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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.)

Polychlorinated biphenyls (PCBs) are ubiquitous, persistent, organic pollutants also considered endocrine-disrupting chemicals. Our study examined the effects of lactational exposure to nondioxin-like PCB-155 and/or dioxin-like PCB-169 on longitudinal femur growth at the distal epiphyseal growth plate (EGP) in young rats at three different ages [postnatal days (PNDs) 9, 22, and 42]. After delivery, lactating rats were divided into four groups (PCB-169, PCB-155, PCB-155 + 169, and control) and administered PCBs intraperitoneally. The femurs of offspring were used to estimate growth rate (µm/day), and histomorphometric analysis on the distal femur included the thickness of the EGP and zones of proliferation and hypertrophy with calcification. Stereometry was used to determine trabecular bone volume density. In the PCB-169 and PCB-155 + 169 groups, PCB-169 affected longitudinal bone growth in the early postnatal period by interfering with chondrocytes in the EGP zone of proliferation and, to a lesser extent, the zone of hypertrophy. Morphometric alterations in EGP structure diminished until puberty. A slow growth rate persisted in the PCB-169 group until PND 42, while in the PCB-155 group, a fast growth rate between PNDs 9 to 22 was significantly reduced between PNDs 22 to 42. Sterometric assessment showed decreased trabecular bone volume in the PCB-155 + 169 group compared with that in the control on PND 9 and increased in the PCB-169 group compared with that in the PCB-155 group on PND 42. To summarize, studied PCB congeners exerted congener- and age-dependent effects on femur growth rate and its histomorphometric characteristics.

The proliferation and hypertrophy of chondrocytes play important roles in endochondral ossification, which is tightly regulated during skeleton development. However, the regulation mechanism remains largely unknown. Here we show that DDB1 (Damaged DNA Binding Protein 1) has a critical function in the development of growth plates. Using chondrocyte-specific DDB1 knockout mice, we found that DDB1 deletion in chondrocytes results in dwarfism due to the aberrant skeleton development. The structure of growth plate in tibia becomes disordered at P21, not in femur. But at P70, the changes are severer in femur than tibia. Chondrocyte proliferation and differentiation are attenuated and asynchronous in both tibia and femur at P7 and P21. Furthermore, DDB1 deficiency induces p27 upregulation and subsequent cell cycle arrest in primary chondrocytes. Therefore, our data reveal that DDB1 is essential for the skeleton development by controlling chondrocyte proliferation and differentiation., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Progressive hip displacement is one of the most common and debilitating deformities seen in children with cerebral palsy (CP). The aim of this study was to evaluate the results of temporary medial hemiepiphysiodesis of the proximal femur (TMH-PF) using a transphyseal screw to control hip migration during growth in children with CP., Methods: This was a retrospective study of children with CP and hip dysplasia, age 4 to 11 years and GMFCS levels III-V. There were 28 patients with 56 hips that underwent TMH-PF surgery between 2007 and 2010. Clinical and radiologic evaluation was performed preoperatively, at 6, 12, and 60 months following the index surgery. Acetabular index (AI), neck-shaft angle (NSA) and migration percentage (MP) were measured. All complications were recorded., Results: All radiographic measurements were significantly improved at the final follow-up. Positive correlations were found between NSA, MP, and AI. Multiple regression analysis revealed that MP, time from surgery, and age were influenced by the decrease of the NSA. The femoral physis grew off the screw in 9 hips within 36 months. The screw head broke during attempted screw exchange in 1 hip. The remain cases (4 hips) were treated by placing a second screw parallel to the existing one. Finally, progressive subluxation occurred in 3 hips when the physis grew off the screw and were treated by skeletal reconstruction., Conclusions: TMH-PF was effective in controlling progressive subluxation of the hip in the majority of cases, obviating the need for major reconstructive surgery in these children with CP., Level of Evidence: Level IV.

The growth plate is a cartilaginous layer present from the gestation period until the end of puberty where it ossifies joining diaphysis and epiphysis. During this period several endocrine, autocrine, and paracrine processes within the growth plate are carried out by chondrocytes; therefore, a disruption in cellular functions may lead to pathologies affecting bone development. It is known that electric fields impact the growth plate; however, parameters such as stimulation time and electric field intensity are not well documented. Accordingly, this study presents a histomorphometrical framework to assess the effect of electric fields on chondroepiphysis explants. Bones were stimulated with 3.5 and 7 mV/cm, and for each electric field two exposure times were tested for 30 days (30 min and 1 h). Results evidenced that electric fields increased the hypertrophic zones compared with controls. In addition, a stimulation of 3.5 mV/cm applied for 1 h preserved the columnar cell density and its orientation. Moreover, a pre-hypertrophy differentiation in the center of the chondroepiphysis was observed when explants were stimulated during 1 h with both electric fields. These findings allow the understanding of the effect of electrical stimulation over growth plate organization and how the stimulation modifies chondrocytes morphophysiology., (Copyright © 2018 Elsevier B.V. All rights reserved.)

We evaluated the growth plates (GPs) of rats after a 14-day reduction in food consumption caused by either daily oral dosing with 5-fluorouracil (5-FU: a positive control reducing food consumption and affecting the GPs) or a direct reduction in food consumption to determine whether the observed changes were attributable to a direct effect of drug toxicity. Histomorphometric analyses of the femoral GP were performed for a nontreated (NT) control group, three groups treated with 5-FU (12, 15, and 18 mg/kg/day) and three groups with food intake restricted to levels corresponding to those consumed by the rats in the three 5-FU-treated groups. Compared with the NT group, the GP widths and the number of chondrocytes in the proliferative zone decreased significantly in all the 5-FU-treated groups and the dietary restriction groups. Importantly, no significant differences between the 5-FU-treated groups and the groups with matched dietary restrictions were seen for most parameters. Thus, the 14-day dietary restriction caused significant changes in the proliferative zone of the GP, and similar changes observed in the 5-FU-treated groups were presumed to result from the comparable reduction in food intake rather than being a direct toxic effect of the drug.

Background: Trochlear dysplasia is the most important risk factor for patellofemoral instability among adolescents; therefore, trochleoplasty to reshape the trochlear groove is the treatment of choice for patients with high-grade trochlear dysplasia. However, in the presence of open growth plates, there is a potential risk of injury to the distal femoral growth plate and subsequent growth disturbance. As such, most authors do not recommend trochleoplasty for skeletally immature patients. The effect of trochleoplasty on femoral growth when performed before closure of the distal femoral physis remains unclear., Hypothesis: For patients with open growth plates and an expected growth <2 years, trochleoplasty does not cause growth disturbance of the distal femur., Study Design: Case series; Level of evidence, 4., Methods: Eighteen consecutive adolescents (18 knees) with open physes and severe trochlear dysplasia underwent thin flap trochleoplasty. Pre- and postoperative radiographic examination included anteroposterior and lateral views to assess leg axis and patella alta. A preoperative radiograph of the left hand was performed to measure skeletal age. Magnetic resonance imaging was performed to evaluate trochlear dysplasia and tibial tubercle-trochlear groove distance. Evaluation included pre- and postoperative physical examination with evaluation of leg length and leg axis, Kujala score, and Tegner activity score., Results: The median age at the time of operation was 12.6 years (range, 12.2-13.3 years) for girls and 14.5 years (14.0-15.4 years) for boys. The mean follow-up after operation was 2.3 years after surgery (range, 2.0-3.0 years). At follow-up for all patients, the growth plates of the knee were closed. Impairment of growth of the distal femur was found neither clinically nor radiographically. No recurrent dislocation occurred. The median Kujala score improved significantly from 67 (range, 54-75) preoperatively to 89.5 (range, 78-96) at follow-up ( P < .01). The median visual analog scale showed significant pre- to postoperative improvement from 5 (range, 3-7) to 1 (range, 0-3) ( P < .01). The activity level according to the Tegner activity score did not change significantly., Conclusion: In this study, trochleoplasty as a treatment for patellofemoral instability of patients with open physes and an expected growth of not more than 2 years showed good clinical results without redislocation and with no growth disturbance. Therefore, for selected adolescent patients with high-grade trochlear dysplasia, trochleoplasty can be safely performed up to 2 years before the projected end of growth.

