Masahiko Kanamori

Association between an aggrecan gene polymorphism and lumbar disc degeneration.

STUDY DESIGN A case-control study using magnetic resonance imaging findings and a polymerase chain reaction assay to investigate the association between aggrecan gene polymorphism and lumbar disc degeneration. OBJECTIVE To analyze whether the aggrecan gene polymorphism is related to lumbar disc disease in young women. SUMMARY OF BACKGROUND DATA It has been suggested that a genetic factor or familial predisposition contributes to the development of lumbar disc herniation. However, the precise genetic component related to disc disease remains unclear. Recently, a polymorphism has been identified in the region of the human aggrecan gene. The expressed variable numbers of tandem repeat polymorphism occur in the highly conserved repeat region. METHODS The participants were 64 young women with or without low back problems. Magnetic resonance imaging was used to evaluate the degeneration and herniation of the intervertebral disc. Genomic deoxyribonucleic acid was extracted from all participants. A polymerase chain reaction assay was carried out to detect the alleles of the aggrecan gene. The association of intervertebral disc degeneration and herniation with the distribution of the aggrecan gene alleles was analyzed. RESULTS Findings showed an overrepresentation of alleles with small numbers of repeats in subjects with multilevel disc degeneration, thus indicating a significant distribution difference. There also was a significant difference between the distribution of alleles and the severity of disc degeneration. No significant association was found between any of the alleles either in number or type of disc herniation. CONCLUSIONS The current study showed that multilevel and severe disc degeneration was present in the participants with shorter variable numbers of tandem repeat length of the aggrecan gene. This suggests that subjects with shorter variable numbers of tandem repeat length of the aggrecan gene have a risk of having multilevel disc degeneration develop at an early age.

The Association of Lumbar Disc Disease with Vitamin-D Receptor Gene Polymorphism

Background: Although the etiology of lumbar disc disease is unknown, it has been suggested that a genetic factor contributes to its development. Recently, some genetic polymorphisms have been found to be related to clinical disorders. We investigated the association between vitamin-D receptor gene and estrogen receptor gene polymorphisms and lumbar disc disease in young adults.Methods: The participants included 205 young adults (166 women and thirty-nine men) with or without low-back problems. A magnetic resonance imaging scan of the lumbar spine was performed for all subjects, and the grade of disc degeneration was determined, according to the four-grade classification system of Schneiderman et al. The presence or absence of disc herniation was also evaluated. Genomic DNA was extracted from peripheral blood samples. The polymorphisms of the vitamin-D receptor and estrogen receptor genes were detected with use of a polymerase-chain-reaction assay. The restriction fragment length polymorphisms (RFLPs) for the vitamin-D receptor gene were analyzed by TaqI and ApaI restriction enzymes. XbaI and PvuII restriction enzymes were used for the estrogen receptor gene analysis. The distribution of polymorphism in subjects with disc degeneration and/or disc herniation was compared with that in the normal subjects.Results: The allelic frequencies of both vitamin-D receptor gene and estrogen receptor gene polymorphisms were similar to those in previous analyses of Japanese subjects. The allelic variation in the vitamin-D receptor gene was associated with multilevel and severe disc degeneration and disc herniation. The Tt allele was found to be more frequently associated with multilevel disc disease, severe disc degeneration, and disc herniation than was the TT allele. No additional associations were found.Conclusions: This study revealed that the Tt allele of the vitamin-D receptor gene was more frequently associated with multilevel and severe disc degeneration and disc herniation than was the TT allele, pointing to an increased risk of disc disease at an early age in subjects with the Tt allele in the vitamin-D receptor gene.

