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[New classification of epiphyseal-plate injuries with regard to therapy and prognosis (author's transl)].

In this report a new simple classification of epiphyseal-plate injuries with regard to therapy and prognosis is pointed out. The classification can be used for each epiphysis and will be demonstrated on the injuries of the distal lower leg. Type I: There is complete separation of the epiphysis from the metaphysis without and with a metaphyseal fragment. The prognosis for growth is excellent after conservative or operative treatment. Type II: The fracture which is intraarticular (epiphyseal fragment) and the fracture across the full thickness of the epiphyseal plate and through a portion of the metaphysis needs accurate reduction. The prognosis for growth is good only after open operation. Type III: This relatively uncommon injury results from a very severe crushing force applied through the epiphysis to one area of the epiphyseal plate. The prognosis in this type is decidedly poor. The need for regular follow-up observation in these cases is obvious. At the end the good results of 40 patients after epiphyseal-plate injuries of the distal lower leg are presented.

Epiphyses↗

[Distribution of trabecular microfractures in the proximal femur--with the epiphyseal scar as a landmark].

The distribution of the trabecular microfractures in normal human proximal femora was investigated to see whether they were related to the femoral neck fracture of the elderly. In this study the epiphyseal scar was employed as an anatomical landmark in the proximal femur, since the authors' observation suggested that it remained throughout life and was located in constant connection with the margin of the articular cartilage. The medial aspect of the proximal femur was divided into three anatomical zones, which were called epiphyseal, subepiphyseal and subcapital ones, respectively. There were two areas in which trabecular microfractures concentrated; one was about the lateral end of the epiphyseal scar and another the subepiphyseal zone. Few microfractures were noted on the principal compressive trabeculae. A femoral neck fracture of the elderly usually provides a fracture line running from the lateral end of the epiphyseal scar down to the subcapital zone. Thus the fracture takes place just within the area of concentration of trabecular microfractures laterally, whereas it passes caudad to the medial group of microfractures. The authors hypothesize that the trabecular microfractures arising about the lateral end of the epiphyseal scar may have an etiological significance for the femoral neck fracture, in contrast that those in the subepiphyseal zone may not.

Adult↗

Effects of fracture trauma, estrone treatment, and 2-G environment on the epiphyseal cartilage zones of developing avian radii.

Female birds subjected to closed fracture of the right radius at 2 weeks post-hatching were allowed to heal for 14 d at either earth gravity (1 G) or a 2-G hypergravity state, with saline-injected controls and 0.2- and 0.4-mg estrone (estrogen) treated groups. Animals were sacrificed following the last injection and radii were routinely processed histologically for micrometer measurements of the mid-coronal height and width of the cartilage zones of the proximal and distal epiphyses. Proximal epiphyses of estrone-treated, normo-gravity chicks showed a decreased growth in height of the articular, proliferating, and hypertrophic cartilage zones and an increased interstitial growth of the hypertrophic and calcified layers of estrone-treated, 2-G animals. Growth in height of the cartilage layers of the distal epiphyses of fractured radii was primarily stimulated when estrone-treated chicks were also exposed to the 2-G state. Appositional growth of all cartilage layers of the proximal and distal epiphyses of normo-gravity birds was increased by 0.2 mg estrone. In addition, growth in the width of all cartilage layers of the distal epiphyses of 2-G animals was increased with the administration of 0.4 mg estrone.

Animals↗

Age related changes and osteochondrosis in swine articular and epiphyseal cartilage: light ane electron microscopy.

