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The distal femoral epiphyseal ossification center in the assessment of third-trimester menstrual age: sonographic identification and measurement.

The distal femoral epiphyseal secondary ossification center (DFE), which can be reliably identified and measured sonographically, may assist the sonologist in predicting third-trimester menstrual age. Between 28 and 35 menstrual weeks, the percentage of fetuses with a DFE progressively increases. Although the mean age at DFE appearance is approximately 32-33 menstrual weeks, the DFE may be seen as early as 29 menstrual weeks. Nevertheless, the age of a fetus without an identifiable DFE is most likely less than or equal to 34 menstrual weeks. Measurements of the DFE show that its size increases linearly: the menstrual age of a fetus whose DFE measures greater than or equal to 7mm is most likely greater than or equal to 37 weeks.

Embryonic and Fetal Development↗

Acute epiphyseal osteomyelitis in children.

Nine children over 20 months of age had acute osteomyelitis of the epiphysis of a long bone. The clinical features varied, but all of the patients had pain at the infected site and an elevated erythrocyte sedimentation rate. The distal femur was involved in seven cases, the proximal tibia in two, and the proximal humerus in one. In two patients there was a contiguous metaphyseal lesion, while the other seven patients (eight sites) had lesions limited to the epiphysis. Bone scintigraphy clearly identified the infected sites in all seven patients in whom it was performed, and allowed an early diagnosis in four cases. Radiographs showed a lytic lesion of the epiphysis that corresponded to the scintigraphic findings in all cases. The vascular supply to the epiphysis and the microscopic structure of the epiphyseal venous sinusoids provide locations that favor lodgement of blood-borne organisms. The epiphysis of the child should be recognized as another site of hematogenous osteomyelitis.

Acute Disease↗

Epiphyseal involvement in osteosarcoma.

Plain radiography and magnetic resonance (MR) imaging were used to assess the extent of transphyseal involvement in 15 consecutive patients with long bone osteosarcoma and nonfused epiphyses. The findings were correlated with those from surgical and microscopic pathologic examinations. There were no cases of false-positive findings with either MR imaging or plain radiography. Conventional radiography accurately helped predict transphyseal spread in only nine of 15 cases (60%). Spread to the epiphysis was present in 12 of the 15 cases (80%) and was accurately predicted with MR imaging in all 12 cases. This finding contradicts the common misconception that the physis acts as a "barrier" to tumor spread.

Adolescent↗

Imaging of epiphyseal injuries.

There have been many advances in the diagnosis and treatment of epiphyseal injuries in the 30 years since the publication of the landmark article by Drs Robert Salter and William Harris. They are the subject of this review. The anatomic features of the physis, epiphysis, and metaphysis are presented, and histologic studies of human and experimental physeal injuries are described. The recently recognized histologic, anatomic, and imaging characteristics of bone bridging of the physis resulting in growth disturbances are reviewed. Modification in and additions to the original Salter-Harris classification system have been proposed. The role and technique of computed tomography and magnetic resonance imaging in the assessment of the initial injury and analysis of subsequent growth disturbance are discussed.

Adolescent↗

Effects of corticosteroid hormone on the epiphyseal growth center of immature pregnant mice.

Immature pregnant mice treated with glucocorticoid hormone (triamcinolone hexacetonide) were killed 1 week following delivery. The epiphyseal growth plates of the humerus and their cellular constituents were analyzed quantitatively. It became evident that pregnancy per se evokes a marked suppressive effect upon young cartilage cells, thus interfering with the normal process of endochondral bone formation. Pregnant mice treated with glucocorticoid hormone experienced an even higher degree of chondrocytic derangement, however, to a lesser extent than chondroxytes of nonpregnant mice treated with the hormone. It therefore appears that pregnancy-induced elevation of systemic estrogens and progesterone provides some kind of a protection against the antianabolic activity of glucocorticoids upon chondrocytes.

Adrenal Cortex Hormones↗

Influence of tetracycline on the calcification of epiphyseal rat cartilage. Transmission and scanning electron-microscopic studies.

