PURPOSE: Previous reports on the outcome of conservative treatment for dropped head syndrome (DHS) are scarce. The purpose of this study was to elucidate the efficacy of conservative treatment for DHS and to identify possible predictive factors relating to the outcome. METHODS: Among 76 DHS patients, conservative treatment (2-3 months collar application, active neck range of motion exercise, and occasional prescription of analgesics) succeeded in 17 patients (22.4%, group S, 4 male, 13 female, mean age 75.9 years). The treatment failed in the remaining 59 patients (group F). Clinical and radiological parameters were compared between the groups. Radiological findings of group S were compared between before treatment and at follow-up. RESULTS: Duration of disease was 6.6 ± 9.3 months in group S and 20.0 ± 27.6 months in group F. C2-7 angle (degree), the incidence of anterior slippage of the vertebra (%), reducibility (%), and upper thoracic kyphosis angle (degree) in group S/F were - 19.2 ± 17.5/- 34.6 ± 26.6, 23.5/62.7, 100/52, and 6.7 ± 8.6/17.9 ± 13.7, respectively. C2-7 angles were - 19.2 ± 17.5 degrees at pre-treatment and 10.2 ± 20.7 degrees at follow-up. These differences were statistically significant. CONCLUSIONS: The present study indicated that conservative treatment was successful in 22% of DHS patients, with improvement in their cervical kyphotic alignment. Shorter duration of disease, relatively smaller cervical kyphosis without anterior slippage of the vertebra, reducibility, and abundant compensation at the upper thoracic region were good indications for the success of conservative treatment.

PURPOSE: The pathology of dropped head syndrome (DHS) is diverse, and reports of surgery for DHS are scarce. We aimed to describe surgery for DHS and to investigate the surgical outcomes thereof. METHODS: We enrolled 40 consecutive patients (six males and 34 females; average age at surgery, 72.0 years) with DHS who underwent correction surgeries at a single institute. Short fusion (SF), with the extent of fixation mainly at the cervical region, was performed for 27 patients; long fusion (LF), involving the cervical and thoracic spine, for 13. Clinical and radiological outcomes were investigated, and factors analyzed using the Japanese Orthopedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ). RESULTS: All patients were able to gaze horizontally at the follow-up. Instances of five transient C5 palsy results, and five distal junctional kyphosis results were found, but no revisions were reported due to recurrence. Patients whose T1 slope-20° was smaller than the C2-7 angle postoperatively exhibited better clinical outcomes in the three domains of the JOACMEQ, regardless of the extent of fixation. CONCLUSION: For cases where the T1 slope is relatively small, and approximately 10° of cervical lordosis is predicted to be obtained postoperatively, SF is appropriate. Alternatively, for cases with higher T1 slope, obtaining a cervical lordosis over 20° has a risk of postoperative complications. For such cases, it is an option to perform an LF involving the cervical and thoracic spine.

BACKGROUND: K-line is widely recognized as a useful index for evaluating cervical alignment and the size of the cervical ossification at the posterior longitudinal ligament (OPLL). The purpose of this study was to investigate whether the K-line could be a useful clinical tool for predicting the prognosis of laminoplasty (LP) for cervical spondylotic myelopathy (CSM). METHODS: Adult CSM patients scheduled for cervical LP were recruited for this study. C2-7 angle, local kyphosis angle, and K-line was evaluated by T2-weighted sagittal magnetic resonance imaging (MRI). Clinical findings were evaluated by the JOA score and the recovery rate. Clinical and radiological findings were evaluated preoperation and final follow-up. Patients were grouped into K-line ( +) and K-line (-). Patients with Kline (-) were further divided into two sub-groups: disc type (anterior cord compression due to disc protrusion with kyphosis) and osseous type (due to osseous structure such as osteophyte). RESULTS: Sixty-eight patients were included in the analysis. The recovery rate of K-line (-) group (n = 11,19.4%) was significantly worse than that of K-line ( +) group (n = 57, 50.6%, p<0.05). Among 11 K-line (-) patients, 7 were disc type and 4 were osseous type. Over the period of follow-up, the disc type K-line (-) patients changed to K-line ( +) and showed significantly better recovery rate (27.6%) compared to the osseous type K-line (-) group (5.0%, p < 0.05). CONCLUSION: The present of this study indicate that K-line may have a predictive value for clinical outcome in patients undergoing LP for CSM. K-line (-) of osseous type was worse than k-line (-) of disc type.

