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Preoperative radiotherapy without femoral shielding for prevention of heterotopic ossification in hydroxyapatite-coated hip prostheses.

Twenty-seven consecutive patients at high risk of developing heterotopic ossifications (HO) after implantation of a hydroxyapatite (HA)-coated hip prosthesis were irradiated with a single dose of 7 Gy, at least 4 h before the operation. The femoral stem was not shielded during radiotherapy (RT). After a median follow-up of 14.8 months, no clinically significant HO could be found, while 12 (52%) patients in this high-risk population had only minor HO (grade I). No reoperation was needed, and no evidence of prosthesis migration was observed. We conclude that single-dose, preoperative RT for HA-coated hip prosthesis can effectively inhibit HO. Not blocking the femoral stem does not result in prosthesis migration.

Adult↗

Ossification of the yellow ligament causing thoracic cord compression.

Ossification of the yellow ligament (OYL) is not infrequent in the cervical and lumbar regions but is very rare in the thoracic spine, with no more than 40 cases reported in the literature. We describe a 50-year-old male with progressive paraparesis and sensory dysfunction, secondary to OYL at T10-T11, studied by computed tomography (CT) and magnetic resonance imaging (MRI). Decompressive laminectomy and removal of the ligament resulted in marked clinical improvement. Patients with OYL may initially develop sensory dysfunction associated with leg weakness. This pathological entity can be well defined by CT and MRI, and surgery by decompressive laminectomy is advised for all cases. The OYL should be removed both posteriorly and laterally to the dural sac to obtain sufficient decompression of the spinal canal.

Decompression, Surgical↗

Risk factors for heterotopic ossification in total hip arthroplasty.

This study prospectively evaluated 928 patients with 1318 primary total hip replacements for heterotopic ossification (HO). The mean clinical and radiological follow-up was 2.5 years (range 1.5-3.6 years). HO was noted in 44.6% of all total hips replaced. It was graded as mild (Brooker 1) in 29.2%, moderate (Brooker 2) in 10.5%, and severe (Brooker 3 and 4) in 4.2%. The following factors showed a significantly increased risk of HO: hypertrophic osteoarthritis, HO after contralateral total hip replacement, trochanteric osteotomy, lateral or anterolateral approach, previous hip surgery, subtrochanteric femoral osteotomy, and male gender (p < 0.05 in chi-square analysis of independence and multivariable analysis). Patients with rheumatoid arthritis showed less HO. A combination of any of these factors resulted in a significant increase in the risk of developing HO.

Aged↗

PTHrP, PTHr, and FGFR3 are involved in the process of endochondral ossification in human osteophytes.

To elucidate the process of endochondral ossification in human osteophytes we have studied the expression of parathyroid hormone-related protein (PTHrP), its receptor (PTHr), and fibroblast growth factor receptor 3 (FGFR3). Osteophytes from patients undergoing total knee replacement ( n=13), and fetal growth plate cartilages ( n=4) were processed for safranin O staining and immunohistochemistry. Chondrocytes and their matrix were preferentially stained for PTHrP in the middle and deep zones of the osteophytes examined. Ossified areas did not show a positive staining. In fetal joints the cartilaginous surface and the perichondrium as well as the osteoblasts in the trabecular bone were positive. PTHr was expressed at large in chondrocytes and osteoblasts of all osteophytes and fetal joints. Cells of the perichondrium were also positive. The FGFR3 antibody stained only single chondrocytes in some osteophytes, and groups of cells in others. In fetal samples, chondrocytes of the proliferating and the hypertrophic zone showed staining for FGFR3. This is the first report on the expression of PTHrP, PTHr, and FGFR3 in human osteophytes. As in fetal joints these mediators might regulate proliferation and differentiation of chondrocytes playing an important role in osteo(chondro)phyte growth.

Aged↗

A comparative analysis of phenotype expression in human osteoblasts from heterotopic ossification and normal bone.

BACKGROUND AND AIMS: Heterotopic ossification (HO) is a pathological bone formation process in which ectopic bone is formed in soft tissue. The formation of bone depends on the expression of the osteoblast phenotype. Earlier studies have shown conflicting results on the expression of phenotype markers of cells originating from HO and normal bone. The hypothesis of the present study is that cells from HO show an altered expression of osteoblast-specific phenotype markers compared to normal osteoblasts. The aims of the study were to further characterize the expression of osteoblast phenotypemarkers and to provide a comparison with other study results. PATIENTS AND METHODS: Using an in vitro technique, reverse transcription polymerase chain reaction (RT-PCR), real-time PCR and immunohistochemistry, we compared the phenotype gene expression (type I collagen, alkaline phosphatase, Cbfa-1, osteocalcin) of osteoblasts from resected HO and normal bone (iliac crest). RESULTS: Cells from HO expressed the osteoblast phenotype (type I collagen, alkaline phosphatase) but were characterized by a depleted osteocalcin expression. The expression of Cbfa-1 (osteocalcin transcription gene) showed a large variety in our study. Preoperative radiotherapy had no effect on phenotype expression in cells from HO. CONCLUSION: Our results provide a characterization of cells originating from HO and support the thesis of an impaired osteoblast differentiation underlying the formation of HO. The transcription axis from Cbfa-1 to osteocalcin could be involved in the pathogenesis of HO.

