An integrative approach to studying plasticity in growth disruption and outcomes: A bioarchaeological case study of Napoleonic soldiers.

OBJECTIVES: The aim of this study was to investigate how much variation in adult stature and body mass can be explained by growth disruption among soldiers who served in Napoleon's Grand Army during the Russian Campaign of 1812. METHODS: Linear enamel hypoplasia (LEH) were recorded as representations of early life growth disruption, while the impact on future growth was assessed using maximum femur length (n = 73) as a proxy for stature and maximum femoral head diameter (n = 25) as a proxy for body mass. LEH frequency, severity, age at first formation, and age at last formation served as explanatory variables in a multiple regression analysis to test the effect of these variables on maximum femur length and maximum femoral head diameter. RESULTS: The multiple regression model produced statistically significant results for maximum femur length (F-statistic = 3.05, df = 5 and 67, P = .02), with some variation in stature (adjusted r2 = 0.13) attributable to variation in growth disruption. The multiple regression model for maximum femoral head diameter was not statistically significant (F-statistic = 1.87, df = 5 and 19, P = .15). CONCLUSIONS: We hypothesized stress events during early life growth and development would have significant, negative, and cumulative effects on growth outcomes in adulthood. The results did not support our hypothesis. Instead, some variables and interactions had negative effects on stature, whereas others had positive effects. This is likely due to catch-up growth, the relationship between acute and chronic stress and growth, resilience, and plasticity in human growth over the life course.

Osthole stimulates bone formation, drives vascularization and retards adipogenesis to alleviate alcohol-induced osteonecrosis of the femoral head.

Characteristic pathological changes in osteonecrosis of the femoral head (ONFH) include reduced osteogenic differentiation of bone mesenchymal stem cells (BMSCs), impaired osseous circulation and increased intramedullary adipocytes deposition. Osthole is a bioactive derivative from coumarin with a wide range of pharmacotherapeutic effects. The aim of this study was to unveil the potential protective role of osthole in alcohol-induced ONFH. In vitro, ethanol (50 mmol/L) remarkably decreased the proliferation and osteogenic differentiation of BMSCs and impaired the proliferation and tube formation capacity of human umbilical vein endothelial cell (HUVECs), whereas it substantially promoted the adipogenic differentiation of BMSCs. However, osthole could reverse the effects of ethanol on osteogenesis via modulating Wnt/ß-catenin pathway, stimulate vasculogenesis and counteract adipogenesis. In vivo, the protective role of osthole was confirmed in the well-constructed rat model of ethanol-induced ONFH, demonstrated by a cascade of radiographical and pathological investigations including micro-CT scanning, haematoxylin-eosin staining, TdT-mediated dUTP nick end labelling, immunohistochemical staining and fluorochrome labelling. Taken together, for the first time, osthole was demonstrated to rescue the ethanol-induced ONFH via promoting bone formation, driving vascularization and retarding adipogenesis.

Desferoxamine protects against glucocorticoid-induced osteonecrosis of the femoral head via activating HIF-1α expression.

Glucocorticoid-induced osteonecrosis of the femoral head (GIOFH) is one of the most common complications of glucocorticoid administration. By chelating Fe2+ , desferoxamine (DFO) was reported to be able to activate the HIF-1α/VEGF pathway and promote angiogenesis. In the present study, we examined whether DFO administration could promote angiogenesis and bone repair in GIOFH. GIOFH was induced in rats by methylprednisolone in combination with lipopolysaccharide. Bone repair was assessed by histologic analysis and microcomputed tomography (micro-CT). Vascularization was assessed by Microfil perfusion and micro-CT analysis. Immunohistochemical staining was performed to analyze the expression of HIF-1α, VEGF, and CD31. Our in vivo study revealed that DFO increased HIF-1α/VEGF expression and promoted angiogenesis and osteogenesis in GIOFH. Moreover, our in vitro study revealed that DFO restored dexamethone-induced HIF-1α downregulation and angiogenesis inhibition. Besides, our in vitro study also demonstrated that DFO could protect bone marrow-derived stem cells from dexamethone-induced apoptosis and mitochondrial dysfunction by promoting mitophagy and mitochondrial fission. In summary, our data provided useful information for the development of novel therapeutics for management of GIOFH.

