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Increased VEGF expression in the epiphyseal cartilage after ischemic necrosis of the capital femoral epiphysis.

UNLABELLED: Ischemic injury to the immature femoral head produces epiphyseal cartilage damage and cessation of endochondral ossification. This study suggests that VEGF facilitates the repair of the necrotic epiphyseal cartilage, which is essential for restoration of endochondral ossification and re-establishment of the growth of the immature femoral head after ischemic necrosis. INTRODUCTION: Legg-Calve-Perthes disease (LCPD) is a childhood form of osteonecrosis that produces growth arrest of the secondary center of ossification. The cessation of growth is caused by ischemic damage to the hypertrophic zone of the epiphyseal cartilage where endochondral ossification normally occurs. The role of vascular endothelial growth factor (VEGF) in restoring endochondral ossification in the epiphyseal cartilage after ischemic necrosis was investigated in a piglet model of LCPD because the resumption of normal growth is important for maintaining the spherical shape of the femoral head. MATERIALS AND METHODS: Piglet femoral heads were assessed 24 h to 8 weeks after the surgical induction of ischemia. Western blot analysis, ribonuclease protection assay (RPA), immunohistochemistry, and in situ hybridization were performed. RESULTS: Western blot analysis and RPA showed increased VEGF protein and mRNA expression, respectively, in the epiphyseal cartilage of the infarcted heads compared with the contralateral normal heads. In the normal femoral heads, VEGF-immunoreactivity (VEGF-IR) and transcripts were observed in the hypertrophic zone of the epiphyseal cartilage. In the infarcted heads, VEGF-IR and transcripts were no longer observed in the hypertrophic zone because of diffuse cell death in that zone from ischemia. However, VEGF-IR and transcripts were observed in the proliferative zone above the necrotic hypertrophic zone. At 8 weeks, vascular granulation tissue invasion of the necrotic hypertrophic zone was observed with active resorption of the necrotic cartilage. In some areas where the necrotic cartilage was completely resorbed, restoration of endochondral ossification was observed. In these areas, VEGF transcripts were observed in the newly formed hypertrophic zone. CONCLUSIONS: VEGF expression was increased, and its spatial expression was altered in the epiphyseal cartilage after ischemic necrosis of the immature femoral head. VEGF upregulation in the proliferative zone after ischemic damage may play a role in stimulating vascular invasion and granulation tissue formation in the necrotic hypertrophic zone of the epiphyseal cartilage. This may be an important step toward facilitating the resorption of the necrotic cartilage and restoration of endochondral ossification leading to further growth and development of the femoral head.

Animals↗

Epiphyseal and physeal cartilage vascularization: a light microscopic and tritiated thymidine autoradiographic study of cartilage canals in newborn and young postnatal rabbit bone.

The vascular pattern of newborn and early postnatal epiphyseal and physeal cartilage is integral to long bone development and differs from later postnatal patterns. In the present study, we supplement light microscopic histology with tritiated thymidine autoradiography to help assess the position of cartilage canals and the dynamics of cartilage vascularity in relation to growth. Tritiated thymidine labeling studies to assess cell proliferation activity were done by using 2 microc/g body weight intraperitoneal injections into newborn and 3-, 4-, and 7-day-old New Zealand white rabbits that were killed 1 hr after the injection. Proximal humeral, distal femoral, and third metatarsal epiphyses were assessed by routine histology and serial section autoradiography. Cartilage canals were seen in each epiphysis. Transphyseal vessels were seen in each epiphysis continuous from the epiphysis to the metaphysis or were present within the physis traversing the proliferating and hypertrophic cell zones. Histologic sections showed vessels from the perichondrium continuous with those of the epiphyseal cartilage canals at proximal humeral, distal femoral, and metatarsal epiphyses. Serial sections showed vascular buds and connective tissue cells lying in indentations at the periphery of and present within the epiphyseal cartilage. Autoradiographic studies showed extensive labeling of vessel wall cells and surrounding connective tissue cells of the cartilage canals (a) within the epiphyseal cartilage, (b) traversing the physis, and (c) within the epiphyseal cartilage but continuous with the perichondrial vessels. The labeling was always far more extensive than in the surrounding chondrocytes and was always present throughout the entire extent of the canals. In conclusion, the cell labeling activity strongly supports an active dynamic phenomenon underlying the vascularization of epiphyseal and physeal cartilage.

