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PubMed1978

Autoradiographic analysis of altered glycosaminoglycan synthesis in the epiphyseal cartilage of neonatal brachymorphic mice.

Brachymorphic (bm/bm) mice are disproportionately short in stature. Past biochemical studies on neonatal mice (Orkin et al., '76) demonstrated that epiphyseal cartilage from these mutants synthesizes glycosaminoglycans (GAG) that are undersulfated. In this study, synthesis of GAG, as determined autoradiographically with Na2 35SO4 and 3H-glucosamine was reduced in all areas of bm/bm epiphyses both in vivo and in vitro as compared to normal C57BL/6J mice. Incorporation of both isotopic precursors into GAG of the brachymorphic proliferative zone was reduced to a greater extent than in the reserve zone. In addition, incorporation of these precursors into GAG of epiphyseal cartilages in vitro, as determined biochemically, was reduced by 40%. In contrast, the incorporation of 3H-leucine and 3H-proline into protein did not show differences between mutant and normal epiphyses. These results suggest that alterations in GAG synthesis in bm/bm epiphyseal growth plates are not exclusive to any one zone, but do appear to be most pronounced in the proliferative zone.

Animals↗
PubMed1993

CT evaluation of primary epiphyseal bone abscesses.

We reviewed the clinical, radiographic, and computed tomographic (CT) findings in eight children with a histologically proven diagnosis of epiphyseal or apophyseal osteomyelitis. In all cases the femur was involved: in five the osteomyelitis was localized in the femoral condyle, in two it was in the greater trochanter, and in one it was in the femoral head epiphysis. In four of the six cases of epiphyseal involvement there was associated joint effusion or septic arthritis. CT examination may demonstrate a serpentine tract, a sequestrum, cortical destruction or adjacent soft tissue swelling and can differentiate osteomyelitis from other epiphyseal lucent lesions, particularly chondroblastoma and osteoid osteoma. CT yielded important new diagnostic information in seven of the eight patients, failing to do so in only one. In one case, CT showed a wooden splinter in an abscess cavity, which had been mistaken for a sequestrum. When combined with accurate clinical and laboratory information and good quality plain radiographs, CT can lead to an early diagnosis of epiphyseal infection. Early diagnosis helps avoid delays in initiating antibiotic or surgical treatment caused by the unusual (epiphyseal or apophyseal) location of the bone abscess.

Abscess↗
PubMed1981

Fractures Involving the Distal Epiphyseal plate of the femur.

Forty-two fractures involving the distal femoral epiphyseal plate in 41 patients were reviewed. The average age at injury was 11.2 years. The follow up period ranged from one year to 20.3 years, with an average of 6.3 years. The Salter-Harris classification of epiphyseal plate injures proved to be a good indicator of the mechanism of injury and prognosis. Using stringent criteria to classify the end results, 2 out of 3 of the total group and 3 out of 4 of 29 Salter-Harris Type I and Type II injuries had good or excellent results. Type V crushing injuries of the growth plate, open injuries, fractures caused by high velocity motor vehicle accidents with severe displacement or multiple associated fractures, and incompletely reduced epiphyseal injuries gave only poor or fair results. Major problems responsible for poor or fair results were varus or valgus angulation, loss of joint motion and shortening due to premature epiphyseal closure. Orthoradiographs revealed the presence of some degree of shortening in 20 of 29 Salter-Harris Type I and Type II injuries which averaged 1.0 cm, but was of no clinical significance in most patients. These injuries must be reduced accurately. In the Type II epiphyseal separations unsatisfactory results were due to inadequate reduction or to associated injuries.

Adolescent↗
PubMed2002

[Spontaneous epiphyseal injury as a complication of a simple bone cyst of the femoral neck? Case report and review of the literature].

