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[Injuries to the epiphyseal groove and bone growth].

Lesions of the epiphyseal cartilage of the growing bone lead to disturbances of growth. Experiments in the proximal epiphyseal cartilage of the rabbit tibia was carried out as an instruction about the disturbances of growth after Küntscher-nailing. The injured plane of the epiphyseal cartilage amounted to 2%. The disturbances of growth were analysed in dependence on the produced diaphysis fracture and the placement period of the osteosynthetic material. Functionally significant disturbances of growth are not caused after the lesion of the epiphyseal cartilage less than 2% of its plane and removal of the metal after the consolidation of the fracture.

Animals↗

Epiphyseal tilt produced by experimental overload.

After segmental resection of the diaphysis of the radius in growing dogs, the distal ulna epiphyseal plate is submitted to a mechanical overload which provokes a progressive tilt of the epiphysis. A full exail realignment is developed in two or three months as shown in radiographic follow-up studies. Histologically, the first lesion is a fissure starting and the convex side of the growth line, passing along the epiphyseal plate and located somewhere between the proliferative layer which is seldom affected and the zone of enchondral ossification. The separated segment of the growth cartilage situated between the fissure and metaphysis stops growing and the cartilaginous tissue becomes disorganized and necrotic. It is then reabsorbed, and replaced by vascular-connective tissue coming from the bone marrow. Growth usually goes on form the deep proliferative layer of the epiphyseal plate when its vascular connections are intact. After three months a normal epiphyseal line is rebuilt correcting the defective axis of the bone.

Animals↗

Slipped capital femoral epiphyses in a patient with primary hyperparathyroidism.

Slipped capital femoral epiphyses are rarely associated with primary hyperparathyroidism, and only four cases have been documented in the English literature. We report such a case. A 13-year-old boy presented with bilateral slipped capital femoral epiphyses. Investigation showed that he had primary hyperparathyroidism due to a parathyroid adenoma. The adenoma was removed, and then the epiphyses were pinned in situ 3 weeks later. The pins were removed 3 months postoperatively when the physes had closed. The patient had a painless hip 1 year later at follow-up. We concluded that identification and excision of the hyperparathyroid adenoma and in situ pinning of the slipped epiphyses results in satisfactory treatment of the condition.

Adenoma↗

TGF-beta 1 prevents hypertrophy of epiphyseal chondrocytes: regulation of gene expression for cartilage matrix proteins and metalloproteases.

Using an in vitro model of rat epiphyseal chondrocyte differentiation in which cells are maintained in a three-dimensional cell pellet, we show that exogenous TGF-beta 1 reversibly prevents terminal differentiation of epiphyseal chondrocytes into hypertrophic cells. Through maintenance of gene expression for the cartilage matrix proteins type II collagen and aggrecan core protein, and with coordinate inhibition of expression of genes encoding the metalloproteases collagenase and stromelysin, TGF-beta 1 stabilizes the phenotype of the prehypertrophic epiphyseal chondrocyte. This ability of TGF-beta 1 to stabilize the cartilage phenotype is critically dependent on culture conditions. Epiphyseal chondrocytes cultured as a subconfluent monolayer of cells dedifferentiate (reduce type II collagen and aggrecan core protein expression, increase metalloprotease expression, and acquire a spindled morphology) in response to short-term TGF-beta 1 treatment. Increasing the initial seeding density and allowing the cells to become multilayered prior to the addition of growth factor reverse the effects of TGF-beta 1 on type II collagen and transin/stromelysin gene expression and maintain a rounded cellular morphology. This finding emphasizes the importance of considering cell density and environmental context in the analysis of the regulatory action of peptide growth factors in general and of the TGF-beta s in particular. We propose that one function of TGF-beta 1 during endochondral ossification is regulation of chondrocyte growth and differentiation through modulation of the relative expression of cartilage matrix proteins and metalloproteases. This function of TGF-beta 1 helps illustrate how the regulation of diverse cellular processes such as matrix synthesis, matrix degradation, and cell growth and differentiation may be coordinated at the molecular level by a single peptide growth factor.

Animals↗

A mathematical modelling study of epiphyseal cartilage calcification.