Limb-length inequality is a clinical problem in children with hypertrophy associated with vascular malformations. The purpose of this study was to determine a pattern of growth, predict discrepancy at maturity, and evaluate the timing and results of epiphysiodesis. Hypertrophy with vascular malformation, follow-up from childhood until maturity, annual physical examination, and annual orthoroentgenograms and anteroposterior left hand-wrist radiographs were the inclusion criteria. The developmental pattern of the growth discrepancy was established. Limb-length discrepancy and remaining growth were calculated. All 3 patients underwent distal femur or proximal tibia and fibula percutaneous epiphysiodesis. All cases showed the constant upward slope of the developmental pattern of discrepancy until the time of epiphysiodesis. The length of the uninvolved limb at maturity corresponded to the length predicted by the methods that used skeletal age, allowing calculation of the proper timing for epiphysiodesis. The multiplier and the rule of thumb methods failed, with skeletal age not corresponding to chronological age. In these 3 cases, limb-length discrepancy was successfully treated with percutaneous epiphysiodesis, and there were no complications. [Orthopedics. 2018; 41(4):e574-e579.]., (Copyright 2017, SLACK Incorporated.)

Background: There is evidence that oblique tension band plating can affect torsional growth in long bones. This study sought to determine if the torsional growth could be modulated based on the angles of the tension band plating and whether or not oblique plating affected overall longitudinal growth., Methods: New Zealand White rabbits (10.5 wk old) had one screw placed on the metaphyseal side and one on the epiphyseal side of both medial and lateral sides of the right knee distal femoral physis. The sham group (n=5) included screw placement only. For the plate group (n=13), unlocked plates, angled from 0 to 76 degrees, connected the screws and spanned the physis. Radiographs were taken at biweekly intervals. After 6 weeks of growth, hindlimbs were harvested and microCT scans performed. Femoral length, distances between screw heads and angle between the plates were measured on radiographs. Femoral length differences were compared between groups. Femoral version was measured from 3D microCT. Plate angle changes were correlated to the difference in femoral version between limbs using Pearson correlation (significance was set to P<0.05 for all comparisons)., Results: Femur length difference between the contralateral and the operative side was significantly greater in the plate group compared with the sham group over time (P=0.049). Medial and lateral screw distances changed significantly more in the sham group than the plate group on both sides (P<0.001). A greater initial angle between plates resulted in a greater change in the angle between plates (P<0.001). Significant correlations were found between right-left side femoral version differences and initial plate angle (P=0.003) and plate angle change (P=0.014)., Conclusions: The torsional effect of oblique plating seems to correlate with the amount of initial plate angle, with an additional, not negligible, longitudinal growth effect., Clinical Significance: Placing plates at given angles across open physes may result in predictable changes in bone torsion allowing for a safer and less invasive option when treating childhood torsional deformities, but the resulting shortening of the ipsilateral femur must be considered.

Background Context: The process of linear growth is driven by axial elongation of both long bones and vertebral bodies and is accomplished by enchondral ossification. Differences in regulation between the two skeletal sites are mirrored clinically by the age course in body proportions. Whereas long bone growth plates (GPs) can easily be discriminated, vertebral GPs are part of the cartilaginous end plate, which typically shows important species differences., Purpose: The objective of this study was to describe and compare histologic, histomorphometric, and regulatory characteristics in the GPs of the spine and the long bones in a porcine model., Materials and Methods: Two- and six-week-old piglet GPs of three vertebral segments (cervical, thoracic, and lumbar) and eight long bones (proximal and distal radius, humerus, tibia, and femur) were analyzed morphometrically. Further, estrogen receptors, proliferation markers, and growth factor expressions were examined by immunohistochemistry., Results: Individual vertebral GPs were smaller in width and contained fewer chondrocytes than long bone GPs, although their proliferation activity was similar. Whereas the expression pattern of growth hormone-associated factors such as insulin-like growth factor (IGF)-1 and IGF-1 receptor (IGF-1R) was similar, estrogen receptor (ER)-ß and IGF-2 were distinctly expressed in the vertebral samples., Conclusions: Vertebral GPs display differential growth, with measurements similar to the slowest-growing GPs of long bones. Further investigation is needed to decipher the molecular basis of the differential growth of the spine and the long bones. Knowledge on the distinct mechanism will ultimately improve the assessment of clinically essential characteristics of spinal growth, such as vertebral elongation potential and GP fusion., (Copyright © 2017 Elsevier Inc. All rights reserved.)

This is a retrospective observational study. Greater trochanteric epiphysiodesis (GTE) has been recommended to prevent Trendelenburg gait and limitation of the hip joint motion due to trochanteric overgrowth after femoral varus osteotomy (FVO) in Legg-Calvé-Perthes disease (LCPD). However, capital femoral physeal arrest frequently occurs in patients with severe disease (lateral pillar C), so GTE might not be as effective in these patients. The aim of this study was to compare trochanteric growth inhibition due to GTE after FVO between 2 age groups (<8 or >8 years) in patients with lateral pillar B and B/C border LCPD and evaluate the effectiveness of GTE compared with the normal, unaffected hip.This study included 19 children with lateral pillar B and B/C border LCPD in 1 leg who underwent FVO followed by GTE. Of the 19 children, 9 underwent GTE before the age of 8 years and 10 underwent GTE after 8 years of age. On radiographs taken at the immediate postoperative period and at skeletal maturity, the articulo-trochanteric distance (ATD), center-trochanteric distance (CTD), and neck-shaft angle (NSA) were compared between the 2 age groups. The amount of correction was compared between groups. The contralateral, unaffected hip was used as a control for trochanteric growth. The patients were clinically evaluated with Iowa hip score at the final follow-up.There was no significant difference between the 2 age groups in terms of time to GTE, length of follow-up, or lateral pillar classification. In the affected hip, the amount of correction of the ATD, CTD, and NSA was significantly greater in patients < 8 years than in patients > 8 years. However, in the unaffected hip, the change in the ATD, CTD, and NSA did not differ significantly between the 2 groups.We suggest that FVO followed by GTE for lateral pillar B and B/C border LCPD in patients under the age of 8 years can affect growth of the greater trochanter. However, effective growth inhibition due to GTE was not achieved after 8 years of age.

