinical Relevance: The relationship of the MPFL origin footprint to the femoral physis in the skeletally immature is not well understood. These dissections may be useful to surgeons performing MPFL reconstructions in skeletally immature patients.

Purpose: To analyze the accuracy of growth-plate thickness measurements detected on 1.5-T and 7-T MR images using histology sections as a standard of reference., Materials and Methods: Four defrosted pig tibiae were 1.5-T MR scanned and one fresh tibia was 7-T MR scanned. The height of the growth plate was measured and compared to histology., Results: Histology measurements showed a mean growth plate thickness of 467 μm (SD = 82.2). The mean growth plate thickness measured in the 7-T MR images was 465 μm (SD = 62.2) and 1,325 μm (SD = 183.5) on 1.5-T MR measurements. We found a better correspondence between the growth plate thickness measured on the 7-T MR and histology samples compared to 1.5 T., Conclusions: The growth plate can be identified and measured with high accuracy using 7-T MR. 1.5-T MR can only describe some morphological characteristics.

Objective: To assess the MRI appearance of normal skeletal development of the glenoid and glenoid-coracoid interface in the pediatric population. To the best of our knowledge, this has not yet been studied in detail in the literature., Materials and Methods: An IRB-approved, HIPAA-compliant retrospective review of 105 consecutive shoulder MRI studies in children, ages 2 months to 18 years was performed. The morphology, MR signal, and development of the following were assessed: (1) scapular-coracoid bipolar growth plate, (2) glenoid and glenoid-coracoid interface secondary ossification centers, (3) glenoid advancing osseous surface., Results: The glenoid and glenoid-coracoid interface were identified in infancy as a contiguous, cartilaginous mass. A subcoracoid secondary ossification center in the superior glenoid was identified and fused in all by age 12 and 16, respectively. In ten studies, additional secondary ossification centers were identified in the inferior two-thirds of the glenoid. The initial concavity of the glenoid osseous surface gradually transformed to convexity, matching the convex glenoid articular surface. The glenoid growth plate fused by 16 years of age. Our study, based on MRI, demonstrated a similar pattern of development of the glenoid and glenoid coracoid interface to previously reported anatomic and radiographic studies, except for an earlier development and fusion of the secondary ossification centers of the inferior glenoid., Conclusions: The pattern of skeletal development of the glenoid and glenoid-coracoid interface follows a chronological order, which can serve as a guideline when interpreting MRI studies in children.

Background: No published study has ever described the relationship of the medial patellofemoral ligament (MPFL) attachment to the distal femoral physis in skeletally immature cadaveric specimens. As such, there continues to be much confusion about this relationship, which is important when considering MPFL reconstruction in the skeletally immature patient., Hypothesis: The MPFL footprint is distal to the medial border of the distal femoral physis., Study Design: Descriptive laboratory study., Methods: Sixteen skeletally immature cadaveric specimens were used for this study. The average age of the specimens was 12 years (range, 10-15 years). The MPFL femoral attachment, adductor tubercle, and medial epicondyle were identified in all specimens, and the topography of the distal femoral physis was carefully described. Measurements were then taken of the distance from the medial aspect of the distal femoral physis to the MPFL femoral attachment and the horizontal distance from the MPFL femoral attachment to the point where a femoral tunnel would intersect the undulating femoral physis. All measurements were made with digital calipers., Results: The MPFL attachment was distal to the medial aspect of the femoral physis in all specimens. The MPFL attachment was an average of 8.5 mm distal to the medial aspect of the distal femoral physis. In the coronal plane, the undulating physis was 10.5 mm medial to the MPFL attachment. In all specimens, the undulations of the medial physis were concave directly posterior and lateral to the MPFL attachment and convex anterior to the MPFL attachment. Both the adductor tubercle and the medial epicondyle were also distal to the femoral physis in all specimens., Conclusion: This study has confirmed the findings of others, who have shown that the MPFL femoral attachment lies distal to the medial aspect of the distal femoral physis. In addition, the study findings show that the MPFL femoral attachment is in very close proximity to the distal femoral physis., Clinical Relevance: To facilitate anatomic MPFL reconstruction, Schottle et al described a radiographic method to identify the MPFL femoral attachment on lateral radiographs in skeletally mature patients. Because of the complex physeal anatomy, much confusion exists concerning whether an MPFL femoral tunnel can be placed safely in the pediatric patient. The findings of this study suggest that anatomic MPFL reconstruction may be accomplished with a tunnel angled distally and anteriorly to avoid injury to the distal femoral physis., (© 2014 The Author(s).)

