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The timing of ossification of the limb bones, and growth rates of various long bones of the fore and hind limbs of the prenatal and early postnatal laboratory mouse.

In order to study the pattern of ossification of the skeletal components of the fore and hind limb of the mouse, intact embryos were isolated between days (d) 15 and 19 of pregnancy (the morning of finding a vaginal plug is termed d 1 of pregnancy), and postnatal animals isolated on d 1 (newborns), 7 and 14 after birth. The total number of fore and hind limbs studied for each day of pregnancy or postnatal day for the bone growth study is given in parentheses: d 15 (2), d 16, 17, 18 and 19 of pregnancy (5 specimens for each of these days), d 1 (newborn), wk 1 and 2, postnatal (4 specimens analysed at each of these times), since only the right limbs were studied. For the study involving the time of first appearance of ossification centres, either the right or the left limb of each of these prenatal and postnatal specimens was analysed. All specimens were fixed in 80% ethanol, bulk-stained using alizarin and Alcian blue, in order to stain ossification centres and cartilage, respectively, and cleared. The limbs were then disarticulated from the axial skeleton at the sternoclavicular and sacroiliac joints to facilitate (1) the determination of the sequential pattern of ossification in the various cartilage primordia analysed, and (2) the analysis of the pattern of growth of the humerus, ulna, femur and tibia. The latter values were plotted graphically, and the individual growth rate of each of the long bones studied was then deduced and also plotted graphically. The findings demonstrated that, with the exception of the femur and ulna, all of the long bones studied had significantly different growth patterns. The time of appearance of the various centres of ossification in the skeletal elements studied proceeded in a similar order to that described by previous authors, though there was some discrepancy in the exact time of first appearance of certain ossification centres. Of particular interest was the somewhat unusual pattern of ossification of the first digits of both the fore and hind limb compared with that of the other digits. The data presented here provide useful baseline information on the normal sequential pattern of ossification in the fore and hind limb, and the characteristic growth pattern of the individual long bones of the limbs in this species.

Animals↗

A new look at the sequential development of elbow-ossification centers in children.

The pattern and sequence of ossification of the six secondary ossification centers around the elbow in the child were mainly derived from studies done >30 years ago. This series reexamined the sequence and pattern based on a cross-sectional study of the elbow radiographs of 1,577 Chinese children with elbow injuries; age range, from newborn to 17 years. The ratio of girls to boys was 1:2. Each child had a radiograph of the normal and the injured elbow giving a total of 3,154 radiographs. A percentile chart of ossification was constructed for each of the ossification centers in both sexes for easy reference. No differences in the timing and ossification pattern were found between the right and left elbow or between the normal and injured elbow in this study. The sequence of ossification in both boys and girls was found to be the same (i.e., the capitulum first, followed by the radial head, medial epicondyle, olecranon, trochlea, and last, the lateral epicondyle). The ages at which 50% of the girls were found to have positive radiologic ossification for each of these centers were ages 1, 5, 5, 9, 9, and 10 years, respectively. In boys, with the exception of the capitulum, an average delay of 2 years was found in each of the ossification centers, although the sequence remained similar.

Adolescent↗

Paravertebral ligamentous ossification: DISH, OPLL and OLF.

This is an overview of paravertebral ligamentous ossification based on our 5-year experience in ossification of posterior longitudinal ligament (109 cases) and ossification of ligamentum flavum (18 cases). Paravertebral ligamentous ossification is designated as the disorder caused by frequently coexisting ossification of paravertebral ligaments, DISH, OPLL, and OLF. The frequency of the occurrence of isolated ossification of PLL and OLF in Japan is still uncertain. DISH, which is not rare in Europe or North America, is frequently associated with ossification of the posterior aspect of the vertebral bodies, but it may be less symptomatic. The major cause of the probably higher incidence of symptomatic patients in Japan may be due to associated narrowing of the spinal canal.

Female↗

Parathyroid hormone-related protein in gastric cancers with heterotopic ossification.