Age related changes and osteochondrosis in swine were studied using light microscopy and electron microscopy in articular cartilage and light microscopy and epiphyseal cartilage of swine from three days to 30 weeks of age. Thickness, cellularity and vascularity of both the epiphyseal and articular cartilage, decreased as the swine aged. Osteochondrotic changes included formation of "plugs" of cartilage indicating localized failure of ossification and separation and space formation in epiphyseal cartilage. Eosinophilic streaks and space formation in epiphyseal cartilage was observed in relation to epiphyseal separation. Electron microscopy showed a continuous fibrillar layer on the surface of the cartilage corresponding to the lamina splendens of light microscopy. This layer increased in the thickness and showed accumulation of amorphous material between the fibrils with aging. In the matrix, the orientation and distribution of the collagen fibers changed with growth and thicker fibers with clear sub banding were more common in older age groups. Also, necrotic cells, glycogen containing bodies and cellular debris were noticed in the matrix of normal cartilage in old animals. Chondrocytes in the younger cartilage showed accumulation of organelles responsible for protein synthesis; while Golgi bodies, vesicles, lysosomes, well developed foot processes and other inclusions were noticed in older cartilage. Cartilage erosions had a clumped and disrupted lamina splendens on the surface and electron lucent patches in the ground substances of the matrix and chondrocyte cytoplasm.

Aging↗

Stages of epiphyseal union for thoracic and lumbar vertebral centra as a method of age determination for teenage and young adult skeletons.

Many current methods of age determination available to forensic anthropologists are limiting in that the age ranges provided are often broad, particularly for individuals in their late teens to early 20's. This study introduces an improved method for aging teenagers and young adults. The pattern and stages of union of the superior and inferior epiphyses of the vertebral centra (or ring epiphyses) were examined in 55 individuals, females and males, black and white, between ages 11 and 32 years. Vertebral ring epiphyseal union was found to be a good predictor of age. The correlation between stages of union and known age was 0.78 (P < .0001). The standard deviation was 2.566 years at the 99.9% confidence level. Sex differences were observed, but were not statistically significant. A larger sample size may perhaps demonstrate statistically significant differences in sex, and may or may not yield differences in race. A preliminary interobserver bias test showed high replicability. Results of this study compare favorably with results of other aging studies. Current age information for the progress of vertebral ring epiphyseal union is supplied for young males--and for the first time--females. This improved aging method provides necessary corroborative information for use with observations from other skeletal age indicators. Data collected from epiphyseal union of the vertebral centra aid in lessening the gap for early adult age determination.

Adolescent↗

Epiphyseal scar of the femoral head: a three-dimensional anatomic observation.

The purpose of this study was to inspect the three-dimensional structure of the epiphyseal scar of the femoral head. Three adult human femoral head specimens with a dense epiphyseal scar shown by radiography were used to study the morphology of the scar. One femoral head was cut in the coronal plane to show the cross-section. A trabecular pattern in the femoral head was demonstrated by radiography. The second femoral head specimen, was cut by a wafering saw in a plane parallel to the epiphyseal scar into 1.5 mm thick slices. Microradiographs of these specimen slices were taken to trace the scar from the proximal part of the femoral head to its distal end. In the third specimen, the epiphysis was chipped away to uncover the whole epiphyseal scar for a topographic examination by dissecting microscope and scanning electron microscope. The epiphyseal scar was found to consist of multiple layers of plate-like bony structure capping the metaphysis similar to an inverted cup with a defect adjacent to the fovea. Differences between the trabecular pattern in the epiphysis and metaphysis were distinctive. These morphologic characteristics of the femoral head should be taken into account when investigating stress distribution in the femoral head.

Adult↗

Short-term response of epiphyseal plate cell populations following selective devascularization and microsurgical revascularization.

The distal femoral epiphyseal plates of 21 8-week-old New Zealand white rabbits were totally or partially (nutrient artery only) devascularized, or devascularized and then microsurgically revascularized. Sacrifice was at 24, 48 or 72 hours postoperatively. The heights of the proliferative and hypertrophic zones of the epiphyseal plates operated upon were compared with the contralateral control epiphyseal plates for both the central and the peripheral regions of the epiphyseal plate. Neither extent of devascularization nor revascularization had a significant effect on the height of the proliferative zone of chondrocytes at any of the follow-up intervals. Selective devascularization of the nutrient artery led to a significant increase in height of the central region of the hypertrophic zone of chondrocytes at 48 and 72 hours. Microsurgical revascularization did not lead to a significant change in the height of either the central or the peripheral regions of the hypertrophic zone of chondrocytes at any of the follow-up intervals. This study is another 'building block' experiment toward vascularized epiphyseal plate transplantation in humans.

Animals↗

PTHrP expression in chondrocytes, regulation by TGF-beta, and interactions between epiphyseal and growth plate chondrocytes.

