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PubMed1985

Sternal ossification in normal newborn infants.

The lateral chest radiographs of 200 Nigerian newborn infants, whose gestational age was estimated by the Dubowitz examination, were analysed for the pattern of ossification of sternal segments. The length of each visible centre was also measured. The manubrium was ossified in all infants over 35 weeks. All infants 37 weeks and above demonstrated ossification of the first and second mesosternal segments. Ten infants had ossification of the xiphisternum. The average number of ossified segments seen in this study is more than previously reported amongst Caucasian infants. The length of each segment correlated better with birth weight than gestational age. Our findings indicate that any infant with two ossified sternal segments, including the manubrium, is at least 30 weeks and those with 3 and 4 segments 34 and 37 weeks gestation, respectively. There is no difference in the pattern of sternal ossification between the sexes.

Birth Weight↗
PubMed2003

Studies on the time frame for ossification of the medial clavicular epiphyseal cartilage in conventional radiography.

Radiological assessment of the degree of ossification of the medial clavicular epiphyseal cartilage plays a vital part in forensic age diagnosis of living adolescents and young adults. A total of 873 plain chest radiographs requested by the staff medical officer for members of staff aged 16-30 at the University Hospital Charité were evaluated retrospectively. Of these X-rays 699 permitted an assessment of ossification of at least 1 side of the clavicle. In addition to the customary stages (1: non-ossified epiphysis, 2: discernible ossification centre, 3: partial fusion, 4: total fusion) a stage 5 was also defined, characterised by the disappearance of the epiphyseal scar following total fusion. The earliest age at which stage 3 was detected in either gender was 16 years. Stage 4 was first observed in women at 20 years and in men at 21 years. In both genders, the earliest observation of stage 5 was at 26 years. It was concluded that plain chest radiographs can essentially be used to assess clavicular ossification. In practice, if overlap in posterior-anterior views impedes evaluation, a lateral view should also be taken to facilitate age estimation. In forensic practice the reference values of the present paper should be applied.

Adolescent↗
PubMed2005

The influence of slice thickness on assessment of clavicle ossification in forensic age diagnostics.

Computed tomography scans originally obtained to assess the ossification status of the medial clavicular epiphyses of 40 live subjects for forensic age estimation purposes were analysed. From the data acquired we reconstructed images with slice thicknesses of 1, 3, 5 and 7 mm, and based on the classification of stages by Schmeling et al. (Int J Legal Med 118:5-8, 2004), we determined the ossification stage for each reconstructed slice thickness, separately for both sides. Of the 80 clavicular epiphysial plates examined, seven displayed slice-thickness-dependent differences at certain ossification stages. In one case a slice thickness of 1 mm led to a different diagnosis of the ossification stage than a slice thickness of 3 mm, in three cases the diagnoses differed between the slice thicknesses of 3 and of 5 mm, and in another three cases, between 5 and 7 mm. We therefore conclude that for age estimation purposes, the slice thickness should be 1 mm to ensure maximum accuracy and diagnostic reliability.

Age Determination by Skeleton↗
PubMed1989

Increase of chondroitin 4-sulfate concentration in the endochondral ossification cartilage of normal dogs.

The absolute concentrations of chondroitin 4- and 6-sulfate are compared in articular and endochondral ossification cartilage from normal dogs. In newborn dogs, the absolute concentration of chondroitin 4-sulfate decreases nearly 3-fold from the deeper endochondral ossification cartilage to the articular surface, whereas that of chondroitin 6-sulfate does not change. In cartilage from the articular surface of the epiphysis in adults, where the ossification process is complete, the concentration of chondroitin 4-sulfate is also low. These observations suggest that chondroitin 4-sulfate may be important in the ossification process. The pathogenesis of heritable disorders involving the sulfation of chondroitin sulfate is discussed in view of these findings.

Aging↗
PubMed2004

VEGF expression in adult permanent thyroid cartilage: implications for lack of cartilage ossification.

