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PubMed1993

Heterotopic ossification. The utility of osteocalcin in diagnosis and management.

The status of 12 patients after severe traumatic brain injury was investigated to determine the clinical significance of serum osteocalcin levels during the active phase of neurogenic heterotopic ossification. The diagnosis of heterotopic ossification was confirmed on the basis of radiologic findings. The mean interval between the initial injury and diagnosis of heterotopic ossification was 29 weeks. At the time of diagnosis, serum osteocalcin and total alkaline phosphatase levels were determined along with 24-hour urinary calcium and hydroxyproline excretion. The mean serum osteocalcin level was normal at 4.3 ng/ml (normal range 1.6-6.6 ng/ml) in contrast to the elevated mean values for serum alkaline phosphatase (mean = 173 units/liter; normal range 0-105 units/liter) and urinary hydroxyproline concentration (mean = 39.6 mg/24 h; normal range 7-25 mg/24 hr). Only 17% of the subjects demonstrated an elevated serum osteocalcin level, whereas 58% of the patients had an elevated serum alkaline phosphatase level. Urinary calcium excretion and hydroxyproline excretion were elevated in 33% and 70% of subjects, respectively. These data did not reveal a significant correlation between serum osteocalcin and serum alkaline phosphatase, urinary calcium excretion or urinary hydroxyproline at the time of diagnosis or in serial measurements. Therefore, serum osteocalcin is not a valuable adjunct in confirming the diagnosis of neurogenic heterotopic ossification once the diagnosis has been suggested on the basis of clinical findings and it does not appear to play a role in assessing the maturation of heterotopic ossification.

Adolescent↗
PubMed1995

Bone mineral density of the lumbar spine in patients with ossification of the posterior longitudinal ligament of the cervical spine.

Bone mineral density (BMD) of the lumbar spine in patients with ossification of the posterior longitudinal ligaments of the cervical spine (OPLL) was measured to elucidate the relation of spinal ossification with systemic hyperostotic condition. BMD in the lateral projection had a statistically significant correlation with that in the anteroposterior projection, and the former was considered to reflect the condition more accurately than was the latter, which may include the ossified spinal ligaments. BMD of patients with continuous and mixed types of OPLL was higher than that of those with the segmental type. Patients with OPLL and ossification of the other spinal ligaments had higher BMDs than did those without ossification. These results suggest that the BMD of the lumbar spine may reflect the systemic hyperostotic tendency and advancement of the ossification.

Absorptiometry, Photon↗
PubMed1996

[Eight days of naproxen therapy can prevent heterotopic ossification after total hip alloplasty].

The effect of one week of treatment with naproxen on the formation of heterotopic ossification after cemented total hip arthroplasty was studied in a prospective trial. Twenty-seven patients received 500 mg naproxen twice daily for seven days postoperatively. The medication was started on the morning of the operation. The results were compared to a control group of 23 patients from a previous study who had not received any kind of nonsteroidal anti-inflammatory drug. All radiographs were randomly mixed and patient identification was blinded. Three months after the operation 12/23 patients in the control group and 3/27 in the naproxen-treated group had developed heterotopic ossification. One year after the operation 4/27 in the naproxen-treated group and 12/23 in the control group had heterotopic ossification (p < 0.05). Three patients in the control group and none in the naproxen-treated group developed severe ossification. It is concluded that naproxen given for one week can decrease the incidence of heterotopic ossification after total hip arthroplasty.

Aged↗
PubMed1995

Clinical effect of etidronate disodium (EHDP) on heterotopic ossification following total hip arthroplasty.

We investigated the status of the development of heterotopic ossification and compared the frequency of heterotopic ossification in the EHDP group with that in the untreated (control) group to evaluate the efficacy and safety of EHDP. Seventy-seven patients who had undergone total hip arthroplasty or femoral head prosthesis for the treatment of osteoarthritis and femoral neck fracture were enrolled in the study. Heterotopic ossification surrounding the hip joint was evaluated according to the roentgenographic classification. In the control group, heterotopic ossification was found in 10 patients (20%) during the period, while in the EHDP group, it was found in one patient (3.7%) during the treatment period after the operation. Gastrointestinal disorder, in one case only was a side effect observed during EHDP treatment. It was revealed that EHDP inhibits heterotopic ossification following total hip replacement in patients with osteoarthritis.