Objective: To determine the effect of oral iron administration on pregnant rats on the diameter of cells of growth plate of rat pups., Study Design: Experimental study., Place and Duration of Study: Anatomy Department, Army Medical College, Rawalpindi in collaboration with National Institute of Health (NIH), Islamabad from March to November 2016., Methodology: Group Acontaining 8 pregnant rats was control group, and group B containing same number of pregnant rats was the study group. Control group Awas on standard diet throughout pregnancy. Iron was given to the experimental group B for 21 days (throughout pregnancy) in the form of syrup 0.5ml daily (2.75 mg of elemental iron) given in water. Rat infants were born via spontaneous vaginal delivery. Inclusion criteria for infants was pups born at term which were active and taking feed. Femur from each rat infant of right side was removed for the growth plate investigation. Processing, embedding and staining with Hematoxylin and Eosin, Perl's stain for histological study was done. The cell diameter in hypertrophy and proliferative zone was evaluated. Mean values of the diameter of chondrocytes in both the zones of growth cartilage of femur were measured., Results: Diameter of the cells in hypertrophy and proliferative zones was considerably decreased in group B as compared to group A., Conclusion: Administration of iron during pregnancy with normal iron status can disturb growth of the rat infant through its accumulation in the epiphyseal plate of femur. The cell diameter of the hypertrophy and proliferative zones was markedly reduced in iron administered group as compared to the control group.

In long bones the growth plate is a cartilaginous structure located between the epiphysis and the diaphysis. This structure regulates longitudinal growth and helps determine the structure of mature bone through the process of endochondral ossification. During human growth the femur's proximal growth plate experiences changes in its morphology that may be related to its mechanical environment. Thus, in order to test this hypothesis from a computational perspective, a finite element analysis on a proximal femur was performed on which we modeled different physeal geometries corresponding to the shapes acquired for this structure in a child between the ages of five to eleven. Results show augmented Von Mises stress values with increasing irregularities in physeal geometry, whereas displacement decreased with increased irregularities in the growth plate's morphology. Such observations suggest that growth plate's shape changes follows a possible mechanical adaptation on imposed loads to sustain a person's increasing body mass during growth., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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.)

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.

The hypoxic growth plate cartilage requires hypoxia-inducible factor (HIF)-mediated pathways to maintain chondrocyte survival and differentiation. HIF proteins are tightly regulated by prolyl hydroxylase domain-containing protein 2 (Phd2)-mediated proteosomal degradation. We conditionally disrupted the Phd2 gene in chondrocytes by crossing Phd2 floxed mice with type 2 collagen-α1-Cre transgenic mice and found massive increases (>50%) in the trabecular bone mass of long bones and lumbar vertebra of the Phd2 conditional knockout (cKO) mice caused by significant increases in trabecular number and thickness and reductions in trabecular separation. Cortical thickness and tissue mineral density at the femoral middiaphysis of the cKO mice were also significantly increased. Dynamic histomorphometric analyses revealed increased longitudinal length and osteoid surface per bone surface in the primary spongiosa of the cKO mice, suggesting elevated conversion rate from hypertrophic chondrocytes to mineralized bone matrix as well as increased bone formation in the primary spongiosa. In the secondary spongiosa, bone formation measured by mineralizing surface per bone surface and mineral apposition rate were not changed, but resorption was slightly reduced. Increases in the mRNA levels of SRY (sex determining region Y)-box 9, osterix (Osx), type 2 collagen, aggrecan, alkaline phosphatase, bone sialoprotein, vascular endothelial growth factor, erythropoietin, and glycolytic enzymes in the growth plate of cKO mice were detected by quantitative RT-PCR. Immunohistochemistry revealed an increased HIF-1α protein level in the hypertrophic chondrocytes of cKO mice. Infection of chondrocytes isolated from Phd2 floxed mice with adenoviral Cre resulted in similar gene expression patterns as observed in the cKO growth plate chondrocytes. Our findings indicate that Phd2 suppresses endochondral bone formation, in part, via HIF-dependent mechanisms in mice.

Adult Ibsp-knockout mice (BSP-/-) display shorter stature, lower bone turnover and higher trabecular bone mass than wild type, the latter resulting from impaired bone resorption. Unexpectedly, BSP knockout also affects reproductive behavior, as female mice do not construct a proper "nest" for their offsprings. Multiple crossing experiments nonetheless indicated that the shorter stature and lower weight of BSP-/- mice, since birth and throughout life, as well as their shorter femur and tibia bones are independent of the genotype of the mothers, and thus reflect genetic inheritance. In BSP-/- newborns, µCT analysis revealed a delay in membranous primary ossification, with wider cranial sutures, as well as thinner femoral cortical bone and lower tissue mineral density, reflected in lower expression of bone formation markers. However, trabecular bone volume and osteoclast parameters of long bones do not differ between genotypes. Three weeks after birth, osteoclast number and surface drop in the mutants, concomitant with trabecular bone accumulation. The growth plates present a thinner hypertrophic zone in newborns with lower whole bone expression of IGF-1 and higher IHH in 6 days old BSP-/- mice. At 3 weeks the proliferating zone is thinner and the hypertrophic zone thicker in BSP-/- than in BSP+/+ mice of either sex, maybe reflecting a combination of lower chondrocyte proliferation and impaired cartilage resorption. Six days old BSP-/- mice display lower osteoblast marker expression but higher MEPE and higher osteopontin(Opn)/Runx2 ratio. Serum Opn is higher in mutants at day 6 and in adults. Thus, lack of BSP alters long bone growth and membranous/cortical primary bone formation and mineralization. Endochondral development is however normal in mutant mice and the accumulation of trabecular bone observed in adults develops progressively in the weeks following birth. Compensatory high Opn may allow normal endochondral development in BSP-/- mice, while impairing primary mineralization.

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.)

Mice lacking ADAM10 in endothelial cells (Adam10ΔEC mice) have shorter femurs, tibiae, and humeri than controls, raising questions about how endothelial cells could control long bone growth. We performed a histopathological evaluation of the femur and tibia growth plates at different postnatal stages, and assessed the distribution of TRAP-positive osteoclasts and endothelial cells at the growth plate. The growth plates in Adam10ΔEC mice appeared normal at P7 and P14, but a thickened zone of hypertrophic chondrocytes and increased trabecular bone density were apparent by P21 and later. The number of TRAP+ cells at the COJ was normal at P7 and P14, but was strongly reduced at P21 and later. Moreover, the density of endomucin-stained endothelial cells at the COJ was increased starting at P7. The defects in long bone growth in Adam10ΔEC mice could be caused by a lack of osteoclastogenesis at the COJ. Moreover, ADAM10 appears to regulate endothelial cell organization in the developing bone vasculature, perhaps in a similar manner as in the developing retinal vascular tree, where ADAM10 is thought to control Notch-dependent endothelial cell fate decisions. This study provides evidence for the regulation of osteoclast function by endothelial cells in vivo., (© 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Fractures of the growth plate region were performed with cadaver specimens obtained from the ovine distal femur and proximal tibia. Specimens of 6 different ages, ranging from 1 week to 4 years, were investigated in order to determine changes in the fracture characteristics. Mechanical properties (crack resistance and notch tensile strength), supported by microscopy of the distal tibia (thickness of growth plate and its zones, trabecular bone volume ratio) were determined. The crack propagated through different regions depending on age, which was observed both in microscopy and mechanical tests. In specimens of younger animals the fracture typically went through trabecular bone, often parallel to the growth plate, and only sometimes through the growth plate cartilage. Specimens of older animals fractured directly through the growth plate cartilage, while trabecular bone was not affected at all. Adult specimens had significantly higher mechanical values than the young ones. The results reveal the underlying mechanical properties that induce different fracture patterns of the epiphyseal growth plate at different stages of growth. The possibility of fractures through trabecular bone parallel to the growth plate in newborns and infants should be considered when clinical radiographs of paediatric fractures are analysed and classified., (© 2013 Elsevier Ltd. All rights reserved.)