Vascular endothelial growth factor (VEGF) has been shown to play an important role during endochondral bone formation in hypertrophic cartilage remodeling, ossification, and angiogenesis, but it is not expressed in normal adult articular cartilage. Thyroid cartilage undergoes only partial ossification beginning at the age of about 20. Because it never completely ossifies, we investigated a possible role of VEGF and its receptors (VEGFRs) as well as the angiogenetic inhibitor endostatin in this permanent cartilage. In analysis of cartilage samples from all specimens evaluated, VEGF121 and VEGF165 were identified as the only VEGF splice forms expressed. In addition to VEGF, VEGFR-2 (kinase domain region/fetal liver kinase 1), but not VEGFR-1 (fms-like tyrosine kinase 1), was detectable by RT-PCR in cartilage. However, VEGFR-2 expression was only detectable up to the age of 19 years. Deposition of VEGF and VEGFR was confirmed by immunohistochemistry. VEGF concentrations measured by ELISA in thyroid cartilage increased with age in males but decreased in females. Endostatin concentrations measured by ELISA in thyroid cartilage were three times lower than in articular cartilage and showed no change with age, either in females or males. VEGF was immunostained within the intra- and pericellular matrices of some but not all chondrocytes. Thus, apart from its production in hypertrophic chondrocytes of growth plates, VEGF is also produced in single chondrocytes of thyroid cartilage. The data allow us to speculate that thyroid cartilage persists in an embryological state until it has reached its final size. After reaching its final size at the end of the second decade, VEGFR-2 is downregulated and ossification starts in the posterior part of the thyroid cartilage, proceeding ventrally. Both proteins, VEGF121 and VEGF165, should contribute to this process. VEGF concentration is high and changes in an age-related and sex-specific manner. Therefore, we postulate that VEGF is at least one of the key factors that is important for the lifelong ossification in thyroid cartilage.

Base Sequence↗
PubMed2006

The function of proprioceptors in bone organization: a possible explanation for neurogenic heterotopic ossification in patients with neurological damage.

Neurogenic heterotopic ossification is characterized by the formation of extra osseous bone in soft tissue surrounding peripheral joints in neurological patients. It occurs in 25% of spinal cord injury patients, and in 20% of these the pathologic process is severe enough to cause limitations in joint motion. Vascular and metabolic changes resulting from autonomic nervous system impairment may play a role in the etiology of heterotopic ossification. Repetitive vigorous passive manipulation of the joint to preserve range of motion, in the presence of reduced defense mechanisms, may also traumatize soft tissue, thereby initiating the pathological process. Nerve terminals within ligaments and capsules that allow for proprioception have a determinant role in triggering on and off muscle contraction, permitting acceleration and deceleration during gait. The Sarah Network of Rehabilitation Hospitals has treated over 20,000 patients with spinal cord and brain injury in the past 20 years. Based on the observation of heterotopic ossification development in some of these patients, and its tendency to relapse, this present article speculates whether, after an interruption in the neural pathways: (1) altered proprioception can forge a different relationship between tissues; and (2) chaotic new bone formation can occur. We postulate that heterotopic ossification in patients with injury to the central nervous system (CNS) may be related to a dysfunction of proprioception. With interruption of the neural tract of a given limb, ligaments lose control and coordination of their proprioceptive function and begin to react to direct stimulus in an independent, isolated and haphazard way. Free of CNS control and directly stimulated by such independent signals, mesenchymal osteoprogenitor cells located in soft tissues begin to occasion tissue maturation and differentiation into bone: heterotopic bone.

Bone and Bones↗
PubMed1991

Experimental hypophosphataemia in growing pigs: effects on endochondral ossification in comparison to osteochondrosis.

Hypophosphataemia was induced in growing pigs by dietary supplementation with aluminium hydroxide. The effect on endochondral ossification was studied morphologically in comparison with normophosphataemic pigs given aluminium phosphate or left untreated. The aim of the investigation was to elucidate further the role of nutritional factors in the pathogenesis of disturbed endochondral ossification, occurring in osteochondrosis. In all pigs, focal arrestment of endochondral ossification with subsequent cartilage retention in the epiphyseal or metaphyseal growth zones was seen. In normophosphataemic pigs, focal degenerative cartilage changes were associated with impairment of vascular penetration. The lesions had morphological characteristics of early osteochondrosis. In hypophosphataemic pigs, a more generalized disturbance, endochondral ossification, was seen with impaired vascular penetration and excessive deposition of osteoid in the primary spongiosa. Focal cartilage retentions were associated with necrotic changes in the primary spongiosa and not with cartilage degeneration. The lesions were similar to rickets and it was concluded that hypophosphataemia is not an aetiological factor in the development of osteochondrosis. The differentiation between the cartilage retention seen in early stages of osteochondrosis and rickets must be based on histological examination.

Aluminum↗
PubMedDate not supplied

Radiographic monitoring of the ossification of long bones in kori (Ardeotis kori) and white-bellied (Eupodotis senegalensis) bustards.