Tetracyclines are known to interfere with bone calcification. We therefore studied their effects on matrix vesicle production and initial calcification of cartilage. 15-day-old rats were injected intraperitoneally with oxytetracycline 100 mg/kg, 6 consecutive injections every 12 h. Epiphyseal plates were examined by scanning and transmission electron microscopy and compared to light microscopy findings. It was found that high doses of tetracyclines cause degeneration of the chondrocytes in the proliferating and hypertrophic zones. Chondrocytes had short processes with only few matrix vesicles covering their surface. In the chondrocytic lacunae of the longitudinal septa of hypertrophic and calcifying cartilage there were fewer matrix vesicles as compared to controls, and their ability to aggregate and form mineralized calcospherites was impaired. This was further proven when bones were immersed in 7% NaOCl or ashed, as minerals containing calcospherites were hardly seen. It is therefore presumed that interference with intracellular and probably extracellular accumulation of calcium by tetracycline might inhibit matrix vesicle production and aggregation, thus inhibiting calcification.

Animals↗

Epiphyseal growth and osteoarthrosis in blotchy mice.

Blotchy mice which carry a gene causing inadequate cross-linking of collagen were investigated for the progress of epiphyseal growth and for the appearance of changes in the knee joints following cessation of growth. In male mice of the strain, which are hemizygous for the gene, early growth proceeded in a histologically normal fashion, although the metaphyseal bone was less abundant than usual. From the age of 3 1/2 months on, the animals developed osteoarthrosis of the knee joints and at the time of death at 5-6 1/2 months of age, 88% of the animals had osteoarthrosis. The findings are discussed with special reference to a possible role of the collagen of the articular cartilage in the pathogenesis of some forms of osteoarthrosis.

Animals↗

Partition of calcium, phosphate, and protein in the fluid phase aspirated at calcifying sites in epiphyseal cartilage.

A reproducible method, adapted from renal micropuncture techniques, was developed for sampling 10-40 mmul of a clear fluid from epiphyseal cartilage of normal or rachitic rats in vivo, either from the hypertrophic cell zone (C(f1)) or surface resting cell cartilage (L(f1)). Characterization of this fluid depended upon quantitation of protein, total inorganic phosphate (P(it)), total calcium (Ca(t)), nucleotide, and hemoglobin in volumes of 20 mmul. Established methods for macroscale measurements of each of these parameters have been modified to permit direct spectrophotometric readings on samples of 10(-10)-10(-11) g. The fluid from hypertrophic and peripheral resting cell cartilage was of an extracellular nature as evidenced by a high chloride and sodium, as well as low potassium, protein, and nucleotide content. The pH of fluid isolated from endochrondral plates in vivo was measured under oil as a function of P(CO2) and the computed bicarbonate was elevated above concurrent serum levels. After ultracentrifugation of C(f1) of normal, rachitic, and healing rachitic animals, nonprotein-bound calcium (Ca(f)) and phosphate (P(if)) were determined on supernatant fluids. The hypertrophic cell cartilage fluid of rachitic rats was distinguished by a high ratio C(f1)/serum of P(if). This ratio returned to normal during treatment of rickets. The upper limit for ionic activity A(1) Ca(++) x A HPO(4) (=) was too low to initiate precipitation of brushite or dicalcium phosphate but was in a range of supersaturation in respect to crystalline apatites. Thus these data are consistent with initiation of calcification by heterogeneous nucleation of mineral in the septal matrix but can be reconciled alternately with a precipitation mechanism only if the site of initial mineral phase separation is outside the septal matrix.

Animals↗

Birth injuries to the epiphyseal cartilage.

A birth injury in the vicinity of a joint might lead to a fracture through the epiphyseal cartilage. The criteria for diagnosing such a fracture at radiography are considered and the continued remodelling of the bone demonstrated. The history of 2 cases with late diagnosis and serious long-term sequelae are described, in order to emphasize the necessity of early radiography.

Birth Injuries↗

Differences in cartilage formed intramuscularly or in joint surface defects by syngeneic rat chondrocytes isolated from the articular-epiphyseal cartilage complex.