ß-ecdysone promotes osteogenic differentiation of bone marrow mesenchymal stem cells.

BACKGROUND: ß-ecdysone (ßEcd) has numerous pharmacological effects, although its role in the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) has not yet been explored. METHODS: In cell experiments, BMSCs were induced to differentiate by osteogenic induction medium (OIM) or ßEcd. In animal experiments, an osteonecrosis of the femoral head (ONFH) rat model was established using lipopolysaccharide plus methylprednisolone and treating the rats with ßEcd. The osteogenic differentiation capacity of human BMSCs (hBMSCs) was analyzed by alkaline phosphatase and alizarin red S staining. Histopathological changes in rat femoral head tissues were observed by hematoxylin and eosin staining. The expression levels of RUNX2, COL1A1, OCN and phosphorylated Akt in BMSCs from rat femoral head tissues were measured by a quantitative real-time polymerase chain reaction or western blot analysis. RESULTS: Alkaline phosphatase activity and calcium nodules in the ßEcd-treated BMSC group dose-dependently increased compared to those in the control and OIM groups. The hematoxylin and eosin staining results indicated that femoral head tissues of ONFH rats showed typical osteonecrosis, which could be ameliorated by ßEcd. Western blot, quantitative real-time polymerase chain reaction and immunohistochemistry assays demonstrated that the expression levels of RUNX2, COL1A1 and OCN in hBMSCs and femoral head tissue models were obviously increased after ßEcd treatment, and phosphoinositide 3-kinase and Akt phosphorylation were also increased. CONCLUSIONS: ßEcd may be beneficial for the recovery of ONFH patients by accelerating osteogenic differentiation of BMSCs, which may be a novel therapy for related diseases.

Collagen IX deficiency leads to premature vascularization and ossification of murine femoral heads through an imbalance of pro- and antiangiogenic factors.

OBJECTIVE: The vascular invasion of cartilage is an essential process in the endochondral ossification of long bones. In contrast, vascularization of articular cartilage constitutes a pathological mechanism in the development of osteoarthritis. Polymorphisms of Col9a1 have been described as risk factors for hip osteoarthritis (OA) and the loss of collagen IX is known to lead to premature OA of the hip joint in mice but the underlying mechanism is so far unknown. DESIGN: To understand the contribution of collagen IX to OA development in the hip joint, we analyzed the early development of murine Col9a1-/- femoral heads between newborn stage and 16 weeks of age. RESULTS: We found significantly accelerated ossification of the femoral heads in the absence of collagen IX as well as premature vascular and osteoclast invasion, even though hypertrophic differentiation was delayed. The loss of collagen IX led to anatomically altered femoral heads lacking the epiphyseal tubercle. Interestingly, this region was found to contain highest levels of the antiangiogenic protein thrombospondin-1 (TSP-1). Hence, TSP-1 levels were strongly reduced in the Col9a1-/- femoral heads. In addition, antiangiogenic matrilin-1 was found to be decreased, while proangiogenic active MMP-9 levels were increased in the collagen IX deficient mice compared to wildtype controls. CONCLUSION: We conclude that collagen IX protects against premature vascularization and cartilage to bone transition in femoral heads by increasing the levels of antiangiogenic TSP-1 and matrilin-1 and decreasing the levels of proangiogenic active MMP-9.

Overgrowth of the lower limb after treatment of developmental dysplasia of the hip: incidence and risk factors in 101 children with a mean follow-up of 15 years.