Background and Purpose: Percutaneous physiodesis in the knee region is a well-established method for treating leg-length inequality. Longitudinal growth in the physis is believed to stop almost immediately after the operation. The extent of physis ablation required has never been investigated by any kind of tomography in humans. Using radiostereometric analysis (RSA), we determined when definite growth arrest occurred after surgery. We also studied the correlation between the extent of physis ablation and postoperative growth. Finally, we assessed any bone bridging across the physis., Methods: 6, 12, and 30 weeks after surgery, we used RSA to measure longitudinal growth in 27 patients (37 physes) with a mean age of 13 years. CT scanning of the knee region was performed 12 weeks after surgery to measure the percentage of the ablated physis and to determine the distribution of bone bridges across the physis., Results: RSA showed that growth rate was reduced to less than half of the expected rate after 6 weeks. During the next 6 weeks, the growth ceased completely. CT scans revealed a large variation in the extent of ablated physes (17-69%). In the ablated areas, tissues of various densities were mixed with mature bone. Bridges were found both laterally and medially across the physes in all of the patients. There was a negative correlation between the extent of ablation and total postoperative growth (rho = -0.37, p = 0.03)., Interpretation: Growth across the physis is effectively stopped by percutaneous physiodesis. RSA is well-suited for observation of this phenomenon. Volume CT scanning can be used to detect bone bridges that cross the physis and to calculate the extent of physis ablation.

Both nonoperative and operative treatments for anterior cruciate ligament (ACL) deficient knees in skeletally immature patients have reported potentially negative outcomes. This study describes primary ACL reconstruction patients with open physes and their concurrent injuries and evaluates whether these patients are at a higher early risk of revision and reoperation than closed physes patients. A retrospective analysis of prospectively collected data was performed. Patients were identified using an ACL Reconstruction Registry. Summary statistics comparing open and closed physes patients of similar ages in regard to patient characteristics and incidence of early revision and reoperation are provided. Adjusted Cox regression models assessed risk of early revision and reoperation for open physes patients. Of 1,867 patients identified, 232 (12.4%) patients had open physes and 1,635 (87.6%) patients had closed physes. Patients with open physes were younger, less likely to be women, and had less medial meniscal injuries than closed physes patients. No significant differences were observed in cartilage injury, overall menisci injury and repair, and early revision and reoperation rate. According to the our results, no significant differences in risk of early revision or early reoperation in open physes compared with closed physes patients when adjusting for age were observed, nor were there any reoperations for physeal closure., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Introduction: This study describes the results achieved using a combination of allogeneic mesenchymal stem cells (MSCs) with chondrocytes (CHC) and a new scaffold consisting of type-I collagen and chitosan nanofibers in the prevention of partial growth plate arrest after iatrogenic injury in pigs., Material and Methods: The miniature pig was selected as an experimental model to compare the results in the left femoral bones (MSCs and CHC in scaffold transplantation into the iatrogenic partial distal growth plate defect) and right femoral bones (scaffold alone transplantation). The experimental group consisted of 10 animals. Bone marrow from os ilium as the source of MSCs was used. A porous cylinder consisting of 0.5% by weight type-I collagen and 30% by weight chitosan, was the optimal choice. The length of the bone and angular deformity of distal femur after the healing period was measured and the quality and structure of the newly formed cartilage was histologically examined., Results: Transplantation of the composite scaffold in combination with MSCs and chondrocytes led to the prevention of growth disorder and angular deformity in the distal epiphysis of the left femur. Compared to the right (control) femur, tissue similar to hyaline cartilage with signs of columnar organization typical of the growth plate occurred in most cases., Conclusions: The promising results of this study reveal the new and effective means for the prevention of bone bridge formation after growth plate injury.

Retinoids are effective and widely prescribed in the treatment of severe acne. However their use can be associated with numerous side effects. Some rare cases of premature epiphyseal closure were reported. We present the case of a sixteen-year-old soccer player referred for progressive anterior pain in both knees, evoking a patellar problem. Careful pharmacological questioning revealed use of isotretinoin for several months. MRI findings showed an irregularity of the growth plate and an important metaphyso-epiphyseal oedema, more noticeable in the left knee. Retinoid-induced premature epiphyseal closure was diagnosed. The treatment was stopped, with a resolution of pain within two months. After recovery a persisting small sequelar thumbprint-like growth plate lesion was observed on the control MRI. Retinoids induce an invasion of the growth plate by osteoclasts and a decrease in proteoglycans synthesis. It seems that the knee is the most affected joint. This complication being rare, a radiological follow-up of the young patients treated by retinoids is not proposed., (Copyright © 2011 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Purpose: To determine the influence of low-level laser therapy on femoral growth plate in rats., Methods: Thirty male Wistar rats aged 40 days were divided into two groups, G1 and G2. In G1 the area of the distal growth plate of the right femur was irradiated at one point using GaAlAs laser 830 nm wavelength, output power of 40 mW, at an energy density of 10 J/cm(2). The irradiation was performed daily for a maximum of 21 days. The same procedure was done in G2, but the probe was turned off. Five animals in each group were euthanized on days 7, 14 and 21 and submitted to histomorphometric analysis., Results: In both groups the growth plate was radiographically visible at all moments from both craniocaudal and mediolateral views. On the 21st day percentage of femoral longitudinal length was higher in G2 than G1 compared to basal value while hypertrophic zone chondrocyte numbers were higher in G1 than G2. Calcified cartilage zone was greater in G1 than in G2 at all evaluation moments. Angiogenesis was higher in G1 than in G2 at 14th and 21st days., Conclusion: The low-level laser therapy negatively influenced the distal femoral growth plate.

Physeal fracture is a common pediatric fracture that would result in premature physeal closure in long bones, and there is currently no gold standard for its management. In this study, we investigated the application of a Bioengineered Cartilage Pellet (BCP) in repairing a rabbit physeal fracture model, and the possible effects of Low Intensity Pulsed Ultrasound (LIPUS) treatment. Rabbits with physeal fracture created were assigned to the NC group (no BCP, no LIPUS), GC group (BCP, no LIPUS), and GT group (BCP and LIPUS). Femoral lengths and cartilage area were assessed at 4, 8, and 16 weeks post-defect. After transplantation, the BCP showed continuous growth in the host and demonstrated resemblance to a natural growth plate. The GC group showed 34.1, 32.1, and 41.1% advantage in lengthening over the NC group and the GT group showed 51.1, 41.6, and 26.9% improved lengthening than the NC group, at 4 (p = 0.203), 8 (p = 0.543) and 16 weeks (p = 0.049), respectively. Cartilage area was shown to be significantly higher in GC and GT group compared to NC group (p < 0.05). No significant difference was found between GC and GT group. Femoral longitudinal growth was shown to be improved by the BCP, however no additional enhancement effect was shown to be provided by LIPUS., (Copyright © 2011 Wiley Periodicals, Inc.)