Recent studies in this laboratory have suggested that proteoglycan may function as a Ca ion-exchanger in the calcification of epiphyseal growth plate cartilage. Specifically, it has been proposed that phosphate liberated from hypertrophic chondrocytes may displace calcium ions bound to the anionic groups of proteoglycans, thereby raising the Ca x PO4 activity product above the threshold for precipitation of hydroxyapatite. In order to determine whether this mechanism is quantitatively feasible, a mathematical model of the interaction between Ca, Na, proteoglycan and phosphate has now been developed. This model is based on a general binding theory, and utilizes previously-determined values for the binding constants of the Ca-proteoglycan interaction, inhibition constants for the effect of Na and phosphate on this interaction, and literature values for the concentrations of proteoglycan, Na and Ca in epiphyseal cartilage. Using this approach, it was predicted that the free Ca concentration in epiphyseal cartilage in the absence of phosphate will be 1.55 mM. At 0.7 mM phosphate, the approximate concentration in non-calcified cartilage matrix, the free Ca concentration will be 2.40 mM, corresponding to a Ca x PO4 product of 1.68 (mM)2. In order to achieve a Ca x PO4 product sufficient for spontaneous precipitation of hydroxyapatite [approximately 4.3 (mM)2], a phosphate concentration of approximately 1.40 mM is required. Therefore, calcification of epiphyseal cartilage matrix by the mechanism described above will require an approximate doubling of the phosphate concentration in the pre-calcifying zones, indicating that the release of a fraction of the intracellular phosphate could trigger the calcification process.

Calcification, Physiologic↗

Effect of testosterone administration on the epiphyseal cartilage of hypophysectomized rats.

For the study of the mechanism of action of testosterone histological, carbohydrate-, and enzyme histochemical investigations were carried out on the epiphyseal cartilage of (1) hypophysectomized rats treated with testosterone [(THX group); (2)] hypophysectomized rats without hormonal treatment (HX group), and (3) intact, untreated control rats. The results were compared with the data obtained in a previous experiment in which intact rats were treated with testosterone (T group). The experiments showed that testosterone exerts a peripheral direct effect on the enzyme system of the epiphyseal cartilage cells by changing their metabolism in the direction of early ageing. This effect elicits characteristic changes in enzyme activity of the cartilage cells if normal hypophyseal activity is present. Impairment and ossification of the epiphyseal cartilage ensue also in hypophysectomized animals treated with testosterone (THX), even faster than in animals subjected only to hypophysectomy (HX), but this process has lost its characteristic feature: the initial increase of enzyme activity in the cartilage cells. Thus, the presence or absence of the hypophysis only modifies the effect of testosterone. Presumably, the latter effect - though not asserting itself through the hypophysis - is highly dependent on hypophyseal activity, that is, on the presence of the hormones produced or mediated by the hypophysis. If testosterone does influence the secretion of these hormones and the activity of the hypothalamus, a central effect of testosterone seems also to be involved in the changes of the epiphyseal cartilage disc.

Alkaline Phosphatase↗

Estimation of age from epiphyseal union at the wrist and ankle joints in the capital city of India.

Various studies conducted in and outside India for estimation of age from long bone joints revealed that unlike other vital parameters no uniform pattern exists for epiphyseal union of long bones in different countries of the world and also in different parts of the same country. A radiological study was conducted in 180 boys and girls of the capital city of India, Delhi, between the age group of 14-20 years to find out the age at which epiphyseal union at wrist and ankle joint takes place. The result of the study showed that the wrist joint epiphyseal union is completed in all cases in the age group of 19-20 years in males and 18-19 years in females. In the ankle joint, 17-18 years was the age group in males and 16-17 years the age group in females which showed complete epiphyseal union in all cases.

Adolescent↗

[Sonographically detectable fetal epiphyseal centers as a criterion for maturity in comparison to L/S ratio].

In 62 pregnant women between the 31st and 39th week of gestation who underwent amniocentesis for determination of the lecithin: sphingomyelin ratio in the amniotic fluid, sonographical identification and measurement of epiphyseal centres around the foetal knee joint were performed. If an epiphyseal centre in the proximal area of the tibia and/or an epiphyseal centre of 6 mm or more in the distal area of the femur could be identified, this showed that a lecithin: sphingomyelin ratio greater than or equal to 2 was present. This noninvasive method of measurement of epiphyseal centres by ultrasound allows not only an exact determination of gestational week in late pregnancy, but also supplies particularly in cases of nondiabetic pregnancies, an indirect pointer to foetal maturity.

Amniocentesis↗

Does it always have to be Perthes' disease? What is epiphyseal dysplasia?