Background and purpose - There are few studies on overgrowth of the affected limb after treatment of developmental dysplasia of the hip (DDH). We investigated the incidence of overgrowth and its risk factors in DDH patients.Patients and methods - 101 patients were included in this study. Overgrowth was defined by 2 criteria: when the height of the femoral head of the affected side was higher than that of the contralateral side by more than 10 mm, or by more than 15 mm. The potential risk factors of distinct overgrowth were retrospectively examined using multivariable analysis.Results - When overgrowth was defined as femoral head height difference (FHHD) > 10 mm, its incidence was 44%, and only femoral osteotomy was identified as a significant risk factor with a relative risk (RR) of 1.6 (95% confidence interval [CI] 1.0-2.5). When overgrowth was defined as FHHD > 15 mm, its incidence was 23%, and femoral osteotomy was identified as the only significant risk factor with an RR of 2.3 (CI 1.2-4.5). Overgrowth developed more frequently in patients who underwent femoral osteotomy at the age of 2 to 4 years (87%) than in the others (46%) (p = 0.04).Interpretation - Overgrowth of the affected limb is common in DDH patients. Patients who underwent femoral osteotomy, especially at the age of 2 to 4 years, may require careful follow-up because of the substantial risk for overgrowth.

GC-MS method for metabolic profiling of mouse femoral head articular cartilage reveals distinct effects of tissue culture and development.

OBJECTIVE: The metabolic profile of cartilage is important to define as it relates to both normal and pathophysiological conditions. Our aim was to develop a precise, high-throughput method for gas/chromatography-mass/spectrometry (GC-MS) semi-targeted metabolic profiling of mouse cartilage. METHOD: Femoral head (hip) cartilage was isolated from 5- and 15-week-old male C57BL/6J mice immediately after death for in vivo analyses. In vitro conditions were evaluated in 5-week-old samples cultured ±10% fetal bovine serum (FBS). We optimized cartilage processing for GC-MS analysis and evaluated group-specific differences by multivariate and parametric statistical analyses. RESULTS: 55 metabolites were identified in pooled cartilage (4 animals per sample), with 29 metabolites shared between in vivo and in vitro conditions. Multivariate analysis of these common metabolites demonstrated that culturing explants was the strongest factor altering cartilage metabolism, followed by age and serum starvation. In vitro culture altered the relative abundance of specific metabolites; whereas, cartilage development between five and 15-weeks of age reduced the levels of 36 out of 43 metabolites >2-fold, especially in TCA cycle and alanine, aspartate, and glutamate pathways. In vitro serum starvation depleted six out of 41 metabolites. CONCLUSION: This study describes the first GC-MS method for mouse cartilage metabolite identification and quantification. We observed fundamental differences in femoral head cartilage metabolic profiles between in vivo and in vitro conditions, suggesting opportunities to optimize in vitro conditions for studying cartilage metabolism. In addition, the reductions in TCA cycle and amino acid metabolites during cartilage maturation illustrate the plasticity of chondrocyte metabolism during development.

Physiologic and Pathologic Development of the Infantile and Adolescent Hip Joint: Descriptive and Functional Aspects.

The basic law of mechanobiology states that the external form and internal architecture of the skeleton and joints follow the functional stimuli that act upon them. Radiographs and magnetic resonance imaging reflect the loading history of the growing child, enabling an experienced radiologist to analyze the clinical functioning of patients by interpreting imaging studies. Concerning the hip joint, the physes of the coxal femoral end, the coxal femoral epiphysis with its epiphyseal growth plate, as well as the apophysis of the greater trochanter with its trochanteric growth plate, are the essential organ structures subject to internal forces. They determine the definitive geometric shape of the proximal femur. Indirectly they influence the appearance of the acetabulum and the centration of the hip joint.

Acetabular Version Increases During Adolescence Secondary to Reduced Anterior Femoral Head Coverage.