BACKGROUND: Parathyroid hormone-related protein (PTHrP) has been regarded as one of the substances causing humoral hypercalcemia of malignancy. METHODS: The immunohistochemical localization of PTHrP was investigated in 33 cases of gastric cancer (4 with heterotopic ossification and 29 without heterotopic ossification) to clarify the role of PTHrP in heterotopic ossification by using the anti-PTHrP monoclonal antibody, 4B3. RESULTS: The four cases with heterotopic ossification showed positive staining at primary or metastatic sites, and in one case fibroblasts in the stroma surrounding the heterotopic ossifying foci also showed positive. On the other hand, of the 29 cases without heterotopic ossification, only 5 showed positive staining. CONCLUSIONS: The presence of PTHrP in ossifying gastric carcinomas at a relatively high rate indicates that PTHrP also might be related to heterotopic ossification associated with malignancies. It is speculated that PTHrP would contribute to heterotopic ossification by facilitating the process of mineralization.

Adenocarcinoma↗

Immunohistochemical characterization of the small proteoglycans decorin and proteoglycan-100 in heterotopic ossification.

Heterotopic ossification is a metabolically active process which shares several properties of orthotopic bone formation and, therefore, represents an excellent model for studying bone matrix components. Immunohistochemical methods were used to investigate the distribution pattern of the small proteoglycans decorin and proteoglycan-100 during different stages of heterotopic ossification of pressure sores of paraplegic patients. Decorin and proteoglycan-100 exhibited a substantially divergent distribution pattern. Decorin was detectable in the perivascular matrix of granulation tissue as well as in the stroma of heterotopic ossification. The ossification zone was stained most strongly. In contrast, proteoglycan-100 was predominantly detectable in fibroblasts and preosteoblasts in early areas of osteogenesis. In more mature forms of heterotopic ossification immunostaining was markedly reduced in osteoblasts and osteocytes and even absent in so-called bone-lining cells. However, at least some osteoclasts were strongly positive. These results suggest indicate that decorin and proteoglycan-100 are important components during the formal pathogenesis of heterotopic ossification. The expression of the small proteoglycans, especially of proteoglycan-100, correlates with different phases during heterotopic ossification, showing a maximum for proteoglycan-100 in matrix-forming cells in early phases of bone formation, but in osteoclasts in mature bone.

Bone and Bones↗

Ossification of Achilles tendon--report of three cases.

BACKGROUND: Ossification of the Achilles tendon is reportedly an unusual condition. The microscopic features of such ossifications have been not well documented. METHODS: We treated three patients with bilateral ossification of the Achilles tendon and examined the specimens microscopically. The patients were all male. Their ages ranged from 41 to 59 years with an average of 48 years. The chief complaint was pain in two cases and rupture of the Achilles tendon in one case. The ossification site was near the insertion in five feet and in the tendon body in one foot. They had no laboratory abnormalities. RESULTS: Removal was performed in two cases. Microscopic examination revealed no active inflammation of the ossified tendon. Lamellar bone formation with bone marrow continuous with the extensive cartilage metaplasia, namely enchondral ossification, and osteoid formation in the granulation tissue, namely intramembranous ossification, were observed. CONCLUSIONS: Judging from the heavy work and bilateral occurrence in the present cases, repetitive microtrauma to the Achilles tendon and some predisposition are implicated as causative factors in the ossification.

Achilles Tendon↗

The origin of osteoprogenitor cells responsible for heterotopic ossification following hip surgery: an animal model in the rabbit.