Purpose: High-resolution visualization of cartilage canals has been restricted to histological methods and contrast-enhanced imaging. In this study, the feasibility of non-contrast-enhanced susceptibility weighted imaging (SWI) for visualization of the cartilage canals was investigated ex vivo at 9.4 T, further explored at 7 and 3 T and demonstrated in vivo at 7 T, using a porcine animal model., Methods: SWI scans of specimens of distal femur and humerus from 1 to 8 week-old piglets were conducted at 9.4 T using 3D-GRE sequence and SWI post-processing. The stifle joints of a 2-week old piglet were scanned ex vivo at 7 and 3 T. Finally, the same sites of a 3-week-old piglet were scanned, in vivo, at 7 T under general anesthesia using the vendor-provided sequences., Results: High-contrast visualization of the cartilage canals was obtained ex vivo, especially at higher field strengths; the results were confirmed histologically. In vivo feasibility was demonstrated at 7 T and comparison of ex vivo scans at 3 and 7 T indicated feasibility of using SWI at 3 T., Conclusions: High-resolution 3D visualization of cartilage canals was demonstrated using SWI. This demonstration of fully noninvasive visualization opens new avenues to explore skeletal maturation and the role of vascular supply for diseases such as osteochondrosis., (Copyright © 2013 Wiley Periodicals, Inc.)

Background: Understanding the relationship of the posterior cruciate ligament (PCL) and the lateral collateral ligament (LCL) to the femoral and tibial physes is important to reducing the risk of physeal injury during surgical reconstruction. The purpose of this study was to identify the location of the attachments of the PCL and LCL in skeletally immature cadaveric knee specimens and to determine their position relative to the physes., Methods: Seven skeletally immature cadaveric knee specimens were examined through gross dissection. These specimens were divided into two groups: infants (an age at death of one month for one specimen and eleven months for two specimens) and children (an age at death of eight years for one specimen, ten years for one specimen, and eleven years for two specimens). Metallic markers were placed at the femoral origins of the PCL and LCL and at the tibial insertion of the PCL. Computed tomography (CT) scans were made for each specimen and analyzed with the use of OsiriX imaging software. The width of the PCL tibial insertion footprint and the height of the PCL femoral origin footprint, the distance from the midpoints of the PCL and LCL femoral origin to the distal femoral physis, and the distance from the PCL insertion footprint midpoint to the proximal tibial physis were measured., Results: The mean distance from the midpoint of the femoral origin footprint of the PCL to the femoral physis was 11.1 mm (range, 10.6 to 11.7 mm) and 18.8 mm (range, 18.2 to 19.2 mm) distal to the physis for infants and children, respectively. The mean distance from the midpoint of the tibial insertion footprint of the PCL to the tibial physis was 3.1 mm (range, 0.0 to 5.7 mm) and 5.8 mm (range, 2.5 to 8.9 mm) proximal to the physis for infants and children, respectively. The mean width of the tibial insertion of the PCL was 5.5 mm (range, 1.1 to 8.3 mm) for infants and 10.2 mm (range, 8.4 to 11.9 mm) for children. The mean distance from the midpoint of the femoral origin of the LCL to the femoral physis was 6.3 mm (range, 3.9 to 7.7 mm) and 5.9 mm (range, 0.0 to 10.0 mm) distal to the physis for infants and children, respectively., Conclusions: The relationship of the PCL and LCL attachments to physeal structures has not been well described. We found the midpoints of the PCL and LCL femoral origins at or distal to, and the midpoint of the PCL tibial insertion at or proximal to, the respective physis in all specimens. This study with CT-scan correlation provides unique information on the location of ligament attachments in relation to the physes., Clinical Relevance: A better understanding of the spatial relationship between the PCL and LCL attachments and their respective physes may help guide drill-hole placement during ligament reconstructions and reduce the risk for iatrogenic physeal injury in skeletally immature patients.