BACKGROUND: Acetabular version influences joint mechanics and the risk of impingement. Cross-sectional studies have reported an increase in acetabular version during adolescence; however, to our knowledge no longitudinal study has assessed version or how the change in version occurs. Knowing this would be important because characterizing the normal developmental process of the acetabulum would allow for easier recognition of a morphologic abnormality. QUESTIONS/PURPOSES: To determine (1) how acetabular version changes during adolescence, (2) calculate how acetabular coverage of the femoral head changed during this period, and (3) to identify whether demographic factors or hip ROM are associated with acetabular development. METHODS: This retrospective analysis of data from a longitudinal study included 17 volunteers (34 hips) with a mean (± SD) age of 11 ± 2 years; seven were male and 10 were female. The participants underwent a clinical examination of BMI and ROM and MRIs of both hips at recruitment and at follow-up (6 ± 2 years). MR images were assessed to determine maturation of the triradiate cartilage complex, acetabular version, and degree of the anterior, posterior, and superior acetabular sector angles (reflecting degree of femoral head coverage provided by the acetabulum anteriorly, posteriorly and superiorly respectively). An orthopaedic fellow (GG) and a senior orthopaedic resident (PJ) performed all readings in consensus; 20 scans were re-analyzed for intraobserver reliability. Thereafter, a musculoskeletal radiologist (KR) repeated measurements in 10 scans to test interobserver reliability. The intra- and interobserver interclass correlation coefficients for absolute agreement were 0.85 (95% CI 0.76 to 0.91; p < 0.001) and 0.77 (95% CI 0.70 to 0.84), respectively. All volunteers underwent a clinical examination by a senior orthopaedic resident (PJ) to assess their range of internal rotation (in 90° of flexion) in the supine and prone positions using a goniometer. We tested investigated whether the change in anteversion and sector angles differed between genders and whether the changes were correlated with BMI or ROM using Pearson's coefficient. The triradiate cartilage complex was open (Grade I) at baseline and closed (Grade III) at follow-up in all hips. RESULTS: The acetabular anteversion increased, moving caudally further away from the roof at both timepoints. The mean (range) anteversion angle increased from 7° ± 4° (0 to 18) at baseline to 12° ± 4° (5 to 22) at the follow-up examination (p < 0.001). The mean (range) anterior sector angle decreased from 72° ± 8° (57 to 87) at baseline to 65° ± 8° (50 to 81) at the final follow-up (p = 0.002). The mean (range) posterior (98° ± 5° [86 to 111] versus 97° ± 5° [89 to 109]; p = 0.8) and superior (121° ± 4° [114 to 129] to 124° ± 5° [111 to 134]; p = 0.07) sector angles remained unchanged. The change in the anterior sector angle correlated with the change in version (rho = 0.5; p = 0.02). The change in version was not associated with any of the tested patient factors (BMI, ROM). CONCLUSIONS: With skeletal maturity, acetabular version increases, especially rostrally. This increase is associated with, and is likely a result of, a reduced anterior acetabular sector angle (that is, less coverage anteriorly, while the degree of coverage posteriorly remained the same). Thus, in patients were the normal developmental process is disturbed, a rim-trim might be an appropriate surgical solution, since the degree of posterior coverage is sufficient and no reorientation osteotomy would be necessary. However, further study on patients with retroversion (of various degrees) is necessary to characterize these observations further. The changes in version were not associated with any of the tested patient factors; however, further study with greater power is needed. LEVEL OF EVIDENCE: Level II, prognostic study.

Similar femoral growth and deformity with one screw versus two smooth pins for slipped capital femoral epiphysis.