There is no consensus on a treatment strategy for spinal giant cell tumor of bone (GCTB) because of the difficulty in their treatment. Treatment options often include the use of the controversial denosumab, an antibody therapy aimed at tumor shrinkage, different curettage techniques, resection, or a combination of these therapies. The current study aimed to identify treatment methods associated with favorable outcomes in patients with spinal GCTB. We retrospectively reviewed 5 patients with spinal GCTB, including patients with tumors of the sacrum, treated at our hospital between September 2011 and November 2020. Two men and 3 women were included in the study. The median follow-up period was 74 months (range: 14-108 months). We surveyed the tumor site, treatment method, denosumab use, and outcomes. The median age was 17 years (range: 17-42 years). There were 2 cases of sacral GCTB and 1 case each of lumbar, cervical, and thoracic vertebral GCTB. The comorbidities observed included hepatitis, malignant lymphoma, atopic dermatitis, and asthma. The treatment method included zoledronic acid after embolization and denosumab, denosumab only, curettage and posterior fusion, and curettage resection after embolization and anterior and posterior fusion. Denosumab was used in all cases. Three patients were continuously disease-free, 1 patient with no evidence of disease, and 1 patient alive with disease. Aggressive treatment, especially surgical treatment, may lead to good results in spinal GCTB.

Once-weekly teriparatide treatment is widely used in the treatment of osteoporosis in Japan but the mechanisms causing the increase in bone mineral density (BMD) of the lumbar spine remain unknown. Methods: This prospective study examined the effects of once-weekly teriparatide treatment on the serum levels of sclerostin, osteocalcin, and bone formation markers as well as BMD of the lumbar spine and femoral neck in 32 postmenopausal women with osteoporosis. Results: The mean age of subjects was 76.3 +/- 7.0 years old. Teriparatide significantly reduced serum sclerostin levels at 12 and 18 months in postmenopausal women with osteoporosis, and significantly increased serum osteocalcin levels at 3,12 and 18 months and PINP levels at 1 and 3 months, respectively. Teriparatide treatment significantly increased BMD of the lumbar spine at 6, 12, and 18 months, but did not affect BMD of the femoral neck. Examination of the relationships between percent changes in bone metabolic indices and BMD of the lumbar spine during the teriparatide treatment showed serum sclerostin changes at 3 months were negatively correlated with BMD changes of the lumbar spine at 6, 12, and 18 months. Serum osteocalcin changes were not correlated with BMD changes in the lumbar spine at 12 months. Conclusions: The present study showed that once-weekly teriparatide treatment reduced serum sclerostin levels in postmenopausal women with osteoporosis. The effects of teriparatide on sclerostin may be associated with the response of the BMD of the lumbar spine. (C) 2018 Published by Elsevier B.V. on behalf of The Japanese Orthopaedic Association.