A case of a spontaneous epiphyseal injury of the femoral neck in an 8-year-old boy is reported. The same boy had been seen 8 months before for a pathological fracture caused by a simple bone cyst of the femoral neck on the same side. At the second visit the boy showed spontaneous severe pain of the hip, and radiography was performed under the presumed diagnosis of a slipped capital femoral epiphysis. However, it demonstrated a separation through the growth plate cranially and a fracture through the metaphysis inferiorly, leading to the differential diagnosis of a Salter-Harris type II fracture despite a nontraumatic patient history.A review of the literature failed to reveal a similar report of simultaneous occurrence of a simple bone cyst and epiphyseal injury of the femur. However, slipping of the proximal humeral epiphysis in connection with a simple bone cyst has been described by some authors. We propose a pathophysiological model for the simultaneous occurrence of epiphyseal injury and a simple bone cyst. Physeal involvement by a simple bone cyst and varus deformity of the femoral neck could cause weakening of the growth plate and predispose for epiphyseal injury. Based on these findings, we suggest that a simple bone cyst of the proximal femoral metaphysis can develop into a severe condition. Children presenting with this clinical picture should be treated vigorously and monitored for the development of complications leading to epiphyseal injury.

Bone Cysts↗
PubMed2002

[Development and functional structure of the epiphyseal plate].

The longitudinal growth of long bones occurs in the epiphyseal plates at their ends. After a center of ossification has developed in the epiphysis, a cartilaginous plate, characterized by a typical zonal arrangement is formed. The cartilaginous plate proliferates using cells from a reservoir at the epiphyseal (i.e. articular) side of the plate. The cells are orientated to longitudinal rows and become thickened towards the metaphysis. The extracellular matrix between the hypertrophic chondrocytes becomes calcified and is subsequently replaced in an ossification process by lamellar bone. Cell proliferation in the epiphyseal plate is regulated by a number of different factors (e.g. IGF-I and BMP-7). The extracellular matrix is rich in glycosaminoglycans, proteoglycans and type II collagen, whereas especially at the edges type I and type VI collagen can be observed, too. The three dimensional orientation of the epiphyseal plate is determined by local mechanical influences. The adjacent bony endplates exhibit a higher central mineralization pattern with lower density values at their edges. The region of failure predominantly concerns the proximal zone of the longitudinal rows. The mechanical properties of the epiphyseal plate are influenced by endocrine as well as by metabolic factors. Any case of an epiphysiolysis is caused by a misproportion between acting shear forces and cartilaginous strength.

Adolescent↗
PubMed2004

Expression of VEGF isoforms by epiphyseal chondrocytes during low-oxygen tension is HIF-1 alpha dependent.

OBJECTIVE: To establish the role of hypoxia and HIF-1 alpha for VEGF expression of murine epiphyseal chondrocytes. To analyze the effect of hypoxia on VEGF isoform expression. MATERIALS AND METHODS: VEGF mRNA and VEGF isoform expression was investigated in epiphyses of murine newborns by in situ hybridization and real-time PCR. Further, epiphyseal chondrocytes were isolated from newborn mice with homozygous flanking of the HIF-1 alpha gene with lox-P sites. HIF-1 alpha was deleted by infection with adenovirus containing cre-recombinase. After chondrocytes reached confluency they were exposed to 0.5% or 20% oxygen, respectively. Total VEGF and VEGF isoform mRNA expression levels were measured by real-time PCR. Secreted VEGF protein was determined by ELISA. RESULTS: VEGF mRNA signals were detected in the hypertrophic zone and in the center of the proliferative zone of the murine epiphysis, which is considered to be hypoxic. Real-time PCR revealed that VEGF(120)is the dominant isoform in vivo. In cultured epiphyseal chondrocytes strongly increased VEGF gene expression levels were detected after exposure to hypoxia. Furthermore, secretion of VEGF protein was significantly enhanced under 0.5% oxygen. Remarkably, functional inactivation of HIF-1 alpha abolished the hypoxic increase of VEGF expression in chondrocytes completely. Furthermore, the soluble isoforms VEGF(120)and VEGF(164)are the most abundantly expressed splice variants in chondrocytes exposed to low oxygen levels. CONCLUSIONS: The data presented here clearly indicate that hypoxia is able to induce the synthesis of soluble VEGF isoforms by epiphyseal chondrocytes, most likely through stabilization of HIF-1 alpha. Thus it can be speculated that HIF-1 alpha is an essential prerequisite for hypoxic VEGF synthesis in the epiphysis, thereby contributing to the formation and invasion of blood vessels in long bone development.

Animals↗
PubMed2000

Hyperbaric oxygen: a means of decreasing ischemic epiphyseal damage in a pediatric rabbit model.