Minimum 10-year Follow-up Study of Anterior Lumbar Interbody Fusion for Isthmic Spondylolisthesis

The aims of the current study were to evaluate the long-term clinical and radiologic results of anterior lumbar interbody fusion (ALIF) for isthmic spondylolisthesis. Between 1981 and 1988, a total of 35 patients underwent ALIF for isthmic spondylolisthesis. Of these, 23 patients were followed clinically and radiographically for more than 10 years (average, 13.3 years). The Japanese Orthopaedic Association low-back pain score was used to evaluate the outcome of subjective symptoms and clinical signs. The preoperative and postoperative percentage of slip, preoperative and postoperative intervertebral disk height, interbody graft union, and pars defect union were evaluated by serial radiographs. The adjacent disk degeneration was also evaluated by radiographs and magnetic resonance imaging. Although the low-back pain score worsened after 5 years, ALIF provides satisfactory overall long-term clinical results. The preoperative percentage of slip and the disk height were corrected after surgery, but at the time of interbody graft union, slip and disk height recurred as a result of grafted bone collapse. The rate of union in the grafted area was 83%. In the nonunion cases, the scores gradually deteriorated with time, but the overall results were not different from those of union cases. Radiographs showed adjacent disk degeneration in 52% of cases in the upper adjacent level and in 70% of cases in the lower adjacent level, but these changes were not correlated with clinical outcomes.

Minimum 10-year followup after en bloc cervical laminoplasty

The long-term outcome (> 10 years) after cervical laminoplasty was assessed and the postoperative problems were clarified. One hundred thirty-three patients had laminoplasty between 1981 and 1989 for treatment of cervical myelopathy and 126 patients were available for the current study. The clinical results were evaluated using the Japanese Orthopaedic Association score. The radiologic findings were analyzed by postural anomalies and range of motion. The average preoperative score was 9.1 points, and the postoperative score improved to 13.7 points within a year. The Japanese Orthopaedic Association score and recovery rate were maintained at 13.4 points and 55.1% at the last followup. In 20 patients, the Japanese Orthopaedic Association score worsened during the followup. The causes of deterioration were axial spread of ossification of the posterior longitudinal ligament, other spinal lesions, cerebral infarction, and peripheral neuropathy. Postoperative cervical radiculopathy occurred in nine patients. Postoperative radiculopathy resolved in five patients, but remained in four patients. Kyphotic changes were observed in eight patients. The recovery rate in patients with kyphosis was poor. The postoperative range of motion decreased to 25.1% of preoperative range of motion. Sixty one percent of patients had a reduction of range of motion. Satisfactory results of cervical laminoplasty were maintained for more than 10 years after surgery; however, there were several postoperative problems, such as neurologic deterioration, postoperative radiculopathy, progression of kyphosis, and range of motion limitation.

Familial Predisposition for Lumbar Degenerative Disc Disease: A Case-control Study

Study Design. A case‐control study using magnetic resonance imaging and plain radiography to evaluate whether a family history of lumbar disc herniation is a risk factor for disc degeneration. Objectives. To evaluate the significance of a family history of operated lumbar disc herniation in the development of lumbar disc degeneration and lumbar disc herniation. Summary of Background Data. There are only a few epidemiologic studies indicating that a family history of intervertebral disc herniation is a risk factor for juvenile disc herniation. Recently, similarities in degenerative findings of the lumbar spine between identical twins have been reported. Methods. In the case group, 24 patients who were the immediate relatives of patients who had undergone surgery for disc herniation and who presented or had a history of low back pain and/or unilateral leg pain were included. Control individuals included 72 age‐ and gender‐matched outpatients who reported low back pain and/or leg pain without a family history of operated disc herniation. The incidence, level, and topographic location of disc herniation/diffuse bulge; the incidence and grade of disc degeneration observed on magnetic resonance images; and degenerative changes suggesting disc degeneration observed on plain radiographs were compared between the relatives of patients with disc herniation (cases) and the controls. Results. The incidence of disc degeneration at L4‐L5 and L5‐S1 in cases (L4‐L5, 18/24; L5‐S1, 18/24) and controls (L4‐L5, 45/72; L5‐S1, 43/72) was similarly high. However, the grade of disc degeneration according to magnetic resonance imaging signal intensity on the T2‐weighted sagittal image using Schneidermans four‐grade classification was significantly more severe in cases (L4‐L5: Grade 1, 6/24; Grade 2, 4/24; Grade 3, 13/24; Grade 4, 1/24; L5‐S1: Grade 1, 6/24; Grade 2: 3/24, Grade 3: 12/24, Grade 4: 3/24) than in controls (L4‐L5: Grade 1, 27/72; Grade 2, 24/72; Grade 3, 20/72; Grade 4, 1/72; P = 0.034; L5‐S1: Grade 1, 29/72; Grade 2, 23/72; Grade 3, 13/72; Grade 4, 7/72; P = 0.023; Mann‐Whitney U test). The incidence of disc herniation/diffuse bulge at L4‐L5 (16/24) and L5‐S1 (11/24) in cases was higher than that in controls (L4‐L5, 33/72; P = 0.07; L5‐S1, 17/72; P = 0.04; chi‐square test). Conclusion. The current study provided evidence that a family history of operated lumbar disc herniation has a significant implication in lumbar degenerative disc disease. There may be a genetic factor in the development of lumbar disc herniation as an expression of disc degeneration.