Syngeneic rat chondrocytes isolated from the articular-epiphyseal cartilage complex were suspended in hyaluronic acid and transplanted intramuscularly or into joint surface defects. Transplants were fixed in ruthenium hexammonium trichloride and embedded in glycol methacrylate. In cartilage nodules produced intramuscularly, chondrocyte hypertrophy and matrix calcification were observed after 2 wk. Partial ossification occurred after 4 wk and the cartilage was almost completely replaced by an ossicle after 8 wk. Only small, dispersed groups of chondrocytes remained within the ossicle. In cartilage formed in joint surface defects a superficial and a deep zone were distinguished. Chondrocytes in the superficial zone did not hypertrophy and cartilage remained unossified. In the deep zone matrix calcification and bone formation occurred. These processes were, however, retarded in comparison with intramuscular transplants. Thus, either intraarticular environment exerted an inhibitory effect on chondrocyte hypertrophy and matrix calcification or articular chondrocytes present among transplanted cells accumulated close to the joint lumen and reconstructed normal articular cartilage.

Animals↗

Cartilage calcification: an ultrastructural, histochemical, and analytical x-ray microprobe study of the zone of calcification in the normal avian epiphyseal growth plate.

Sections from the zone of calcification of ruthenium red-fixed normal avian epiphyseal growth plates were analyzed by various morphological (histochemical) and analytical techniques. Calcium and phosphorus were identified in the chondrocyte pericellular rim, the uncalcified extracellular (territorial) matrix, and in both the peripheral and central aspects of the calcified accumulations within extracellular matrix. Cartilage proteoglycan, as determined by ruthenium binding, positive staining with acidic phosphotungstic acid, and the X-ray spectroscopic detection of sulfur, was identified in the same four zones. Thus, it appears that proteoglycans, in some form, are indeed retained at sites of biological calcification. Additionally, these macromolecules, synthesized in chondrocytes, may be involved in extracellular calcium translocation.

Animals↗

Ultrastructural visualization of complex carbohydrates in epiphyseal cartilage with the tannic acid-metal salt methods.

The present study has ultrastructurally applied the tannic acid-ferric chloride (TA-Fe) and the TA-uranyl acetate (TA-UA) methods to thin sections of glutaraldehyde-fixed, unosmicated embedded epiphyseal cartilage from rat tibiae to demonstrate complex carbohydrates. The strongest TA-Fe and TA-UA staining was observed after fixation of the specimens in glutaraldehyde containing TA. TA-Fe (pH 1.5) strongly stained matrix granules presumed to be proteoglycan monomers and chondrocyte secretory granules at various maturational stages but did not stain collagen fibrils and glycogen. TA-UA (pH 4.2) strongly stained matrix granules, intracellular glycogen, and chondrocyte secretory granules, and moderately stained collagen fibrils in the cartilage matrix. Ribosomes and nuclei were not stained above background staining with UA alone. In alpha-amylase-digested specimens, all TA-UA-reactive cytoplasmic glycogen was selectively removed. Testicular hyaluronidase digestion of specimens selectively removed TA-UA staining in matrix granules and all TA-Fe staining. When the pH of the UA solution was reduced to 1.5, TA-UA staining of glycogen and collagen was markedly decreased or absent, whereas staining of anionic sites was unaltered and significantly greater than with UA staining alone. Thus the TA-metal salt methods are pH dependent and allow differential intracellular and extracellular localization of complex carbohydrates in cartilage tissues at the electron microscope level.

Animals↗

Effects of TGF-beta1 on proliferation and IGFBP-3 production in a primary culture of human fetal epiphyseal chondrocytes (HFEC).

Proliferation and differentiation of chondrocytes from growth cartilage are modulated by hormones and growth factors, among which TGF-betas have been recognized as some of the more potent regulators although their specific cell effects on cartilage physiology are not fully understood. Primary human fetal epiphyseal chondrocytes (HEFC) constitutively produce TGF-beta1 at different times of culture progression. Treatment of 48-h. serum-deprived semiconfluent HFEC with 0.1-50 ng/ml of TGF-beta1 for 48-h. decreased (3H)Thymidine incorporation by 25-50 % and cell number by 25 %. In addition, IGFBP-3, the main insulin-like bonding protein produced by HFEC, showed a slight increase by TGF-beta1 in culture media. The changes in IGFBP-3 protein levels correlated well with its mRNA, indicating that TGF-beta1 is able to up-regulate IGFBP-3 synthesis in chondrocytes. Nevertheless, the IGFBP-3 accumulation in culture media does not produce a clear growth inhibitory effect on chondrocytes. Thus, we conclude that even though TGF-beta1 is able to up-regulate IGFBP-3, the growth inhibitory action produced by TGF-beta1 is not mediated by IGFBP-3 increase and appears to be mainly a direct TGF-beta1 effect on HFEC.