Purpose: To elucidate the usefulness of the pedicle marker (PM) for more accurate insertion of cervical pedicle screws (CPSs).Methods: Artificial bone study. Fifty pedicles of five artificial bone specimens were examined. PMs were inserted in five different positions (confirmed by computed tomography (CT)); (1) insertion angle correct, insertion point too medial, (2) both insertion angle and insertion point correct, (3) insertion angle correct, insertion point too lateral, (4) insertion point correct, insertion angle too big, and (5) insertion point correct, insertion angle too small. Oblique radiographs were taken to assess the relationships between the pedicle and the PM as IN and OUT. Clinical series. A total of 228 CPSs were inserted in 59 consecutive patients using either CT cutout technique or navigation. During surgery, PMs were inserted, and the locations were confirmed on oblique fluoroscopic views in CT cutout technique and intraoperative CT in navigation. Intraoperative misplaced PM and postoperative misplaced CPS were assessed.Results: Artificial bone study. Evaluation found 67% of Types 1 and 100% of Type 5 seemed to be IN on the oblique views at 10, 20, and 30 degrees because the pedicle and PM overlapped. All cases of Type 2 were IN at any angles. Almost all Types 3 and 4 were OUT at any angle. Clinical series. The route was modified under the recognition of misplaced PM during surgery in 3.7% (all Type 4) of CT cutout and 4.2% (four Type 4 and one Type 5) of navigation. One CPS was malpositioned (0.9%, Type 1) in CT cutout and none in navigation by postoperative CT.Conclusions: By applying PM, lateral displacement is easier to recognize in fluoroscopy. Medial misplacement should be aware because the PM and the rim of the pedicle overlap. Even after launching navigation, PM helped to indicate the wrong route before inserting the CPS during surgery. (C) 2018 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

Purpose: Correction surgery for cervical degenerative kyphosis (CDK) may carry a greater risk of causing neural complications such as spinal cord injury and C5 nerve palsy because spinal canal stenosis, osteoarthritis of the facet, and consequent foraminal stenosis may coexist with CDK. We have produced an algorithmic strategy of surgical intervention for CDK, and report the outcome.Methods: Thirty-one patients who underwent correction surgery for CDK, with a kyphotic angle of 20 degrees or more (from 20 to 74) were involved. An algorithmic surgical strategy is shown. Clinical and radiological outcomes were examined amongst the groups.Results: Recovery rate of the JOA score was a mean of 44%. Preoperative kyphotic angle and correction angle were; 24.4 degrees and 26.5 degrees in P, 38.4 degrees and 41.1 degrees in AP, and 42.0 degrees and 46.9 degrees in PAP respectively. No spinal cord injury was found. Five cases of C5 nerve palsy occurred in P, and one in AP. Four cases of C5 palsy occurred in seven patients in PAP, although prophylactic foraminotomy was performed. All C5 palsy patients recovered fully at follow-up.Conclusions: This study showed that our algorithmic surgical strategy for CDK is acceptable because we obtained good outcomes, and no catastrophic complications occurred. Although we did not intend to obtain excessive postoperative lordosis, we still had several incidence of C5 nerve palsy. We have to be aware of this incidence in PAP, which required a massive range of realignment. The incidence occurred even after we performed prophylactic foraminotomy, however, this procedure may lessen the severity of C5 palsy because those were all transient. (C) 2018 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

PURPOSE: Correction surgery for cervical degenerative kyphosis (CDK) may carry a greater risk of causing neural complications such as spinal cord injury and C5 nerve palsy because spinal canal stenosis, osteoarthritis of the facet, and consequent foraminal stenosis may coexist with CDK. We have produced an algorithmic strategy of surgical intervention for CDK, and report the outcome. METHODS: Thirty-one patients who underwent correction surgery for CDK, with a kyphotic angle of 20° or more (from 20 to 74) were involved. An algorithmic surgical strategy is shown. Clinical and radiological outcomes were examined amongst the groups. RESULTS: Recovery rate of the JOA score was a mean of 44%. Preoperative kyphotic angle and correction angle were; 24.4°and 26.5°in P, 38.4°and 41.1°in AP, and 42.0°and 46.9°in PAP respectively. No spinal cord injury was found. Five cases of C5 nerve palsy occurred in P, and one in AP. Four cases of C5 palsy occurred in seven patients in PAP, although prophylactic foraminotomy was performed. All C5 palsy patients recovered fully at follow-up. CONCLUSIONS: This study showed that our algorithmic surgical strategy for CDK is acceptable because we obtained good outcomes, and no catastrophic complications occurred. Although we did not intend to obtain excessive postoperative lordosis, we still had several incidence of C5 nerve palsy. We have to be aware of this incidence in PAP, which required a massive range of realignment. The incidence occurred even after we performed prophylactic foraminotomy, however, this procedure may lessen the severity of C5 palsy because those were all transient.

