[PATHOLOGICAL OSSIFICATION IN MULTIPLE FOCI OF THE GLUTEAL REGION].
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OBJECTIVE: To investigate the function of bone morphogenic protein-2 (BMP-2) in the ossification of the spinal ligament (OSL). METHODS: Total RNA was prepared from the cultured spinal ligament cells from patients with OSL and analysed by reverse transcription-polymerase chain reaction using specific primers for BMP-2. BMP-2 mRNA expression in ligament tissues was examined by in situ hybridization. Spinal ligament cells from patients without OSL were treated with BMP-2 and examined for alkaline phosphatase activity. RESULTS: Expression of the BMP-2 gene was detected in cultured spinal ligament cells. In ligament tissues, BMP-2 mRNA was present in the chondrocyte-like cells in the fibrocartilage zone. Exogenous BMP-2 increased alkaline phosphatase activity in spinal ligament cells from patients without OSL. CONCLUSION: The BMP-2 gene is expressed in the spinal ligaments of OSL patients, and exogenous BMP-2 stimulates osteogenic differentiation of spinal ligament cells. The expression of BMP-2 in the spinal ligaments could be a clue in elucidating how heterotrophic osteogenesis develops in ligament tissue.
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Ossification of the posterior longitudinal ligament (OPLL) is a pathological ossification in the spinal ligament, with formation of ectopic bone mainly through endochondral ossification. Bone morphogenetic proteins (BMPs) and activins are multifunctional proteins that belong to the transforming growth factor-beta superfamily and that have been implicated in the formation of new bone and cartilage. BMPs and activins signal via type I and type II receptors for BMPs (BMPRs) and activins (ActRs), respectively. OP-1/BMP-7 binds to BMPR-II and ActR-II and forms complexes with BMPR-IA and -IB and ActR-I. We studied the expression of BMPR-IA, -IB, and -II, ActR-I, ActR-II, and OP-1/BMP-7 by immunohistochemistry in ossified ligament tissues of patients with OPLL and control ligament tissues from patients with cervical disc herniation. The expression of BMPRs and ActRs was elevated in OPLL compared with controls. Expressions of BMPR-IA, -IB, and -II were observed not only in chondrocytes at the fibrocartilage tissue around the calcified zone but also in fibroblast-like spindle cells at the nonossified ligament. ActR-I and -II were found co-localized in the hypertrophic chondrocytes near the calcified zone and in the ossified tissue. OP-1/BMP-7 was expressed in chondrocytes near the calcified zone. In the control cases, the BMPRs and ActRs were only weakly expressed in the fibrocartilage tissue at the site of ligament attachments to bone and OP-1/BMP-7 was not detected. Enhanced expression of BMPRs at the nonossified ligament in OPLL patients suggests that these cells have a greater potential to differentiate into osteogenic cells than ligament cells from non-OPLL patients. The high expression of BMPRs and ActRs in the ectopic ossified ligament suggests that BMPs and activin may be tightly involved in the pathological ossification process of OPLL.
We analysed nine autopsy cases of ossification of the posterior longitudinal ligament (OPLL) to elucidate the relationship between morphology and pathology of the spinal cord. The cross-sectional shape of the spinal cord at the most severely affected segment was classified into two categories: boomerang (convex lateral surfaces and concave anterior surface) and triangular (angular lateral surfaces and flat anterior surface). In the cases with a boomerang shape, even when the compression was severe, major pathological changes were restricted to the grey matter and the white matter was relatively well preserved. No secondary descending degeneration of the lateral columns was seen, and ascending degeneration of the posterior column was restricted to the fasciculus cuneatus whose fibres were derived from the affected segments. In the cases with a triangular shape, pathological changes were more severe, both white matter and grey matter were involved, and only the anterior columns were free of pathological changes. There were severe pathological changes over more than one segment, and both descending degeneration of the lateral pyramidal tracts and ascending degeneration of the posterior column, including the fasciculus gracilis, were observed. The transverse area of the spinal cord was > 60% of normal in most of the cases with a boomerang shape, but it was reduced to < 60% of normal in more than one segment in the cases with a triangular shape. The compression ratio of the spinal cord (sagittal diameter/transverse diameter x 100%) was not related to pathological changes. In conclusion, a triangular-shaped spinal cord with transverse area of < 60% of normal in more than one segment appeared to be associated with severe and irreversible pathological changes in cases of OPLL.