PURPOSE: To compare longitudinal growth and cam deformity of the proximal femur after treatment for slipped capital femoral epiphysis (SCFE) with one screw versus two smooth pins. METHODS: We studied 43 patients (29 males, 14 females; mean age, 12.1 years; range, 9.5-14 years) with idiopathic unilateral SCFE treated with in situ fixation with one cannulated screw (group A, n = 23) or two smooth pins (group B, n = 20). Anteroposterior and frog-leg radiographs of the pelvis were evaluated for each patient at initial presentation, post-operatively and at physeal closure. Longitudinal growth was evaluated using the femoral neck length (FNL), the caput-collum-diaphyseal (CCD) angle, and the articulo-trochanteric distance (ATD). Cam deformity was assessed using the anterior offset α-angle and the head-neck offset ratio (HNOR). The mean follow-up was 5.1 years (range, 4-7 years). RESULTS: Postoperatively, the mean CCD angle was 138.3°, the mean α-angle was 66.1° and the mean HNOR was - 0.030. At physeal closure, mean CCD angle significantly decreased to 133.6°, mean α-angle significantly reduced to 52.1°, and mean HNOR significantly improved to + 0.039. CCD, FNL, ATD, α-angle, and HNOR were not different between groups. CONCLUSIONS: One screw or two smooth pins result in similar longitudinal growth and deformity of the proximal femur after SCFE. The femoral head-neck junction remarkably improves until physeal closure; however, residual cam deformity is not avoided after in situ pinning. The complication rate with smooth pins is higher.

Acetabular Version Increases After Closure of the Triradiate Cartilage Complex.

BACKGROUND: Although the etiology of primary femoroacetabular impingement (FAI) is considered developmental, the underlying pathogenic mechanisms remain poorly understood. In particular, research identifying etiologic factors associated with pincer FAI is limited. Knowledge of the physiologic growth patterns of the acetabulum during skeletal maturation might allow conclusions on deviations from normal development that could contribute to pincer-related pathomorphologies. QUESTIONS/PURPOSES: In a population of healthy children, we asked if there were any differences related to skeletal maturation with regard to (1) acetabular version; (2) acetabular depth/width ratio; and (3) femoral head coverage in the same children as assessed by MRIs obtained 1 year apart. METHODS: We prospectively compared 129 MRIs in 65 asymptomatic volunteers without a known hip disorder from a mixed primary/high school population (mean age, 12.7 years; range, 7-16 years). All participants underwent two MRI examinations separated by a minimum interval of 1 year. Based on the status of the triradiate cartilage complex (open versus closed [TCC]), all hips were allocated to the following groups: "open-open" = open TCC at both MRIs (n = 45 hips [22 bilateral]); "open-closed" = open TCC at initial and closed TCC at followup MRI (n = 26 hips [13 bilateral]); and "closed-closed" group = closed TCC at both MRIs (n = 58 hips [29 bilateral]). We assessed acetabular version in the axial plane at five different locations (5, 10, 15, 20 mm below the acetabular dome and at the level of the femoral head) as well as three-dimensional (3-D) acetabular depth/width ratio and 3-D femoral head coverage on six radial MRI sequences oriented circumferentially around the femoral neck axis. Using analysis of variance for multigroup comparisons with Bonferroni adjustment for pairwise comparisons, we compared the results between the initial and followup MRI examinations and among the three groups. RESULTS: Acetabular version was increased in hips of the "open-closed" group at the followup MRI compared with the initial MRI at 5 mm (-6 ± 4.6 [95% confidence interval {CI}, -7.6 to -3.6] versus -1 ± 5.0 [95% CI, -3.3 to 0.7]; p < 0.001), 10 mm (0 ± 4.0 [95% CI, -1.6 to 2.1] versus 7 ± 4.6 [95% CI, 4.4-8.7]; p < 0.001), and 15 mm (8 ± 5.0 [95% CI, 6.1-10.2] versus 15 ± 4.6 [95% CI, 13.3-17.4]; p < 0.001) below the acetabular dome. Acetabular version did not change between the initial and followup MRI in the "open-open" and "closed-closed" groups. Independently of the groups, acetabular version was increased in all hips with a fused TCC compared with hips with an open TCC (mean difference measured at 5 mm below the acetabular dome at initial MRI examination: 2° ± 5.9° [95% CI, 0.2°-3.4°] versus -9° ± 4.4° [95% CI, -9.9° to -7.8°]; p < 0.001; at followup MRI examination: 1° ± 5.7° [95% CI, 0.1°-2.7°] versus -9° ± 3.8° [95% CI, -10° to -7.6°]; p < 0.001). Both acetabular depth/width ratio and femoral head coverage did not differ among the groups or between the initial and followup MRI examinations within each group. CONCLUSIONS: Although acetabular depth/width ratio and femoral head coverage remain relatively constant, acetabular version increases with advancing skeletal maturity. There seems to be a relatively narrow timeframe near physeal closure of the TCC within which acetabular orientation changes to more pronounced anteversion. Further studies with greater numbers and longer followup periods are required to support these findings and determine whether such version changes may contribute to pincer-type pathomorphologies. LEVEL OF EVIDENCE: Level II, prospective study.