Age Factors↗

Epiphyseal and physeal cartilage: normal gadolinium-enhanced MR imaging.

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.

Animals↗

Morphometric changes in the epiphyseal plate of the growing and young adult male rat after long-term salmon calcitonin administration.

The function of the epiphyseal plate is related to the differentiation and maturation of the chondrocytes, especially of the hypertrophic zone. Salmon calcitonin exerts a positive effect on chondrocytes of different types of cartilage, e.g., articular cartilage, osteochondral callus formation, and the epiphyseal plate. In the present study, the effect of long-term daily salmon calcitonin treatment upon epiphyseal plate function was examined in 80 male Wistar rats aged 12 weeks at the beginning of the experiment. A daily dose of 6 IU of salmon calcitonin enhanced the number of the chondrocytes of the hypertrophic zone of the upper tibial epiphyseal plate, increased the mean thickness of the epiphyseal plate, and accelerated the longitudinal growth of long bones. It was found that the peripheral growth of the epiphyseal plate was delayed after calcitonin treatment in comparison with the placebo-treated animals. The most effective period for calcitonin treatment on epiphyseal plate function seems to be the late accelerated period of growth, i.e., puberty. In conclusion, long-term salmon calcitonin treatment has a beneficial effect on longitudinal skeletal growth and this effect remains throughout the adult life of the animal. Salmon calcitonin does not enlarge the surface of the epiphyseal plate.

Aging↗

Epiphyseal plate transplantation: an historical review.

Non-vascularized and vascularized transplantation of epiphyseal plate autografts have been performed both clinically and experimentally for over 100 years. However, the ultimate clinical goal of vascularized transplantation of epiphyseal plate allografts for paediatric extremity reconstruction remains elusive, due primarily to the lack of suitably nontoxic techniques to prevent graft rejection. We have summarized the published clinical and experimental investigations of vascularized epiphyseal plate transplantation, and organized the experiments and clinical operations into four main groups: (1) local vascular studies on unmanipulated epiphyseal plates, (2) studies of epiphyseal plate behaviour after orthotopic replantation, (3) studies of epiphyseal plate behaviour after heterotopic transplantation, and (4) studies of epiphyseal plate behaviour after allograft transplantation. Prior investigations into the non-vascularized transplantation of epiphyseal plate autografts and allografts are presented as background. These groups of studies serve as the building blocks for the more clinically applicable experimental investigations outlined in the final section of this review.

Animals↗

Direct administration of testosterone increases rat tibial epiphyseal growth plate width.

Local injection of hormones into the tibial epiphyseal growth plate offers a possible model to answer whether sex steroids can affect bone growth directly. To answer this question, we injected different doses of testosterone enanthate (4, 40, 120 and 400 micrograms/100 g of rat weight) once into the tibial epiphyseal growth plate of castrated 35-day-old male rats. The contralateral tibia was injected with sesame oil and served as control. All animals were sacrificed at age 42 days. Tibias were removed for measurement of epiphyseal growth plate width and blood was collected for measurement of serum IGF-I and testosterone. The lower doses of testosterone enanthate (4, 40 and 120 micrograms/100 g) did not produce any significant change in epiphyseal growth plate width. Testosterone at the largest dose tested (400 micrograms/100 g) increased epiphyseal growth plate width by about 15% compared to control (p less than 0.01). At this dose, serum testosterone was not increased, suggesting that the effect on epiphyseal growth plate width was not due to higher systemic testosterone concentrations. No differences in IGF-I levels were observed among the groups. We conclude that direct administration of testosterone enanthate at a dose of 400 micrograms/100 g into the rat tibial epiphyseal growth plate can increase epiphyseal growth plate width.

Animals↗

[Chondrogenesis in vitro by epiphyseal chondrocytes seeding into three-dimensional scaffolds].