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.
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STUDY DESIGN: Vertebral columns from 11 normal human fetuses (10-24 weeks of gestation) derived from spontaneous abortions were examined as part of the legal autopsy procedure including spinal cord analysis. OBJECTIVES: To study the localization of the dorsal root ganglion in the normal fetal spine and to relate the dorsal root ganglion location to the ossification of the vertebral bodies and vertebral arches. SUMMARY OF BACKGROUND DATA: The normal and pathologic ossification pattern of the fetal human spine has been studied. There has been no study addressing the localization of the dorsal root ganglion in normal and pathologic axial development. METHODS: The dorsal root ganglion were studied by using histology (horizontal sections) and morphometric measurement. RESULTS: The study showed: 1) The dorsal root ganglion appeared before ossification of the spine; 2) The dorsal root ganglion had an oval shape in all cases; 3) The longitudinal axis of dorsal root ganglion was directed anterolaterally in the cervical and lumbosacral segments and mainly laterally in the thoracic segment; 4) During development, the dorsal root ganglion changed position according to the body axis; and 5) The para-axial ossification protected the dorsal root ganglion differently in the different axial segments. CONCLUSIONS: The dorsal root ganglion appeared before ossification. The distance from the dorsal root ganglion to the body axis increased during development. In the different segments of the spine, different orientations and different locations of the dorsal root ganglion were observed in relation to osseous spine components. The results can be used as reference data for future studies on the dorsal root ganglion in pathologic spines.
Heterotopic ossification is a frequent complication following spinal cord injury with 16 per cent to 53 per cent of patients developing varying degrees of pathologic ossification. The diphosphonates are known to block the transformation of amorphous calcium phosphate into crystalline hydroxyapatite. Therefore, one of the diphosphonates, disodium etidronate (generic name of disodium ethane-1-hydroxy-1, 1-diphosphonate (EHDP) was selected fro clinical trials to study the effectiveness of EHDP in preventing heterotopic ossification following spinal cord injury. In a double-blind, clinical study of 149 spinal cord injury patients, disodium etidronate has proven its effectiveness in the prevention of heterotopic ossification. The extent of heterotopic ossification development as measured by the total heterotopic ossification X-ray grade was significantly less in EHDP-treated patients compared to placebo-treated patients (P less than 0-05). For maximal effectiveness, EHDP treatment must be started before the onset of the pathological process initiating the development of heterotopicossification. Further studies are necessary to determine the optimal time to institute EHDP treatment, length of treatment, and minimal effective dose. EHDP is the first hterapeutic agent known to alter the formation of heterotopic ossification after spinal injury and may prove useful in other conditions where heterotopic ossification prevention is clinically indicated.
The sacro-iliac joint of a patient who had been ill with ankylosing spondylitis for half a year was investigated histologically at necropsy. Two basic histological phenomena were apparent: inflammation and aggressive proliferating chondroid metaplasia at the chondro-osseous junction and in the subchondrium. Joint cartilage degeneration, joint cartilage fusion, capsule ossification and subchondral bone apposition were observed as epiphenomena at the sacro-iliac joint. Both basic morphological phenomena are due to the same cause which has not yet been clarified. They progress independently of each other with varying intensity. This assumption explains differing opinions and the relation of inflammation and pathological ossification of the skeletal axis as well as the unsatisfactory objective results of treatment. Only a combination therapy directed against both morphological basic phenomena will result in an objective therapeutic success and not only in a symptomatic improvement of ankylosing spondylitis.