PDGF Receptor β Is a Potent Regulator of Mesenchymal Stromal Cell Function

Mesenchymal stromal cells (MSCs) in bone marrow are important for bone homeostasis. Although platelet‐derived growth factor (PDGF) has been reported to be involved in osteogenic differentiation of MSCs, the role remains controversial and the network of PDGF signaling for MSCs has not been clarified. To clarify the underlying regulatory mechanism of MSC functions mediated by PDGF, we deleted the PDGF receptor (PDGFR)β gene by Cre‐loxP strategy and examined the role of PDGF in osteogenic differentiation of MSCs and fracture repair. In cultured MSCs, the mRNA expression of PDGF‐A, ‐B, ‐C, and ‐D as well as PDGFRα and β was detected. Depletion of PDGFRβ in MSCs decreased the mitogenic and migratory responses and enhanced osteogenic differentiation as evaluated by increased alkaline phosphatase (ALP) activity and mRNA levels of ALP, osteocalcin (OCN), bone morphogenetic protein (BMP) 2, Runx2, and osterix in quantitative RT‐PCR. PDGF‐BB, but not PDGF‐AA, inhibited osteogenic differentiation accompanied by decreased ALP activity and mRNA levels, except for BMP2. These effects of PDGF‐BB were eliminated by depletion of PDGFRβ in MSCs except that PDGF‐BB still suppressed osterix expression in PDGFRβ‐depleted MSCs. Depletion of PDGFRβ significantly increased the ratio of woven bone to callus after fracture. From the combined analyses of PDGF stimulation and specific PDGFRβ gene deletion, we showed that PDGFRβ signaling distinctively induces proliferative and migratory responses but strongly inhibits osteogenic differentiation of MSCs. The effects of PDGFRα on the osteogenic differentiation were very subtle. PDGFRβ could represent an important target for guided tissue regeneration or tissue engineering of bone.

Histochemistry and morphology of the multifidus muscle in lumbar disc herniation: Comparative study between diseased and normal sides