OBJECTIVE: To observe the efficiency and biological characteristics in regenerating in vitro tissue-engineered cartilage from epiphyseal chondrocyte-scaffold complex. METHODS: The first passage epiphyseal chondrocytes were collected and mixed with the biological gel-matrix, the chondrocyte-gel fluid was dropped into the scaffold to form a complex. The complexes were in vitro cultivated. The changes of complexes in morphology and synthesis of collagens type II and type I and aggrecan were observed under the gross and the inverted and light microscopes. The sulfate GAG content in complexes was measured by the the modified dimethylmethylene blue method. RESULTS: During cultivation, the complexes could keep its original shape with the stable homogeneous three-dimensional distribution of chondrocytes, gradually became milk white and translucence with their rigidity increasing. In the 1st week, the chondrocytic lacunae formed in the complexes. After 2 weeks, the complex was gradually reorganized into the mature engineered cartilage with rich collagen type II and aggrecan and typical cartilage histological structure, but with negative immunological staining of collagen type I. In the 4th week, the engineered cartilage resembled the nature epiphyseal plate in the characteristic of histological structure, and had over 34% of the sulfate GAG content of the natural epiphyseal plate. CONCLUSION: The epiphyseal chondrocyte-scaffold complex can be reorganized into typical cartilage with the epiphyseal-like histological structure, and be fit for repairing the epiphyseal defect. The tissue engineered cartilage cultivated for 1-2 weeks may be a good choice for repairing epiphyseal defect.

Animals↗

[Physiology and pathology of the epiphyseal cartilage (author's transl)].

Knowledge of the physiology of the epiphyseal cartilage, respectively epiphyseal plate, is essential for an understanding of defective growth and abnormal modeling of the long bones. The epiphyseal cartilage develops from the embryonal, cartilaginous long bone structure. The histology of the epiphyseal cartilage is characterised by definable zones representing the individual differentiation steps from the reformation of cartilage to chondrolysis. Modeling of the ends of the long bones is also influenced by a transversal and longitudinal direction of growth in the epiphyseal cartilage. The intercellular substance mainly contains collagin, proteoglycanes and non-collagenic proteins. These macromolecules are compounded by means of physicochemical bonds and are responsible for the special mechanical qualities of the hyaline cartilage. The process of mineralisation at the base of the epiphyseal cartilage is an essential differentiating step for the ossification processes which take place in the metaphysis. Two pathogenetic principles at the epiphyseal cartilage appear to be important for the defective growth of the long bones. On the one hand, the flowing equilibrium between the differentiation steps of cartilage reformation, transformation of the hyaline cartilage into a mineralised cartilaginous tissue and chondrolysis is changed, whereas on the other hand the turnover of these differentiation steps is retarded or accelerated.

Animals↗

Repair of articular cartilage lesions in aged chickens by allogeneic transplantation of fresh embryonic epiphyses.

INTRODUCTION: The potential of fresh whole chick epiphyses of embryonic origin to serve as implant material for cartilage defects of aged chicken was tested. MATERIALS AND METHODS: Fresh epiphyses of 11-day-old embryos were collected from 24 animals and transplanted into defects created in the weight-bearing areas of tibiotarsal joint cartilage of 2-year-old chicks. Upon sacrifice, samples were examined macroscopically and microsections were prepared for histology. RESULTS: Macroscopically, control defects remained empty at all the time intervals. Defects of the experimental group were, on the other hand, filled with cartilaginous tissue as early as 2 weeks posttransplantation, although individual epiphyses could still be noted in the implant tissue. At 4 weeks and later, defects were filled with cartilaginous material indistinguishable from hyaline cartilage. Histologically, all grafts remained within the defect's pits, showing mitotic and metabolic activity typical to proliferating hyaline cartilage. The engrafted epiphyses showed a partial incorporation and integration with the surrounding host tissues already at 2 weeks. At 4 weeks and later, the integration was complete. CONCLUSIONS: It is concluded that a chick embryonic epiphyseal cartilage is suitable as a graft source for articular cartilage transplantation. The embryonic epiphyses provide immediate inherent stability to the graft and supply a good mix of mesenchymal progenitor cells responsible for the high rate of cell proliferation and adhesion to the differentiated committed chondrocytes of the host that create the typical favorable chondrogenic milieu. Based on the present findings, it is postulated that human embryonic epiphyses may, in the future, represent an alternative source to the commonly used techniques of hyaline cartilage repair.