Bone bridges linking the epiphysis and metaphysis termed "tethers" have been found in the femoral growth plates of C57Bl/6 mice and are disrupted when the vitamin D receptor (VDR) is ablated. It is unknown if tethers are found in other growth centers, if they are regulated in a comparable manner, or if they have a functional role in skeletal development or stability. To address this, distal femoral growth plates (GPs) and spheno-occipital synchondroses (SOSs) of wild-type C57Bl/6 mice from 2 to 15 weeks of age were analyzed using μCT scans. The GPs and SOSs of VDR+/+ and VDR-/- mice fed regular or rescue diets to restore mineral homeostasis until 10 weeks of age were also scanned. Tethers in GPs and SOSs both thickened and accumulated in number as these growth centers decreased in size. Ablating the VDR made GPs and SOSs rachitic and nearly eliminated tether formation. Rescue diets restored the volume of both growth centers but only partially restored growth center thickness and tether formation, suggesting that lα,25-dihydroxy vitamin D(3) partially regulates tether formation in these growth centers via its receptor. In VDR+/+ mice 2-15 weeks in age, growth center thickness was inversely correlated to animal weight whereas tether phenotype (tether volume/growth center volume, tether number/mm, tether width, tether spacing) was significantly related to animal weight. In both 2-15 week old VDR+/+ and 10 week old VDR+/+ and VDR-/- mice on normal and rescue diets, tether phenotype (tether number/mm, tether spacing) had strikingly similar relationships to growth center thickness. These results show that tethers are present in growth centers in different anatomic and undergo developmental changes in a comparable manner; in both sites, VDR-regulated tether formation is strongly linked to growth center morphology; and tether formation is associated with body weight, suggesting a role in maintaining growth plate stability during growth., (Copyright © 2011 Elsevier Inc. All rights reserved.)

During long bone development the original cartilaginous model in mammals is replaced by bone, but at the long bone endings the avascular articular cartilage remains. Before the articular cartilage attains structural maturity it undergoes reorganization, and molecules such as vascular endothelial growth factor (VEGF) and endostatin could be involved in this process. VEGF attracts blood vessels, whereas endostatin blocks their formation. The present study therefore focused on the spatio-temporal localization of these two molecules during the development of the articular cartilage. Furthermore, we investigated the distribution of the chondro/osteoclasts at the chondro-osseous junction of the articular cartilage with the subchondral bone. Mice served as our animal model, and we examined several postnatal stages of the femur starting with week (W) 4. Our results indicated that during the formation of the articular cartilage, VEGF and endostatin had an overlapping localization. The former molecule was, however, down-regulated, whereas the latter was uniformly intensely localized until W12. At the chondro-osseous junction, the number of tartrate-resistant acid phosphatase (TRAP)-positive chondro/osteoclasts declined with increasing age. Until W3 the articular cartilage was not well organized but at W8 it appeared structurally mature. At that time only a few TRAP cells were present, indicative of a low resorptive activity at the chondro-osseous junction. Subsequently, we examined the metaphyseal growth plate that is closed when skeletal maturity is attained. Within its hypertrophic zone, localization of endostatin and VEGF was observed until W6 and W8, respectively. At the chondro-osseous junction of the growth plate, chondro/osteoclasts remained numerous until W12 to allow for its complete resorption. According to former findings, VEGF is critical for a normal skeleton development, whereas endostatin has almost no effect on this process. In conclusion, our findings suggest that both VEGF and endostatin play a role in the structural reorganization of the articular cartilage and endostatin may be involved in the maintenance of its avascularity. In the growth plate, however, endostatin does not appear to counteract VEGF, allowing vascular invasion of hypertrophic cartilage and bone growth., (© 2011 The Authors. Journal of Anatomy © 2011 Anatomical Society of Great Britain and Ireland.)

We report a case of spontaneous physeal growth arrest of the distal femur in a nine-year-old child with Ewing's sarcoma of the proximal femur treated with chemotherapy and endoprosthetic replacement. Owing to the extent of disuse osteoporosis at the time of surgery, the entire intramedullary canal up to the distal femoral physis was filled with cement. Three years later, the femur remained at its pre-operative length of 19 cm. Pre-operative calculations of further growth failed to account for the growth arrest, and the initial expandable growing prosthesis inserted has been revised to a longer one in order to address the leg-length discrepancy. To our knowledge, this is the only reported case of distal femoral physeal growth arrest following cemented endoprosthetic replacement of the proximal femur.

Ambient temperature and physical activity modulate bone elongation in mammals, but mechanisms underlying this plasticity are a century-old enigma. Longitudinal bone growth occurs in cartilaginous plates, which receive nutritional support via delivery of solutes from the vasculature. We tested the hypothesis that chronic exercise and warm temperature promote bone lengthening by increasing solute delivery to the growth plate, measured in real time using in vivo multiphoton microscopy. We housed 68 weanling female mice at cold (16°C) or warm (25°C) temperatures and allowed some groups voluntary access to a running wheel. We show that exercise mitigates the stunting effect of cold temperature on limb elongation after 11 days of wheel running. All runners had significantly lengthened limbs, regardless of temperature, while nonrunning mice had shorter limbs that correlated with housing temperature. Tail length was impacted only by temperature, indicating that the exercise effect was localized to limb bones and was not a systemic endocrine reaction. In vivo multiphoton imaging of fluoresceinated tracers revealed enhanced solute delivery to tibial growth plates in wheel-running mice, measured under anesthesia at rest. There was a minimal effect of rearing temperature on solute delivery when measured at an intermediate room temperature (20°C), suggesting that a lasting increase in solute delivery is an important factor in exercise-mediated limb lengthening but may not play a role in temperature-mediated limb lengthening. These results are relevant to the study of skeletal evolution in mammals from varying environments and have the potential to fundamentally advance our understanding of bone elongation processes.

Initiation of mineralization during endochondral ossification is a multistep process and has been assumed to correlate with specific interactions of annexins A5 and A6 and collagens. However, skeletal development appears to be normal in mice deficient for either A5 or A6, and the highly conserved structures led to the assumption that A5 and A6 may fulfill redundant functions. We have now generated mice deficient of both proteins. These mice were viable and fertile and showed no obvious abnormalities. Assessment of skeletal elements using histologic, ultrastructural, and peripheral quantitative computed tomographic methods revealed that mineralization and development of the skeleton were not significantly affected in mutant mice. Otherwise, global gene expression analysis showed subtle changes at the transcriptome level of genes involved in cell growth and intermediate metabolism. These results indicate that annexins A5 and A6 may not represent the essential annexins that promote mineralization in vivo., (2010 American Society for Bone and Mineral Research)