Although PTHrP has been identified as a key regulator of chondrocyte differentiation in the growth plate, the factors directly regulating PTHrP expression have not been identified. Furthermore, while cells from the epiphysis are considered the physiologic source of PTHrP, the relative expression of PTHrP in epiphyseal and growth plate chondrocytes has not been defined. PTHrP expression was examined in chondrocytes isolated from 3- to 5-week-old chick long bones. The expression of PTHrP mRNA was 10-fold higher in epiphyseal chondrocytes compared to cells from the growth plate. Growth plate chondrocytes were isolated into populations with distinct maturational characteristics by countercurrent centrifugal elutriation and analyzed for PTHrP expression. The expression was highest in the least mature cells and progressively declined with the onset of maturation. The regulation of PTHrP expression was further examined in epiphyseal chondrocytes. Both TGF-beta1 and cis-retinoic acid stimulation markedly increased PTHrP mRNA levels, while BMP-2 and PTHrP stimulation decreased the expression of this transcript. The effects of TGF-beta1 (8.9-fold stimulation) and TGF-beta3 (9.2-fold) were slightly greater than the effects of TGF-beta2 (4.9-fold). The effect of TGF-beta was dose-dependent and increases could be detected after 68 h of treatment. To analyze the paracrine effect of epiphyseal and growth plate chondrocytes on each other, these cells were placed in coculture and the mRNA from each of the populations was harvested separately after 24 h. Following coculture the PTHrP mRNA levels increased in the epiphyseal cells while the expression of type X collagen and Indian hedgehog transcripts decreased in growth plate chondrocytes. The results demonstrate potentially important paracrine interactions between these cell populations, possibly mediated by TGF-beta and PTHrP.

Animals↗

[Epiphyseal injuries of the distal tibia. Does MRI provide useful additional information?].

Plain film radiography often underestimates the extent of injury in children with epiphyseal fracture. Especially Salter-Harris V fractures (crush fracture of the epiphyseal plate) are often primarily not detected. MRI of the ankle was performed in 10 children aged 9-17 (mean 14) years with suspected epiphyseal injury using 1.0-T Magnetom Expert. The fractures were classified according to the Salter-Harris-Rang-Odgen classification and compared with the results of plain radiography. In one case MRI could exclude epiphyseal injury; in four cases the MRI findings changed the therapeutic management. The visualisation of the fracture in three orthogonal planes and the possibility of detection of cartilage and ligamentous injury in MR imaging makes this method superior to conventional radiography and CT. With respect to radiation exposure MRI instead of CT should be used for the diagnosis of epiphyseal injuries in children.

Adolescent↗

Histological and biological changes in the epiphyseal plate during fracture healing.

The alterations that the epiphyseal plate undergoes during fracture healing are well documented microscopically, yet there are no reports in the literature which discuss the cellular and molecular changes that accompany this process. We studied fracture healing in 49 Wistar rats (5 weeks old) in which we inflicted a fracture to the distal third of the femur of the right hind leg (experimental side). The rats were killed 2 weeks later, and we dissected both hind legs from the hip joint to the knee joint, detaching all the surrounding soft tissues. We manually detached the distal epiphyses and the epiphyseal plates from both femurs. A piece of the epiphyseal plate was removed from the epiphyseal side of the femurs. In 25 animals, and we analyzed the DNA content. In 8 animals, the specimen was studied under an electron microscope, and in the remaining 16 animals, the control and experimental sides were studied histologically. We found that healing was accompanied by an increase in DNA content, by a change in cellular activity, and by greatly accelerated apoptosis.

Animals↗

Epiphyseal lesions of the femur and tibia in rats following oral chronic administration of zinc dimethyldithiocarbamate (ziram).