Recent data suggest that the lectin-like oxidized low-density lipoprotein (ox-LDL) receptor-1 (LOX-1)/ox-LDL system may be involved in the pathogenesis of arthritis. We aimed to demonstrate the roles of the LOX-1/ox-LDL system in arthritis development by using LOX-1 knockout (KO) mice. Arthritis was induced in the right knees of C57Bl/6 wild-type (WT) and LOX-1 KO mice via zymosan injection. Saline was injected in the left knees. Arthritis development was evaluated using inflammatory cell infiltration, synovial hyperplasia, and cartilage degeneration scores at 1, 3, and 7 days after administration. LOX-1, ox-LDL, and matrix metalloproteinase-3 (MMP-3) expression in the synovial cells and chondrocytes was evaluated by immunohistochemistry. The LOX-1, ox-LDL, and MMP-3 expression levels in synovial cells were scored on a grading scale. The positive cell rate of LOX-1, ox-LDL, and MMP-3 in chondrocytes was measured. The correlation between the positive cell rate of LOX-1 or ox-LDL and the cartilage degeneration score was also examined. Inflammatory cell infiltration, synovial hyperplasia, and cartilage degeneration were significantly reduced in the LOX-1 KOmice with zymosan-induced arthritis (ZIA) compared to WT mice with ZIA. In the saline-injected knees, no apparent arthritic changes were observed. LOX-1 and ox-LDL expression in synovial cells and chondrocytes were detected in the knees of WT mice with ZIA. No LOX-1 and ox-LDL expression was detected in the knees of LOX-1 KOmice with ZIA or the saline-injected knees of both mice. MMP-3 expression in the synovial cells and chondrocytes was also detected in knees of both mice with ZIA, and was significantly less in the LOX-1 KO mice than in WT mice. The positive cell rate of LOX-1 or ox-LDL and the cartilage degeneration score showed a positive correlation. Our data show the involvement of the LOX-1/ox-LDL system in murine ZIA development. LOX-1-positive synovial cells and chondrocytes are potential therapeutic targets for arthritis prevention.

骨粗鬆症性椎体を4椎体以上あるいはグレード3の椎体骨折を有する場合に立位矢状面バランスが不良になる。特にSVAが95mmを超える脊柱バランス破綻を引き起こすと腰椎機能、歩行機能が著しく障害される。(著者抄録)

Progression of kyphotic deformity at the middle/lower cervical spine can cause difficulty with horizontal gaze, so compensation at other spinopelvic parts may occur. However, the precise mechanism remains unclear. The present study investigated the effect of correction surgery for cervical kyphosis on the compensatory mechanisms in overall spinopelvic sagittal alignment. Forty-one patients, comprising 23 males and 18 females (mean age 67 years), underwent correction surgery for cervical kyphosis using the posterior screw-rod system. Spinopelvic lateral radiographs in the standing position were taken before and after surgery. C0-1 angle, C1-2 angle, clivo-axial angle (CAA), C2-7 angle, thoracic kyphosis, lumbar lordosis, pelvic incidence, pelvic tilt, and sacral slope were measured. Correlations between C2-7 angle and these parameters before surgery, and correlations between the correction angle of cervical kyphosis and postoperative changes of these parameters were evaluated. Negative correlations were found between the C2-7 angle and CAA (R = -0.640, p < 0.01), and C2-7 angle and C0-1 angle (R = -0.762, p < 0.001) before surgery. Negative correlations were found between the correction angle of C2-7 and change of CAA (R = -0.718, p < 0.001), and between the correction angle of C2-7 and change of C0-1 angle (R = -0.672, p < 0.01) after surgery. The present study demonstrated that C0-1 angle and CAA are more important in the compensatory mechanism for kyphotic deformity at the middle/lower cervical spine compared to downward parameters. That is, to maintain horizontal gaze, lordosis increases at the cranio-cervical junction with greater kyphosis at the middle/lower cervical spine. Correction of cervical kyphosis in the middle/lower cervical spine resulted in normalization of the C0-1 angle and CAA because the compensatory mechanism at the cranio-cervical junction for obtaining horizontal gaze was no longer necessary after surgical intervention.