Changes in femoral head size and growth rate in young children with severe developmental dysplasia of the hip.

BACKGROUND: Developmental dysplasia of the hip (DDH) is known to result in smaller femoral head size in toddlers; however, alterations in femoral head size and growth have not been documented in infants. OBJECTIVE: To determine with ultrasound (US) whether femoral head size and growth are altered in infants (younger than 1 year of age) with severe DDH. MATERIALS AND METHODS: We identified all patients at our tertiary care children's hospital from 2002 to 2014 who underwent US for DDH. We included studies with at least one hip with severe DDH, defined as <25% coverage of the femoral head, and excluded teratological DDH. We constructed a control group of randomized patients with normal US studies. Two pediatric radiologists blinded to diagnosis measured bilateral femoral head diameter. Inter-reader variability and femoral head diameter difference between dislocated and contralateral normal femoral heads were evaluated. Mean femoral head diameters were compared across types of hip joint; femoral head growth rates per month were calculated. RESULTS: Thirty-seven children with DDH (28 female) were identified (median age: 33 days). The control group contained 75 children (47 female) with a median age of 47 days. Fifty-three of the 74 hips in the study group had severe DDH. Twenty-four children with DDH had completely dislocated hips (nine bilateral, five with contralateral severe subluxations). Thirteen other children had severe subluxation, two bilaterally. There was good inter-reader agreement in the normal femoral head group and moderate agreement in the severe DDH group. In the study group, severe DDH femoral head diameter was significantly smaller than their contralateral normal hip. Severe DDH femoral head diameter was significantly smaller than normal femoral head diameter in the control group. The severe DDH femoral head growth rate was slightly less but not significantly slower than normal femoral head growth rate in the study group. CONCLUSION: On US during infancy, femoral head size is significantly reduced in severe cases of DDH.

Normal radiological unossified hip joint space and femoral head size development during growth in 675 children and adolescents.

Evaluation of hip joint space width during child growth is important to aid in the early diagnosis of hip pathology in children. We established reference values for hip joint space and femoral head size for each age. Hip joint space development during growth was retrospectively investigated medial and cranial in 1350 hip joints of children using standard anteroposterior supine plain pelvic radiographs. Maximum capital femoral epiphysis diameter and femoral radii were further more investigated. Hip joint space values show a slow decline during growth. Joint space was statistically significantly (p < 0.006) larger in boys than girls. Our hip joint space measurements on supine subjects seem slightly larger than those reported by Hughes on standing subjects. Evaluation of the femoral head diameter and the radii showed a size curve quite parallel to the known body growth charts. Radii medial and perpendicular to the physis are not statistically significantly different. We recommend to compare measurements of hip joint space at two locations to age dependent charts using the same imaging technique. During growth, a divergence in femoral head size from the expected values or loss of the spherical shape should raise the question of hip disorder. Clin. Anat. 30:267-275, 2017. © 2016 Wiley Periodicals, Inc.

MicroRNA-337 is associated with chondrogenesis through regulating TGFBR2 expression.

