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Ossification and pseudoepiphysis formation in the "nonepiphyseal" end of bones of the hands and feet.

Metacarpals, metatarsals, and phalanges were studied to assess the developmental morphology of "secondary" ossification in the "nonepiphyseal" ends of these bones as well as the formation of the pseudoepiphysis as an epiphyseal ossification variant. Both direct ossification extension from the metaphysis into the epiphysis and pseudoepiphysis formation preceded, and continued to be more mature than, formation and expansion of the "classic" epiphyseal (secondary) ossification center at the opposite end of each specific bone. Direct metaphyseal to epiphyseal ossification usually started centrally and expanded hemispherically, replacing both physeal and epiphyseal cartilage simultaneously. In contrast, when remnants of "physis" were retained, while juxtaposed epiphyseal cartilage was replaced, a pseudoepiphysis formed. There were three basic patterns of pseudoepiphysis formation. First, a central osseous bridge extended from the metaphysis across the "physis" into the epiphysis and subsequently expanded to create a mushroom-like osseous structure. In the second pattern a peripheral osseous bridge formed, creating either an osseous ring or an eccentric bridge between the metaphysis and the epiphysis. In the third pattern, multiple bridging occurred. In each situation the associated remnant "physis" lacked typical cell columns and was incapable of significantly contributing to the postnatal longitudinal growth of the involved bone. Pseudoepiphyses were well formed by 4-5 years and coalesced with the rest of the bone months of years before skeletal maturation was attained at the opposite epiphyseal end, which ossified in the typical pattern (i.e., formation of a secondary center de novo completely within the cartilaginous epiphysis). This process may also affect the development and appearance of ossification within the longitudinal epiphyseal bracket ("delta phalanx").

Adolescent↗

The impact of economic progress and modernization in medicine on the ossification of hand and wrist.

One of the main criteria used for age estimations of young living subjects is the developmental status of the ossification of hand bones. The impact of economic progress and modernization in medicine on ossification rates in a given population still requires further clarification. We selected 36 samples from literature for which the ossification status had been determined with the Greulich-Pyle method and analyzed specific economic data (per capita income) and demographic data (life expectancy at birth) as parameters of modernization. To describe the influence of these parameters on the rate of ossification, we performed a regression analysis and found that a relatively high level of economic progress and modernization in medicine coincides with high ossification rates, while relatively low modernization seems to delay ossification. When performing age estimations, the expert opinion should therefore pay attention to the issue of different modernization levels.

Age Determination by Skeleton↗

Assessment of the three-dimensional relationship of the ossific nuclei and cartilaginous anlagen in congenital clubfoot by 3-D MRI.

PURPOSE: Radiographic measurement is the usual method used to objectively determine the extent of a congenital clubfoot deformity. Although radiographs have been used clinically to estimate the size and location of tarsal bones through measurements of the ossific nuclei, it is not clear to what extent these relationships are actually reflected in these measurements. So, we used a 3-D MRI system that could more objectively estimate sizes and positional relationships. MATERIAL AND METHOD: We evaluated 5 patients with unilateral congenital clubfoot deformity. Magnetic resonance imaging was performed of both feet using 1.5-T magnet. Based on the resulting magnetic resonance imaging volume data, a three-dimensional surface bone model was reconstructed by the Marching Cubes method. We used this model to perform a comparative analysis of the volume and volume ratio of each cartilaginous anlage and ossific nucleus, the length of the talus and the calcaneus, and the position of the center of gravity of ossific nuclei within the cartilaginous anlagen. We measured the relationship between the ossific nuclei and cartilaginous anlagen in the talus and calcaneus of patients with unilateral clubfoot deformity. RESULT: In clubfeet talus volume was reduced by 20.1% and calcaneal volume was reduced by 15.7%. Furthermore, the volume of the talar ossific nucleus was reduced by 42.6% and that of the calcaneal ossific nucleus was reduced by 12.1%. The length of the clubfoot talus was 8.2% shorter than normal, and that of the calcaneus was 4.8% shorter. CONCLUSION: The assessment technique presented herein was shown to be useful in ascertaining the various pathological characteristics associated with clubfoot.