A serial radiographic study was conducted on eight kori bustard (Ardeotis kori) and four white-bellied bustard (Eupodotis senegalensis) chicks to determine the pattern of long bone development and to establish radiographic standards for assessing skeletal maturity. The ossification pattern, appearance of secondary ossification centres, and epiphyseal fusion of the long bones in kori and white-bellied bustards were similar to those in houbara bustards (Chlamydotis undulata macqueenii), rufous-crested bustards (Eupodotis ruficrista), domestic fowl (Gallus gallus), house wrens (Troglodytes aedon aedon), racing pigeons (Columba livia). and barn owls (Tyto alba). Secondary ossification centres were present at the proximal and distal tibiotarsus, proximal tarsometatarsus and proximal metacarpal III. The ossification of long bones occurred earlier in female kori bustards compared with males.

Animals↗
PubMed1988

Heterotopic ossification with total hip endoprostheses in various models of thrombosis prophylaxis.

The influence of thrombosis prophylaxis on the occurrence of heterotopic ossification after implantation of total hip endoprostheses was analyzed in a series of randomized studies. When low-dose heparin or dextran 40 was administered, the rate of ossification was comparatively high (30.1% and 65.1%). When a combination of acetylsalicylic acid and an antirheumatic (oxyphenbutazone) or low-dose heparin with an antirheumatic (indomethacin) was administered, the ossification rate became significantly lower (6.2% and 16.7%). No severe ossification (Arcq degree III) was observed in the groups given an antirheumatic in addition to thrombosis prophylaxis.

Aspirin↗
PubMed1994

Light microscopic observations on the ossification process in the early developing pedicle of fallow deer (Dama dama).

The ossification process of the early developing pedicle was studied in five male fallow deer fawns, aged about seven months. The incipient pedicle was covered by a periosteum, the cambial layer of which was significantly thicker at the apex of the outgrowth than in the more peripheral areas of the pedicle. As was demonstrated histologically, in the central part of the pedicle elongation occurred by a process corresponding to endochondral ossification, whereas in the more peripheral areas the pedicle became enlarged by typical intramembranous ossification. Thus, cartilage formation must be regarded as a normal feature in pedicle growth of fallow deer. The assumption that the transition from pedicle to first antler growth in cervids is reflected by a switch from intramembranous ossification to chondrogenesis at the apex of the growing primary cranial appendage, based mainly on observations in roe deer, does, therefore, not hold for fallow deer. Furthermore, histogenesis of the central part of the fallow deer pedicle closely resembles the developmental events leading to formation of subsequent antlers.

Aging↗
PubMed1997

Expression and localization of bone morphogenetic proteins (BMPs) and BMP receptors in ossification of the ligamentum flavum.

To clarify the pathogenesis of ossification of the ligamentum flavum (OLF), we examined the expression and localization of bone morphogenetic proteins (BMPs) and their receptors (BMPRs) in the ligamentum flavum of the patients with OLF by immunohistochemical staining and compared them with staining patterns in control patients. The BMPRs appeared extensively in mature and immature chondrocytes around the calcified zone and in spindle-shaped cells and round cells in the remote part from ossified foci in examined tissue of OLF. The ligands for BMPRs, BMP-2/-4 and osteogenic protein-1 (OP-1)/BMP-7, colocalized in OLF patients. In the control cases, expression of BMPs and BMPRs was observed around the calcified zone at the insertion of the ligamentum flavum to the bone, and limited expression was found in the smaller range. Thus, the expression profile of BMPs and BMPRs in OLF patients was entirely different from the control patients, suggesting that BMPs may be involved in promoting endochondral ossification at ectopic ossification sites in OLF, and that ossification activity is continuous in these patients.

Activin Receptors↗
PubMed1999

Microvascular features and ossification process in the femoral head of growing rats.

In the epiphysis of long bones, different patterns of development of ossification processes have been described in different species. The development of the vascularisation of the femoral head has not yet been fully clarified, although its role in the ossification process is obvious. Our aim was to investigate ossification and vascular proliferation and their relationship, in growing rat femoral heads. Male Wistar rats aged approximately 1, 5 and 8 wk and 4, 8 and 12 mo were used. Light microscopy frontal sections and vascular corrosion casts observed by scanning electron microscopy were employed. In the rat proximal femoral epiphysis, ossification develops from the medullary circulation of the diaphysis, quickly extending to the neck and the base of the head. Hypertrophic chondrocytes occupy the epiphyseal cartilage, and a physeal plate with regular cell columns is present. Starting from about the end of the third month one or more points of fibrovascular outgrowth, above the physeal line, can be observed in each sample. They are often placed centrally or, sometimes, peripherally. The fibrovascular outgrowths penetrate deeply into the cartilage and extend laterally. At age 8 mo, large fibro-osseous peduncles connect the epiphysis to the diaphyseal tissue. At 12 mo, the entire epiphysis appears calcified with an almost total absence of residual cartilage islands. This situation differs in man and in other mammals due both to differing thickness of the cartilage and to the presence of more extensive sources of blood vessels other than the diaphyseal microcirculation, as supplied by the teres ligament and Hunter's circle. In young rats, subchondral vessels and the synovial fluid could play a role in feeding the ossifying cartilage. Later, a loss of resistance of the physis due to marked degeneration of the cell columns, and extensive chondrocyte hypertrophy permit fibrovascular penetration starting from diaphyseal vessels rather than neighbouring vascular territories, such as those of the periosteum and capsule.