OBJECTIVE: MicroRNAs (miRNAs) have been implicated in regulating diverse cellular pathways and involved in development and inflammation. This study aimed to examine six miRNAs expression during the cartilage development and identify the key miRNA which is associated with chondrogenesis. METHODS: The expression of six miRNAs in cartilage tissue during development was screened by real-time quantitative polymerase chain reaction (RT-qPCR). Rat models of bone matrix gelatin induced endochondral ossification, collagen-induced arthritis and pristane-induced arthritis were established to examine whether miR-337 is involved in chondrogenesis. Furthermore, the regulation of transforming growth factor-b type II receptor (TGFBR2) expression by miR-337 was determined with the luciferase reporter gene assay and Western blot. The expression of some specific genes relevant to cartilage tissue was tested by RT-qPCR after miR-337 mimic or inhibitor transfection. RESULTS: MiR-337 expression was significantly down-regulated and almost disappeared in the maturation phases of endochondral ossification. The results of histology and RT-qPCR from three rat models showed that miR-337 is directly bound up with chondrogenesis. Furthermore, the results from the luciferase reporter gene assay and Western blot indicated that miR-337 regulated TGFBR2 expression. Our study also found that the enhancement of miR-337 may modulate the expression of cartilage-specific genes such as AGC1 in C-28/I2 chondrocytes. CONCLUSION: We proved that miRNA-337 is associated with chondrogenesis through regulating TGFBR2 expression, and miRNA-337 can also influence cartilage-specific gene expression in chondrocytes. These findings may provide an important clue for further research in the arthritis pathogenesis and suggest a new remedy for arthritis treatment.

Femoral morphology and epiphyseal growth plate changes of the hip during maturation: MR assessments in a 1-year follow-up on a cross-sectional asymptomatic cohort in the age range of 9-17 years.

OBJECTIVES: The goal of this prospective study was to characterize the morphology and physeal changes of the femoral head during maturation using MRI in a population-based group of asymptomatic volunteers. MATERIALS AND METHODS: Sixty-four pupils (127 hips) of 331 pupils from a primary and high school were asked to take part in this study and were willing to participate. 3T MRI of the hip was obtained at baseline and 1-year follow-up. With these images, we analyzed the femoral morphology and epiphyseal changes related to age, status of the physis, and location on the femur. RESULTS: The radius of the femoral head and neck increased with age, as expected, (p < 0.001). The epiphyseal extension increased significantly with age (p < 0.05), but epiphyseal tilt and alpha angle showed no differences (p > 0.05). Building groups by using the epiphyseal status, we found that the epiphyseal extension had the highest changes in the "open" group and almost stopped in the "closed" group. The tilt angle did not change significantly (p > 0.05). Significant smaller alpha-angles were found in the "closed" group, however, these were in a normal range in all of them. Correlated to the position, the highest alpha-angle values were located in anterior-superior and superior-anterior position. CONCLUSIONS: Our data can be used as normative values, which can be compared to patients or cohorts with certain risk factors (e.g., professional athletes), this will offer the chance to detect and understand pathological changes.

A longitudinal cohort study of adolescent elite footballers and controls investigating the development of cam morphology.

Cam morphology describes an asphericity of the femoral head that develops during adolescence, is highly prevalent in athletes, and predisposes individuals to future osteoarthritis. However, it's aetiology remains poorly understood. The aim of this study was to perform 3-year longitudinal follow-up of a control population and football club academy cohort to compare the change in hip and growth plate anatomy between athletes and controls. MRI and questionnaires were used to characterise change in hip and growth plate anatomy and quantify activity levels. 121 male academy footballers and 107 male and female controls participated at baseline. Footballers experienced significantly greater increases in femoral head asphericity (4.83 degrees (95% CI: 2.84 to 6.82), p < 0.001) than controls. A positive correlation existed between activity levels and change in femoral head morphology (coefficient 0.79, p ≤ 0.001). Greatest morphological change occurred in individuals aged 11-12 years at baseline, with no significant change in individuals aged 14 years and older at baseline. Cam morphology development was secondary to soft tissue hypertrophy and lateral growth plate extension. In conclusion, excessive loading of the hip joint through exercise prior to 14 years of age may result in growth plate adaptations causing cam morphology. Potential interventions may include training type and load modification in young adolescent football players.