Background: Despite the increased use of arthroscopy in pediatric orthopaedics, there is a paucity of data regarding the potential long-term effects of this procedure on the immature physis. The purpose of this study was to test the hypothesis that elevated intra-articular pressures used during arthroscopic surgery do not result in growth disturbances or morphologic alterations in the epiphyseal plate., Methods: Twenty-seven 6-week-old skeletally immature New Zealand white rabbits were divided into experimental (n=21) and control groups (n=6). In the experimental group, a hydraulic pump was used to pressurize 1 randomly assigned knee joint per rabbit to intra-articular pressures of 120 mm Hg for 2 hours. In the control group, rabbits received a sham intervention. All rabbits were killed at 6 months of age (skeletal maturity), and their tissues were evaluated grossly, radiographically, and histologically. Data collection included gross measurements (femur and tibia lengths, evaluation of varus/valgus angulation, and knee joint range of motion) and histologic analyses to determine whether morphologic changes were present in the articular cartilage or physis. Confidence intervals were used to test for statistical equivalence., Results: The pressurized and control groups had statistically equivalent gross measurements. No significant articular cartilage or physeal lesions were identified in histologic sections or radiographic studies., Conclusion: This study provided no evidence that arthroscopic pressurization of the knee joint to 120 mm Hg for 2 hours significantly affected physeal growth in a skeletally immature rabbit model., Clinical Relevance: This study provides the first direct evidence that arthroscopic pressurization of immature joints has no clinically significant adverse long-term effects. Therefore, novel uses of arthroscopy in pediatric patients should be explored without undue concern with regard to premature physeal closure.

Rat tibial growth plates have X-ray opaque tethers that link the epiphysis and metaphysis and increase with age as the growth plate (GP) becomes thinner. To determine if tether formation is a regulated process of GP maturation, we tested the hypotheses that tether properties and distribution can be quantified by micro-computed tomography (microCT), that rachitic GPs typical of vitamin D receptor knockout (VDR(-/-)) mice have fewer tethers and altered tether distribution, and that tether formation is regulated by signaling via the VDR. Distal femoral GPs from VDR(+/+) and VDR(-/-) 8-week-old mice were analyzed with microCT and then processed for decalcified and undecalcified histomorphometry. A wide range of parameters that assessed GP and tether geometry and morphology, along with tether distribution, were measured using both microCT and histology. Growth plates of 10-week-old VDR(+/+) and VDR(-/-) mice on a high-calcium, phosphorus, lactose, and vitamin D(3) rescue diet were also analyzed. Both microCT and histology showed tethers present throughout normal mice GPs, while reduction in tether number and volume percentage occurred in VDR(-/-) GPs with localization to the central region. Decreased shrinkage in the axial direction during decalcified histological processing correlated with tether formation, suggesting mechanical stability due to tethers. Tether formation increased greatly between 8 and 10 weeks. Rescue diets restored VDR(-/-) GP size but not tether volume percentage. Overall, these results demonstrate microCT imaging's utility for analyzing tether formation and suggest that signaling via the VDR plays a pivotal role in tether formation.

Objective: To develop an epiphyseal slide-traction plate in child, which can supply the fracture a sufficient internal fixation, and will not restrain the growth of epiphyses. Animal experiments were carried out with the plates to compare the slide-traction with traditional plate., Methods: Develop a slide-traction plate for the configuration of the femur condylus of children. Thirty adolescent goats in the experiment were divided into control group (12 goats) and plate group (18 goats). In plate group, right femurs of goats were fixed with common plates and the left femurs with slide-traction plates. All the goats were given X-ray examination at different time after surgery. And the goats were sacrificed at 3 and 6 month, histological method and electron microscopy were performed to evaluate the development of epiphyseal plate., Results: The both femurs of the goats in control group have no difference in evidence in length at all time we examined. And the both femurs of the goats fixed with plates have no difference in evidence in length at 1 day after surgery. However, the both femurs of the goats fixed with plates have difference in evidence in length at 1 month, 2 month, 3 month, 6 month after surgery. The increased length of the femurs at I month, 2 month, 3 month, 6 month after surgery was also compared with the length at 1 day after surgery, there was difference in evidence between the right femurs of the control group and the femurs were fixed with common plates, but no difference in evidence between the left femurs of the normal control group and the femurs were fixed with slide-traction plate (P > 0.05). More thicker epiphyseal plate were found in the left femurs than the right femurs of the group fixed with plates at 3 and 6 month after surgery (P < 0.01). In the plate group, safranine O staining showed epiphyseal plates at the left femurs had more fuscous staining than the right femurs at 3 and 6 month after surgery and electron microscopy also found that the cells of the epiphyseal plates of left femurs were more eugenic than the right femurs at 3 and 6 month after surgery., Conclusion: The epiphyseal slide-traction plate can slide with the growth of epiphyses, which is suitable for fixation of the fracture in this part.

Background: Progressive genu varum with disturbance of medial tibial physeal growth (classic Blount disease) is a well-studied phenomenon, and in rare cases, genu varum can occur because of medial distal femoral physeal growth disturbance (so-called femoral Blount disease). To our knowledge, progressive genu valgum caused by disturbance of lateral distal femoral physeal growth has not been described., Methods: This article presents the history, clinical findings, imaging studies, results of surgical treatment, and speculation regarding the etiology of this disorder in 2 girls., Results: Both patients were overweight girls without a history of injury or prior medical disorder who presented with relatively rapid progression of knock-kneed deformity. Magnetic resonance imaging studies demonstrated unusual circular peglike disturbances of the lateral distal femoral physes. Treatments in both cases included corrective distal femoral osteotomy and epiphysiodesis to prevent further deformity., Conclusions: Obesity and repetitive microtrauma, superimposed on genetic factors (physis that is sensitive to compressive forces), may contribute to the etiology of this rare disorder.

Epiphysiodesis is an operative procedure that induces bony bridges to form across a growth plate of a bone to stop longitudinal growth. This is a very common orthopedic procedure to correct disproportional long-bone growth discrepancies; however, present techniques require an operation and anesthesia. Our study was designed to develop a minimally invasive method of epiphysiodesis by using electrical stimulation with DC current. In a rabbit model, a thin titanium electrode was inserted into a single location of the distal femoral growth plate in three groups: one without current (control), one group with a constant 10 microA (low current, LC), and one group with a 50 microA (high current, HC). The current was delivered for 2 weeks. The nontreated femur served as a control for each animal. Femur lengths were measured and comparisons were made between operated (left) and nonoperated (right) femurs. Digitized histomorphometric and volumetric analyses were performed on each growth plate, and detailed assessments were made of any morphological changes. Using length measurements, the difference in femur length was significantly larger in the HC group and not in the LC or control groups, showing bone growth inhibition at the higher current. In the HC group, bony bridges and disorganized growth plates were observed. This study shows that delivery of an electrical current of 50 microA for as little as 2 weeks can markedly affect bone growth as evidenced by changes in epiphyseal plate volume and architectural organization, and the study supports the use of this minimally invasive approach as a potential method of achieving an epiphysiodesis.

