Kazuhito Sugimori

Progression of Ossification of the Posterior Longitudinal Ligament Following en Bloc Cervical Laminoplasty

Background: Ossification of the posterior longitudinal ligament often causes compressive myelopathy. Ossification is a progressive disease, and it has been reported that the area of ossification increases after decompressive surgery. However, it is uncertain how the progression of ossification affects the long‐term outcome after cervical laminoplasty. This study was performed to clarify the relationship between the progression of ossification of the posterior longitudinal ligament and the clinical results following en bloc cervical laminoplasty. Methods: Forty‐five patients who were followed for more than ten years after laminoplasty participated in this study. Radiographs and tomograms of the cervical spine of each patient were made before and after the operation and at the time of the latest follow‐up. The extent of ossification in the longitudinal and sagittal axes was evaluated. Neurological function was graded with use of the Japanese Orthopaedic Association scoring system. The relationship between the progression of ossification and the score‐based rate of recovery was analyzed. Results: Thirty-three (73%) of the patients had progression of ossification of the posterior longitudinal ligament after laminoplasty. Progression was frequent in patients with the mixed type of ossification and in those with the continuous type, whereas it was rare in patients with the segmental type. The patients with progression of the ossification were significantly younger than those without progression (p = 0.018). The Japanese Orthopaedic Association score improved rapidly within one year and continued to improve up to five years after surgery. The score tended to decrease thereafter. For thirteen patients, the score had worsened at the time of the latest follow-up. Three patients had neurological deterioration following an increase in the thickness of the ossification. Conclusions: Progression of ossification of the posterior longitudinal ligament was often observed during the long-term follow-up period after laminoplasty. Young patients with mixed and continuous types of ossification had the greatest risk for progression. Preventive measures, such as the use of a wider laminar opening during the laminoplasty, should be considered for patients who are at risk for progression of ossification.

BMP-2 prevents apoptosis of the N1511 chondrocytic cell line through PI3K/Akt-mediated NF-κB activation

The signal transduction pathway by which bone morphogenetic protein-2 (BMP-2) regulates apoptosis in chondrocytes remains largely unknown. We investigated the involvement of phosphatidylinositol 3-kinase (PI3K)/Akt-mediated NF-κB activation by BMP-2 stimulation in the modulation of this antiapoptotic process in a chondrocytic cell line, N1511. BMP-2 prevented apoptosis through the inhibition of caspase-3 and -9 and an increase in Bcl-xL expression, and this antiapoptotic effect was inhibited by Noggin. Not only was NF-κB p65 activated transiently in the early phase (5–15 min) after treatment with BMP-2 but p65 at serine 536 was phosphorylated from 5 min as well. Akt was rapidly phosphorylated in response to BMP-2 treatment; however, the inhibition of PI3K by Wortmannin markedly reduced the phosphorylation of Akt by BMP-2. Wortmannin also decreased the NF-κB transcriptional activity that was up-regulated by BMP-2. Thus, BMP-2-induced NF-κB activation is mediated by PI3K/Akt signaling. Wortmannin treatment inhibited the antiapoptotic effect of BMP-2. These data indicate that BMP-2 can utilize a new signal transduction pathway in the NF-κB activation system, which plays a crucial role in the survival of the N1511 chondrocytic cell line.

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 χ2 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.

Association Between Polymorphism of the Transforming Growth Factor-β1 Gene With the Radiologic Characteristic and Ossification of the Posterior Longitudinal Ligament

Study Design. A study was conducted to examine the relation between the transforming growth factor-&bgr;1 (TGF-&bgr;1) polymorphism (T→C transition in the signal sequence) and ossification of the posterior longitudinal ligament (OPLL). Objective. To investigate the association between the polymorphism of TGF-&bgr;1 and the radiologic characteristics of OPLL. Summary of Background Data. Ossification of the posterior longitudinal ligament has a strong genetic background. Several genes contribute to the expression of OPLL. Transforming growth factor-&bgr;1 is present in the ossified matrix and chondrocytes of cartilage adjacent to areas of OPLL. Methods. The difference in the TGF–T&bgr;1 allele distribution (“TT,” “TC,” and “CC”) between 369 patients with OPLL and 258 control subjects was assessed. The relations between the allele frequency and radiologic features of OPLL involving the cervical, thoracic, and lumbar spine and the width of the ossification area were evaluated. Results. There was no statistical difference with respect to the type of OPLL and the width of the ossification area for the TGF–T&bgr;1 allele between the OPLL and the control groups. However, in the patients with “TC” or “CC” alleles, OPLL frequently was found in the cervical, thoracic, and/or lumbar spine. Conclusions. Transforming growth factor-&bgr;1 polymorphism is not a factor associated with the occurrence of OPLL, but rather a factor related to the area of the ossified lesion. The “C” allele might be a risk factor for patients with OPLL in other areas in addition to the cervical lesion.