Adult↗
PubMedDate not supplied

Expression of decorin mRNA in the skin of patients with ossification of the posterior longitudinal ligament.

Ossification of the posterior longitudinal ligament (OPLL) is an intractable disease developing into severe myelopathy and often accompanied by ossification of several other spinal ligaments and articular ligaments. Therefore, it is highly probable that predisposition to systemic ossification underlies the onset of this disease. Terayama et al(1981) reported that the nuchal skin of OPLL patients tended to be tougher than that of healthy individuals. Decorin is a component of the extracellular matrix which antagonistically regulates the action of Transforming growth factor-beta (TGF-beta). Imamura et al(1995) demonstrated immunohistochemically that decorin increased in the epidermis of the nuchal skin of OPLL patients. This suggests an abnormal expression of the extracellular matrix in the skin of OPLL patients. In the present study, in situ hybridization with non-radioactive synthetic oligodeoxynucleotide probes revealed an enhanced expression of decorin mRNA in the epidermal keratinocytes of OPLL patients. The increased expression of decorin mRNA in the epidermis of OPLL patients may be interpreted as reflecting abnormalities of the matrix associated with ossification of the ligaments. Studies on the role of decorin in ossification will contribute to clarification of the pathophysiology and pathogenesis of OPLL.

Adult↗
PubMed1996

Characteristics and mechanism of the ossification of posterior longitudinal ligament in the tip-toe walking Yoshimura (twy) mouse.

To elucidate the mechanism of ossification of the posterior longitudinal ligament (OPLL), we examined the serial changes in the intervertebral disc of tip-toe walking Yoshimura (twy) mouse. At the age of 6 weeks, the volume of the nucleus pulposus increased in all intervertebral discs causing anterior and posterior herniation. Secondary to this herniation, the cartilagineous tissue of the annulus fibrosus was disrupted and showed regenerative proliferation with PCNA-positive cartilagineous cells. These cells were S-100 positive and the matrix was positive for chondroitin-4-sulfate proteoglycan, indicating the development of calcification. At the age of 15 weeks, the regenerative cartilagineous tissue of the annulus fibrosus reached the posterior longitudinal ligament together with neovascularization and appearance of PCNA-positive proliferating primitive mesenchymal cells. These cells were considered to be osteoblasts since they were positive for alkaline phosphatase and the matrix contained type I collagen. Using electron microscopic X-ray analysis, vesicles present in the matrix of regenerative cartilagineous cells of the annulus fibrosus were confirmed to contain calcium phosphate crystals, also indicating the development of calcification. In conclusion, our serial analysis indicates that ossification of posterior longitudinal ligament in twy mouse was triggered by enlargement of the nucleus pulposus followed by herniation, disruption and regenerative proliferation of annulus fibrosus cartilagineous tissues. Enchondral ossification of the new annulus fibrosus cartilagineous cells and membraneous ossification by primitive osteoblasts proceed to the final ossification of the posterior longitudinal ligaments.

Alkaline Phosphatase↗
PubMed1996

Penetrating trauma secondary to heterotopic ossification in a laparatomy scar: a case report.

Heterotopic ossification is a common complication of numerous procedures, including abdominal operation, but traumatic perforation by such ossification is extremely rare. A 45-year-old man suffered traumatic perforation of the jejunum by ossification in a laparotomy scar. The diagnosis was made only at operation. The calcified mass was completely excised and the patient made a smooth recovery. The authors caution that the ossification may recur, and they recommend that such ossifications be removed electively if they are symptomatic or if their morphology is such that any viscera are at risk of perforation.

Cicatrix↗
PubMed1997

Multifocal heterotopic ossification in a patient with sickle cell disease: a case report.

A patient had a sickle cell crisis and developed heterotopic ossification of multiple joints. Many disease entities have been associated with heterotopic ossification; however, heterotopic ossification has rarely, if ever, been associated with sickle cell disease. Only 10% of patients with heterotopic ossification develop ankylosis of their joints. This patient developed ankylosis of several joints. Surgical excision of the periarticular heterotopic ossification allowed full passive motion of the involved joints. After extensive rehabilitation, the patient could perform all activities of daily living and ambulate comfortably without devices.

Activities of Daily Living↗
PubMed1998

Pseudomalignant heterotopic ossification.