PURPOSE: To investigate the source of osteoprogenitor cells responsible for heterotopic ossification (HO) following total hip arthroplasty in an animal model. METHODS: New Zealand White (NZW) rabbits (n = 20) received a radiation treatment 24 h preoperatively to the hip joint of one hindquarter and to the femoral shaft of the contralateral side. Subjects underwent bilateral hip surgery 24 h after treatment. Subjects were euthanized and radiographed 4 months postoperatively. Heterotopic ossification was graded according to a modified Brooker scale. Mean grade, intra-observer reliability, and statistical significance (p < 0.05) were evaluated to compare the severity of heterotopic ossification between hindquarters treated with hip irradiation versus those treated with femoral shaft irradiation. RESULTS: The Fleiss Weighted Kappa Statistic indicated "almost perfect" (0.872) intra-rater reliability of radiographic heterotopic ossification grading. The average heterotopic ossification grade for the group receiving radiation to the hip was significantly greater than that for the group receiving radiation to the femoral shaft (2.575 versus 2.0, p < 0.02). CONCLUSION: Although both have some beneficial effect, our results demonstrate that irradiation of the femoral canal is significantly more effective than irradiation of the hip joint and abductor musculature for heterotopic ossification prophylaxis. This suggests that osteoprogenitor cells responsible for heterotopic ossification originate from both the hip abductors and the femoral canal, but the data provide indirect evidence that the femoral canal may be a more dominant source of these cells in the rabbit model.

Animals↗

[Heterotopic ossification in Guillain-Barré syndrome].

INTRODUCTION: Heterotopic ossification are frequent in central nervous disease, on the opposite just a few cases have been described in peripheral disorders. PURPOSE: To describe three cases of Guillain-Barré syndrome complicated by heterotopic ossification. METHODS: From the detailed case reports and a review of the literature. RESULTS: The authors report three cases of heterotopic ossification in Guillain-Barré syndrome. Each of them had serious symptom and had to go in intensive care. Two of them had encephalopathy. A patient had compression of ulnar nerve as complication of heterotopic ossification. In all cases the consequence of the heterotopic ossifications lead to a great functional handicap. DISCUSSION: Heterotopic ossification is a frequent complication in central neurologic lesions such spinal cord injury or brain injury. Just a few cases following peripheral nerve disorders have been reported. Serious neurologic deficit and encephalopathy may influence the apparition of heterotopic ossifications in patients suffering from Guillain-Barre syndrome. This possibility of complication must be known by the clinicians who should have a special attention to such patients.

Adult↗

Heterotopic ossification after total shoulder arthroplasty.

Fifty-eight primary ingrowth total shoulder arthroplasties, performed between 1989 and 1992, with a minimum of 2 years' radiographic and clinical follow-up (mean, 4.7 years), were reviewed to determine the frequency and clinical significance of heterotopic ossification after total shoulder arthroplasty. Fourteen of the 58 shoulders had radiographic evidence of heterotopic ossification: grade I (12 shoulders) and grade II (2 shoulders). Heterotopic ossification was present on the early postoperative radiographs (1-2 months) in 12 of the 14 shoulders. Among these 12 shoulders, there was no increase in the grade of ossification comparing the early postoperative radiographs with those obtained at a minimum of 2 years. There were no identifiable preoperative patient characteristics associated with the development of heterotopic ossification (P > .05). Range of motion, pain, and result rating were not statistically different comparing patients with and without heterotopic ossification (P > .05). The data from this study suggest that when heterotopic ossification develops after elective total shoulder arthroplasty, it is usually low grade, is present in the early postoperative period, is nonprogressive, and does not adversely affect the clinical results.

Arthroplasty, Replacement↗

[Prophylaxis of heterotopic ossification in hip revisions with 7 Gy single-dose radiation].

AIM OF STUDY: Radiation therapy is an established method for the prevention of heterotopic ossification. The aim of this study was to assess whether radiation therapy is also effective in revision arthroplasties. METHOD: 143 hips were irradiated with 7 Gy anterior-posterior applied single dose radiation, on one of the first four days after revision surgery. RESULTS: After an average follow-up of 18 months, 107 hips were evaluated radiographically using Brooker's criteria. In comparison to the immediate postoperative findings (26 % showed no heterotopic ossification, 66 % had Brooker I, 5 % Brooker II, and 3 % Brooker III), at final follow-up 19 % showed no heterotopic ossification, 66 % had Brooker I, and 7.5 % Brooker II and III. New ossification or an increase of one grade was found in 12 %, of two grades in 4 %. Grade 0 showed significantly more ossifications. Gender (p = 0.43), age (p = 0.43), the type of revision surgery (p = 0.36), the day of radiation (1st day vs. 2nd, 3rd, 4th day; p = 0.46) had no significant influence on this increase. There was no correlation between pain score and Brooker grades (p = 0.755). There was a significantly (p < 0.01) negative correlation (r = - 0.31) between the Brooker grades and flexion. CONCLUSION: Radiation therapy with 7 Gy single dose effectively prevents the new formation of heterotopic ossification or the progression of ossifications after revision surgery. To prevent a decrease in the range of motion due to HO after revision surgery, HO should be removed intraoperatively.