The effect of hyperbaric oxygen on epiphyseal ischemia was evaluated using a pediatric rabbit model. Forty-five animals were compared in this study: 23 from a control pilot study and 22 hyperbaric exposed animals. In each animal the right distal femoral and proximal tibial epiphyses were isolated on a popliteal vascular pedicle. The left leg acted as the control. The growth difference between the rabbit's hindlimbs was the means of comparison throughout the groups established. Warm ischemia was induced by applying a vascular clamp to the right popliteal artery for 12 hours (20 animals) and 7 hours (17 animals). The remaining 8 animals underwent a sham operation without interruption of epiphyseal perfusion. On completion of the ischemic period hyperbaric oxygen therapy (HBOT) was performed on 12 12-hour (12h-HBOT) and 10 7-hour (7h-HBOT) animals at 2 atmospheres for 90 minutes twice per day for 4 postoperative days. The animals were killed on either postoperative day 14 or 90. Measurement of longitudinal bone growth was performed on the 90-day animals from serial radiographs at the time of surgery and then at 1 month, 2 months, and 3 months after surgery. There was no significant difference in longitudinal bone growth between the sham-operated and the 7h-HBOT animals at 1, 2, and 3 months. There was a statistically significant difference, however, between the normal growth of the 7h-HBOT group compared with the abnormal growth of the 7-hour, 12-hour, and 12h-HBOT animals. Histology was consistent, with the bone growth data demonstrating relative normalcy of the 7h-HBOT group epiphyseal plates versus severe architectural aberrance and necrosis of the 12h-HBOT group epiphyses. Our experimental data indicate that a clinical trial should be instituted using HBO for pediatric replantation patients when warm ischemia exceeds 7 hours. (J Hand Surg 2000; 25A:159-165.

Analysis of Variance↗
PubMedDate not supplied

[Changes in the epiphysis and epiphyseal plate in systemic and genetically-induced diseases].

Systemic disorders of the skeleton have either a primary or endogenous, mostly heritable cause like osteochondrodysplasias or they are secondarily or exogenously caused by pathologic influence of the metabolic or endocrine system. The functional unit of growth plate and epiphysis is frequently the target organ of these pathologic influences. The pathogenetic effect on the skeleton is manifested as a disturbance of growth and as an epiphyseal deformity and structural change. Here one must take in consideration the fact that these pathological influences affect not only the epi-and apophyses of tubular bones but also those of the skull, the pelvis and the spine. Because of that and because of the unequal quantitative effect of growth at different growth plates and the chronological different developmental state of the epiphyses, very variable disorders are the result. Disturbances of growth lead to proportional or disproportional short or tall stature. Epiphyseal deformations may have the consequence of contractures and early osteoarthritis. Joint replacement at the hips and knees is inescapable and requires, because of the diminutive skeletal proportions, a special custom -made prosthetic device. Slight epiphyseal deformities, like cone shaped epiphyses, result not so much in functional disturbance but may rather be used as a diagnostic clue. By means of the most typical and important systemic skeletal disorders the pathogenetic principles are discussed.

Adolescent↗
PubMed1994

Parathyroid hormone-related peptide-depleted mice show abnormal epiphyseal cartilage development and altered endochondral bone formation.

To elucidate the role of PTHrP in skeletal development, we examined the proximal tibial epiphysis and metaphysis of wild-type (PTHrP-normal) 18-19-d-old fetal mice and of chondrodystrophic litter mates homozygous for a disrupted PTHrP allele generated via homologous recombination in embryonic stem cells (PTHrP-depleted). In the PTHrP-normal epiphysis, immunocytochemistry showed PTHrP to be localized in chondrocytes within the resting zone and at the junction between proliferative and hypertrophic zones. In PTHrP-depleted epiphyses, a diminished [3H]thymidine-labeling index was observed in the resting and proliferative zones accounting for reduced numbers of epiphyseal chondrocytes and for a thinner epiphyseal plate. In the mutant hypertrophic zone, enlarged chondrocytes were interspersed with clusters of cells that did not hypertrophy, but resembled resting or proliferative chondrocytes. Although the overall content of type II collagen in the epiphyseal plate was diminished, the lacunae of these non-hypertrophic chondrocytes did react for type II collagen. Moreover, cell membrane-associated chondroitin sulfate immunoreactivity was evident on these cells. Despite the presence of alkaline phosphatase activity on these nonhypertrophic chondrocytes, the adjacent cartilage matrix did not calcify and their persistence accounted for distorted chondrocyte columns and sporadic distribution of calcified cartilage. Consequently, in the metaphysis, bone deposited on the irregular and sparse scaffold of calcified cartilage and resulted in mixed spicules that did not parallel the longitudinal axis of the tibia and were, therefore, inappropriate for bone elongation. Thus, PTHrP appears to modulate both the proliferation and differentiation of chondrocytes and its absence alters the temporal and spatial sequence of epiphyseal cartilage development and of subsequent endochondral bone formation necessary for normal elongation of long bones.