Cell Division↗

Effect of strontium on the epiphyseal cartilage plate of rat tibiae-histological and radiographic studies.

Following dietary administration of strontium carbonate, histological and radiographic changes in the epiphyseal cartilage plate of the rat tibiae were examined in the present study. The weight gain of the rat fed a strontium diet was less than that of the control rats. Longitudinal growth of tibiae and endochondral ossification were inhibited by strontium administration. The widths of both proximal and distal cartilage plates increased enormously as has also been shown by other investigators. Sizes of chondroblasts in columns of proximal cartilage plate in rats fed a strontium diet were smaller than those of the control rats and were not different between upper and lower parts. It is suggested that strontium inhibits bone growth through the inhibitory action on the maturation process of chondroblasts and the succeeding endochondral ossification.

Animals↗

Slipping of the upper femoral epiphyses in patients with intracranial tumours causing hypopituitarism and chiasmal compression.

Four cases of slipped upper femoral epiphyses in patients with intracranial tumours causing hypopituitarism and chiasmal compression are presented. Detailed endocrine studies in three cases showed severe deficiencies of growth hormone as well as of gonadotrophin and sex hormones. The literature is reviewed and the aetiology is discussed with special reference to Harris's hypothesis that an increase in growth hormone relative to oestrogen predisposes to slipping of the upper femoral epiphysis in humans, which these cases do not seem to support. In all cases the slip was bilateral, and it is emphasised that surgical treatment can provide only temporary fixation because fusion is dependent on correct hormonal therapy.

Adolescent↗

The blood supply of the lateral epiphyseal arteries in Perthes' disease.

We performed superselective angiography in 28 hips in 25 patients with Perthes' disease in order to study the blood supply of the lateral epiphyseal arteries (LEAs). Interruption of the LEAs at their origin was observed in 19 hips (68%). Revascularisation in the form of numerous small arteries was seen in ten out of 11 hips in the initial stage of Perthes' disease, in seven of eight in the fragmentation stage and in five of nine in the healing stage. Penetration of mature arteries into the depths of the epiphysis was seen in four of nine hips in the healing stage. Vascular penetration was absent in the weight-bearing portion of the femoral head below the acetabular roof. Interruption of the posterior column artery was seen where it passed through the capsule in seven hips when they lay either in internal rotation or in abduction with internal rotation. We suggest that in Perthes' disease the blood supply of the LEAs is impaired at their origin and that revascularisation occurs from this site by ingrowth of small vessels into the femoral epiphysis. This process may be the result of recurrent ischaemic episodes.

Adolescent↗

Expression patterns of matrix metalloproteinases and vascular endothelial growth factor during epiphyseal ossification.

UNLABELLED: In situ hybridization studies allowed for the localization of three MMPs and the angiogenic factor VEGF during secondary ossification. MMPs were widely expressed during ossification of the secondary center, whereas expression of VEGF was restricted to later stages. INTRODUCTION: The spatiotemporal expression patterns of the matrix metalloproteinases gelatinase-B (MMP-9), collagenase-3 (MMP-13), and membrane-type 1 metalloproteinase (MMP-14) and the angiogenic peptide vascular endothelial growth factor (VEGF) were studied during development of the proximal epiphysis of the rat tibia. MATERIALS AND METHODS: Cell expression was analyzed by in situ hybridization. Studies on osteoclastic activity, matrix mineralization, cell proliferation, and vascular progression were also performed. RESULTS: MMP-9, MMP-13, and MMP-14 were expressed in discrete perichondrial cells that gave way to sites of intrachondral canal formation. High expression levels for the three MMPs were found at the blind ends of advancing intrachondral canals and at the expanding borders of the marrow space. Signals for MMP-9 and MMP-13 were in close proximity but did not overlap, whereas MMP-14 was expressed in both MMP-9+ and MMP-13+ cells. VEGF was not expressed during formation of intrachondral vascular canals but was observed in hypertrophic chondrocytes during formation of the bone marrow cavity. CONCLUSIONS: Expression of MMPs and VEGF are constant events during development of the secondary ossification center. We propose that MMPs are involved in targeting proteolytic activity during epiphyseal development. VEGF is not expressed during early formation of vascular canals, but it may have a role in the formation of the bone marrow cavity.

Animals↗