Pseudomalignant heterotopic ossification is a rare, self limited connective tissue disorder of unknown origin that may occur atypically during childhood and can simulate either soft tissue sarcoma or fibrodysplasia ossificans progressiva. A complex constellation of diagnostic features usually enable the differentiation of pseudomalignant heterotopic ossification from extraosseous osteosarcoma and fibrodysplasia ossificans progressiva during a time span of approximately 8 to 12 weeks. Orthopaedic surgeons who treat children with connective tissue tumors should be familiar with pseudomalignant heterotopic ossification and its differential diagnosis. The occasional mild and variable expression of fibrodysplasia ossificans progressiva rarely may make it more difficult to distinguish from pseudomalignant heterotopic ossification. It is possible that pseudomalignant heterotopic ossification is a form fruste of fibrodysplasia ossificans progressiva.

Child↗
PubMed1978

Ectopic ossification after hip arthroplasty.

The incidence of radiographically visible ectopic ossification around the hip joint was redorded in 145 hip joints of 132 patients treated by endoprosthetic replacement. There were 56 total hip replacements with a McKee-Farrar and 39 with a Brunswik type of endoprosthesis; in a further 50 hips the femoral head was replaced with a Moore or Thompson prosthesis. An identical antero-lateral surgical approach was used in all, without detachment of the greater torchanter. The patients were re-examined 3, 6, and12 months after the operation. The extent of ectopic ossification was graded from 0 to III and correlated with pain and with the function and mobility of the operated hip. Ectopic ossification of varied extent was recorded in 37 % after total hip replacement and in 38 % after replacement of the femoral head. Of these ossifications 95 % were recognizable within 3 months; they did not increase in size, but often in density during the following months. One case of bony ankylosis was noted. Ectopic ossification of slight (grade I) to moderate (grade II) degree did not cause pain or affect the function of the operated hip, but reduced the mobility of the affected hip. The difference in mobility between grade I and grade II was significant (p less than 0.05), and between grade 0 and grade II highly significant (p less than 0.001).

Aged↗
PubMed1999

Computer model of endochondral growth and ossification in long bones: biological and mechanobiological influences.

Endochondral growth and ossification, the processes by which cartilage increases in size and is replaced by bone, are affected by biological factors such as intrinsic genetic makeup and systemic chemical agents. In addition, these processes are affected by epigenetic mechanical factors: they may be accelerated in regions of intermittent high shear stress and decelerated in regions of intermittent high hydrostatic pressure. Previous models of bone development have not incorporated both biological and mechanobiological influences on endochondral growth and ossification. We have implemented a finite element analysis to model a developing bone rudiment from 8 weeks of gestational development to approximately 2 years after birth. As a function of time, we calculated a maturity index that reflects the progression of a region of cartilage through the endochondral ossification sequence of proliferation, hypertrophy, mineralization, and replacement by bone. We calculated a specific growth rate for each region of cartilage and estimated overall longitudinal growth of the rudiment. Regions of cartilage replaced by bone were remodeled. The results from the maturity index can be compared with distributions of proliferative, hypertrophic, and mineralized cartilage seen on histology at various stages in development. The results of the simulation predicted prenatal and postnatal developmental events, including formation of a secondary ossific nucleus, a layer of articular cartilage, and a growth plate. Our results demonstrate the necessity to include biological and mechanobiological influences when endochondral growth and ossification are considered.

Animals↗
PubMed2003

Ossification timing of sacral vertebrae by ultrasound in the mid-second trimester of pregnancy.

OBJECTIVES: The aim of the study was to establish the ossification timing of sacral vertebrae by ultrasonography in the second trimester of pregnancy, for the diagnosis of caudal regression syndrome with isolated sacral agenesis. METHODS: The study was carried out on 77 normal single pregnancies, at gestational ages ranging from 15 to 21 weeks, using high-resolution transabdominal echography. The sacral region was visualized in a coronal plane, when the fetus was in anterodorsal position. The level of ossification of sacral vertebrae (S1 to S5) at each gestational age was recorded. Each sacral region was examined three times by the same observer and the nucleus was considered as present when it was visualized at least two times out of three. Blind assessment was performed three times by a second observer, who was not present at the previous examination, for interobserver and intraobserver error analysis. RESULTS: Interobserver and intraobserver error calculation demonstrated the reproducibility of the method. Concordance between the two observers as evaluated by Cohen Kappa index was 0.77 (C.I. 95%, 0.69-0.85).S1 ossification nuclei were visualized in all fetuses at 15 weeks and S2 nucleus was found in all fetuses within 17 weeks. S3 nucleus was detected in 45% of fetuses by the beginning of the 16th week. S4 was visualized in 55% of the cases at 18 weeks and progressively in a higher percentage of cases during the following weeks of gestation. CONCLUSION: The data obtained showed that the sequence of development of sacral region ossification was related to gestational age. This observation allows clinicians to accurately exclude isolated sacral agenesis at 16 to 17 weeks of gestation, when the S1-S2 ossification nuclei are visualized. This opportunity may be of particular value in the offspring of diabetic mothers.