Animals↗
PubMed1957

Turnover of S35-sulfate in epiphyses and diaphyses of suckling rats; nature of the S35-labelled compounds.

S(35)-sulfate was injected intraperitoneally- into 7-day-old rats and their long bones were removed after intervals of time. The epiphyses were separated from the diaphyses for analysis. From the diaphyses freed of bone marrow about 82 per cent of the S(35) which they contained was extracted with a 2.5 N solution of sodium hydroxide. More, about 91 per cent of the S(35), was thus extracted from the epiphyses. Dialysis of the extracts against water showed that the fraction of S(35) which was dialyzable decreased rapidly with time. After 1 hour about 80 per cent and 50 per cent of the S(35) in the extracts of diaphyses and epiphyses, respectively were found in the dialysates, after 24 hours about 20 per cent and 4 per cent, and after 120 hours 12 per cent and 1 per cent. Similar values for the S(35) in inorganic sulfate were found when the extracts were chromatographed on an anion exchange resin, dowex-2. The S(35), other than inorganic sulfate, was in the form of bound sulfate, which was released by acid hydrolysis. Uronic acid and hexosamines, primarily galactosamine, were associated with the S(35). Indeed, on paper electrophoretograms and paper chromatograms the major S(35)-labelled component which was seen resembled chondroitin sulfate in its mobility. On the paper chromatograms, also a second S(35)-labelled component with a mobility lower than that of chondroitin sulfate was found. It is unlikely that the latter is a breakdown product of chondroitin sulfate, produced in the course of extraction with the sodium hydroxide solution. In fact, both components were also found in sodium versenate homogenates which had been dialyzed extensively against water. On the basis of these results it is suggested that the greatest part of the S(35)-labelled materials previously demonstrated by autoradiography to be progressively deposited in the metaphyses after 24 hours,-as the concentration of S(35)-sulfate concurrently decreased in the epiphyseal cartilage plates,-are akin to the chondroitin sulfate of the epiphyseal cartilage plates and are derived from the latter.

Animals↗
PubMed1986

Epiphyseal ossification centers in the assessment of fetal maturity: sonographic correlation with the amniocentesis lung profile.

The epiphyseal ossification centers of the distal femur (DFE) and proximal tibia (PTE) appear and enlarge during the third trimester of pregnancy. Late in the third trimester, the epiphysis of the proximal humerus (PHE) begins to ossify in some fetuses. Using the amniocentesis lung profile to determine the value of sonographic epiphyseal visualization as a predictor of pulmonary maturity, we studied 50 fetuses prospectively and compared the sonographic epiphyseal findings with results from the amniocentesis lung profiles. Nine fetuses with a visible PHE had a mature amniocentesis lung profile (accuracy of positive prediction = 100%), and then fetuses with an immature amniocentesis lung profile had no visible PHE (conegativity = 100%). Fetuses in which the combined DFE and PTE diameters were greater than 11 mm or in which the DFE and the PTE diameters were similar in size (DFE less than or equal to 1 mm larger than PTE) also yielded positive results. Copositivity and accuracy of prediction of an immature amniocentesis lung profile, on the other hand, were low (22%-25%) for the same epiphyseal parameters. These data suggest that antenatal visualization and measurement of the epiphyseal ossification centers of the fetal knee and shoulder may help to identify fetuses that would have a mature amniocentesis lung profile.

Amniocentesis↗
PubMed1991

Epiphyseal marrow in infancy: MR imaging.