Blount disease is a deformity of the knee as a result of abnormal mechanical forces known to influence the growth of the physis. Despite existing studies on mechanical forces on chondrocyte cultures or limited growth plate specimens, very little information characterizes the whole growth plate to asymmetrical loading. In this study, we evaluate the response of 5 ovine proximal tibial growth plates to asymmetrical mechanical loading. Fresh proximal tibia specimens were mounted, and compressive forces were applied via a servohydraulic test frame (MTS Systems Corporation, Minneapolis, Minn) machine at standardized locations while transducers recorded the displacement at different locations. With this method, we demonstrate that loading (cyclical or static) on 1 edge of the tibial surface results in compression through the physis under the site of pressure. In addition, we record statistically significant tensile displacement opposite the compressed side (P < 0.001); this effect diminished as loading cell moved central on the tibial surface. We further show that growth plate topography influences the amount of tension and compression observed. From this study, we conclude that asymmetrical loading (such as that observed in Blount disease) may lead to compression (which retards growth) but also develops tension on the convex side (which may be a mechanism to increase deformity via Depelch phenomenon). The relationship of physeal architecture (more undulations-less physeal strain) may explain why greater deformity is observed on the tibial side of the knee in adolescent Blount disease than on the femoral side.

Radiation therapy encompassing an active epiphysis can negatively impact the potential for bone growth by disrupting cell-cycle progression and accelerating apoptosis and terminal differentiation in physeal chondrocytes. Despite functional derangement following radiation exposure, the irradiated growth plate retains a capacity for regeneration and recovery of growth. The purpose of this study was to characterize the initial sequence of events leading to functional growth recovery in irradiated weanling rat growth plates. We hypothesized that growth in an irradiated epiphysis would be partially restored due to the expansion of chondrocytic clones. Stereological histomorphometry was used to compare chondrocytic cell and matrix turnover between the first and second week following irradiation, and to determine the relative contribution of each of the cellular and extracellular matrix (ECM) compartments to growth. We found that restoration of growth in the irradiated limb was strongly associated with the proliferative activity and production of ECM by these chondrocytic clones, as they expand in average volume, but not in numerical density. We conclude that chondrocytes forming expansive clones and exhibiting increased mitotic and matrix synthesis activity initiate the early restoration of function in the irradiated growth plate, and would be a logical target for strategies to restore full growth potential., (Copyright (c) 2006 Orthopaedic Research Society.)

Background: Administration of quinolone therapy is controversial during growing age as stated by earlier worker. The flroquinolones are currently not indicated for young children, because of arthropathy and adverse effect on growing cartilage shown by studies. However the effects of ciprofloxacin on epiphyseal growth plate has remained undocumented. This study is therefore, undertaken to determine the risk of ciprofloxacin administration an growing cartilage by prospective experimental animal study model using Wistar albino rat pups., Methods: Ciprofloxacin was administered to newly born Wistar albino rat pups with a doze of 20 mg/kg body weight intraperitonealy twice a day from day-1 to day-14 after birth. The animals were sacrificed by deep ether anesthesia. The limbs were disarticulated from axial skeleton, soft tissue was removed. The intact bone mean length in millimeter of right and left humerus and femur was measured with the help of electronic vernier caliper and bones were fixed in 10% buffered farmalin. Decalcification was done in 10% nitric acid and 10% formic acid changes. After paraplast embeding, 4 microm thick longitudinal sections of the proximal long bones were cut by a rotary microtome. Routine staining with haemotoxylin and eosin was performed. Histomorphometry was done measuring the thickness of epiphyseal cartilage and was compared with similar value of control animals. The results were statistically analysed to find out the significance., Results: The ciprofloxacin induces a mordanting effect as abviated by increased basophilia. Our study reveales that cirprofloxacin administration in the newly born pups decreased the width of epiphyseal growth plate cartilage by 10.43% in humerus and 4.72% in femur as compared to the growth of control cartilage. The decrease in the width was brought about mainly by the reduced count of the proliferative cells in the proliferative zone and the diminuation in the average size of the hypertrophic condryocytes in the hypertrophic zone. The reserve zone has become markedly reduced in thickness., Conclusion: The ciprofloxacin post-natal administration effected growth plate retardation by inhibiting the mitosis in the proliferative zone and also effected the mean length of humora and femora leading to reduction in limb length of rat pups.

To investigate the age-related activity of the epiphyseal plates, a retrospective study of (99m)Tc-methylene diphosphonate bone scans was undertaken. The study comprised 81 males and 46 females aged 2 weeks to 24 years. The total percentage (%) whole-body (ratio of total physis activity to whole-body activity) and the regional % whole-body (ratio of physis activity of one region to whole-body activity) were derived. The ratio of physis activity of one region to the total physis activity was defined as % physis. Before age 12, total physis activity was found to contribute about 10% to whole-body activity. All total and regional % whole-body activities followed sigmoid curves with age. The differences of the parameters (transition centers and widths) suggested that there might be a later and longer period for the disappearance of physis activity in males than in females. For all the regions, % physis changed little with age until after puberty. At age <1, the proportion of bone activity in the body was about 30-35% for skull, 20-25% for lower limbs, and 5-15% for the rest of the regions. The maximal changes during growth occurred in the skull and the lower limbs. The age-related changes of physis activity during growth reflect a combination of the potential of bone to grow and the processes of bone growth and bone turnover. Bone scintigraphy is useful in understanding the changes of physis activity during growth.

Although previous theoretical modeling studies have predicted that various mechanical stresses accelerate or inhibit the ossification process of the neonatal chondroepiphysis, there is a paucity of experimental data to verify these models. The present study was designed to provide experimental evidence on whether the ossification of the chondroepiphysis is modulated by mechanical loading on the distal femoral condyle explant of the neonatal (5-day-old) rabbit in organ culture. Upon aseptic dissection, the right condyle explant was immersed in and fixated to an organ culture system, and received cyclic forces at 200 mN and 1 Hz for 12 h (N=8) directly on its slightly convex articular surface, whereas the contralateral, left condyle explant was immersed separately in organ culture (N=8). Subsequently, both loaded and control explants were placed in a bioreactor rotating at 20 rpm for 72 h. In each mechanically loaded specimen, a structure reminiscent of the secondary ossification center (SOC) appeared with an average area of 1.17+/-0.13 mm(2), or 15.2+/-8.2% of the total epiphysis area. In contrast, no SOC was detected in any of the unloaded contralateral control specimens. The SOC in mechanically loaded specimens was stained intensively with fast green, whereas either the rest of the loaded epiphysis or the entire control epiphysis was stained intensely to safranin-O but lacked fast green staining. Immunolocalization revealed that the SOC of the mechanically loaded specimens expressed Run x 2 and osteopontin, both of which were absent in the unloaded control specimens. Type X collagen was expressed surrounding hypertrophic chondrocytes adjacent to the SOC, but was absent in the control specimen. Type II collagen and decorin were absent in the SOC of the loaded specimen, but were expressed throughout the rest of the loaded epiphysis and the unloaded control epiphysis. The intensity of type II collagen and decorin expression was significantly stronger among hypertrophic chondrocytes surrounding the SOC than the control. The numbers of hypertrophic chondrocytes surrounding the SOC and superior to metaphyseal bone were significantly higher in the loaded specimens than the unloaded controls. Taken together, mechanical stresses accelerate the formation of the secondary ossification center, and therefore modulate endochondral ossification., ((c) 2005 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.)

Sex hormones play important roles in the regulation of the proliferation, maturation and death of chondrocytes in the epiphyseal growth plate. We have investigated the effects of male castration on the cell kinetics of chondrocytes as defined by the numbers of proliferating and dying cells. The growth plates of normal rabbits and animals castrated at eight weeks of age were obtained at 10, 15, 20 and 25 weeks of age. Our study suggested that castration led to an increase in apoptosis and a decrease in the proliferation of chondrocytes in the growth plate. In addition, the number of chondrocytes in the castrated rabbits was less than that of normal animals of the same age.