Adult↗
PubMed2000

Ossification centers of human femur.

The purpose of the present work was to investigate the appearance of ossification centers in human femur by Dual-energy X-ray Absorptiometry (DXA), comparing densitometric data with morphogenetic events. Posteroanterior scans were performed on 31 dried femora (from 11.5 weeks of conceptual age to 1 year of postnatal life) by a Hologic QDR 1000 X-ray densitometer with Ultra-Hi-Resolution software. The results were expressed as bone mineral content (BMC, g) and bone mineral density (BMD, g/cm2). The analyses were performed on a rectangular area corresponding to the minimum width and total length of the shaft. The rectangular area was divided into five equal sections along its longitudinal axis, and BMC was calculated on each section. To distinguish the ossification area of the lesser trochanter with respect to the area of the greater trochanter, the proximal femoral end was divided into two portions, medial and lateral, respectively; BMC and BMD were calculated on each portion. Our data show that the ossification center of the femoral shaft extends prevalently in the proximal direction. A denser area was recognizable on the densitometric images at the level of the lesser trochanter from the 19th week of prenatal life and at the level of the greater trochanter at term. During development, the trends of BMC and BMD are similar in both trochanteric areas, but these parameters are fairly constantly higher at the level of the lesser trochanter. Our findings disagree with the data of the current literature on the postnatal appearance of the trochanteric ossification centers and suggest a different biomechanical interpretation of the secondary ossification of the femur.

Absorptiometry, Photon↗
PubMed2002

Calcaneal apophysitis: a quantitative radiographic evaluation of the secondary ossification center.

BACKGROUND: Calcaneal apophysitis in children is a self-limited condition that may interfere with walking and physical performance in sports, thus causing concern to the patient and parents. There is still controversy about the significance of the radiographic changes in children with heel pain, since the report of Sever in 1912. One of the reasons is that normal children may display a considerable variation in the radiographic aspects of the secondary ossification center of the calcaneus at different ages. METHODS: In this investigation, the developmental aspects of primary and secondary ossification centers of the calcaneus were studied in radiographs obtained from healthy boys and from boys with calcaneal apophysitis. The normal population comprised 392 children and adolescents ranging in age from 6 to 15 years. There were 69 individuals with calcaneal apophysitis ranging in age from 8 to 14 years. Lateral standard radiographs were obtained of both heels, and a copper step wedge was used as a calibration to determine bone density. The following parameters were analyzed on the plain films: time of appearance, fusion and number of fragments of the secondary nucleus, area and bone densitometry of the primary and secondary ossification centers of the calcaneus. RESULTS: In the normal population, the ossification of the secondary nucleus began at 7 years of age, and at 15 years of age, the nucleus was fused in all individuals. In the apophysitis group, the secondary ossification center was present and not fused in all individuals. Both secondary nuclei increased in size with age with no difference between the two groups. Regarding bone density, both the primary and secondary nuclei were less dense in the apophysitis group than their counterparts in the normal population. The most significant difference between the two populations referred to the degree of fragmentation, which was greater in the apophysitis group. CONCLUSION: Our data showed that the sclerotic aspect of the secondary nucleus of the calcaneus is a normal feature and, therefore, should not be used to establish the diagnosis of Sever's disease. The most consistent difference between the normal and apophysitis group was related to the more fragmented aspect of the secondary nucleus in the latter individuals, which may suggest a mechanical etiology for that condition.

Adolescent↗
PubMed2001

Ossification of tracheal cartilage in aged humans: a histological and immunohistochemical analysis.