Adult↗

A large-scale genetic association study of ossification of the posterior longitudinal ligament of the spine.

Research to date has identified several genes that are implicated in the etiology of ossification of the posterior longitudinal ligament of the spine (OPLL); however, their pathogenetic relevance remains obscure. The aim of this study is to identify susceptibility genes for OPLL through a large-scale case-control association study and to re-examine previously reported associations. A total of 109 single nucleotide polymorphisms (SNPs) in 35 candidate genes were genotyped for 711 sporadic OPLL patients and 896 controls. The differences in allelic and genotypic distribution between patients and controls were assessed using the chi (2) test with Bonferroni's correction. We also analyzed the association by separating patients into subgroups according to sex, age and the number of ossified vertebrae. The nominal P values fell below 0.05 for five SNPs in three genes. An intronic SNP in the TGF3 gene (P=0.00040) showed the most significant association. Previously reported associations of COL11A2, NPPS and TGFB1 with OPLL could not be reproduced. Further, no significant associations were detected in stratified analyses based on sex, age or the number of ossified vertebrae. TGFB3 warrants further investigation because it is located within a genomic region that has been positively linked with OPLL.

Adolescent↗

Ossification of the posterior longitudinal ligament in Down's syndrome.

Cervical myelopathy in patients with Down's syndrome is not uncommonly the result of atlanto-axial instability, a condition that is caused by ligamentous laxity and which may be associated with congenital osseous anomalies at the occipito-atlanto-axial axis. Ossification of the posterior longitudinal ligament (OPLL) is well described, particularly in the Japanese population, and may be associated with diffuse idiopathic skeletal hyperostosis. This is the first case, to our knowledge, of OPLL occurring in a person with Down's syndrome presenting with myelopathy.

Down Syndrome↗

Activation and localization of cartilage-derived morphogenetic protein-1 at the site of ossification of the ligamentum flavum.

Localization and expression of cartilage-derived morphogenetic protein (CDMP)-1 in tissues at the site of ossification of the ligamentum flavum (OLF) were examined by immunohistochemistry and in situ hybridization. The CDMP-1 protein and messenger ribonucleic acid (mRNA) were localized in spindle-shaped cells and chondrocytes in the OLF tissues. CDMP-1 was not detected in cells in non-ossified sites. These data indicate that CDMP-1 is locally activated and localized in spindle-shaped cells and chondrocytes at the site of OLE. Given the previously reported promoting action of CDMP-1 for chondrogenesis, the current results suggest that CDMP-1 may be involved in the progression of OLF, leading to the narrowing of spinal canal and thus causing severe clinical manifestations.

Aged↗

Possible involvement of vitamin D receptor gene polymorphism in male patients with ossification of spinal ligaments.

Ossification of spinal ligaments (OSL) is a common form of myelopathy characterized by heterotopic bone formation in the spinal ligaments, predominantly in men. Although the etiology of OSL is not fully understood, previous studies have strongly suggested the involvement of genetic factors in this disease. To investigate the possible involvement of vitamin D receptor (VDR) gene polymorphism in Japanese male patients with OSL, we analyzed: (a) the VDR genotype defined by BsmI polymorphism in patients with obvious OSL and controls; and (b) the effect of 1,25-dihydroxyvitamin D3 on alkaline phosphatase (ALP) activity of spinal ligament cells derived from patients without OSL. With regard to the VDR genotype, of the patients with OSL (n = 27), none had the BB genotype (0%), one had the Bb genotype (4%), and 26 had the bb genotype (96%). In the control group (n = 97) three had the BB genotype (3%), 18 had the Bb genotype (19%), and 76 had the bb genotype (78%). As a result, the B allele frequency in patients with OSL (2%) was significantly lower than in controls (12%). 1,25-Dihydroxyvitamin D3, at concentrations of 10-9 and 10-8 M, significantly increased ALP activity of the ligament cells (n = 8), suggesting that 1,25-dihydroxyvitamin D3 is able to promote osteogenic differentiation of normal ligament cells. Among the Japanese, sensitivity to vitamin D has been reported to vary between the alleles of the VDR; i.e., bone mineral density (BMD) in patients without the B allele is increased by vitamin D treatment, whereas patients with the B allele do not show such an increase in BMD. The present investigation is a small preliminary study, but the findings suggest, for the first time, that the B allele of the VDR acts as an inhibitor in the pathogenesis of human male OSL.