Calcaneus↗

The normal development of Mongolian gerbil foetuses and, in particular, the timing and sequence of the appearance of ossification centres.

To elucidate the normal development and growth of Mongolian gerbils, the timing and sequence of the appearance of ossification centres within foetuses were investigated. Average foetus body weight and tail length on the 15th day of pregnancy were found to be 0.042 g and 6.2 mm, respectively. For the 25th day of pregnancy, these measurements were 2.601 g and 29.4 mm, respectively. The body weight and tail length of foetuses increased significantly from the 20th day of pregnancy. Also, the first ossification centre of Mongolian gerbil foetuses appeared in the clavicle at the 17th day of pregnancy. The order in which ossification centres appeared in Mongolian gerbils resembles the pattern for rats and mice, except in some areas of the skull. Except for the clavicle, in which ossification centres appeared rather early, most ossification centres appeared in the last quarter of pregnancy. These results suggest that Mongolian gerbil foetal development is near completion by the last gestational stage. Also, ossification centres appear sooner in the skull and nasal bones than in other rodents.

Animals↗

The surgical treatment of established congenital dislocation of the hip: results of surgery after planned delayed intervention following the appearance of the capital femoral ossific nucleus.

It has been proposed that the presence of the capital femoral ossific nucleus confers protection against ischemic injury or avascular necrosis (AVN) at the time of reduction of a congenitally dislocated hip. The current literature is contradictory. A prospective study was undertaken of the clinical and radiologic outcomes following closed or open reduction. Fifty hips were included in the study. These cases had presented late or had failed conservative treatment. In 28 hips treatment was intentionally delayed until the appearance of the ossific nucleus (but not beyond 13 months) and in 22 the ossific nucleus was present at clinical presentation. Six hips reached the age of 13 months without an ossific nucleus appearing and progressed to treatment. The significant AVN rate (more than grade 1) was 7% for closed reduction and 14% for open. However, the amended rate if hips were excluded that had failed Pavlik harness treatment was 0.0% and 9%, respectively (4% overall). Further surgical procedures were necessary in 57% of hips undergoing closed reduction and 41% after open, which compares favorably with other series. The authors conclude that the presence of the ossific nucleus is an important factor in the prevention of AVN, particularly after late closed reduction. Intentional delay in the timing of surgery does not condemn a hip to open surgery, but there is a comparable rate of secondary procedures becoming necessary, particularly after closed reduction. A simultaneous pelvic procedure may be appropriate after late closed reduction. The delayed strategy to await the appearance of the ossific nucleus for previously untreated dislocation allows a simple treatment algorithm to be employed that produces good clinical and radiologic outcomes.

Female↗

Sex-difference in the ossification rate of the appendicular skeleton in Capra pyrenaica Schinz, 1838, and its utility in the sex identification of long bones.

The main goal of our work is to quantify differences in the rate of ossification in post-cranial Iberian ibex skeletons, related to sex. Another objective is to improve criteria for assessing the sex of post-cranial bones by combining the degree of ossification of the distal epiphysis and biometrical data. Forty Capra pyrenaica skeletons were examined in order to determine the degree of ossification by means of an Ossification Index. Our results evidence that sexual differences in the rate of ossification become visible at 6 months of age. On average, females complete their bone development 2 years before males do. Finally, by means of lineal classification functions which take into account both biometrical and anatomical criteria, we can achieve, in average, a 95.5% of correct sex discrimination within a sample consisting of ibex metacarpi and metatarsi from individuals aging from <1 to 12 years. Therefore, we conclude that the rhythm of ossification in the post-cranial skeleton of C. pyrenaica may be used as a criterion for assessing the sex of skeletal remains and could be applicable to other dimorphic ungulates. Nevertheless, the results obtained for specimens belonging to a particular population may have limited application to other populations with different medium sizes and living at particular densities within habitats with variable quality.