Tracheal cartilage has been considered as permanent cartilage without endochondral ossification. We examined ossification of the tracheal cartilage in 25 adults (mean age 67.8 years; range 20-87 years; male:female = 17:8). Thirteen cases (52%) demonstrated ossification of the tracheal cartilage, accompanied by the formation of lamellar bones with fatty bone marrow. Ossification was observed at the lateral peripheral region of the tracheal cartilage, while vascular invasion into the cartilage was seen even where no ossification was present. Twenty-two cases (88%) showed marked hyalinization in the central region of the tracheal cartilage. Type II collagen was immunolocalized in the cartilage matrix, except for in the central hyalinized area, while type I collagen was immunolocalized around the perichondrium and ossified areas in the tracheal cartilage. Type X collagen immunolocalized on territorial matrices around the lacunae near the ossified regions. These results suggest that tracheal cartilage in aged humans frequently ossifies physiologically, and that aging promotes osteogenesis, even in permanent cartilage.

Adult↗
PubMed1976

Skeletal ossification and the adolescent growth spurt.

Fourteen ossification events in the hand and wrist were studied in relation to the age of peak growth velocity in body height in fifty-two boys and thirty-six girls. The subjects were aborigines enrolled in a longitudinal growth study. Peak growth velocity and the ossification events occurred in aborigines at about the same ages as in Caucasian children. The results indicate that the ossification events can be used by the orthodontist to assess a child's growth activity. The accelerative phase of the adolescent growth spurt is accompanied by epiphyseal widths reaching diaphyseal widths in the fingers and radius and by ossification of the pisiform and hamate Stage 1. Peak growth velocity occurs at about the time of epiphyseal capping in the fingers and radius and ossification of the sesamoid and hamate Stage 2. The decelerative phase of growth is indicated by epiphyseal union in the third finger, progressively from distal to proximal phalanges, and in the radius. The value of these indicators in orthodontic practice is discussed.

Adolescent↗
PubMed2005

Prenatal ethanol exposure has differential effects on fetal growth and skeletal ossification.

There is increasing evidence suggesting that the intrauterine environment may influence long-term bone health and the risk of developing osteoporosis in later life. Alcohol (ethanol) is one factor whose presence in the prenatal environment has long-term consequences for the offspring, including permanent growth retardation. Moreover, prenatal ethanol exposure retards both fetal and postnatal bone development. It is unknown if ethanol's effects on skeletal development result from generalized growth retardation or effects specific to skeletal development. Furthermore, the level of ethanol exposure required to produce skeletal effects is unknown. The objectives of this study were to determine (1) if ethanol exerts specific effects on fetal skeletal development that are independent from its effects on general growth, and (2) the level of prenatal ethanol exposure required to affect fetal growth and skeletal ossification. Rats were fed isocaloric diets with ethanol (15%, 25%, or 36% ethanol-derived calories (EDC), approximating low, moderate, and high exposure levels), or without ethanol (pair-fed, PF, or control, C groups), prior to and throughout 21 days of gestation. The degree of E-induced delay in development was determined by comparison of E fetuses on d21 gestation to C fetuses on d17-d21 gestation. Prenatal ethanol exposure at 36% EDC decreased fetal body weight, length, and skeletal ossification compared with PF and C fetuses on d21 gestation. Importantly, effects on ossification, but not body weight or length, were also seen at the more moderate dose of 25% EDC, and the number of bones affected and the severity of effects on ossification tended to increase with dose of ethanol. Comparison of E fetuses on d21 gestation with C fetuses from d17 to 21 gestation indicated that the ethanol-induced delay in development differed for weight and skeletal ossification, and was not uniform among skeletal sites. Taken together, these data suggest that prenatal ethanol exposure has effects on fetal skeletal development that are independent of those on overall fetal growth, and that these effects occur even at moderate levels of maternal drinking. Effects of prenatal ethanol exposure on fetal skeletal development could potentially increase the offspring's risk of osteoporosis later in life.

Animals↗
PubMed2004

Matrix remodeling during endochondral ossification.

Endochondral ossification, the process by which most of the skeleton is formed, is a powerful system for studying various aspects of the biological response to degraded extracellular matrix (ECM). In addition, the dependence of endochondral ossification upon neovascularization and continuous ECM remodeling provides a good model for studying the role of the matrix metalloproteases (MMPs) not only as simple effectors of ECM degradation but also as regulators of active signal-inducers for the initiation of endochondral ossification. The daunting task of elucidating their specific role during endochondral ossification has been facilitated by the development of mice deficient for various members of this family. Here, we discuss the ECM and its remodeling as one level of molecular regulation for the process of endochondral ossification, with special attention to the MMPs.

Animals↗