Hypointense epiphyseal marrow on T1-weighted magnetic resonance images often suggests disease. To determine whether hypointense marrow sometimes represents normal red marrow in a recently ossified epiphyseal center, the authors studied 38 infants without known marrow disease. Patients with hypointense epiphyseal marrow on T1-weighted images were younger (3.9 months +/- 3.2) than those with hyperintense marrow (9.6 months +/- 3.9) (P less than .001). T1-weighted imaging and histologic correlation were also performed in animals. The signal was hypointense and the marrow was red in the epiphyseal centers of all newborn animals, while all 6-week-old animals had hyperintense signal and yellow marrow. The authors conclude that hypointense marrow on T1-weighted images represents normal red marrow in a recently formed ossification center in newborn rabbits and lambs, and the same is probably true in humans. Epiphyseal marrow becomes hyperintense within a few months of development of the secondary center of ossification.

Animals↗
PubMed2002

Structural stages in the development of the long bones and epiphyses: a study in the New Zealand white rabbit.

BACKGROUND: Histologic delineation of the events involved in the development of long bones and the developmental age at which these events occur is needed to elucidate the genetic and molecular mechanisms associated with these events. This report describes the sequence of histologic events involved in the formation of long bones and their epiphyses in the New Zealand White rabbit. METHODS: Prenatal studies were performed on twelve, fourteen, fifteen, sixteen, eighteen, twenty-one, twenty-four, and twenty-seven-day-old rabbit embryos, and postnatal studies were performed on newborn rabbits and on three-to-four-day-old; one, two, four, and six-week-old; and two, three, four, six, and eight-month-old rabbits. Histologic specimens from embryos were embedded in plastic and stained with toluidine blue or safranin O-fast green, and specimens from postnatal rabbits were embedded in paraffin and stained with hematoxylin and eosin or safranin O-fast green. RESULTS: Studies of twelve-day-old embryos demonstrated upper and lower limb buds filled with undifferentiated mesenchymal cells, and studies of fourteen-day-old embryos showed mesenchymal condensation and beginning cartilage formation outlining major long bones. Long-bone and epiphyseal development progressed through sixteen structural stages, and the developmental age at which these stages occurred was determined. These stages included limb-bud formation with uniform distribution of mesenchymal cells and formation of an apical ectodermal ridge (stage 1); mesenchymal condensation (stage 2); cartilage differentiation (stage 3); formation of a primary center of ossification (stage 4a); epiphyseal cartilage vascularization with formation of cartilage canals (stage 7); vascular invasion of the developing secondary ossification center (stage 9); bone formation and marrow cavitation in the secondary ossification center with formation of hematopoietic marrow (stage 10); fullest relative extent of secondary-ossification-center development in epiphyseal cartilage (stage 14); thinning of the physis (stage 15); and resorption of the physis with establishment of continuity between epiphyseal and metaphyseal circulations (stage 16).

Animals↗
PubMed2006

Endothelin-1-induced femoral head epiphyseal artery constriction is enhanced by long-term corticosteroid treatment.

BACKGROUND: With regard to the pathogenesis of corticosteroid-associated femoral head osteonecrosis, only intravascular and extravascular factors have been discussed. Wall constriction of the lateral epiphyseal arteries, which are the main supplying arteries within the femoral head, has not previously been investigated. This study examined the effect of long-term corticosteroid treatment on vasoconstriction of the lateral epiphyseal arteries of the femoral head in a porcine model. METHODS: The immature female Danish Landrace pig was chosen as the model for our study because femoral head osteonecrosis can be induced in this animal and because the lateral epiphyseal arteries of the femoral heads are of the appropriate size for myographic investigation. Twenty-four female Danish Landrace pigs (two siblings from each of twelve litters for a total of twelve sibling pairs) were divided by randomly separating the sibling pairs into two groups, with a total of twelve pigs in each group. One group of twelve animals received a daily dose of 100 mg of methylprednisolone orally for three months. The other group of twelve pigs served as controls and received no corticosteroids. After the animals were killed with an intravenous injection of pentobarbital, the lateral epiphyseal arteries of the femoral head were isolated from the cancellous bone. These arteries were mounted as ring preparations on a small-vessel myograph for measurement of isometric force development. The effects on the resected vessels of the vasoactive agents endothelin-1, noradrenaline, bradykinin, substance P, and nitrous oxide were investigated. RESULTS: Vasoconstriction induced by increasing doses of endothelin-1 was increased after three months of methylprednisolone treatment compared with the vasoconstriction in vessels from control animals. Sensitivity to noradrenaline was not altered by this treatment. After submaximal precontraction by noradrenaline, vasorelaxation was elicited by substance P, nitrous oxide, and increasing doses of bradykinin without differences between the corticosteroid-treated and the control groups. CONCLUSIONS: Endothelin-1-induced vasoconstriction of the epiphyseal arteries of the femoral head was increased in this corticosteroid-treated pig model. Such vasoconstriction may lead to a reduction in femoral head blood flow and to local ischemia and thus may be a newly described factor in the multifactorial pathomechanism of osteonecrosis of the femoral head.