Animals↗

[Lesions of the epiphyses - classification - therapy - prognosis (author's transl)].

Between 1970 and 1980 53 children with epiphyseal injuries were treated. Analysing these 53 cases we found that metaphyseal lesions of the epiphyseal plate (i.e. epiphyseolysis, separation of the epiphysis with triangular metaphyseal fragment) heal completely, even in those cases in whom an open reduction was necessary. Conservatively treated epiphyseal injuries (i.e. fracture of the epiphysis, crushing of the epiphyseal plate) showed bad results. Contrary to these results 80% of open reduced injuries showed good results. We can conclude that epiphyseal injuries do not necessarily end in disturbances of growth or malformation if surgical correction of the injury is done as early as possible and if the injured extremity is immobilised at least 3 to 5 weeks. Destruction of the epiphyseal vascular system can only be avoided by surgical reposition of the epiphyseal injury.

Child↗

Normal maturation of the distal femoral epiphyseal cartilage: age-related changes at MR imaging.

PURPOSE: To determine how signal intensity in the cartilaginous distal part of the femoral epiphysis varies with (a) age, (b) sex, and (c) distribution to the medial or lateral condyle on magnetic resonance (MR) images. MATERIALS AND METHODS: Sixty-six sagittal T2-weighted or inversion-recovery MR images of the distal femoral epiphysis in children aged 2 months to 5 years 5 months were evaluated. Epiphyses were categorized into five types on the basis of progressive signal intensity changes within the epiphyseal cartilage along the weight-bearing region and posterior condyles. Epiphyseal type was compared with age, sex, and distribution of signal intensity changes within the condyle. RESULTS: In early infancy, epiphyseal cartilage was homogeneous. During the 2nd year, signal intensity along the weight-bearing region decreased. With further advancing age, signal intensity in the posterior femoral condyles increased and became progressively more focal. The increase in epiphyseal grade correlated with age for both the medial and the lateral femoral condyles (r = 0.71 and r = 0.77, respectively; P < .001). There was no significant difference in epiphyseal changes between boys and girls or between medial and lateral condyles. CONCLUSION: There is normal age-related variation in MR imaging signal intensity within the cartilaginous epiphysis of the distal femur. This may be related to weight bearing and epiphyseal maturation and should not be confused with disease.

Bone Development↗

Deficiency of insulin receptor substrate-1 impairs skeletal growth through early closure of epiphyseal cartilage.

UNLABELLED: Morphological analyses in and around the epiphyseal cartilage of mice deficient in insulin receptor substrate-1 (IRS-1) showed IRS-1 signaling to be important for skeletal growth by preventing early closure of the epiphyseal cartilage and maintaining the subsequent bone turnover at the primary spongiosa. INTRODUCTION: IRS-1 is an essential molecule for intracellular signaling by IGF-I and insulin, both of which are potent anabolic regulators of cartilage and bone metabolism. To clarify the role of IRS-1 signaling in the skeletal growth, morphological analyses were performed in and around the epiphyseal cartilage of mice deficient in IRS-1 (IRS-1(-/-)), whose limbs and trunk were 20-30% shorter than wildtype (WT) mice. MATERIALS AND METHODS: The epiphyseal cartilage and the primary spongiosa at proximal tibias of homozygous IRS-1(-/-) and WT male littermates were compared using histological, immunohistochemical, enzyme cytohistochemical, ultrastructural, and bone histomorphometrical analyses. RESULTS: In and around the WT epiphyseal cartilage, IRS-1 and insulin-like growth factor (IGF)-1 receptors were widely expressed, whereas IRS-2 was weakly localized in bone cells. Chronological observation revealed that height of the proliferative zone and the size of hypertrophic chondrocytes were decreased in WT mice as a function of age, and these decreases were accelerated in the IRS-1 (-/-) cartilage, whose findings at 12 weeks were similar to those of WT at 24 weeks. In the IRS-1(-/-) cartilage, proliferating chondrocytes with positive proliferating cell nuclear antigen (PCNA) or parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor immunostaining had almost disappeared by 12 weeks. Contrarily, TUNEL+ apoptotic cells were increased in the hypertrophic zone, at the bottom of which most of the chondrocytes were surrounded by the calcified matrix, suggesting the closure of the cartilage. In the primary spongiosa, bone volume, alkaline phosphatase (ALP)+ osteoblasts, TRACP+ osteoclasts, and the osteopontin-positive cement line were markedly decreased. Bone histomorphometrical parameters for both bone formation and resorption were significantly lower in IRS-1(-/-) mice, indicating the suppression of bone turnover. CONCLUSION: The IRS-1(-/-) epiphyseal cartilage exhibited insufficient proliferation of chondrocytes, calcification of hypertrophic chondrocytes, acceleration of apoptosis, and early closure of the growth plate. Thus, the data strongly suggest that IRS-1 signaling is important for the skeletal growth by preventing early closure of the epiphyseal cartilage and by maintaining the subsequent bone turnover at the primary spongiosa.