The epiphyseal dysplasias are classified as osteochondral dysplasias in a heterogeneous group of skeletal dysplasias. The common feature of these hereditary conditions is short stature attributable to skeletal dysplasia at various sites. Multiple epiphyseal dysplasia and spondyloepiphyseal dysplasia are of interest to the authors, because the two syndromes are similar in their morphologic features and at first glance suggest the diagnosis of Perthes' disease. Spondyloepiphyseal dysplasia (Wiedemann-Spranger syndrome) is a disorder of growth in which there is an abnormality of enchondral ossification affecting the vertebral bodies and the epiphyses of the long bones. The two forms are the more severe congenita form (Type I), which is inherited as an autosomal dominant condition and is associated with a highly disproportional reduction in growth and severe coxa vara, and the milder tarda form which is an X-linked recessive condition, in which growth in adolescence is defective after normal childhood development. Multiple epiphyseal dysplasia is an abnormality of enchondral ossification, especially of the femoral head epiphysis, and it is an autosomal dominant condition. Depending on its severity, a distinction is made between the severe Fairbank form, the milder Ribbing form, and a mild localized Meyer form.

Adolescent↗

Growth hormone potentiates colony formation of epiphyseal chondrocytes in suspension culture.

The effect of human GH (hGH) on colony formation of rat epiphyseal plate chondrocytes was studied in suspension culture. Chondrocytes were isolated enzymatically from epiphyseal plates of the proximal tibia of 28-day-old normal male rats, and were cultured in a suspension stabilized with 0.5% agarose. After approximately 7 days of culture in the presence of 10% newborn calf serum (NCS), chondrocyte colonies developed consisting of varying numbers of cells in matrix. No colonies developed in the absence of NCS, and the number of formed colonies was proportional to the concentration of NCS (5-20%) in the medium. hGH potentiated the formation of large size colonies (diameter greater than 90 microns) after a culture period of 10 or 14 days. The lowest effective concentration of hGH was 10 ng/ml, while 40 ng/ml hGH gave a maximal stimulatory effect (40-50%). Higher concentrations of hGH (80 and 160 ng/ml) showed reduced potentiation of colony formation. The stimulatory effect of hGH was expressed at 10-15% of NCS at 14 days of culture. There was a linear relation between the number of seeded cells and the number of colonies formed, both in the absence and presence of hGH. These results show that GH potentiates colony formation in chondrocytes of the epiphyseal growth plate, providing further support for the contention that GH exert a direct stimulatory effect on epiphyseal cartilage and thus stimulates longitudinal bone growth directly. The finding that GH preferentially potentiated the formation of large size colonies suggests that GH promoted the differentiation of early proliferative chondrocytes or stem cell chondrocytes with an inherent high capacity to proliferate.

Animals↗

Differential effects of growth hormone and insulin-like growth factor I on colony formation of epiphyseal chondrocytes in suspension culture in rats of different ages.

The effect of human GH (hGH) and insulin-like growth factor I (IGF-I) on the colony formation of rat epiphyseal chondrocytes was studied in suspension culture. Chondrocytes from epiphyseal growth plates of the proximal tibia of 7-, 20-, and 28-day-old normal male rats were enzymatically isolated and cultured in the presence of 10% newborn calf serum in suspension stabilized with 0.5% agarose. The cloning efficiency (number of formed colonies per 1000 seeded cells) was 13.7 +/- 1.9, 3.2 +/- 0.6, and 3.5 +/- 0.4 for chondrocytes isolated from 7-, 20- and 28-day-old rats and cultured for 14 days, respectively. The colonies were classified according to size (colony diameter), and the number of colonies was estimated as a function of colony size (distribution of cloning efficiency). IGF-I (25-200 ng/ml) increased the total colony number among chondrocytes isolated from the three different age groups and particularly increased the number of small colonies. However, IGF-I did not significantly change the distribution of cloning efficiency as compared to the control group. hGH potentiated colony formation at concentrations of 10-80 ng/ml, but no stimulatory effect of hGH was apparent at a concentration of 160 ng/ml. GH caused an assymetric distribution of cloning efficiency that was significantly different from the control group due to an increased number of large colonies (diameter exceeding 80 microns). The differential effects of GH and IGF-I were apparent after an extended period of culture (28 days) at various concentrations of the peptides. These results show that GH as well as IGF-I induced colony formation among epiphyseal chondrocytes in suspension culture, although the effects of GH and IGF-I are different in terms of distribution of cloning efficiency. The observation that GH particularly potentiated the formation of large size colonies suggests that GH promotes the differentiation of prechondrocytes, or young chondrocytes as suggested earlier. The finding that IGF-I stimulation resulted in a higher proportion of small size chondrocyte colonies, compared to the control group, suggests that IGF-I stimulates epiphyseal chondrocytes at a later stage of differentiation.