Animals↗
PubMed1979

Remodelling after distal forearm fractures in children. I. The effect of residual angulation on the spatial orientation of the epiphyseal plates.

The effect of residual fracture angulation on the distal radial and ulnar epiphyseal plates was studied in children aged 1 to 15 years. Thirty-eight fractures located in the distal fifth of the forearm bones were observed for 1 to 25 months after the fractures had healed. The forearms were examined radiographically on two to five occasions and the inclinations of the epiphyseal plates in relation to the long axis of the proximal fragments were measured. The results showed that an abnormal inclination of the epiphyseal plate after healing of a distal forearm fracture induced an alteration of growth in the epiphyseal plate. The redistribution of growth tended to correct the abnormal inclination. The rate of correction followed an exponential course. The age of the child at the time of the fracture and the distance from the fracture to the epiphyseal plate did not influence the capacity for correction.

Adolescent↗
PubMedDate not supplied

Epiphyseal separations after neonatal osteomyelitis and septic arthritis.

Complete separation of an epiphysis is a rare complication of neonatal osteomyelitis and septic arthritis. We report two cases of pathologic epiphyseal separation after neonatal osteomyelitis, involving the distal and proximal femoral epiphyses with a follow-up of 2 and 7.5 years, respectively. Birth trauma, scurvy, and nonaccidental injury should be considered in the differential diagnosis of pathologic epiphyseal slip. The pitfalls in diagnosis are many, and plain radiograms of unossified epiphyses are often misleading. A high index of suspicion and the use of imaging modalities are useful in making an early diagnosis of epiphyseal slip. The optimal treatment is controversial, and the long-term prognosis is uncertain. The potential for recovery appears to be excellent, provided an early diagnosis is made and prompt treatment by anatomic reduction of the displaced epiphysis is instituted.

Arthritis, Infectious↗
PubMedDate not supplied

Early diagnosis of multiple epiphyseal dysplasia.

In 20 children with multiple epiphyseal dysplasia, an objective assessment of epiphyseal size was made to determine its value in early diagnosis of this condition. All had wrist radiographs taken at age less than 15 years, and 16 children had knee radiographs. Before the epiphyses become fully ossified, abnormalities of size and shape may be difficult to assess, but carpal length/width ratios were abnormal in 60%, and distal femoral epiphyseal/metaphyseal ratios were abnormal in 56%. When both measurements were combined, 80% could be classified as abnormal. Objective radiologic assessment of epiphyses is of value in early diagnosis of multiple epiphyseal dysplasia.

Adolescent↗
PubMed2005

Age ranges of epiphyseal fusion in the distal tibia and fibula of contemporary males and females.

The range of variation in epiphyseal fusion in North American populations has not been sufficiently established. This significant oversight can lead to exclusion of persons of interest in a forensic investigation. This study evaluates epiphyseal fusion of the distal tibia and fibula in 570 European-, African-, and Mexican-American children and young adults. Radiographs of 270 females aged 9 to 17 and 300 males aged 11 to 20 were analyzed to assess the range of variation of epiphyseal fusion at each age. Results indicate that complete fusion in females occurs as early as 12 years in the distal tibia and fibula. All females demonstrated complete fusion by 16 years with no significant differences between ancestral groups. Complete fusion in males occurs as early as 14 years in both epiphyses. All males demonstrated complete fusion by 19 years. Significant differences in the earliest age of complete fusion showed that African- and Mexican-American males demonstrate complete fusion as early as 14 years in both epiphyses while European-American males do not express complete fusion until 16 years.

Adolescent↗