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PubMed2005

Enlargements of the distal third metacarpus and metatarsus in Thoroughbred foals at pasture from birth to 160 days of age.

AIMS: To assess the relationship between the radiographic and microscopic appearance of the physeal regions of the distal third metacarpal (Mc3) and metatarsal (Mt3) bones of Thoroughbred foals at 160 days of age, and to clinically assess changes in contour of the distal Mc3 and Mt3 physeal regions from birth to 160 days of age. To assess relationships between maximum clinical physis scores and age, time of year, foal's sex, condition score, growth rate, copper (Cu) concentration in the liver of the foal, and supplementation of the dam with Cu in late gestation. METHODS: Dams were given Cu (n=5 and n=11, in Years 1 and 2, respectively) or saline (n=5 and n=12, in Years 1 and 2, respectively) injections in late gestation. Liver biopsies were harvested from foals in the first week of life, and the whole liver homogenised after the animals were euthanised at around 160 days of age, to determine Cu concentrations. Pasture samples were collected every 4-8 weeks for analysis of mineral composition. During Year 1, 10 foals were weighed and examined every 2 weeks from birth to 160 days of age for evidence of pain and lameness in the distal Mc3/Mt3. In Year 2, 23 foals were weighed, condition-scored and examined for evidence of pain and lameness weekly for the first 5 weeks of life, then every 2 weeks from birth to 160 days of age, and a clinical physis score for the distal Mc3/Mt3 given. Cabinet radiographs of frontal slices of the physeal region of the distal Mc3/Mt3 at around 160 days of age were given a radiographic physis score. Physes were then examined histologically for evidence of abnormal endochondral ossification. RESULTS: Gross enlargements of the distal Mc3 and Mt3 were observed in all foals in this study, but were not associated with lameness, pain or inflammation. The most severe clinical physis scores occurred over 2 months in late summer/autumn, and were not influenced by the foal's growth rate, sex, or Cu concentration in the liver, or treatment of dams with Cu in late gestation. The clinical physis score was highly correlated to radiographic evidence of shouldering in the forelimb and hindlimb (both p<0.001). Focal disturbances in endochondral ossification were evident radiographically and histologically in the some of the physes at 160 days of age. The mineral composition of pasture was similar in Years 1 and 2, and concentrations of Cu and zinc were below those currently recommended for growing horses. CONCLUSIONS: Gross enlargements of the distal Mc3 and Mt3 were not consistent with previous descriptions of physitis. Results suggest that while many Thoroughbred foals at pasture will have visible boney enlargements of the distal Mc3/Mt3 in the first 5 months of life, few have physeal cartilage abnormalities or significant compromise of endochondral ossification. The importance of these clinical swellings may be overestimated, and they may more appropriately be called physiological enlargements associated with remodelling of bone.

Aging↗
PubMed1975

[Hypertrophic osteodystrophy of the dog (author's transl)].

The clinical and radiological findings of 21 dogs with hypertrophic osteodystrophy are described. In three cases a detailed pathologico-anatomic examination was performed also. The dogs concerned were young animals of large breeds with clinical symptoms of lameness, fever, pain, and thickened metaphyses of the long bones. Radiologically the condition was characterised by enhancement of the metaphyses and periosteal new growths of the bone. The pathologico-anatomic examination revealed a disturbed endochondral and periosteal ossification. Overnutrition as a possible cause of the condition is discussed.

Analgesics↗
PubMed1990

Theoretical stress analysis of organ culture osteogenesis.

In a series of in vitro organ culture experiments by Klein-Nulend et al., intermittent ambient hydrostatic pressure was found to significantly increase the rate of calcification in the diaphysis of mouse rudiments while proteoglycan production was increased in the noncalcified epiphyses. In this study, we have conducted finite element stress analyses of this organ culture system in an effort to better understand the distribution of local tissue stresses which were created. Furthermore, we sought to clarify how these experimental results relate to our theory for skeletal morphogenesis which postulates that endochondral ossification is accelerated in regions of octahedral shear (deviatoric) stress and inhibited in areas of compressive hydrostatic (dilatational) stress. The results of the stress analyses show that externally applied hydrostatic pressure produces significant shear stresses at the cartilage/calcified cartilage interface and pure hydrostatic pressure at the rudiment ends. The accelerated osteogenesis in regions of high shear and the increased synthesis of proteoglycans in regions of high compressive hydrostatic stress are therefore consistent with our theory which predicts the regulation of cartilage maintenance and endochrondral ossification by intermittent tissue stresses.