Aging↗

Effects of triiodothyronine (T3) and identification of specific nuclear T3-binding sites in cultured human fetal epiphyseal chondrocytes.

The effects of T3 on cultured human fetal epiphyseal chondrocytes were assessed by studying its effects on DNA synthesis and alkaline phosphatase activity. DNA synthesis was evaluated as follows: after 48-h incubation in Ham's F-12 serum-free medium, cultured chondrocytes were incubated with or without T3 (0.1-100 nM) in MCDB-104 serum-free medium for different periods of time (2-10 days), with the addition of [3H]thymidine (5 microCi/mL) for the last 24 h. Confluent cultured chondrocytes in 25-cm2 tissue culture flasks were incubated in Ham's F-12 serum-free medium for up to 9 days with or without T3 (0.1-100 nM); the cellular cytoplasmic fraction was obtained, and alkaline phosphatase activity was evaluated using paranitrophenylphosphate as a substrate. No significant effects of T3 (0.1-100 nM) on DNA-[3H]thymidine incorporation were observed in any experiment (n = 17) for any gestational age (12-39 weeks) or for any incubation period studied (2-10 days). However, a significant (P less than 0.025 or more) stimulatory effect of T3 (0.1-100 nM) on alkaline phosphatase activity was observed after 9 days of incubation. This effect was highest for 5 nM T3 and was present in cultured chondrocytes from human fetuses of all ages studied (13-40 weeks). Cultured human fetal epiphyseal chondrocytes from human fetuses 12-40 weeks old (n = 8) showed specific nuclear binding sites for T3. The binding capacity was 27.14 +/- 2.84 fmol/100 micrograms DNA, and the Kd was 0.66 +/- 0.14 x 0.1 nM (mean +/- SEM), with no significant differences among fetal ages. In conclusion, our results show that T3 elicits a biological response in cultured human fetal epiphyseal chondrocytes and has specific nuclear binding sites. Since alkaline phosphatase is closely related to the mineralization of epiphyseal cartilage, these results suggest that thyroid hormones could regulate this process.

Alkaline Phosphatase↗

Epiphyseal fractures of the finger middle joints in young sport climbers.

OBJECTIVE: As competition climbing becomes increasingly popular, younger climbers are entering the sport, and some are among the top-level athletes. This early start combined with intensive training methods can lead to radiographic changes in the fingers and even osteoarthrosis. Since 1994, we have been observing an increasing number of nontraumatic epiphyseal fractures in young athletes. METHODS: Twenty-four cases of young climbers with nontraumatic epiphyseal fractures of the finger middle joints are presented. RESULTS: The average age of the climbers was 14.5 (+/- 0.9) years; 23 were boys, and 1 was a girl. Eight (33%) fractures were in an early stage, whereas in 16 (67%) a longer time interval elapsed between the onset of symptoms and the presentation for evaluation. All radiographs showed an epiphyseal fracture of the dorsal base of the middle phalanx of the finger; 20 patients presented a Salter-Harris III fracture and 4 presented a Salter-Harris II epiphysiolysis. An acute injury was not evident in any of the patients. All fractures were thus fatigue fractures caused by repetitive stress. CONCLUSIONS: Chronic finger pain in young and intensively training climbers must be carefully evaluated, and radiographic studies need to be performed. The risk of epiphyseal injuries must be minimized by eliminating intensive power training in the schedules of athletes of this age.

Adolescent↗

Regulation by GH of insulin-like growth factor-I mRNA expression in rat epiphyseal growth plate as studied with in-situ hybridization.

Expression of insulin-like growth factor I (IGF-I) mRNA and its dependence on GH was studied in rat epiphyseal growth plate by in-situ hybridization. Methodological aspects of the technique were first evaluated on fixed sagittal cryosections from 28-day-old rat epiphyseal growth plates to ascertain specific hybridization. In-situ hybridization was compared on sections from 10- and 28-day-old rats and the GH-dependence was studied in 35-day-old hypophysectomized rats. Expression of IGF-I mRNA was apparent in chondrocytes of the proliferative, hypertrophic and early degenerative zones of the growth plate of 28-day-old rats. The epiphyseal growth plate from 10-day-old rats showed a weak hybridization signal compared with 28-day-old rats. In contrast, the mesenchymal cells of the periosteum of 10-day-old rats showed a rather strong hybridization signal. Hypophysectomy resulted in a reduction in hybridization signal and cell number of the growth plate compared with 35-day-old age-matched normal rats. GH-Replacement therapy (200 micrograms GH s.c. every 4 h for 24 h) resulted in partially restored expression of IGF-I mRNA. The present study has shown that the IGF-I gene is expressed in the rat epiphyseal growth plate chondrocytes and that the expression is dependent on GH. The results support a paracrine/autocrine role of IGF-I for the expression of the stimulatory effect of GH on longitudinal bone growth.