Animals↗

Schizophrenic psychosis with a tendency of systemic ossification.

We report here a case of schizophrenic psychosis with a tendency of systemic ossification. Upon further examinations, she exhibited ossification of the spinal ligament (diffuse idiopathic skeletal hyperostosis, DISH) resulting from a coappearance of ossification of the posterior longitudinal ligament (OPLL), ossification of the yellow ligament (OYL) and ankylosing spinal hyperostosis (ASH). There have been a very few reports where a tendency of hyperostosis was observed for ossification of the spinal ligaments such as OPLL, OYL and ASH. In addition, she exhibited hyperostosis frontalis interna (HFI). It appears in this case that both DISH and HFI resulted from similar ossification and exhibited respective clinical symptoms. Although it is thought that these diseases resulted from some metabolic abnormality, no abnormality was detected.

Female↗

Relationship between ossification of the cartilages of the foot and conformation and radiographic measurements of the front feet in Finnhorses.

One hundred Finnhorse cadaver front feet were measured and examined both radiographically and visually to report the incidence of various foot problems and their relationship to ossification of the cartilages of the foot. Ossification extending above the proximal border of the navicular bone and/or separate centres of ossification were found in 36 feet, and the lateral cartilages showed more ossification than the medial cartilages. The feet were generally broad with well developed frogs, but the long toe-low heel syndrome was a relatively common finding. Ossification of the cartilages correlated with the length of the heels but was not related to any clinically significant foot abnormalities such as contracted or under-run heels or signs of unequal weightbearing. Ossification of the cartilages did not seem to be either the cause or the result of general conformational adaptations of the front feet.

Animals↗

Cyclic GMP-dependent protein kinase II plays a critical role in C-type natriuretic peptide-mediated endochondral ossification.

Longitudinal bone growth is determined by endochondral ossification at the growth plate, which is located at both ends of long bones and vertebrae, and involves many systemic hormones and local regulators. C-type natriuretic peptide (CNP), a third member of the natriuretic peptide family, occurs at the growth plate and acts locally as a positive regulator of endochondral ossification through the intracellular accumulation of cyclic GMP (cGMP). The increase in cGMP concentrations is known to activate different signaling mediators, such as cyclic nucleotide phosphodiesterases, cGMP-regulated ion channels, and cGMP-dependent protein kinases (cGKs). The type II cGK (cGKII)-deficient mice (Prkg2(-/-) mice) develop dwarfism as a result of impaired endochondral ossification, suggesting that cGKII is important for the CNP-mediated endochondral ossification. However, given that Prkg2(-/-) mice differ from CNP-deficient mice (Nppc(-/-) mice) in the growth plate histology, which downstream mediator(s) of cGMP play key roles in the process is still an enigma. Here we show that targeted expression of CNP in the growth plate chondrocytes fails to rescue the skeletal defect of Prkg2(-/-) mice. Using cultured fetal mouse tibias, an in vitro model system of endochondral ossification, we also demonstrated that CNP cannot increase the longitudinal bone growth, and chondrocytic proliferation and hypertrophy, and cartilage matrix synthesis in Prkg2(-/-) mice. This study provides in vivo and in vitro genetic evidence that cGKII plays a critical role in CNP-mediated endochondral ossification.

Animals↗

Ossification process and lumbar spine morphology in the prenatal period.