A 24-month chronic feeding toxicity study with zinc dimethyldithiocarbamate (ziram) was performed on Fischer 344 rats of both sexes (80 animals/sex per group) at dietary levels of 0, 20, 200, or 2000 ppm. Eight animals of either sex from each group were sacrificed after 26, 52 and 78 weeks, and all surviving animals were killed after 104 weeks. Epiphyseal abnormalities in the long bones of the hind legs were observed in both sexes at 2000 ppm. Clinically, 3 male rats showed partial paralysis of the hind legs. At necropsy, marked curvature of the proximal end of the crus which could cause a restricted extension of the tibio-femoral joint was seen in 11 of 34 males killed at terminal sacrifice. While females had neither clinical signs nor gross abnormalities during the study, histopathological examination revealed retarded epiphyseal closure of the proximal end of the tibia in both sexes. Females also showed the epiphyseal lesion at the distal end of the femur. In severely affected rats marked proliferation of epiphyseal cartilaginous tissue was also noted together with the irregular arrangement of chondrocytes. These changes were evident only in aged animals. The incidence of the lesions in all males and females examined in this group was 22/77 (29%) and 13/73 (18%), respectively. The occurrence of the lesions appeared to be caused by impaired regulation of epiphyseal closure which might be related to the treatment with ziram.

Administration, Oral↗

Autoradiographic localization of 24R,25-dihydroxyvitamin D3 in epiphyseal cartilage.

There is emerging evidence for specific binding sites and biologic action for 24,25(OH)2D3 in the epiphyseal cartilage. The present study was undertaken to identify the target cells of 24,25(OH)2D3 in the epiphyses of rat bone using an autoradiographic technique. Pieces of epiphyseal cartilage obtained from 4-day-old vitamin D-deficient rats were incubated for 15 or 60 min with [3H]-24,25(OH)2D3 in the presence or absence of 100-fold excess of 25(OH)D3, 1,25(OH)2D3, or 24R,25(OH)2D3. The pieces were prepared for autoradiographic study by a new modified fixation method. Cytoplasmic and nuclear concentration of radioactivity was observed in all cell layers of the epiphyseal cartilage except for the hypertrophic cartilage zone. The highest concentration of radioactivity was seen in the proliferating chondroblasts of the columnar zone. After 15 min of incubation the radioactivity was seen mainly in the cell membrane and cytoplasm, whereas at 60 min radioactivity was also prominent in the nuclei. The competition with excess of cold metabolites revealed that only 24R,25(OH)2D3 caused a significant decrease in cytoplasmic and nuclear radioactivity. These data support the biochemical studies showing that the epiphyseal cartilage is a target tissue for 24,25(OH)2D3.

24,25-Dihydroxyvitamin D 3↗

The use of vertebral ring epiphyseal union for age estimation in two cases of unknown identity.

The objective of this case study was to demonstrate the utility of thoracic and first two lumbar vertebral ring epiphyseal union as an accurate and reliable method of age estimation for teenage and young adult skeletons. Vertebral ring epiphyseal union was used as a method of age estimation in two cases of osteological analysis for individuals of unknown identity. Case 1 involved male skeletal remains where postmortem damage by carnivores had destroyed most of the age markers. Data from vertebral ring epiphyseal union contributed to a narrower age estimation when used in conjunction with data from the other skeletal age indicators. Case 2 involved the fresh remains of an unknown female. Union of the vertebral ring epiphyses was consistent with an age range of 18 to 22 years, which was generally compatible with the age ranges obtained from the other skeletal sites (16 to 20 years). From this information, a narrower range of 18 to 20 years was then considered the most likely age at death. For each of the two cases, age information from observations of epiphyseal union of the vertebral centra has (1) been consistent with age information gathered from other skeletal age indicators and or (2) helped narrow down otherwise broader age estimation ranges. This method is recommended for use in estimating age at death from teenage and young adult skeletal remains.

Adolescent↗

Gene expression and immunohistochemical localization of biglycan in association with mineralization in the matrix of epiphyseal cartilage.