Animals↗
PubMed2005

Developmental regulation of Wnt/beta-catenin signals is required for growth plate assembly, cartilage integrity, and endochondral ossification.

Studies have suggested that continuous Wnt/beta-catenin signaling in nascent cartilaginous skeletal elements blocks chondrocyte hypertrophy and endochondral ossification, whereas signaling starting at later stages stimulates hypertrophy and ossification, indicating that Wnt/beta-catenin roles are developmentally regulated. To test this conclusion further, we created transgenic mice expressing a fusion mutant protein of beta-catenin and LEF (CA-LEF) in nascent chondrocytes. Transgenic mice had severe skeletal defects, particularly in limbs. Growth plates were totally disorganized, lacked maturing chondrocytes expressing Indian hedgehog and collagen X, and failed to undergo endochondral ossification. Interestingly, the transgenic cartilaginous elements were ill defined, intermingled with surrounding connective and vascular tissues, and even displayed abnormal joints. However, when activated beta-catenin mutant (delta-beta-catenin) was expressed in chondrocytes already engaged in maturation such as those present in chick limbs, chondrocyte maturation and bone formation were greatly enhanced. Differential responses to Wnt/beta-catenin signaling were confirmed in cultured chondrocytes. Activation in immature cells blocked maturation and actually de-stabilized their phenotype, as revealed by reduced expression of chondrocyte markers, abnormal cytoarchitecture, and loss of proteoglycan matrix. Activation in mature cells instead stimulated hypertrophy, matrix mineralization, and expression of terminal markers such as metalloprotease (MMP)-13 and vascular endothelial growth factor. Because proteoglycans are crucial for cartilage function, we tested possible mechanisms for matrix loss. Delta-beta-catenin expression markedly increased expression of MMP-2, MMP-3, MMP-7, MMP-9, MT3-MMP, and ADAMTS5. In conclusion, Wnt/beta-catenin signaling regulates chondrocyte phenotype, maturation, and function in a developmentally regulated manner, and regulated action by this pathway is critical for growth plate organization, cartilage boundary definition, and endochondral ossification.

ADAM Proteins↗
PubMedDate not supplied

Age-related changes of plasma alkaline phosphatase and inorganic phosphorus, and late ossification of the cranial roof in the Spanish imperial eagle (Aquila adalberti C. L. Brehm, 1861).

Plasma alkaline phosphatase and inorganic phosphorus levels were determined for 52 nestling Spanish imperial eagles from two wild populations and 22 captive adults and subadults (10 adults and 12 subadults). The exact age was known for all birds. Mean alkaline phosphatase and inorganic phosphorus were higher in chicks than in the captive adults and subadults. Sex differences were not observed, and nestlings from different populations showed similar values. No significant regression described the relationship between age and alkaline phosphatase or inorganic phosphorus throughout the nestling period. However, alkaline phosphatase and inorganic phosphorus decreased significantly throughout the subadult period, with age explaining 98.2% and 50.5% of the variation in alkaline phosphatase and inorganic phosphorus levels, respectively. Non-fully-ossified zones were measured in frontal bones of another 12 subadult eagles that died at known ages. Ossification increased throughout the subadult period and was significantly correlated with expected levels of alkaline phosphatase or inorganic phosphorus (i.e., values predicted from the regression equations derived from the first analysis). Minimum alkaline phosphatase levels and full ossification of the cranial roof coincided with puberty onset. We conclude that, in subadult Spanish imperial eagles, decreasing alkaline phosphatase and inorganic phosphorus values are related to the ossification of frontal bones, although a contribution of other unknown processes of late ossification cannot be excluded, and alkaline phosphatase (but not inorganic phosphorus) may be a useful parameter for age-predicting purposes.

Aging↗
PubMedDate not supplied

Avascular necrosis after treatment of DDH: the protective influence of the ossific nucleus.