BACKGROUND: Developmental abnormalities are the causes of numerous pathologies affecting the lumbar segment of the vertebral column. The aim of our study was metrologic assessment and analysis of lumbar vertebral column angioarchitecture during fetal life with particular emphasis on the description of vasculature of ossification centers of vertebral arches and bodies. MATERIAL/METHODS: The study was carried out on 30 fetuses with crown-rump length range of 31-180 mm. Vasculature of the ossification centers was studied using Pickworth's method and computed image analysis techniques in Imtron and Scion for Windows 2001 systems. The analysis involved the use of filters, binarization, linear and non-linear transformations. The assessment of morphology of lumbar spine structural elements was based on detailed measurements and statistical analysis of results. RESULTS: The analysis of vascular system of the ossification centers revealed the presence of numerous sinuses of various morphology. Their long axes were oriented in accordance with the directions of growth. The vasculature of the vertebral arch and body centers was characterized by a laminar structure. Centrally located sinuses and arteriovenous plexuses were covered by disseminated complexes of small blood vessels forming a cortex. The ossification centers were usually supplied with blood from other sources than cartilaginous elements. The analysis of metrological data demonstrated a marked domination of the L2 vertebra. CONCLUSIONS: Ossification of the lumbar vertebral column occurs in one rostro-caudal direction, The vasculature of the centers adjusts its morphology to the growth directions and not tendencies characterizing the object. The ossification process is characterized by marked autonomy and specific regulation mechanisms.

Crown-Rump Length↗

[Development of parietal bone based on ossification in the fetus].

Seventy-two parietal bones from human fetuses aged 15 to 29 weeks were studied. Three age groups were formed: I--15-19 weeks; II--19-24 weeks, III--25-29 weeks. The width and length of each parietal bone was determined. Microradiological studies were done with the Unipan 401 X-ray apparatus. Subsequently, pulverized bone for biochemical studies was prepared. Calcium, magnesium, zinc and iron content was determined using atomic spectrophotometry. Phosphates were measured with a colorimetric method and fluorine was assayed using an ion-selective electrode. The dimensions of fetal parietal bones changed almost linearly with age until the 20th week of life when a deceleration in the growth rate was noted (Tables 1, 2, 3, 4). This finding could be useful for estimation of fetal age when other methods are unavailable. The parietal bone is formed from one or two primary ossification centers lying in the same plane or one above the other (Figs. 1, 2, 3). Fusion of primary ossification centers was observed between 15 and 19 weeks of life (Fig. 3). Trabeculae radiate from the primary ossification center to the periphery of the parietal bone and take the form of a "coral reef" within the tuber (Figs. 2 and 5). Transverse ossification which was not coordinated with the growth of trabeculae from the primary ossification center was observed between week 15 and 19 of intrauterine life (Fig. 2). Fusion of peripheral trabeculae with those from the ossification center takes place at a later stage of osteogenesis (Fig. 4). Parietal bones of 29-week-old fetuses consisted of two layers of trabeculae and a distinct tuber, except for the sagittal and coronal sutures and the anterior fontanel, where a single layer of trabeculae was observed. Trabeculae were well developed and densely packed (Fig. 5). Analysis of the mineral composition of fetal parietal bones confirmed that the major elements are calcium and phosphorus and that their content increases with age (Figs. 6 and 7). Fluorine content differed widely and was unrelated to age (Fig. 9, Tab. 1). The importance of fluorine in the process of mineralization of parietal bones requires further study. Magnesium content increased with age (Fig. 8) and did not correlate with calcium or phosphorus. Apparently, these elements play different roles in the process of mineralization. The content of zinc and iron, two labile components of bone, decreased with age (Figs. 10 and 11). Some of these changes could have taken place during storage of the bones.

Calcium↗

The effects of piezoelectric poly-L-lactic acid films in promoting ossification in vivo.

Uniaxially drawn poly-L-lactic acid (PLLA) films with piezoelectric properties were inserted onto the periosteum of rabbit tibiae, and the effect of the films in promoting ossification was investigated. We also evaluated the optimum method for PLLA film insertion to promote ossification, by comparing three different types of PLLA films which differed from each other in terms of the direction of their molecular orientation. Furthermore, the course of ossification following the film insertion was observed histologically. Drawn PLLA films promoted ossification to a greater extent than undrawn PLLA film. The effect of drawn PLLA films in promoting ossification was greatest when a shearing stress was applied at 45 degrees to the axis of orientation. The newly formed osteoid was observed at 1 week, and matured over 6 to 8 weeks following insertion. The insertion of piezoelectric PLLA films can promote ossification through their piezoelectric effect, and this seems to be clinically applicable.