Animals↗

Effects of free perichondrial graft replacement of epiphyseal cartilage on bone growth.

An experimental study in 24 lambs was carried out to find an alternative tissue for the distal epiphyseal cartilage of the femur. The animals were divided into three groups. In the first group (n = 12) the left femoral distal epiphyseal cartilage was completely removed and replaced by a free perichondrial graft taken from the distal half of the scapula. In the second group (n = 6) the epiphyseal cartilage was removed and was not replaced by any tissue. The third group (n = 6) was used as control. After six months the legs in the first and third groups were of the same normal length while the legs in the second group were significantly shorter. We conclude that free perichondrial graft seems to be able to replace the epiphyseal cartilage and prevent retardation of growth.

Animals↗

Longitudinal epiphyseal bracket: associated foot deformities with implications for treatment.

The longitudinal epiphyseal bracket is a rare ossification defect of bones of the hands and feet and results in an abnormal epiphysis that is C-shaped, longitudinally oriented, and vertically extends into the diaphysis. The longitudinal epiphyseal bracket may exist as an isolated deformity, but is commonly associated with digital deformities such as polydactyly, duplicated digits, congenital hallux varus, and clinodactyly. Five case histories of children with the longitudinal epiphyseal bracket in different bones of the foot are described with three distinct clinical presentations. The development of the longitudinal epiphyseal bracket and implications for treatment are considered.

Adolescent↗

Total hip arthroplasty for a patient with angel-shaped phalango-epiphyseal dysplasia (ASPED). A case report.

Angel-shaped phalango-epiphyseal dysplasia is characterized by the angel shape of the middle phalanx and severe coxarthrosis in adult life. This osteochondrodysplasia shows a further variety of heterogeneous multiple epiphyseal dysplasias. It also shows a late and dysplastic development of the femoral head that leads to osteoarthrotic changes with severe hip pain and gait disturbance. In this report, we show a 35-year-old female with Angel-shaped phalango-epiphyseal dysplasia that was treated by bilateral total hip arthroplasty. She has suffered from her coxalgia since she was 27 and since the age of 30 has been able to walk with the aid of crutches. The radiographs of her bilateral hip showed severe osteochondrotic changes with a progressive disappearance of the joint space. Total hip arthroplasties were performed to treat the osteoarthrosis on the bilateral hip joint due to Angel-shaped phalango-epiphyseal dysplasia. One year after surgery, she is pain-free, and able to walk with a cane. Based on this case, we propose that total hip arthroplasty should be considered one of the treatments for the coxopathy in patients with Angel-shaped phalangoepiphyseal dysplasia.

Adult↗

[Zinc deficiency on pathological changes of femur epiphyseal growth plate in rats].

To study zinc deficiency on pathological changes of femur epiphyseal growth plate in rats thirty Wistar rats were randomly divided into three groups: zinc-deficient group (Zd), control group (Ctr), and pair-fed group (Zp) to study the effects of zinc deficiency on femur epiphyseal growth plate of rats and the mechanism involved. After 8 weeks feeding, the histomorphology of right femur indicated that chondrocytes in the epiphyseal growth plate of Zd group were generally ill-organized and mis-shaped. The number of chondrocytes decreased. Trabecular bone in the epiphyseal of Zd group were also ill-organized, scarce and slim. The cavities of marrow in Zd animals were significantly larger than those of Ctr and Zp. The volume of trabecular bone, the mean trabecular plate density of Zd rats were significantly decreased, but their mean trabecular plate space was significantly increased. In addition, the Zd animals had significantly lower concentration of osteocalcin and growth hormone in sera. The above results suggested that zinc deficiency impaired proliferation and differentiation of chondrocytes and balance between osteoblast and osteoclast function by reduce growth hormone levels in sera. The lack of zinc in diet resulted in disorder of bone molding and ultrastructure.

Animals↗