24,25-Dihydroxyvitamin D 3↗

Histomorphometric study of iliac bones in cervical myelopathy with ossification of the posterior longitudinal ligament.

To investigate whether there was any abnormal systemic bone metabolism in patients with ossification of the posterior longitudinal ligament (OPLL), we measured various histomorphometric indices of the iliac trabecular bones in 19 patients with OPLL (14 men, 5 women). For each index, the Z-score for each patient was calculated, using the SD and mean value for non-OPLL control group (n = 159) who underwent orthopaedic surgeries and had no systemic disease, age-matched for each decade. A Z-score of 1.0 meant that the observed data deviated 1 SD from the normal average, and a distribution from -2 to +2 was considered normal. All the averaged Z-scores were within +/-1.0 and there were no significant differences between the OPLL and the control groups. There was also no difference in Z-score among three types of OPLL (segmental, continuous, and mixed). From these results, we concluded that there was no common abnormal bone metabolism affecting the bone histomorphometry of the iliac bone in OPLL patients. However, in two patients, the Z-score for bone volume (BV/TV) was more than 2.0, with increased osteoid volume (OV/TV) and increased trabecular thickness, suggesting that there was some abnormal bone metabolism in these two patients with OPLL.

Adolescent↗

Activation of nuclear factor kappaB at the onset of ossification of the spinal ligaments.

We examined the correlation between the activation of nuclear factor kappaB (NFkappaB), stimulated by environmental factors involving cytokines and growth factors in ligament cells, and the onset of ossification of the spinal ligaments (OSL) or diffuse idiopathic skeletal hyperostosis (DISH). Aseptic samples were taken carefully from non-ossified sites during surgery (75 patients). We carried out preliminary hematoxylin and eosin and toluidine blue staining, using five portions of each specimen, and excluded samples containing chondrocytic, osteoblastic, or inflammatory cells (n = 25). We used specimens from the remaining 50 patients (35 men and 15 women, ranging in age from 45-81 years); average age, 59.5 years (18 nuchal ligament specimens, and 32 yellow ligament specimens). OSL or DISH had occurred in 25 patients, 20 patients were in the non-OSL group (8 with cervical spondylotic myelopathy, and 12 with lumbar canal stenosis), and the remaining 5 samples were collected from patients with injury. For culture study, we used portions of the 14 largest samples from the above 50 patients. We extracted nuclear proteins and cytoplasmic proteins from non-ossified spinal ligaments in 50 patients and detected p65RelA/NFkappaB by Western blotting. Tumor necrosis factor-alpha (TNF alpha), interleukin 1beta (IL-1beta), platelet-derived growth factor BB (PDGF-BB) and transforming growth factor-beta1 (TGF-beta1) in cytoplasm were quantified by enzyme-linked immunosorbent assays (ELISA). Cultured cells from the 14 samples were then stimulated with 10, 100, 250, or 500 ng/ml of recombinant human (rh)PDGF-B or TGFbeta1. A control experiment was performed without rhPDGF-BB or TGFbeta1 stimulation. Alkaline phosphatase (ALP) activity was standardized by the DNA content of the cells. The number of NFkappaB-positive samples was significantly higher in patients with OSL or DISH than in non-OSL patients. This tendency was obvious in the case of OSL or DISH with non-insulin-dependent diabetes mellitus (NIDDM). In OSL and in DISH patients, significantly greater amounts of PDGF-BB and TGFbeta1 were seen in ligament cells than in non-OSL patients (P < 0.05). There was a positive correlation between the detection of p65RelA/NFkappaB band and the content of PDGF-BB and TGFbeta1 in ligament cells (P < 0.05). ALP activity tended to be higher in cells in the OSL group not receiving any other treatment. Our results indicate the possibility that NFkappaB, stimulated by environmental factors involving PDGF-BB and TGFbeta1 in ligament cells, influences the osteoblastic differentiation of undifferentiated mesenchymal cells.

Actins↗

Ossification of the acetabular labrum.

We report a rare case of extensive ossification of the unilateral acetabular labrum in a 40-year-old man. Radiological manifestations of diffuse skeletal hyperostosis were not found in the spine.

Acetabulum↗

Gender-specific haplotype association of collagen alpha2 (XI) gene in ossification of the posterior longitudinal ligament of the spine.

Among Japanese, ossification of the posterior longitudinal ligament of the spine (OPLL) is a leading cause of myelopathy, showing ectopic bone formation in the paravertebral ligament. We have provided genetic evidence that the collagen alpha2 (XI) (COL11A2) locus of chromosome 6 constitutes susceptibility for OPLL. Five distinct single nucleotide polymorphisms (SNPs), identified in COL11A2, were combined to construct possible haplotypes by the use of a maximum likelihood program. Estimated haplotype frequency was compared in OPLL patients and non-OPLL controls. We report a gender-specific association of the COL11AA2 haplotvpe with OPLL. The frequency of the most commonly observed haplotype was significantly higher in male patients (P = 0.0003) compared with controls, but not in female patients (P = 0.21). OPLL is predominantly observed in males. with a prevalence ratio of 2:1, and our gender-specific associations indicate that genetic factors involving COL11A2 play a specific role in the etiology of OPLL exclusively in males.