This study has used in situ hybridization, Northern blot analysis, and immunohistochemistry at the light and electron microscope levels to localize mRNAs and core proteins of biglycan in developing tibial epiphyseal cartilage of 10-day old Wistar rats. The expression of mRNAs and core proteins of biglycan appeared prominent in hypertrophic and degenerative chondrocytes associated with the epiphyseal ossification centre and the growth plate cartilage, but was not seen in the rest of epiphyseal cartilage. Northern blot analysis confirmed biglycan mRNA expression in the epiphyseal cartilage. Ultrastructural immunogold cytochemistry of the growth plate revealed that prominent immunolabelling was confined to the Golgi apparatus and cisternae of rough-surfaced endoplasmic reticulum of the hypertrophic and the degenerating chondrocytes, the early mineralized cartilage matrices of the longitudinal septum of the lower hypertrophic and the calcifying zones, and fully mineralized cartilage mitrices, which were present in the metaphyseal bone trabeculae. Furthermore, Western blot analysis of biglycan in extracts of fresh epiphyseal cartilage revealed that an EDTA extract, after chondroitinase ABC digestion, contains core proteins of biglycan, indicating the presence of biglycan in mineralized cartilage matrices. These results indicate that the distribution of biglycan is associated with cartilage matrix mineralization.

Animals↗

The effects of epiphyseal peptides on the release of immunoglobulins in Peyer's patches in rats in vitro.

The effects of epiphyseal peptides (1 microg/ml) on the release of immunoglobulins into the incubation medium by isolated Peyer's patches from non-immunized mice and mice immunized orally against ovalbumin were studied during 40-min incubations. The possibility that epiphyseal peptides act on adrenoreceptors of cells in secondary lymphoid organs in the small intestine was assessed using alpha- and beta-adrenoreceptor blockers, i.e., phentolamine HCl (0.02 mg/ml) and anaprilin (0.06 mg/ml) respectively. Basal levels of secretory activity in control Peyer's patches from immunized rats were 2.4 times (p < 0.01) greater than for the lymphoid organs of non-immunized animals. The effects of epiphyseal peptides on the secretory activity of antibody-forming cells depended on the functional state of Peyer's patches. Application of epiphyseal peptides led to a 35% increase (p < 0.05) in the release of immunoglobulins from Peyer's patches in non-immunized rats and a 25% decrease (p < 0.05) in the release of antibody into the incubation medium from the lymphoid organs of immunized animals. These data lead to the suggestion that the activatory effect of epiphyseal peptides on antibody-forming cells in Peyer's patches from non-immunized animals is associated with alpha-adrenoceptors, while their inhibitory action on immunoglobulin release by the small intestine lymphoid organs from immunized animals is not mediated via adrenoceptors.

Adrenergic Agonists↗

Foci of chronic circumscribed osteomyelitis (Brodie's abscess) that traverse the epiphyseal plate.

We observed six children who presented with chronic circumscribed osteomyelitis involving the adjacent metaphysis and epiphysis of a long bone, communicating through and damaging the growth cartilage of the epiphyseal plate. Four of the six children were less than or equal to 10 years of age. All six patients presented with the mild symptoms and subtle clinical findings that are characteristic of "Brodie's abscess," which is usually confined to metaphyseal, or occasionally epiphyseal, bone. Four children were treated with antibiotics and by surgical evacuation of the abscess, with visualization of the defect in the epiphyseal plate. Two children were treated with antibiotics alone, initially by the intravenous route. At follow-up 2-14 years after treatment, all affected children had a normal result without evidence of growth disturbance. There are seven previously reported cases of chronic circumscribed osteomyelitis traversing the epiphyseal plate that resulted in growth disturbance. Based on our experience and that reported in the literature, we believe that the intravenous administration of appropriate antibiotics in high doses, followed by oral antibiotics, is sufficient treatment for some children presenting with this condition. The pathogenic organism is likely to be Staphylococcus aureus. Surgical evacuation of the lesion should be performed for acute osteomyelitis involving the epiphyseal plate, for sinus formation or drainage into a synovial joint, for failure of the patient to respond clinically to nonoperative therapy, and for confirmation of the diagnosis if doubt exists.

Abscess↗

Resistance of epiphyseal cartilage to invasion by osteosarcoma is likely to be due to expression of antiangiogenic factors.