Animals↗
PubMed1991

Alpha 2-HS-glycoprotein: expression in chondrocytes and augmentation of alkaline phosphatase and phospholipase A2 activity.

The alpha 2-HS-glycoprotein is a plasma protein synthesized in liver and enriched in bone. The concentration of alpha 2-HS-glycoprotein dynamically changes in various physiological conditions and is highest in bone during growth, suggesting that it is involved in regulation of endochondral ossification. Northern blot analysis demonstrated that mRNA transcripts from growth zone and resting zone costochondral chondrocyte cultures hybridized with alpha 2-HS-glycoprotein cDNA. However, a difference of mRNA transcript size was observed, with chondrocyte mRNA transcripts being 2.2 kb, while mRNA isolated from liver was 1.6 kb. Presence of alpha 2-HS-glycoprotein in cartilage cells was found by immunohistochemical staining of human fetal epiphyses using anti-human alpha 2-HS-glycoprotein antibody. To understand the role of alpha 2-HS-glycoprotein in cartilage growth, the effects of exogenous alpha 2-HS-glycoprotein were correlated with alkaline phosphatase (ALPase) and phospholipase A2 (PA2) activity in the chondrocyte cultures. Alkaline phosphatase specific activity was stimulated by alpha 2-HS-glycoprotein at concentrations between 0.25 and 1.25 micrograms/mL in the growth zone and resting zone cultures 2.7 and 2.0-fold, respectively. Matrix vesicle PA2 activity was increased only in the growth zone chondrocyte cultures. These results suggested that alpha 2-HS-glycoprotein may contribute to the regulation of the expression of the chondrocyte phenotype. Steady state mRNA levels of ALPase were analyzed in chondrocytes after additions of alpha 2-HS-glycoprotein. The ALPase mRNA levels remained stationary during the stimulation of enzymatic activity, indicating that the effect of alpha 2-HS-glycoprotein upon alkaline phosphatase activity is not at the transcriptional level.

Alkaline Phosphatase↗
PubMedDate not supplied

[Effect of the high molecular weight fraction of non-collagenous bone tissue protein on osteogenesis and hematopoiesis in experimental elongation of an extremity].

High molecular fraction of HCl-extract from mature homologous bone was parenterally administered, during the predistraction period, into 16 rabbits, crus of which was elongated by Ilizarov procedure. The treatment affected positively the adaptation process, hemopoiesis and the ossification of distraction regenerate. Administration of the high molecular protein fraction into mice with depressed hemopoiesis demonstrated that physiological effect of the fraction consisted in stimulating effect on proliferation of both bone tissue and red blood cells.

Animals↗
PubMed1991

[Skeletal development in the dog in relation to nutrition].

Growth hormone (GH) and insulin-like growth factor I (IGF-I) play important roles during growth, including effects on enchondral ossification. GH plasma concentration is strongly influenced by the nutritional status of the dog. Fasting induces a non-responsiveness of the liver to GH, leading to a decrease in IGF-I release by the liver and a delay in growth. Overfeeding leads to abnormal skeletal development, i.e., osteochondrosis and hip dysplasia. Subnormal plasma concentrations of sex hormones lead to a delay in physiologic epiphysiodesis, whereas high levels of sex steroids may induce premature physeal closure. Dietary calcium, phosphorus, and vitamin D are important factors in the process of enchondral ossification. If these nutrients are inadequate, imbalanced, or oversupplemented, skeletal development in young growing dogs can be disturbed, leading tot severe pathologic changes. Energy requirements decrease gradually during the first year of life and unrestricted feeding can easily lead to pups being overweight. The protein requirements are strongly influenced by the quality and digestibility of protein sources in the food. In dog foods 12-14 g protein/1000 kJ appears to be adequate for growth. It is likely that the two most commonly made mistakes in dog nutrition in the Netherlands, are oversupplementation with energy and/or calcium. Restricted feeding is advised during growth and no food-additives are required when commercially prepared complete dog foods are used.