We retrospectively reviewed the results of open or closed reduction for developmental dysplasia of the hip (DDH) in 49 children younger than 12 months old, who had 57 hip dislocations. Group A (18 hips) developed partial or complete avascular necrosis (AVN), and group B (39 hips) did not develop AVN. Thirty-eight hips were treated by closed reduction, and 17 had open reduction. One patient with bilateral hip dislocation initially had closed reductions followed by bilateral open reduction 3 months later. With the numbers available for study, there was no significant difference in the occurrence of AVN with respect to variables such as preliminary traction, closed versus open reduction, Pavlik harness use, and age at the time of operative intervention. However, the presence of the ossific nucleus before reduction, detected either by radiographs (p < 0.001) or ultrasonography (p = 0.033) was statistically significant in predicting AVN. Only one (4%) of 25 hips with an ossific nucleus developed AVN, whereas 17 (53%) of 32 hips without an ossific nucleus before reduction developed AVN. Our results suggest that the presence of the ossific nucleus before closed or open reduction for DDH may decrease the risk of AVN.

Female↗
PubMed1999

Human temporal bone study on the postnatal ossification process of auditory ossicles.

OBJECTIVE: In infancy the head of the malleus and body of the incus normally contain bone marrow, which is gradually replaced by bone and converted into vascular channels with age. This study was carried out to clarify the age at which ossification of the ossicles is complete and to examine factors influencing the ossification process. STUDY DESIGN: Human temporal bone sections from 32 infants and children with or without congenital anomalies, aged 1 day to 9 years, who were born at term were studied. METHODS: The percentage bone marrow area occupying the head of the malleus and body of the incus was calculated in three horizontal temporal bone sections for each case, using computer-aided digital processing of images. RESULTS: Bone marrow was observed in both the malleus and incus in children until 25 months of age, while after the age of 25 months no bone marrow tissue was present in either of the ossicles. It appeared that the bone marrow space disappeared somewhat earlier in the malleus than in the incus. The bone marrow space around the otic capsule disappeared much earlier than that within the ossicles. The age at completion of ossification was correlated with neither the presence of congenital anomalies nor the presence of residual mesenchyme in the middle ear. CONCLUSIONS: Ossification of the ossicles seems to occur steadily throughout fetal life and after birth during development of the middle ear. Although the clinical significance of postnatal residual bone marrow within the ossicles is not known, it possibly plays a role as a blood-forming organ in early infancy.

Bone Marrow↗
PubMed2006

The role of the ossific nucleus in the treatment of established hip dislocation.

UNLABELLED: Timing the reduction of a delayed presenting dislocated hip is controversial if the ossific nucleus of the proximal femoral epiphysis is absent. We formulated a decision model for management of 6- to 13-month-old infants based on two strategies: waiting for the ossific nucleus to appear before reducing the hip or immediate reduction. The model included the occurrence of long-term physical disability within a period of 20 years. A literature synthesis provided outcome probabilities. Outcome was measured by utilities derived by content experts. Waiting for the ossific nucleus was the preferred strategy with an expected value of 0.95 as opposed to 0.86 in the immediate reduction strategy. Sensitivity analyses showed the model was robust. Based on the results of decision analysis, reducing a dislocated hip in the presence of the ossific nucleus is likely to be the better strategy if avascular necrosis and long-term disability are considered. The difference between the two strategies is equivalent to one quality-adjusted life year, which is substantial. LEVEL OF EVIDENCE: Economic and Decision Analyses, Level II-1. See the Guidelines for Authors for a complete description of levels of evidence.

Age Factors↗
PubMed2002

The evolution of development: two portraits of skull ossification in pipoid frogs.

Development creates morphology, and the study of developmental processes has repeatedly shed light on patterns of morphological evolution. However, development itself evolves as well, often concomitantly with changes in life history or in morphology. In this paper, two approaches are used to examine the evolution of skull development in pipoid frogs. Pipoids have highly unusual morphologies and life histories compared to other frogs, and their development also proves to be remarkable. First, a phylogenetic examination of skull bone ossification sequences reveals that jaw ossification occurs significantly earlier in pipoids than in other frogs; this represents a reversal to the primitive vertebrate condition. Early jaw ossification in pipoids is hypothesized to result from the absence of certain larval specializations possessed by other frogs, combined with unusual larval feeding behaviors. Second, thin-plate spline morphometric studies of ontogenetic shape change reveal important differences between pipoid skull development and that of other frogs. In the course of frog evolution, there has been a shift away from salamander-like patterns of ontogenetic shape change. The pipoids represent the culmination of this trend, and their morphologies are highly derived in numerous respects. This study represents the first detailed examination of the evolution of skull development in a diverse vertebrate clade within a phylogenetic framework. It is also the first study to examine ossification sequences across vertebrates, and the first to use thin-plate spline morphometrics to quantitatively describe ontogenetic trajectories.

Animals↗