OBJECTIVES: Epiphyseal cartilage is a barrier to osteosarcoma invasion, however the mechanisms behind this resistance remain unclear. The aim of this study was to examine the chronological and spatial patterns of osteosarcoma growth and invasion of local tissue structures including epiphyseal cartilage. METHODS: We used an in vivomouse model of osteosarcoma to histologically examine tumors at different stages of disease progression. We compared the pattern of osteosarcoma penetration of epiphyseal cartilage with the expression pattern of two potent mediators of angiogenesis; proangiogenic vascular endothelial growth factor (VEGF) and antiangiogenic pigment epithelium-derived factor (PEDF). RESULTS: Epiphyseal cartilage remained intact across its entire length in all sections examined, despite increasing tumor size as well as intra- and extraosseous destruction. In the most advanced cases, only the proangiogenic lowermost layers of the hypertrophic zone of the growth plate were eroded. This corresponded with the growth plate layers which highly expressed the angiogenic factor VEGF. In contrast, the resting, proliferative and upper hypertrophic layers were resistant to osteosarcoma invasion in all cases. This corresponded to the layers with the highest expression of the potent antiangiogenic factor PEDF. CONCLUSION: Epiphyseal cartilage is resistant to local invasion by osteosarcoma. The balance of angiogenesis, influenced by pro- and antiangiogenic factors, is likely to play an important role in this resistance.

Animals↗

The role of autocrine growth factors in radiation damage to the epiphyseal growth plate.

Radiation therapy plays an important role as part of the multimodality treatment for a number of childhood malignancies. Dose-limiting complications of radiotherapy include skeletal abnormalities and disturbances in skeletal development within the irradiated field. The current study was undertaken to investigate the molecular mechanisms involved in radiation-induced arrest of bone growth. Our hypotheses were: (1) Expression of autocrine growth factors that regulate chondrocyte proliferation is inhibited by radiation in a specific pattern; (2) the disparity in radiosensitivity of growth plate chondrocytes and epiphyseal chondrocytes is due to differential modulation of autocrine growth factor expression by radiation. Given the important role these cells play in skeletal growth and development, we examined the comparative effects of radiation on expression of specific mitogenic growth factors in growth plate chondrocytes. The effect of radiation on the expression of autocrine/paracrine growth factors was examined in an established avian model of epiphyseal growth plate maturation. Exposure of growth plate chondrocytes to radiation resulted in a specific pattern of biochemical and morphological alterations that were dependent on dose and were progressive over time. While radiation did not affect the mRNA expression of some of the autocrine and paracrine factors important in endochondral ossification (such as FGF2 and TGFB isoforms), it did lead to a decrease in the mRNA expression of PTHrP, a critically important mitogen in growth plate chondrocytes, and a dose-dependent decrease in the PTH/PTHrP receptor mRNA. Interestingly, PTHrP mRNA levels were not affected in irradiated epiphyseal chondrocytes, the main source of PTHrP. Given evidence indicating a role for intracellular calcium levels in regulating PTHrP expression, basal calcium levels in irradiated growth plate chondrocytes and epiphyseal chondrocytes were examined 24 h after treatment. While cytosolic calcium levels were significantly higher in irradiated growth plate chondrocytes, they were not significantly affected in irradiated epiphyseal chondrocytes. The importance of calcium in mediating radiation damage to growth plate chondrocytes was further demonstrated by the finding that the addition of 4.0 mM EGTA (a calcium chelator) to the cell cultures before irradiation prevented the decrease in PTHrP mRNA levels. Since PTHrP up-regulates BCL2 levels and prevents growth plate chondrocyte maturation and apoptosis, BCL2 mRNA levels were examined in irradiated growth plate chondrocytes, and a dose-dependent decrease was found. An increase in apoptosis was further confirmed by a fivefold increase in caspase 3 levels in irradiated growth plate chondrocytes. The results of the current study suggest that radiation may interfere with proliferation of growth plate chondrocytes in part by causing an increase in cytosolic calcium levels which in turn leads to a decrease in PTHrP mRNA. Growth plate chondrocyte PTHrP receptor mRNA expression is also inhibited by radiation, further decreasing PTHrP signaling. Despite subtle differences between the chick and mammalian growth plates, further studies should provide an enhanced understanding of the mechanism(s) of radiation injury to the growth plate, as well as possibilities for new therapeutic strategies to protect the growing skeleton from the detrimental effects of radiotherapy.

Animals↗