To evaluate the normal appearance of epiphyseal and physeal cartilage on Gadolinium (Gd)-enhanced MR imaging. The appearance and enhancement ratios of 20 proximal and distal femoral epiphyses in 10 normal piglets were analyzed on Gd-enhanced MR images. The correlation of the MR imaging appearance with corresponding histological findings of immature epiphyses was examined. Our results showed that Gd-enhanced MRI could differentiate the differences in enhancement between physeal and epiphyseal cartilage and show vascular canals within the epiphyseal cartilage. Enhanced ratios in the physeal were greater than those in the epiphyseal cartilage (P < 0.005). It is concluded that Gd-enhanced MR imaging reveals epiphyseal vascular canals and shows difference in enhancement of physeal and epiphyseal cartilage.

The purpose of this study is to define the appearance of normal epiphyseal and metaphyseal marrow and normal changes of marrow due to fatty conversion on Gadolinium (Gd)-enhanced MR Imaging. Unenhanced and enhanced T1-weighted MR imaging were performed in proximal and distal femoral ends of 8 healthy piglets at the ages of 2, 4, 6 and 8 weeks, respectively. The changes with age in signal intensity and enhancement ratio of the epiphyseal and metaphyseal marrow with age were examined. The correlation of MRI characteristics with histological findings was studied. Our study showed that marrow of the metaphysis and of periphery of the 2nd ossification center were well vascularized hematopoietic marrow and had great enhancements. The enhancement ratio of metaphysis was greater than that of epiphyseal marrow and both enhancement ratios degraded gradually with age. The central regions of the epiphyseal ossification center and of the diaphysis were of fatty marrow and had little enhancement. It is concluded that on Gd-enhanced MR imaging the hematopoietic marrow of metaphysis and of periphery of the 2nd ossification center had greater enhancement than that of fatty marrow of central region of the 2nd ossification center. All of their enhancements decreased gradually with age.

Objective: To explore how the size of the growth plate changes with age using three-dimensional (3D) models of the distal femoral and proximal tibial growth plates in pediatric patients., Design and Patients: We retrospectively created 3D models of the normal unaffected distal femoral (n=20) and proximal tibial (n=10) growth plates in 14 patients (9 males, 5 females) age range 3.8-15.6 years who were referred for evaluation of premature partial closure of the growth plate or hyaline cartilage abnormality. All patients had one or more 3D fat-suppressed spoiled GRASS sequence from which models were made of normal growth plates. Total projected area was estimated from standardized maximum intensity projection (MIP) views, and volume was computed from the entire model. We also included the total projected area of the distal femur (n=7) or proximal tibia (n=8) in 11 patients (8 males, 3 females, 5-13 years) who had previously been evaluated for bone bridging., Results: The 3D femoral and tibial growth plate anatomy was displayed. Femoral growth plate area varied from 804 mm2 to 3,463 mm2. Femoral physeal cartilage volume varied from 2.1 cm3 to 12.6 cm3. Tibial growth plate area varied from 736 mm2 to 3,026 mm2. Tibial physeal cartilage volume varied from 1.9 cm3 to 13.2 cm3. The growth plate area values appear to increase linearly with increasing age., Conclusions: The distal femoral and proximal tibial physeal plates have complex anatomy. Both area and volume of the growth plates appeared to follow a linear increase with age and reached a plateau in adolescence, although there was some scatter. Area appears to have less measurement variability than volume, and may be a more reliable predictor of growth plate tissue quantity., (Copyright 2004 ISS)

Purpose of the Study: This cohort illustrates growth of the center of ossification of the femoral head during and after orthopedic reduction of congenital hip dislocation., Material and Methods: Thirty files of pediatric patients with congenital hip dysplasia were studied retrospectively. Mean age of the children was 24.5 Months. All had unilateral dysplasia, allowing a comparison of femoral head growth by calculating the centers of ossification on the AP views., Results: Mean ratio between the radiological surface of the center of ossification of the femoral head on the dysplastic side and the normal side was about 1: 2. This ratio progressed rapidly during the first Months after reduction and became 1: 1 at a mean 43 Months after reduction. Beyond this time, growth of the femoral heads followed a similar pattern., Discussion: Growth of the center of ossification of the femoral head is related to biomechanical stress forces. Reduction is the only event in the natural history of the disease, but renewed growth of the femoral head cannot provoke in itself normal acetabular growth. Complementary pelvic osteotomy was required for 13 hips., Conclusion: Accelerated growth of the femoral head ossification center continues to be a good indicator of femoral head vitality. Early and rapid growth observed after reduction, without osteochondritis, can lead to a normal femoral head at the end of growth.

Until recently, the cartilage canals of the epiphyseal growth cartilage have not been associated with any specific disease. However, data support the hypothesis that osteochondrosis could be related to inadequate blood supply from vessels in these channels. We have done a study to investigate the relationship between the regression of cartilage canals and the formation of osteochondrosis latens in the epiphyseal growth cartilage of the distal femur in pigs, and the relationship between these events and age, growth rate, weight and femoral shape of the individual animals. This involved, in part, a comprehensive study of the distribution and pattern of regression of the cartilage canals. We found that the regression is a highly predictable process that follows an age-dependent pattern. However, we failed to prove any association between overall vascular regression and osteochondrosis, between vascular regression and weight, growth rate or femoral shape or between osteochondrosis and weight, growth rate or femoral shape. This may indicate that osteochondrosis latens is not caused by a general failure of vascular supply or general factors such as growth rate, but rather a consequence of local conditions affecting a limited number of vessels. A factor fitting this description is local compression.

Objective: We sought to study the normal enhancement patterns seen on MRIs of the epiphysis, physis, and metaphysis and age-related vascular changes in piglets using gadoteridol, a nonionic gadolinium chelate., Materials and Methods: We quantitatively and qualitatively analyzed the normal changes on sequential T1-weighted images after the IV administration of gadoteridol. In an investigation approved by the research animal care committee at our hospital, we studied the proximal and distal femurs of 26 piglets 1-6 weeks old and correlated the enhanced images with findings on intermediate-weighted, T2-weighted, and gradient-recalled echo images and at histologic examination., Results: We observed early enhancement of the epiphyseal vascular canals, the main physis, the physis of the secondary ossification center, and a metaphyseal band adjacent to the physis. Enhancement of the epiphyseal and metaphyseal marrow and of the epiphyseal cartilage was slower. In the epiphyseal cartilage, we saw three phases of enhancement: vascular, canalicular, and cartilaginous. As the piglets matured, enhancement of the epiphyseal cartilage decreased, and the epiphyseal vascular canals were less conspicuous. Physeal enhancement was greatest during the first week of life, declined at 3 weeks, and subsequently increased again as the physis came to lie adjacent to a larger segment of the epiphyseal ossification center., Conclusion: Gadoteridol-enhanced MRIs showed multiple cartilaginous and vascular structures of the growing skeleton. With maturity and progressive epiphyseal ossification, epiphyseal cartilage enhancement decreased, and physeal cartilage enhancement increased.