Mice with a disruption of the thrombospondin 3 gene differ in geometric and biomechanical properties of bone and have accelerated development of the femoral head.

Thrombospondin 3 (TSP3) is structurally similar to cartilage oligomeric matrix protein (COMP/TSP5), but its function is unknown. To determine the functional significance of TSP3, we generated mice with a targeted disruption of Thbs3. TSP3-null mice are viable and fertile and show normal prenatal skeletal patterning, based on Alcian blue/Alizarin red S staining. However, subtle and transient abnormalities were detected in the developing postnatal skeleton. Young adult TSP3-null mice are heavier than controls, and analyses of the geometric and biomechanical properties of long bones show increases in the moments of inertia, endocortical and periostal radii, and failure load. The bones of 9-week-old TSP3-null male mice also have a significantly greater cortical area. Most of these differences were no longer detected in 15-week-old mice. Micro-computed tomography scans showed that the trabecular bone proximal to the femoral head growth plate developed at an earlier time in TSP3-null mice than in wild-type mice. Thus, vascular invasion and ossification start in the femoral heads of TSP3-null mice at 9 weeks, whereas the wild-type femoral head is still composed of hypertrophic chondroctyes in a calcified matrix at 15 weeks. These results provide evidence for a role for TSP3 in the regulation of skeletal maturation in mice.

[Formation of ossification nucleus in the femoral head in hamsters exposed to laser radiation].

The purpose of the study was to detect the relation between the formation of ossification nucleus in the epiphysis and the ingrowth of vessels into it, using laser radiation of femoral heads. The study was performed in 30 golden hamsters, 20 of them starting at 10 days after birth were exposed to daily irradiation of the right hip joint (during 3-80 days). The left joint was used as control. The radiation was performed with Agnis laser device (radiation power--2 mW, impulse frequency--2500 Hz, exposure duration--8 min, optical fiber diameter--4 mm). Femoral bones of experimental and control animals were histologically studied at days 13 till 90. Laser radiation was found could delay vessel growth from diaphysis into epiphysis for up to 13 days, and the beginning of ossification nucleus formation in the femoral head--for up to 5 days. This suggests the direct relation of the development of bone ossification nucleus in the epiphysis and growing of vessels into its cartilage, since no other factors retarding the vessel growth and formation of bone nucleus were used.

Changes in mRNA gene expression during growth in the femoral head of the young rat.

The rate of physeal growth slows as an animal matures with changes in mRNA gene expression due to the altered cellular activity. To measure the change in gene expression during the juvenile growth period, the femoral head, enclosing the proximal femoral physis, primary spongiosa, and articular cartilage, was collected from both femora of 16 female Sprague-Dawley rats between 4 and 10 weeks of age. One femur of each rat had had a mid-diaphyseal femoral fracture at 4 weeks of age. RNA was extracted and hybridized to 16 Affymetrix Rat Genomic 230 2.0 GeneChip microarrays with probe sets for 31,000 genes of which 18,200 were expressed. Of these, 8002 genes had a significant change in gene expression during growth, about half increasing and half decreasing. These changes included up-regulation with time of genes related to cartilage, blood vessels, osteoprotegerin, osteomodulin, and most ribosomal proteins. There was down-regulation with maturity of genes related to bone, growth-promoting cytokines, G proteins, GTPase-mediated signal transduction factors, cytokine receptors, mitosis, integrin-linked kinase, and the cytoskeleton. In summary, the slowing of growth with maturity was associated with changes in mRNA gene expression in the femoral head for a large number of genes. These changes in gene expression between young and mature rats suggest factors which are important for the support of the rapid linear growth during early life.