Adult↗

[Periarticular ossifications following implantation of cement-free total hip endoprostheses of the Zweymüller-Endler type].

Ectopic ossifications after 158 cementless implanted Total hip endoprostheses Type Zweymüller-Endler have been examined postoperatively within 12 months at the earliest. The rate of ossification was 39.9%. This range is higher than the mean range of cemented hip endoprostheses reported in the literature. The higher range of ossification is found in low grade ossification grade CA I. Severe ossification of grade CA III occurred only in a low percentage. The influence of various factors (as prophylaxis for thrombosis approach, duration of operation, sex, age, other diseases, complications) on the frequency of occurrence is examined. There was no significant result concerning these parameters. The main causes for ectopic ossification seem therefore to be dispositional and constitutional factors. Male patients under the age of fifty show ectopic ossification in the highest degree.

Adult↗

3-dimensional computed tomography of ossification of the spinal ligament.

Ossification of the posterior longitudinal ligament in the cervical spine was studied 3-dimensionally using computed tomography scans of 32 patients. The images produced were classified into 3 types based on the posterior configuration of the ossification: (1) plank shaped, (2) spindle shaped, or (3) rod shaped. Lesions with radiographically continuous and mixed type ossification on 3-dimensional computed tomography were plank shaped or spindle shaped. Rod shaped type lesions usually were radiographically segmented or showed some other type of ossification. The 3-dimensional computed tomography images change with the growth of ossification. Plank shaped type lesions appear to be the final result of ossification. Three-dimensional computed tomography scans of ossification of the longitudinal ligament are useful for decompressive surgery, providing valuable information regarding the site of concentration of compression of the spinal cord or nerve roots and the choice of surgical procedures.

Aged↗

Pathology of ossification of the posterior longitudinal ligament and ligamentum flavum.

Ossification takes place in the posterior longitudinal ligament and ligamentum flavum of the spine under certain conditions of unknown nature. Ossification of these ligaments has the following characteristics: (1) ectopic bone formation occurring within the spinal ligaments; (2) ossification accompanies ligamentous tissue hyperplasia and cell proliferation; (3) before ossification, fibrocartilaginous cell proliferation, calcification and tissue resorption with vascular ingrowth take place sequentially; (4) ossification of the ligament has a specific site of predilection and often occurs in combination with senile ankylosing vertebral hyperostosis (Forestier's disease) or diffuse idiopathic skeletal hyperostosis; and (5) ossification and symptom development are remarkably more frequent in the Japanese population. Recent studies revealed that bone morphogenetic proteins and transforming growth factor-beta played an important role in the matrix hyperplasia and ossification of the spinal ligament, and metabolic and genetic aberration often characterized patients suffering from this disorder.

Humans↗

Genetic study of ossification of the posterior longitudinal ligament in the cervical spine with human leukocyte antigen haplotype.

To evaluate the genetic background of ossification of the posterior longitudinal ligament, the relationship between the presence of absence of ossification and human leukocyte antigen haplotypes was studied in 33 families of patients with ossification of the posterior longitudinal ligament. The study revealed that human leukocyte antigen haplotypes formed certain types of clusters, and that some human leukocyte antigen haplotypes were very rare in the Japanese population, suggesting the involvement of human leukocyte antigen-linked factors in the pathogenesis of ossification of the posterior longitudinal ligament of the cervical spine. In the families of these patients, ossification of the posterior longitudinal ligament was demonstrated by radiography in 56% (10/18) of the siblings. Each of these siblings shared both human leukocyte antigen haplotypes with the patient. None of those who shared only one human leukocyte antigen haplotype with the patient had developed ossification of the posterior longitudinal ligament. From these findings, the presence of both pathogenic human leukocyte antigen haplotypes is considered to be necessary for the development of ossification of the posterior longitudinal ligament, and this genetic predisposition may be activated by multiple factors, including regressive degeneration due to aging and the environment.