Aged↗

Diagnosis and treatment of ossification of the posterior longitudinal ligament of the spine: report of eight cases and literature review.

PURPOSE: Ossification of the posterior longitudinal ligament (OPLL) is a common, well-recognized cause of spinal stenosis and myelopathy in Japan. Although also common in whites, especially among the elderly, it has received little scientific attention. We wish to increase awareness of this important cause of myelopathy, and to determine if the clinical characteristics of OPLL are similar in non-Japanese and Japanese patients. PATIENTS AND METHODS: The clinical and radiologic features of eight cases of OPLL are presented. These cases combined with 73 non-Japanese cases gathered from the English literature are contrasted with 2,125 Japanese cases of OPLL. RESULTS: Similarities among non-Japanese and Japanese cases included: (1) male predominance; (2) peak age at onset of symptoms in the sixth decade; (3) clinical presentation, which ranged from asymptomatic to quadriplegia, with progressive or acute onset of neurologic deterioration; (4) greater than 95% localization to the cervical spine, spastic quadriparesis being the most common neurologic presentation; (5) an association with several rheumatic conditions including diffuse idiopathic skeletal hyperostosis (DISH), spondylosis, and ankylosing spondylitis; and (6) neurologic improvement with either conservative or surgical treatment in a significant proportion of patients. Differences between the two groups were minimal and included a higher mean age at onset (although onset in both groups occurred within the sixth decade) and a greater proportion of patients with DISH and with the continuous type of OPLL in the non-Japanese group. CONCLUSION: The clinical characteristics of OPLL are similar in Japanese and non-Japanese patient populations. Increased awareness of this condition, which has potentially devastating neurologic complications, will favorably influence diagnosis, treatment, and outcome.

Adult↗

Coexistence of deep venous thrombosis and heterotopic ossification in the pediatric patient.

A 14-year-old girl and a 15-year-old boy with severe traumatic brain injuries were noted to have marked asymmetry in the lower extremities. Clinical and radiologic evaluation demonstrated the coexistence of deep venous thrombosis (DVT) and heterotopic ossification (HO). These cases demonstrate that although DVT are rare in children, they can be present and may coexist with the more common presentation of a swollen lower extremity secondary to HO.

Adolescent↗

Disturbed endochondral ossification in the axial skeleton of young broiler fowls.

Physeal lesions have been studied in thoracic vertebrae (T3, T4 and T5) of 51 broiler fowls between 28 and 53 days old. Vascular perfusion studies performed on 10 birds confirmed that the cartilaginous epiphyses of T3, T4 and T5 were essentially avascular and thus differ from those of the major long bones. Findings confirm the observation that a number of morphologically distinct lesions of osteochondrosis occur in broiler fowls and that, when physeal clefts can be implicated in their aetiology, the term "osteochondrosis" is inappropriate. Although the location of clefts often differs in long bone and vertebral physes, when metaphyseal vessels are disrupted, the end-result on endochondral ossification is the same in both the axial and appendicular skeleton. Other lesions were observed both independently and in association with osteochondrosis. Such lesions include necrotic seams devoid of haemorrhage, acellular foci and chondrolysis, all of which were most frequently observed in the same vertebral end-plates. Because osteochondrosis was also most common in the same vertebral end-plates, a common aetiology is suggested. Surface regressive changes were common in the articular cartilage of T3, T4 and T5, and it is noteworthy that such changes, although common in older birds, are present in birds so young.

Animals↗

I. Stylohyoid chain ossification: a discussion of etiology.

Not all patients with cervicopharyngeal pain related to the stylohyoid apparatus can be diagnosed as having Eagle's syndrome. An attempt is therefore made to classify these patients according to etiology. First, a diagnosis of Eagle's syndrome is applied to symptomatic patients in whom elongated, ossified styloid processes develop within a period of time posttraumatically. Second, a diagnosis of stylohyoid syndrome is applied to patients in whom elongated styloid processes and/or stylohyoid chain ossification develop early in life as an anatomic anomaly, and in whom symptoms later develop. Last, a diagnosis of pseudostylohyoid syndrome is applied to patients in whom, because of aging, a tendinosis at the junction of the stylohyoid ligament and the lesser horn of the hyoid bone develops. It is hoped that such a simplified classification may lead to a global understanding of the causes of such symptomatology, a more practical approach to treatment, and less confusion among the professions in regard to terminology.

Facial Pain↗