High-sensitivity analysis of serum C-reactive protein in young patients with lumbar disc herniation

We measured the serum concentration of C-reactive protein (CRP) by a high-sensitive method in patients with lumbar disc herniation. There were 48 patients in the study group and 53 normal controls. The level and type of herniation were evaluated. The clinical data including the neurological findings, the angle of straight leg raising and post-operative recovery as measured by the Japanese Orthopaedic Association (JOA) score, were recorded. The high-sensitive CRP (hs-CRP) was measured by an ultrasensitive latex-enhanced immunoassay. The mean hs-CRP concentration was 0.056 +/- 0.076 mg/dl in the patient group and 0.017 +/- 0.021 mg/dl in the control group. The difference was statistically significant (p = 0.006). There was no other correlation between the hs-CRP concentration and the level and type of herniation, or the pre-operative clinical data. A positive correlation was found between the concentration of hs-CRP before operation and the JOA score after. Those with a higher concentration of hs-CRP before operation showed a poorer recovery after. The significantly high concentration of serum hs-CRP might indicate a systemic inflammatory response to impingement of the nerve root caused by disc herniation and might be a predictor of recovery after operation.

Significance of Bone Formation Markers in Patients With Ossification of the Posterior Longitudinal Ligament of the Spine

Study Design. Serum concentrations of bone formation markers were correlated with the type, location, and progression of ossification of the posterior longitudinal ligament. Objective. To determine the relation between bone formation markers and ossification of the posterior longitudinal ligament. Summary of Background Data. Few reports have correlated bone formation markers with ossification of the posterior longitudinal ligament. Methods. In this study, 43 patients with cervical ossification of the posterior longitudinal ligament and myelopathy underwent laminoplasty. The patients were observed for more than 10 years, after which plain radiographs and tomograms of the cervical region were taken. The radiographs were selectively performed to address thoracic and lumbar ossification of the posterior longitudinal ligament. Serum concentrations of bone formation markers (intact osteocalcin, osteocalcin, carboxyterminal propeptide of human type 1 procollagen, and bone-specific alkaline phosphatase) were measured and correlated with these radiographic studies. Results. A positive correlation was observed between intact osteocalcin, osteocalcin, and carboxyterminal propeptide of human type 1 procollagen in patients with combinations of cervical, thoracic, or lumbar ossification of the posterior longitudinal ligament. Conclusions. Serum concentrations of intact osteocalcin, osteocalcin, and carboxyterminal propeptide of human type 1 procollagen may reflect the activity of general ectopic bone formation in patients with ossification of the posterior longitudinal ligament.

Intraoperative patellar tendon strain: predicting the range of knee flexion after total knee arthroplasty

BackgroundThe preoperative range of motion is an important factor that influences the range of motion after total knee arthroplasty. Because the length and tightness of the extensor mechanism are extracapsular elements with an influence on knee flexion, it is reasonable to assume that the tension of the knee extensor mechanism during surgery has a considerable impact on the postoperative range of motion. The purpose of this study was to determine the influence of the tightness of knee extensor mechanism on postoperative knee flexion.MethodsIn 18 knees undergoing posterior-stabilized type total knee arthroplasty, we measured the longitudinal strain on the patellar tendon with all the components in position during passive knee flexion up to 135°. The patellar tendon strains measured during surgery were compared with the preoperative maximum knee flexion angle and postoperative maximum knee flexion angle at 1 year.ResultsThere was a significant inverse correlation between the patellar tendon strain during surgery at 60° (r = -0.54, P < 0.05), 90° (r = -0.55, P < 0.05), or 135° of flexion (r = -0.65, P < 0.05) and postoperative knee flexion.ConclusionsThe results indicated that subjects with high intraoperative patellar tendon strain during passive flexion of the knee had more restricted postoperative knee flexion. Therefore, the tightness of the knee extensor mechanism measured at total knee arthroplasty is a good predictor of maximum postoperative range of flexion.