Animals↗

Ossification of the calcaneus in the normal fetal foot and in clubfoot.

The ossification of the fetal calcaneus was studied in a series of plastinated sections of 44 normal feet and three clubfeet. The results documented a precise sequence of perichondral and endochondral ossification in the normal calcaneus characterized by ossification grooves and associated cartilage canals. Within the clubfoot calcaneus, the coordination of perichondral and endochondral ossification is disturbed, ossification grooves and associated cartilage canals are not found in regular positions, and the process of endochondral ossification obviously is disturbed. The findings in the clubfoot specimens point to grave irregularities of the extracellular matrix within or outside the calcaneus.

Calcaneus↗

High body mass index after age 20 and diabetes mellitus are independent risk factors for ossification of the posterior longitudinal ligament of the spine in Japanese subjects: a case-control study in multiple hospitals.

STUDY DESIGN: A sex- and age-matched case-control study was carried out. OBJECTIVES: To facilitate early prediction, prevention, and treatment of ossification of the posterior longitudinal ligament of the spine, the authors analyzed histories of past illness, past body mass indexes, and body pliableness by nature, adjusted for other factors considered to be risk factors. SUMMARY OF BACKGROUND DATA: The cause of ossification of the posterior longitudinal ligament of the spine has not yet been elucidated in detail, although many possible causative factors have been suggested, including gender, diabetes mellitus, trauma, hormonal imbalance, and dietary habits. METHODS: A self-administered questionnaire was obtained from 69 patients with ossification of the posterior longitudinal ligament of the spine and 138 sex- and age-matched control participants who were free of spinal disease, randomly selected from participants in a health checkup in a town. After univariate analysis, a stepwise method was applied to select significant factors in multivariate analysis. RESULTS: A multivariate analysis revealed that the following three indicators were independent potent risk factors for ossification of the posterior longitudinal ligament of the spine: history of diabetes mellitus, history of lumbago, and maximum body mass index before manifestation > or =25, after adjustment for other possible lifestyle risk factors. CONCLUSION: Excessive weight gain between 20 and 40 years of age, diabetes mellitus, and lumbago were found to be independent risk factors for ossification of the posterior longitudinal ligament of the spine. Follow-up studies, including the addition of hospital-based control participants and analysis of genetic polymorphisms, will be needed in the future.

Adult↗

Complete ossification of the human falx cerebri.

During the routine dissection of the head and neck of an adult male cadaver complete ossification of the falx cerebri was noted. Anomalous ossification was not found in any other dural component or other parts of the body. The brain appeared grossly normal. Histological sections showed normal ossification processes involving the falx cerebri. In addition, rare scattered deposits of metastatic poorly differentiated carcinoma within the trabecular spaces were seen. Reports of isolated islands of ossification involving primarily the most anterior part of the falx cerebri in man are found in the literature. Our case report represents to our knowledge, the first report of complete ossification of this dural partition. Whether this is simply an anomalous configuration or due to the few metastatic cells found within this region remains unclear.

Aged↗

Free radical scavengers are more effective than indomethacin in the prevention of experimentally induced heterotopic ossification.