Cervical Vertebrae↗

Long-term follow-up evaluation of surgery for ossification of the posterior longitudinal ligament.

STUDY DESIGN: We compared anterior and posterior surgery for cervical myelopathy resulting from ossification of the posterior longitudinal ligament. Surgical techniques, based on shape and distribution of ossification of the posterior longitudinal ligament, were divided into four technical phases. OBJECTIVES: Long-term follow-up data on anterior and posterior surgery were analyzed to establish guidelines for surgical treatment. SUMMARY OF BACKGROUND DATA: Comparison of anterior and posterior surgery is difficult because surgical techniques, ossification of the posterior longitudinal ligament shape classifications, and surgical criteria varied. No reports have accurately assessed spinal changes over a 10-year follow-up period. METHODS: Fifty patients received anterior surgery and 65 received posterior surgery between 1968 and 1993. Assessment after surgery was based on the recovery rate using the scoring system of the Japanese Orthopaedic Association. Spinal changes in the anterior group were assessed radiographically. RESULTS: Recovery and final results improved with phase after anterior, but not posterior, surgery. Neurologic deterioration after initial recovery was lower for the anterior group. One third of patients in the anterior group followed for more than 7 years exhibited neurologic deterioration, with most showing these changes within 10 years. Worsening was attributed to insufficient removal of lateral, superior, or inferior ossification of the posterior longitudinal ligament, reossification at the excision site, kyphotic malalignment, growth of ossification at upper cervical levels, or untreated complicated hypertrophy of the posterior longitudinal ligament. Many patients showed a good outcome after surgery. Accurate alignment and long-range fusion improved results. If the cord was compressed in a canal narrowed to under 3 mm, anterior surgery was considered "too risky." CONCLUSIONS: Complete extirpation of ossification of the posterior longitudinal ligament as confirmed by ultrasonography during surgery and long-range fusion with fibular grafts is advocated in the management of ossification of the posterior longitudinal ligament.

Follow-Up Studies↗

Long-term follow-up study of anterior decompression and fusion for thoracic myelopathy resulting from ossification of the posterior longitudinal ligament.

STUDY DESIGN: This was a retrospective study of the results of anterior decompression and fusion in patients with thoracic myelopathy secondary to ossification of the posterior longitudinal ligament with a minimum follow-up time of 5 years. OBJECTIVES: To clarify the effectiveness and limits of anterior decompression and fusion for thoracic ossification of the posterior longitudinal ligament. SUMMARY OF BACKGROUND DATA: Posterior decompression for the surgical management of thoracic ossification of the posterior longitudinal ligament has had an uncertain success record. Anterior decompression and fusion have been considered the treatment of choice however, there are few reports describing the long-term results. METHODS: The participants in this investigation were 33 patients whose cases were followed for an average period of 8 years and 2 months. The factors that were investigated included changes in the Japanese Orthopedic Association score and in recovery rates, postoperative complications, and radiographic findings of bone union and progression of ossification of the posterior longitudinal ligament within the area of anterior decompression. RESULTS: Although the recovery rates were relatively stable from 1-5 years after surgery, the rates declined thereafter. The average recovery rate at the final follow-up visit was 53.2%. Postoperative complications included three cases of deterioration of thoracic myelopathy and four cases of extrapleural cerebrospinal fluid leakage. Except for the one case of deterioration of thoracic myelopathy, the remainder of the complications were transient. CONCLUSIONS: Anterior decompression and fusion is an effective surgical procedure for thoracic ossification of the posterior longitudinal ligament with good, stable, long-term results; when thoracic ossification of the posterior longitudinal ligament was extensive or coincident with ossification of the intraspinal ligament, however, the results were not as predictable.