Background: DVT is one of the major postoperative complications of joint replacement surgery of the lower extremity which can cause catastrophic complications such as pulmonary embolism. However, little is known about the incidence of DVT after spine surgery. The purpose of this study was to examine predictable factors of DVT after spine surgery. Methods: This study included 194 patients who underwent spine surgery (104 males, 90 females, mean age 65.7 years). Postoperative DVT was detected using duplex ultrasonography (DUS). Age, sex, BMI, operation time, amount of bleeding, preoperative ambulatory status, usage of instrumentation, and preoperative serum levels of D-dimer were compared between the DVT(+) and DVT(-) groups to establish predictors for postoperative DVT. Cut-off value of the preoperative level of D-dimer was calculated using ROC analysis. Results: Postoperative DVT was detected in 57 patients (29.4%). No patients showed clinical signs of DVT or pulmonary embolism. Sex, age, BMI, preoperative non-ambulatory status, and preoperative levels of D-dimer were significantly different between the DVT(+) and DVT(-) groups. However, age and BMI was not significantly different factor in logistic regression analysis. Cut-off value of preoperative D-dimer was 1.4 mu g/ml. Conclusion: It was suggested that perioperative application of DUS for detecting DVT in the lower extremities should be performed on patients undergoing spine surgery who are female, non-ambulatory, and with higher preoperative D-dimer serum level. (C) 2016 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

骨粗鬆症の一次予防としてSERMの有効性を検討した。対象は閉経後の女性30名(平均年齢71.1歳)で、治療薬としてSERM、バゼドキシフェンを3年以上服用し、追跡可能な患者とした。その結果、腰椎YAM値が80〜65%、既存骨折を伴わない患者の大腿骨YAM値は腰椎に比して低値であった。この領域の患者群への治療介入は3年間の結果から早期というより適正な時期であったと考えられた。以上より、SERMによる治療は腰椎BMDが維持され。骨折の発生を認めないことが示唆された。

Objectives. Glucocorticoid (GC) is usually used for the treatment of systemic inflammatory diseases. We performed the prospective study to clarify the effects of alendronate or alfacalcidol on bone metabolic indices and bone mineral density (BMD) in 90 patients treated with GC for ophthalmologic diseases without systemic disorders for 12 months. Methods. BMD was measured with dual-energy X-ray absorptiometry. Serum bone-specific alkaline phosphatase (BAP) and urinary Type I collagen cross-linked N-telopeptide (NTx) were measured as bone metabolic indices. Results. BMD values in the alendronate group were significantly higher than those in the alfacalcidol group during 12 months. Alendronate significantly reduced urinary NTX levels from the baseline during 12 months, although alfacalcidol did not affect them. Serum BAP levels in the alendronate group were significantly lower than those in the alfacalcidol group during 9 months. The effects of alendronate on BMD and NTx in male patients seemed to be somewhat potent compared with those in female patients. Conclusions. Alendronate is effective to prevent BMD loss and bone resorption induced by GC treatment in patients with ophthalmic diseases without systemic disorders. There might be sex differences in the potency of alendronate effects.