The pathogenesis of heterotopic ossification is still unclear and the preventive therapies are usually insufficient. The present study was designed to investigate the possible preventive effect of free radical scavengers on the development of experimentally induced heterotopic ossification in a rabbit model and to compare free radical scavengers with indomethacin to determine whether they act synergistically. A standard immobilization-manipulation model was used to induce heterotopic ossification in the hind legs of 40 1-year-old female New Zealand albino rabbits. The animals were divided into four groups and received daily either placebo, a free radical scavenger cocktail [allopurinol and N-acetylcysteine (A/A)], indomethacin or the combination of A/A and indomethacin in a randomized double-blind fashion. Every 4 days an X-ray was taken and the thickness and length of new bone formation was measured at the thigh. A marked statistically significant difference was found between the four groups. In the groups that received A/A, either alone or combined with indomethacin, an inhibition of bone growth, both in thickness and in length was demonstrated. In this experimental model free radical scavengers had a superior inhibitory effect on heterotopic ossification than indomethacin. Free radicals could play an important role in the pathogenesis of heterotopic ossification.

Acetylcysteine↗

[Prospective study on the prevention of heterotopic ossification after total hip replacement. Non-steroidal anti-inflammatory agents versus radiation therapy].

PURPOSE: Two prospective trials were undertaken to assess the comparative efficacy of early postoperative irradiation with different radiation doses versus the postoperative use of nonsteroidal antiinflammatory drugs (NSAID) for prevention of heterotopic ossification (HO) following prothetic total hip replacement (THP). PATIENTS AND METHOD: Between 1992 and 1994 585 patients received THP. These patients were randomed in two longitudinal studies each with 3 treatment arms comparing postoperative irradiation with 4 x 3 Gy (101 patients), 1 x 5 Gy (93 patients), 1 x 7 Gy (95 patients) and the postoperative use of the NSAID indometacin for 7 days (113 patients) respectively for 14 days (90 patients) und acetyl salicyl acid (ASS) for 14 days (93 patients). Heterotopic ossification was scored according to the Brooker grading system. One hundred patients receiving no prophylactic therapy after total hip arthroplasty between 1988 and 1992 were analysed and defined as historical control group. RESULTS: Incidence of heterotopic ossification was 5% in the 4 x 3 Gy group (Brooker grade I 5%, grade II 0%, grade III 0%), 30.5% in the 1 x 5 Gy group (Brooker grade I 24.7%, grade II 4.1%, grade III 1.0%) and 10.5% in the 1 x 7 Gy group (Brooker grade I 10.5%, grade II 0%, grade III 0%). 15.9% of the indometacin-7 days-group developed heterotopic ossification (Brooker grade I 8%, grade II 6.2%, grade III 1.7%, grade IV 0%), 12.2% of the indometacin-14 days-group (Brooker grade I 8.9%, grade II 2.2%, grade III 1.1%) and 37.5% of the ASS-group (Brooker grade I 27.9%, grade II 4.3%, grade III 5.3%). The lowest incidence of heterotopic ossification was found for the 4 xx 3 Gy and the 1 x 7 Gy group, but no significant difference between these two different treatments was observed. CONCLUSION: Prophylactic irradiation of the operative site after hip replacement is more effective than the use of NSAID. Because no significant difference between the fractionated ingle dose irradiation was found and the latter is more comfortable for patients and more economical, irradiation with single 7 Gy fraction should be preferred.

Aged↗

[Ossification in lung metastases of primary colorectal adenocarcinomas].

Ossification of lung tissue is a rare phenomenon, which can be found in association with carcinoid tumors of the lung or pulmonary blastomas. Very rarely, ossifications are observed in lung metastases of extrathoracal epithelial tumors. In these cases, the most probable primary focus is a colorectal adenocarcinoma. Our question was, whether ossifications in lung metastases are pathognomonic for colorectal adenocarcinomas and how they can be pathogenetically arranged. A total of 15 lung metastases with ossifications from 5 patients suffering from a colorectal adenocarcinoma were examined by means of immunohistochemistry. Thereby, we found an increased expression of bone morphogenetic protein (BMP) 2/4 and osteonectin in tumor cells, as well as an increased stromatogenous expression of collagen type III. We conclude that there is strong evidence of a primary colorectal adenocarcinoma when ossifications in lung metastases are found. In these cases, a common metastatic spread of tumor cells and tumor stroma seems to be probable.

Adenocarcinoma↗