Adult↗

Morphologic limitations of posterior decompression by midsagittal splitting method for myelopathy caused by ossification of the posterior longitudinal ligament in the cervical spine.

STUDY DESIGN: This is a retrospective study of the morphologic limitations of posterior decompression for ossification of the posterior longitudinal ligament in the cervical spine. OBJECTIVES: To determine the morphologic limitations of the posterior approach in the management of ossification of the posterior longitudinal ligament. SUMMARY OF BACKGROUND DATA: Thirty-eight patients who underwent laminoplasty by midsagittal splitting for ossification of the posterior longitudinal ligament were reviewed. Fifteen patients were included in the noncontact group, in which the spinal cord was free of the ossified lesion after posterior decompression. Twenty-three patients were included in the contact group, in which the spinal cord was not free of the ossified lesion even after posterior decompression. METHODS: The preoperative sagittal alignment of the cervical spine and preoperative maximal thickness of ossification were compared between the two groups. In addition, the morphologic limitations of posterior decompression for ossification of the posterior longitudinal ligament were investigated. RESULTS: The following factors were found to contribute significantly to contact between the spinal cord and ossification of the posterior longitudinal ligament after posterior decompression: 1) lordosis of less than 10 degrees or kyphosis in the preoperative sagittal alignment, and 2) preoperative maximal thickness of ossification of more than 7 mm. CONCLUSIONS: Patients who exhibit significant risk factors for continued contact of the spinal cord should be morphologically considered for anterior decompression.

Adult↗

Hypertrophy of the posterior longitudinal ligament is a prodromal condition to ossification: a cervical myelopathy case report.

STUDY DESIGN: A histopathologic examination of a specimen that showed hypertrophy of the posterior longitudinal ligament of the cervical spine. OBJECTIVES: To illustrate the possibility of hypertrophy of the posterior longitudinal ligament as a prodromal condition to ossification of the posterior longitudinal ligament. SUMMARY OF BACKGROUND DATA: Despite much study, the pathology of ossification of the posterior longitudinal ligament still remains unclear. Hypertrophic change often is seen in the part of the ossified ligament; however, there have been few histopathologic reports on hypertrophy of the posterior longitudinal ligament. Some reports have suggested that hypertrophy of the posterior longitudinal ligament is a prodrome of ossification of the posterior longitudinal ligament. METHODS: A 64-year-old man was admitted to the hospital because of gait disturbance and developed oliguria. In a plain radiograph, segmental ossification of the posterior longitudinal ligament was found at C4, C5, and C6. Computed tomograph myelogram revealed a soft tissue shadow, maximum 3.8 mm in diameter, on the dorsal side of the ossification of the posterior longitudinal ligament at C5 and C6. Magnetic resonance T1-weighted image (T1WI) showed an equivalent signal with the intervertebral disc on the dorsal side of ossification of the posterior longitudinal ligament. This lesion was enhanced with Gd-DTPA and confirmed as hypertrophy of the posterior longitudinal ligament. Cervical anterior decompression and fusion were performed using Yamaura's technique. The ossified and thickened lesion was elevated and removed en bloc. Then, hematoxylin-eosin and toluidine blue staining was performed to detect metachromasia. RESULTS: Macroscopic examination of the specimen revealed that soft tissue formation was connected with the C4-C5 intervertebral space and extended downward to C6-C7. Histopatholgically, collagen fibers were proliferating in the long-axis direction on both ventral and dorsal sides. This was surrounded by extended nucleus pulposus-like chondrocyte tissue, where endplate cartilage was detected around the C4 pedicle. Roux staining was low, and partial vascular and cellular infiltration was observed, although it was not marked. CONCLUSION: The herniated nucleus pulposus involving endplate cartilage from C4-C5 was limited to the superficial layer, and proliferation of nucleus pulposus-like chondrocytes occurred in the herniated tissue, where they might undergo a change in cell phenotype. The results of the present study support the hypothesis that hypertrophy of the posterior longitudinal ligament is a prodromal condition to ossification of the posterior longitudinal ligament.

Cervical Vertebrae↗