当科で経験した原発性骨粗鬆症女性患者118例を対象に、骨折の有無で骨折を認めない74例(N群)、脊椎骨折を有する28例(S群)、大腿骨近位部骨折を有する16例(H群)に分け、FRAXのhip fracture riskとHSAを用いた大腿骨強度を比較検討した。その結果、H群はN群と比べ、FRAXによる骨折リスク、骨密度、骨強度がいずれも有意に劣っていた。S群はリスク、骨密度、骨強度共にN群とH群の中間に位置した。HSAを用いた大腿骨強度では、H群はN群と比べ、大腿骨頸部・転子部におけるCT、CSA、SM、BRの全項目が有意に劣っていた。大腿骨近位部骨折の発生群は強い骨粗鬆症状態であり、FRAXでの大腿骨近位部骨折の発症に注意が必要なHipリスクは8%未満になると考えられた。

研究について説明・同意の得られた膠原病、糖尿病などの内科的疾患を伴わない骨粗鬆症治療薬内服歴がない47名(男性40名、女性7名、23〜51歳・平均33.4歳)を対象に、HSA(hip structure analysis)による大腿骨骨質評価の精度について検討した。DXA機器で骨密度(BMD)測定を行い、得られた情報をHSAソフトで解析し、骨強度評価項目section modulus(SM)、buckling ratio(BR)を求め、各値のCV値および最小有意変化(LSC)を算出した。大腿骨BMD測定のCV値は1.2%、LSCは2.8%であった。この条件下でSMのCV値は頸部3.7%、転子部5.1%、骨幹部2.0%、これに伴い、LSCは頸部8.7%、転子部11.9%、骨幹部4.7%であった。BRのCV値は頸部4.0%、転子部3.7%、骨幹部5.7%、LSCは頸部9.3%、転子部8.8%、骨幹部13.4%であった。

We encountered an example of a diagnosis of anaplastic large cell lymphoma (ALCL), i.e. a fourteen-year-old-boy with persistent spike fever for 2 months who was found to have an osteolytic lesion. At the time of admission, when the first biopsy was performed, an osteolytic lesion in his lumbar vertebra (L1) was revealed, and the finding was a pathological diagnosis of osteomyelitis. Then, as the high fever still persisted with increasing serum levels of C-reactive proteins and the soluble form IL-2 receptor despite performing antibiotic therapy, a second examination was carried out 2 months later and found additional osteolytic lesions located in the right ilium and lymphadenopathy in the pelvic cavity. The second biopsy specimens from the lymphadenopathy were positive for CD30 and anapestic lymphoma kinase. Chemotherapy, which was conducted according to ALCL99, resolved his symptoms. At the time of admission, IL-6 was high, hypercytokinemia, spike fever and bone lesions occurring before ALCL developed. Therefore, these findings suggest that the prior occurrence of hypercytokinemia such as IL-6 plays an important role in the development of ALCL.

Objective. Intraarticular administration of hyaluronic acid (HA) has been widely used for the treatment of osteoarthritis (OA). Fibrinolysis is closely related to the pericellular proteolysis involved in inflammation. However, the role of HA in the regulation of fibrinolytic factors is not yet known. We investigated the effect of HA on the pericellular fibrinolytic system of human synovial fibroblasts derived from OA and rheumatoid arthritis (RA). Methods. Human synovial fibroblasts obtained from OA and RA were cultured in the presence and absence of HA. The antigen of urokinase-type plasminogen activator (u-PA) and plasminogen activator inhibitor-1 (PAI-1) were measured by ELISA, and u-PA activity was evaluated by electrophoretic enzymography. The binding assay of u-PA and the immunohistochemical analysis of u-PA were employed to detect u-PA receptor (u-PAR). Results. HA suppressed the secretion of both u-PA and PAI-1 antigens from the synovial fibroblasts of OA to their conditioned medium. Suppression of u-PA activity in OA synovial fibroblasts was more marked than in those of RA. The u-PA binding assay of OA and RA synovial fibroblasts revealed a single class of binding site: dissociation constant (Kd) 23.7 nM, maximal number of binding sites (B(max)) 3.11 x 104 binding sites/cell Kd 16.5 nM, B(max) of 9.88 x 104 binding sites/cell, respectively. HA decreased B(max) in fibroblasts of both OA and RA. Immunohistochemical analysis showed that u-PAR was constitutively expressed in both synovial fibroblasts, but if these cells were treated with HA, the decrease of the staining of u-PAR was more pronounced in the cells of RA than in OA. Conclusion. Pericellular fibrinolytic activity mediated by the u-PA/u-PAR system and PAI-1 was attenuated by HA in synovial fibroblasts derived from OA and RA. Thus, HA may be a useful agent to inhibit the inflammation of arthritis.