Little is known about changes in human cartilage thickness and subchondral bone plate area (tAB) during growth. The objective of this study was to explore longitudinal change in femorotibial cartilage thickness and tAB in adolescent athletes, and to compare these data with those of mature former athletes. Twenty young (baseline age 16.0 ± 0.6 years) and 20 mature (46.3 ± 4.7 years) volleyball athletes were studied (10 men and 10 women in each group). Magnetic resonance images were acquired at baseline and at year 2-follow-up, and longitudinal changes in cartilage thickness and tAB were determined quantitatively after segmentation. The yearly increase in total femorotibial cartilage thickness was 0.8% (95% confidence interval [CI]: -0.5; 2.1%) in young men and 1.4% (95% CI: 0.7; 2.2%) in young women; the gain in tAB was 0.4% (95% CI: -0.1; 0.8%) and 0.7% (95% CI: 0.2; 1.2%), respectively (no significant difference between sexes). The cartilage thickness increase was greatest in the medial femur, and was not significantly associated with the variability in tAB growth (r=-0.19). Mature athletes showed smaller gains in tAB, and lost >1% of femorotibial cartilage per annum, with the greatest loss observed in the lateral tibia. In conclusion, we find an increase in cartilage thickness (and some in tAB) in young athletes toward the end of adolescence. This increase appeared somewhat greater in women than men, but the differences between both sexes did not reach statistical significance. Mature (former) athletes displayed high rates of (lateral) femorotibial cartilage loss, potentially due to a high prevalence of knee injuries., (Copyright © 2013 Elsevier GmbH. All rights reserved.)

Introduction: Magnetic resonance imaging (MRI) is used to assess trabecular bone microarchitecture in humans; however, image processing can be labor intensive and time consuming. One aim of this study was to determine the pattern of trabecular bone microarchitecture in the distal femur of typically developing children. A second aim was to determine the proportion and location of magnetic resonance images that need to be processed to yield representative estimates of trabecular bone microarchitecture., Materials and Methods: Twenty-six high resolution magnetic resonance images were collected immediately above the growth plate in the distal femur of 6-12year-old typically developing children (n=40). Measures of trabecular bone microarchitecture [i.e., apparent trabecular bone volume to total volume (appBV/TV), trabecular number (appTb.N), trabecular thickness (appTb.Th) and trabecular separation (appTb.Sp)] in the lateral aspect of the distal femur were determined using the twenty most central images (20IM). The average values for appBV/TV, appTb.N, appTb.Th and appTb.Sp from 20IM were compared to the average values from 10 images (10IM), 5 images (5IM) and 3 images (3IM) equally dispersed throughout the total image set and one image (1IM) from the center of the total image set using linear regression analysis. The resulting mathematical models were cross-validated using the leave-one-out technique., Results: Distance from the growth plate was strongly and inversely related to appBV/TV (r(2)=0.68, p<0.001) and appTb.N (r(2)=0.92, p<0.001) and was strongly and positively related to appTb.Sp (r(2)=0.86, p<0.001). The relationship between distance from the growth plate and appTb.Th was not linear (r(2)=0.06, p=0.28), but instead it was quadratic and statistically significant (r(2)=0.54, p<0.001). Trabecular bone microarchitecture estimates from 10IM, 5IM, 3IM and 1IM were not different from estimates from 20IM (p>0.05). However, there was a progressive decrease in the strength of the relationships as a smaller proportion of images were used to predict estimates from 20IM (r(2)=0.98 to 0.99 using 10IM, 0.94 to 0.96 using 5IM, 0.87 to 0.90 using 3IM and 0.66 to 0.72 using 1IM; all p<0.001). Using the resulting mathematical models and the leave-one-out cross-validation analysis, measures of trabecular bone microarchitecture estimated from the 10IM and 5IM partial image sets agreed extremely well with estimates from 20IM., Conclusions: The findings indicate that partial magnetic resonance image sets can be used to provide reasonable estimates of trabecular bone microarchitecture status in the distal femur of typically developing children. However, because the relative amount of trabecular bone in the distal femur decreases with distance from the growth plate due to a decrease in trabecular number, careful positioning of the region of interest and sampling from throughout the region of interest is necessary., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Study Design: Histological features of the intervertebral disc (IVD)-endplate interface were analyzed., Objective: To define cartilaginous and bony vertebral endplate in commonly used laboratory animals and compare with that of the humans., Summary of Background Data: Endplates are crucial for the IVD nutrient supply: the IVDs have limited blood supply; most nutrients diffuse through endplates to nourish the discs. Various animal models of IVD and endplate degeneration have been used to study the etiology and treatments of spinal disorders. However, because humans are biped, the spine mechanics differ significantly from other mammals. Translation of animal research findings requires a characterization and comparison of the vertebral endplate in the respective species. In this study, we compared the endplate structure of laboratory animal species at the age range commonly used for modeling spine degeneration with that of an adult human., Methods: Mouse, rat, rabbit, goat, and human IVDs and the adjacent vertebral bodies were isolated from the lower lumbar spine. Tissues were stained with Alcian Blue, counterstained with hematoxylin and eosin., Results: Structure of the vertebral endplate varied significantly between the adult animal species and that of the humans. Growth plates persisted in all adult animals studied, whereas the growth plate is absent in the adult humans. In the mice and rats, the cartilaginous endplates are in continuation with the growth plates, with only a small bony center. Rabbits and goats have a bony layer between cartilaginous endplate and the growth plate. The human endplate consist of a cartilaginous layer and the bony endplate., Conclusion: Significant differences exist in histological features of the endplate across animal species and that of the humans. Consideration should be given when animal models are used to study IVD degeneration and surgical treatments., Level of Evidence: 5.