Study Design. This comparative study was conducted on 19 patients (13 men and 6 women) with lumbar disc herniation (LDH). The histologic and histochemical differences and changes in the back muscles of the diseased and normal sides were evaluated. Objectives. To determine the histologic differences in the back muscles between the diseased and normal sides in lumbar disc herniation. Summary of Background Data. The morphologic changes of back muscles between the diseased and normal sides in lumbar disc herniation were examined using histologic and histochemical methods. Few studies have reported the difference in these changes based on quantitative analyses. Methods. All samples were harvested bilaterally from the multifidus muscle at the level of L4–L5 or L5–S1 in patients with lumbar disc herniation and then were examined by histologic and histochemical methods (hematoxylin–eosin, Gomori trichrome, NADH-TR, and ATPase stains). The percentage, cross-sectional area (CSA), and lesser diameter (LD) of muscle fibers were measured using computerized image analysis. The Wilcoxon, paired t, Kruskal Wallis, and Fisher tests were used for statistical analysis. Results. Both Type I and II fibers in the diseased side were significantly smaller than those from the normal side. In the diseased side, the potential strength of Type II fibers was weakened. Some pathologic changes (fiber type grouping, small angulated fibers, group atrophy, moth-eaten appearance, and internal nuclei, etc.) in the diseased side were more obvious than those in the normal side. When the straight leg raising test results were abnormal, both Type I and II fibers in the diseased side were smaller than those in the normal side. The Type I fibers of the diseased side were significantly smaller when the patients had symptoms of central low back pain. The size of the Type I fibers as well as of the Type II fibers did not differ between the diseased and normal sides in patients with unilateral and bilateral low back pain. Conclusions. The present study indicated that there were differences in the characteristics of the multifidus muscle between the diseased and normal sides in patients with lumbar disc herniation. The changes in muscle characteristics primarily were related to the disc protrusion. In addition, different locations of the low back painseemed to cause different secondary effects on the muscle characteristics.

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.

Preventive measures for axial symptoms following cervical laminoplasty

We have modified the operative procedure of laminoplasty and changed the postoperative therapy since 1997. In the modified group, several modifications were incorporated. The open door type of cervical en bloc laminoplasty was performed. 1) Bone grafts in the open gap were placed at three levels only. 2) Bone grafting in the hinged side was not performed. 3) The neck collar was worn for only 1 month. 4) The doctors explained the importance of the neck muscle and advised patients to perform early exercise of the posterior neck muscle. The patients who had the original operation and postoperative therapy served as the control (control group). The original operation and postoperative therapy were as follows: Bone grafts from dissected spinous processes were put in the opened laminae and fixed with braided wires or nylon threads. Bone grafts in the open gap were placed to extend from three to five levels. Bone chips were also placed in the hinged side. The orthosis was applied for up to 1 months after surgery, and a neck collar was recommended for 1 additional month. Postoperative neurologic recovery and axial symptoms after cervical laminoplasty were compared between the two groups. There was no statistical difference in postoperative neurologic recovery. However, the incidence of axial symptoms was much lower in the modified group compared with the control group. Radiologic examination showed that postoperative range of motion of the cervical spine in the modified group was significantly well preserved and the number of postoperative fused laminae in the modified group was less than that in the control group. Based on these results, we concluded that the modified method is beneficial for the postoperative status of cervical laminoplasty patients.

Radiologic findings of the lumbar spine in patients with rheumatoid arthritis, and a review of pathologic mechanisms.

We have analyzed the radiologic findings on the lumbar spine and the clinical symptoms in patients with rheumatoid arthritis (RA). A total of 106 patients who fulfilled the revised criteria of the American Rheumatism Association were subjected. All of the patients were asked to fill out a questionnaire about the existence of low back pain, leg pain, and leg numbness. Radiologic features of the lumbar spine, including scoliosis, spondylolisthesis, disc space narrowing, endplate erosion, osteophyte, and osteoporosis, were checked. Radiographs of the cervical spine were also taken. The clinical background of RA, such as mutilating disease or not, was assessed. Forty-two patients (40%) had the symptoms of low back pain. Abnormal radiologic findings in lumbar spine were detected in 57%. The prevalence of clinical symptoms tended to be higher in the patients with endplate erosion. Forty-two percent of the patients had both lumbar and cervical lesions. The prevalence of lumbar lesion was not high in the mutilating type of RA, except for facet erosion and severe osteoporosis. The patients with pulse steroid therapy revealed a higher prevalence of vertebral fracture. From these results, we concluded that lumbar lesions were frequently observed in patients with RA. The possibility of lumbar lesions as well as the lesions in the cervical spine and peripheral joints should be examined in patients with RA.