Objective. Intraarticular administration of hyaluronic acid (HA) has been widely used for the treatment of osteoarthritis (OA). Fibrinolysis is closely related to the pericellular proteolysis involved in inflammation. However, the role of HA in the regulation of fibrinolytic factors is not yet known. We investigated the effect of HA on the pericellular fibrinolytic system of human synovial fibroblasts derived from OA and rheumatoid arthritis (RA). Methods. Human synovial fibroblasts obtained from OA and RA were cultured in the presence and absence of HA. The antigen of urokinase-type plasminogen activator (u-PA) and plasminogen activator inhibitor-1 (PAI-1) were measured by ELISA, and u-PA activity was evaluated by electrophoretic enzymography. The binding assay of u-PA and the immunohistochemical analysis of u-PA were employed to detect u-PA receptor (u-PAR). Results. HA suppressed the secretion of both u-PA and PAI-1 antigens from the synovial fibroblasts of OA to their conditioned medium. Suppression of u-PA activity in OA synovial fibroblasts was more marked than in those of RA. The u-PA binding assay of OA and RA synovial fibroblasts revealed a single class of binding site: dissociation constant (Kd) 23.7 nM, maximal number of binding sites (B(max)) 3.11 x 104 binding sites/cell Kd 16.5 nM, B(max) of 9.88 x 104 binding sites/cell, respectively. HA decreased B(max) in fibroblasts of both OA and RA. Immunohistochemical analysis showed that u-PAR was constitutively expressed in both synovial fibroblasts, but if these cells were treated with HA, the decrease of the staining of u-PAR was more pronounced in the cells of RA than in OA. Conclusion. Pericellular fibrinolytic activity mediated by the u-PA/u-PAR system and PAI-1 was attenuated by HA in synovial fibroblasts derived from OA and RA. Thus, HA may be a useful agent to inhibit the inflammation of arthritis.

Twelve patients with osteoarthritis of the knee were administrated hyaluronic acid (HA), and measured for fibrinolytic factors on synovial fluids. It was observed that urokinase-type plasminogen activator (u-PA) activity is enhanced 3 h after administration of HA, and that the activity gradually decreased from the 2nd to the 4th week on the patients whose clinical parameters showed improvement. Antigen of u-PA and PA inhibitor-1 (PAI-1) were increased 3 h after the administration of HA in the cases that improved. However, u-PA antigen gradually decreased from the 2nd to the 4th week similarly to u-PA activity. On the other hand PAI-1 antigen was increased from the 2nd to the 4th week in the improved cases. These results demonstrate that the decrease of fibrinolytic activity in synovial fluid is associated with the improvement of osteoarthritis by treatment with HA.

Twelve patients with osteoarthritis of the knee were administrated hyaluronic acid (HA), and measured for fibrinolytic factors on synovial fluids. It was observed that urokinase-type plasminogen activator (u-PA) activity is enhanced 3 h after administration of HA, and that the activity gradually decreased from the 2nd to the 4th week on the patients whose clinical parameters showed improvement. Antigen of u-PA and PA inhibitor-1 (PAI-1) were increased 3 h after the administration of HA in the cases that improved. However, u-PA antigen gradually decreased from the 2nd to the 4th week similarly to u-PA activity. On the other hand PAI-1 antigen was increased from the 2nd to the 4th week in the improved cases. These results demonstrate that the decrease of fibrinolytic activity in synovial fluid is associated with the improvement of osteoarthritis by treatment with HA.