Animal Nutritional Physiological Phenomena↗
PubMed2001

Dwarfism and early death in mice lacking C-type natriuretic peptide.

Longitudinal bone growth is determined by endochondral ossification that occurs as chondrocytes in the cartilaginous growth plate undergo proliferation, hypertrophy, cell death, and osteoblastic replacement. The natriuretic peptide family consists of three structurally related endogenous ligands, atrial, brain, and C-type natriuretic peptides (ANP, BNP, and CNP), and is thought to be involved in a variety of homeostatic processes. To investigate the physiological significance of CNP in vivo, we generated mice with targeted disruption of CNP (Nppc(-/-) mice). The Nppc(-/-) mice show severe dwarfism as a result of impaired endochondral ossification. They are all viable perinatally, but less than half can survive during postnatal development. The skeletal phenotypes are histologically similar to those seen in patients with achondroplasia, the most common genetic form of human dwarfism. Targeted expression of CNP in the growth plate chondrocytes can rescue the skeletal defect of Nppc(-/-) mice and allow their prolonged survival. This study demonstrates that CNP acts locally as a positive regulator of endochondral ossification in vivo and suggests its pathophysiological and therapeutic implication in some forms of skeletal dysplasia.

Animals↗
PubMed2001

The bone morphogenetic proteins antagonist Noggin inhibits membranous ossification.

Bone morphogenetic proteins (BMPs) are expressed and secreted during fracture repair. Although they are likely to be required for this process, little is known about their physiological role in bone regeneration. Noggin is a protein that specifically binds and inactivates several BMPs. It plays fundamental roles during early embryonal development and limb morphogenesis by this BMP-inactivating activity. This study shows that Noggin can modify bone formation in vivo in the adult animal and, thus, indirectly, that BMP signaling is indispensable in this process. A noggin mutein (hNgdeltaB2-Fc) engineered so as to display increased bioavailability was used. Bilateral titanium bone chambers were inserted in 70 rats, and side comparisons for bone formation in the chambers were done. The hNgdeltaB2-Fc had no effect on total amount of tissue formed in the chamber but decreased the amount of bone compared with both buffer controls and a control made up of an Fc-tagged IL-6Ralpha protein, which had no effects of its own. Also, wild-type noggin inhibited bone formation. Thus, endogenous BMP signaling is necessary for normal bone regeneration.

Animals↗
PubMed1993

[Physiology of craniofacial development].

This topic summarizes basic principles of the development and the postnatal growth of the craniofacial skeleton. The different stages involved in the progressive ossification of facial bones are exposed: the intramembranous ossification, the endochondral (intracartilagenous) ossification and the changes (remodelling and relocation) associated with periosteal and endosteal membranes.

Adolescent↗
PubMed1993

[New method for evaluating ossification of the carpal bone. From a study with 5225 Spanish children].

The author present a new method of assessment of bone age derived from the analysis of carpal osseous development of 5,225 Spanish children and adolescents. The method is based upon the determination of a carpal index from the measurement of the largest diameter of the eight carpal bones, the proximal epiphysis of the first metacarpal and the distal cubital and radial epiphyses. There is a highly significant correlation of this carpal index with chronological age (P < 0.0001). From this index the author has set up an equation defining an index of evaluation of carpal ossification which helps to estimate bone age according to six different ranges of significance: significant retardation, moderate non significant retardation, borderline normality, complete normality, moderate non significant advance, significant advance. The method is simple to realize. It reduces the risk of errors in the evaluation of bone age due to asynchronisms of maturation of the ossification centres and to the individual subjective factor occurring with a morphologic assessment. Furthermore it takes into account the physiological variations of bone age on both sides of the mean normal value.

Adolescent↗
PubMed2005

Does traumatic brain injury result in accelerated fracture healing?

In patients who have sustained a traumatic brain injury with an associated extremity fracture there is often a clinical perception that the rate of new bone formation around the fracture site is increased. Whether this rapidly forming new bone is fracture callus or a variant of heterotopic ossification, a common complication of traumatic brain injury, is the subject of some debate. This review will provide a comprehensive analysis on this topic and will discuss clinical and physiological evidence as well as potential areas for future research in this field.

Bone Remodeling↗