Animals↗

Studies on the pathogenesis of avian rickets II. Necrosis of perforating epiphyseal vessels during recovery from rickets in chicks caused by vitamin D3 deficiency.

This study involved comparison of the distribution and integrity of perforating epiphyseal and marrow vessels with the stage of development and integrity of chondrocytes and the distribution of insoluble calcium in the proximal tibial growth plate of 3-week-old vitamin-D3-deficient hypocalcemic chicks and 3-week-old D3-deficient chicks 12, 36, 72, and 120 hours after an oral dose of 10,000 units vitamin D3. The aim was to clarify the mechanisms responsible for chondrocyte hypertrophy and cartilage calcification in the avian growth plate. Within 12 hours after administration of vitamin D3, serum calcium levels rose to normocalcemic levels. The following morphologic changes were first recognizable at the times indicated. Distal portions of previously elongated perforating epiphyseal vessels and adjacent proliferative and maturing chondrocytes underwent necrosis by 12 hours. Chondrocyte necrosis was not preceded by hypertrophy. By 36 hours, vascular and chondrocyte necrosis involved large portions of the thickened proliferating and maturing zone, and perforating epiphyseal vessels were shortened to a normal length. By 72 hours, chondrocyte hypertrophy and calcification resumed around the shortened epiphyseal vessels. By 120 hours, marrow had removed the necrotic cartilage, and morphologically normal growth plate was restored, with perforating epiphyseal and marrow vessels, both ending in a narrow hypertropic cartilage zone. The results indicate that proximity of chondrocytes to perforating epiphyseal vessels is necessary for their viability, but loss of these vessels does not cause hypertrophy. Since hypertrophy and calcification both occur in the proximity of perforating epiphyseal vessels in normocalcemic animals but not in hypocalcemic animals, it is likely that the vessels influence hypertrophy and calcification by delivering calcium to chondrocytes.

Animals↗

Heterotopic microvascular epiphyseal plate transplantation: a new model using the rabbit metatarsal.

The purpose of this study is to develop a new vascularized epiphyseal plate model in the New Zealand White rabbit using a metatarsal epiphyseal plate having limited longitudinal growth potential. Such a model could be utilized in various experiments aimed at manipulating epiphyseal plate growth. The viability of the harvested live subject grafts was demonstrated with continued epiphyseal uptake during Tc99-MDP radionuclide bone scanning. The currently described models used in epiphyseal transplant research all involve long bone epiphyseal plates with significantly greater growth potential than the new metatarsal model. This new model therefore fills a void in the field by allowing investigators to transplant a growth plate with limited growth potential into any heterotopic site and study the effects of various hormonal and physical influences upon epiphyseal plate growth performance.

Animals↗

Microcirculation of the distal humeral epiphyseal cartilage: implications for post-traumatic growth deformities.

The purpose of this study was to determine if there is an anatomic basis for development of the avascular necrosis infrequently seen after elbow trauma. The microcirculation to the distal humeral epiphyseal cartilage was studied in 38 elbow joints from 19 skeletally immature individuals. The findings of this study were as follows: (1) Vascularity is centripetal within the epiphyseal cartilages of the capitellum, trochlea, and medial and lateral epicondyles. Because of this vascularity pattern, it is not easy for avascular necrosis to develop after trauma within these epiphyses. (2) Vascularity is longitudinal in the epiphyseal cartilage between the capitellum and trochlea. The longitudinal vessels appear susceptible to fractures around the elbow in childhood. (3) A rich vascular network exists in the olecranon fat pad, and a vascular arch forms from the vascular network adjacent to the distal humeral epiphyseal cartilage. The vascular arch sends several large branches into the epiphyseal cartilage in a vertical fashion. Disruption of either the longitudinal intraosseous vasculature (vertical extraosseous blood supply) or the vascular arch in more than 2 places may lead to selective avascular necrosis of the epiphyseal cartilage between the capitellum and trochlea. These findings suggest vascular compromise as a possible explanation for "fish-tail" deformities seen as sequellae of different fracture patterns.

