Kazuaki Sonofuchi

Chondrogenic and fibrotic process in the ligamentum flavum of patients with lumbar spinal canal stenosis.

Study Design. A histological, biological, and immunohisto-chemical study of human lumbar ligamentum flavum. Objective. To analyze changes in the hypertrophied ligamentum flavum and clarify their etiology. Summary of Background Data. Hypertrophy of the ligamentum flavum has been considered a major contributor to the development of lumbar spinal canal stenosis (LSCS). Although previous studies have reported some factors related to ligamentum flavum hypertrophy, its etiology is still unclear. Methods. Ligamentum flavum samples were collected from 20 patients with LSCS (LSCS group) and 10 patients with lumbar disc herniation (LDH group) as a control. The thickness of the ligamentum flavum was measured histologically. The amounts of elastic fibers and proteoglycans were assessed by Elastica-Masson staining and alcian blue staining, respectively. Gene and protein expressions related to fibrosis, inflammation, and chondrogenesis were analyzed by quantitative reverse transcription–polymerase chain reaction and immunohistochemistry. The total genes of the 2 groups were compared by DNA microarray analysis. Results. The ligamentum flavum was significantly thicker in the LSCS group, which had a smaller amount of elastic fibers and a larger amount of proteoglycans. The gene expression related to fibrosis was significantly higher in the LSCS group; however, the immunoreactivities of collagen types I and III were weaker on the dorsal side of the ligamentum flavum in the LSCS group. The gene expression related to chondrogenesis and proteoglycan synthesis was significantly higher in the LSCS group. There was no significant difference in the gene expression related to inflammation between the 2 groups. Conclusion. Synthesis of the collagenous fibers and degradation of the elastic and collagenous fibers are both accelerated in the ligamentum flavum of patient with LSCS, which may be the reason for hypertrophy of the tissue. In addition, chondrogenesis and proteoglycan synthesis may have critical roles in the pathogenesis of the ligamentum flavum hypertrophy. Level of Evidence: 5

Thoracic radiculopathy caused by ossification of the ligamentum flavum.

Abstract Thoracic ossification of the ligamentum flavum (OLF) has been widely recognized as a main cause of thoracic myelopathy in Asia, particularly in Japan. However, thoracic OLF rarely causes radiculopathy. We report a rare case of thoracic radiculopathy caused by OLF. A 67-year-old male presented with a chief complaint of back pain radiating to the right of the abdomen. Neurological examination revealed mild sensory deficit at the right side of the abdomen at the T9–10 level. Magnetic resonance imaging and computed tomography demonstrated OLF at the right T9–10 level. Thoracic radiculopathy caused by OLF was suspected. Because conservative treatment was not effective to this lesion, surgical intervention was performed, and the pain disappeared immediately after the operation. Thoracic OLF rarely causes radiculopathy, but it should be considered as a differential diagnosis of thoracic radicular pain. When conservative treatment is not effective in this lesion, surgical treatment should be considered.

Quantitative in vivo biocompatibility of new ultralow-nickel cobalt-chromium-molybdenum alloys.

Nickel (Ni) eluted from metallic biomaterials is widely accepted as a major cause of allergies and inflammation. To improve the safety of cobalt–chromium–molybdenum (Co–Cr–Mo) alloy implants, new ultralow‐Ni Co–Cr–Mo alloys with and without zirconium (Zr) have been developed, with Ni contents of less than 0.01%. In the present study, we investigated the biocompatibility of these new alloys in vivo by subcutaneously implanting pure Ni, conventional Co–Cr–Mo, ultralow‐Ni Co–Cr–Mo, and ultralow‐Ni Co–Cr–Mo with Zr wires into the dorsal sides of mice. After 3 and 7 days, tissues around the wire were excised, and inflammation; the expression of IL‐1β, IL‐6, and TNF‐α; and Ni, Co, Cr, and Mo ion release were analyzed using histological analyses, qRT‐PCR, and inductively coupled plasma mass spectrometry (ICP‐MS), respectively. Significantly larger amounts of Ni eluted from pure Ni wires than from the other wires, and the degree of inflammation depended on the amount of eluted Ni. Although no significant differences in inflammatory reactions were identified among new alloys and conventional Co–Cr–Mo alloys in histological and qRT‐PCR analyses, ICP‐MS analysis revealed that Ni ion elution from ultralow‐Ni Co–Cr–Mo alloys with and without Zr was significantly lower than from conventional Co–Cr–Mo alloys. Our study, suggests that the present ultralow‐Ni Co–Cr–Mo alloys with and without Zr have greater safety and utility than conventional Co–Cr–Mo alloys.

Decreased elastic fibers and increased proteoglycans in the ligamentum flavum of patients with lumbar spinal canal stenosis.

Elastic fibers and proteoglycans are major components of the extracellular matrix and their changes have been reported in some pathological conditions. Further, recent studies have indicated that some glycosaminoglycans and proteoglycans inhibit elastic fiber assembly. The purpose of this study was to investigate changes of the elastic fibers and proteoglycans in the ligamentum flavum and analyze their relationships to thickening of the ligamentum flavum from lumbar spinal canal stenosis (LSCS). Ligamentum flavum samples were collected from 20 patients with LSCS (thickened flavum group) and 10 patients with lumbar disc herniation (non‐thickened flavum group) as a control. Elastica–Masson staining and alcian blue staining were used to compare the relationship between the changes in the elastic fibers and proteoglycans. Gene and protein expressions of the elastic fibers and proteoglycans were analyzed by quantitative reverse transcription polymerase chain reaction and immunohistochemistry. Histological changes indicated that proteoglycans mainly increased on the dorsal side of the ligamentum flavum in accordance with the decreased elastic fibers in the thickened flavum group. The gene and protein expressions of fibrillin‐2 and DANCE were significantly lower and decorin, lumican, osteoglycin, and versican were significantly higher in the thickened flavum group. Our study shows that elastic fibers decrease and proteoglycans increase in the thickened ligamentum flavum. Decreased gene expression of elastogenesis and disrupted elastic fiber assembly caused by increased proteoglycans may lead to a loss of elasticity in the thickened ligamentum flavum. Decreased elasticity may cause buckling of the tissue, which leads to thickening of the ligamentum flavum.

135 HYPOXIC CONDITIONS IN THE CAPSULE AFTER JOINT IMMOBILIZATION

Suda, H; +Hagiwara, Y; Ando, A; Onoda, Y; Chimoto, E; Hatori, K; Itoi, E Tohoku University, Sendai, Japan, Takeda General Hospital, Aizuwakamatsu, Japan, Funabashi Orthopaedic Clinic, Funabashi, Japan hagi@mail.tains.tohoku.ac.jp Introduction: Joint immobilization is a useful and commonly performed treatment modality in orthopaedics. However, it also causes unfavorable outcomes such as joint contracture, periarticular osteoporosis, and cartilage degeneration. Once joint contracture is established, it is extremely difficult to regain a full range of motion (ROM) with vigorous and extensive rehabilitation, or even with surgical treatment. In our previous reports, ROM increased after the posterior capsular release in a rat knee flexion contracture model, which indicated the capsule was one of the main causes of joint contracture (1). Further, angiogenesis factors of transforming growth factor-β1 and connective tissue growth factor were increased in the capsule after prolonged immobilization (2). This result might indicate presence of hypoxia in the capsule after immobilization. The purpose of this study was to elucidate changes in the number of blood vessels in the capsule and presence of hypoxia by hypoxyprobe-1 (HP-1) stain in the rat knee contracture model.