Epiphyseal cartilage is hyaline cartilage tissue with a gelatinous texture, and it is responsible for the longitudinal growth of the long bones in birds and mammals. It is located between the epiphysis and the diaphysis. Epiphyseal cartilage also is called a growth plate or physis. It is protected by three bone components: the epiphysis, the bone bar of the perichondrial ring and the metaphysis. The epiphysis, which lies over the epiphyseal cartilage in the form a cupola, contains a juxtaposed bone plate that is near the epiphyseal cartilage and is in direct contact with the epiphyseal side of the epiphyseal cartilage. The germinal zone corresponds to a group of cells called chondrocytes. These chondrocytes belong to a group of chondral cells, which are distributed in rows and columns; this architecture is commonly known as a growth plate. The growth plate is responsible for endochondral bone growth. The aim of this study was to elucidate the causal relationship between the juxtaposed bone plate and epiphyseal cartilage in mammals. Our hypothesis is that cells from the germinal zone of the epiphyseal side of the epiphyseal cartilage are involved in forming a second ossification front that is responsible for the origin of the juxtaposed bone plate. We report the following: (a) The juxtaposed bone plate has a morphology and function that differs from that of the epiphyseal trabeculae; (b) on the epiphyseal edge of the epiphyseal cartilage, a new ossification front starts on the chondrocytes of the germinal area, which forms the juxtaposed bone plate. This ossification front is formed by chondrocytes from the germinal zone through a process of mineralisation and ossification, and (c) the process of mineralisation and ossification has a certain morphological analogy to the process of ossification in the metaphyseal cartilage of amphibians and differs from the endochondral ossification process in the metaphyseal side of the growth plate. The close relationship between the juxtaposed bone plate and the epiphyseal cartilage, in which the chondrocytes that migrate from the germinal area play an important role in the mineralisation and ossification process of the juxtaposed bone plate, supports the hypothesis of a new ossification front in the epiphyseal layer of the epiphyseal plate. This hypothesis has several implications: (a) epiphyseal cartilage is a morphological entity with two different ossification fronts and two different functions, (b) epiphyseal cartilage may be a morphological structure with three parts: perichondrial ring, metaphyseal ossification front or growth plate, and epiphyseal ossification front, (c) all disease (traumatic or dysplastic) that affects some of these parts can have an impact on the morphology of the epiphyseal region of the bone, (d) there is a certain analogy between metaphyseal cartilage in amphibians and mammalian epiphyseal cartilage, although the former is not responsible for bone growth, (e) comparative histological and anatomy studies are also warranted, to shed light on the phylogenetic study of epiphyseal cartilage throughout the changes that occur in the animal species., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: There is a close relation between cartilage health and its hydration state. Current magnetic resonance methods allow visualizing this tissue. However, a quantitative analysis is more useful when studying disease. The purpose of this study was to quantify water content in cartilage using magnetic resonance without contrast agents., Materials and Methods: Water-content estimations using T1 magnetic resonance mapping were done first in eight gelatin samples where the water content was previously known. The same method was used in the physeal areas of eight skeletally immature 30-kg pigs. To calculate accuracy, T1 calculations were compared to dry-freeze, which is considered the gold standard because it can remove the total water content form a tissue. Four fresh cartilage and seven gelatin samples were dry-frozen. Water content obtained from dry-freeze was compared to the one calculated from T1 map values. A mathematical model and statistical analysis were used to calculate the predictive value of the method and its significance., Results: T1-map-based magnetic resonance method can calculate water content in cartilage with an accuracy of 97.3 %. We calculated a coefficient of variance for this method against dry-frozen sample of 3.68 (SD = 1.2) in gelatin samples, and 2.73 (SD = 1.3) in in vivo samples. Between two independent observers, the coefficient of variance was 0.053, which suggests it can be easily reproduced., Conclusions: Magnetic resonance was able to calculate, with high accuracy, the cartilage water content using T1 mapping sequences.