Female↗

Articular cartilage reconstruction using xenogeneic epiphyses slices.

Reconstruction of articular cartilage defects using adult osteochondral allografts is an established clinical procedure, whose principal drawback is lack of lateral integration of the grafts to the surrounding tissue. Autologous chondrocytes transplantation is a sophisticated technique requiring cell culture and a staged operation. Its main draw back is the lack of mechanical strength early on. This study was conducted in order to evaluate the possibility of using embryonal epiphyses as a cartilage reconstruction tissue. A xenogeneic human to rabbit sub-acute osteochondral defect model was designed to evaluate the possibility of allogeneic implantation in humans. The following procedures were perfomed (n = 5): transplantation of 1. live epiphyses 2. live epiphyses with autogeneic periosteum 3. de-vitalized epiphyses and 4. devitalized epiphyses with autogeneic articular chondrocytes. A fifth control group did not receive any implant. Animals in groups 1 and 2 had a viable reconstruction of the articular surface with little evidence of rejection and without pannus formation. Animals in groups 3 and 4 became severely arthritic and the graft was resorbed. Nitric oxide synthase accumulation was reduced in group 1 and 2 as compared to groups 3, 4, and 5, indicating a joint preserving function of the epiphyseal grafts. Epiphyseal grafts appear to be a feasible procedure for reconstruction of articular cartilage defects even in a xenogeneic model.

Journal Article↗

Clinical features of multiple epiphyseal dysplasia expressed in the knee.

The purpose of this study is to clarify the clinical features of the knee affected by multiple epiphyseal dysplasia. Thirty-one cases of multiple epiphyseal dysplasia were reviewed. Of the patients, 11 were male and 20 were female. The average age at onset of symptoms was 22.5 years. The average age at initial visit to the authors' hospital was 28.9 years. Radiographic findings showed epiphyseal abnormality of the knee in all but two (93%) cases. Irregularity, segmentation of the epiphysis, widening of the joint space, and genu valgum deformity were the dominant findings before epiphyseal closure. After epiphyseal closure, the most characteristic finding was a shallow femoral trochlear groove, which was observed in 56.5% of the cases. Other findings in adult patients included early onset osteoarthritic change, genu valgum, depression of the lateral tibial plateau, and multiple free bodies. However, there still is a possibility that multiple epiphyseal dysplasia exists, even if the patient lacks a shallow femoral trochlear groove. If genu valgum or varum, free bodies, and premature osteoarthritis are observed, one should evaluate other joints, keeping a diagnosis of multiple epiphyseal dysplasia in mind. Patients with knees that have a femoral trochlear groove of normal or near normal shape do exist, and premature osteoarthritic changes may develop in such patients.

Adolescent↗

Transplantation of epiphyseal plate allografts between animals of different ages.

The purpose of the experiment was to study growth of epiphyseal plate allografts after transplantation into subjects of a different age, thus preparing for future transplantation of epiphyseal plate or extremity allografts in children. Microvascular transplantation of proximal tibial epiphyseal plate allografts was performed in skeletally immature New Zealand White female rabbits. The growth of 9-week-old epiphyseal plate allografts was examined in both 9-week-old and 17-week-old recipients, as was the growth of 17-week-old epiphyseal plate allografts in 17-week-old recipients. Immunosuppression was with cyclosporine (Cyclosporine A). Successful transplants were confirmed with 99mTc-MDP isotope scanning, and growth was evaluated with weekly standardized radiographs until death. Growth rate was found to depend on the age of the donor epiphyseal plate and was independent of the age of the recipient. This has clinical implications for the procurement of donor tissue in potential transplantation of epiphyseal plate allografts in children.

Age Factors↗