Medial meniscus extrusion is invariably observed and consistent with tibial osteophyte width in elderly populations: The Bunkyo Health Study.

We reported that the full-length width of medial tibial osteophytes comprising cartilage and bone parts correlates with medial meniscus extrusion (MME) in early-stage knee osteoarthritis (OA). However, no data exist on the prevalence of MME and its relationship with osteophytes in the elderly population. 1191 elderly individuals (females 57%; 72.9 years old on average) in the Bunkyo Health Study underwent standing plain radiograph and proton density-weighted MRI on knee joints. MRI-detected OA changes were evaluated according to the Whole-Organ Magnetic Resonance Imaging Score. A new method of assessing the cartilage and bone parts of osteophytes was developed using pseudo-coloring images of proton density-weighted fat-suppressed MRI. Most subjects showed Kellgren-Lawrence grade 1 or 2 radiographic medial knee OA (88.1%), MME (98.7%, 3.90 ± 2.01 mm), and medial tibial osteophytes (99.3%, 3.27 ± 1.50 mm). Regarding OA changes, MME was closely associated with the full-length width of medial tibial osteophytes (ß = 1.114; 95% CI 1.069-1.159; p < 0.001) in line with osteophyte width (intraclass correlation coefficient, 0.804; 95% CI 0.783-0.823). Our data revealed that MME and medial tibial osteophytes are observed in the elderly and demonstrate that the degree of MME is consistent with the full-length width of medial tibial osteophytes, suggesting that osteophytes might be implicated in MME.

Anterior meniscus extrusion is associated with anterior tibial osteophyte width in knee osteoarthritis - The Bunkyo Health Study.

Background: In knee osteoarthritis (OA), medial meniscus extrudes both medially and anteriorly. We reported that full-length width of medial tibial osteophyte, which comprises cartilage and bone parts, is directly associated with medial meniscus extrusion in early-stage knee OA and hypothesized that anterior tibial osteophyte (ATO) is also associated with anterior meniscus extrusion (AME). Thus, we aimed to examine their prevalence and relationship. Methods: Elderly subjects (638 females and 507 males; average 72.9 years old) in the Bunkyo Health Study cohort were enrolled. MRI-detected OA changes were evaluated according to the Whole Organ Magnetic Resonance Imaging Score. ATO was evaluated using the method which can assess both cartilage and bone parts of osteophyte by pseudo-coloring images of proton density-weighted fat-suppressed MRI. Results: Most subjects showed the Kellgren-Lawrence grade 1/2 of the medial knee OA (88.1%), AME (94.3%, 3.7 â€‹± â€‹2.2 â€‹mm), and ATO (99.6%, 4.2 â€‹± â€‹1.5 â€‹mm). Among the OA changes, AME was most closely associated with full-length width of ATO (multivariable ߠ​= â€‹0.877, p â€‹< â€‹0.001). The area under the receiver operating characteristic curve for determining the presence of AME as evaluated by ATO width was 0.75 (95% confidence interval 0.60-0.84, p â€‹< â€‹0.001). The odds ratio for the presence of AME as evaluated by ATO width at 2.9 â€‹mm was 7.16 (4.23-12.15, p â€‹< â€‹0.001, age, gender, BMI, and K-L adjusted). Conclusions: AME and ATO were inevitably observed in the elderly subjects and AME was closely associated with full-length width of ATO. Our study provides the first evidence on the close relationship between AME and ATO in knee OA.

Medial meniscus extrusion is directly correlated with medial tibial osteophyte in patients received reconstruction surgery for anterior cruciate ligament injury: A longitudinal study.

Objective: Anterior cruciate ligament (ACL) injury is one of the causes for post-traumatic knee osteoarthritis (OA), and ACL reconstruction surgery is reportedly unable to prevent OA development. In early-stage knee OA, medial meniscus extrusion (MME) is closely correlated with tibial medial osteophyte width, which consists of bone and cartilage -parts. However, the relationship between MME and osteophyte in ACL-injured patients remains elusive. We examined MME and osteophyte and their relationship in ACL-injured patients before and after surgery. Design: Thirty ACL-injured patients who underwent surgery (30.7 years old, on average) were enrolled. Correlations between magnetic resonance imaging (MRI)-detected OA changes and MME before and after surgery (7.6 months interval) were analyzed. Results: MME (>3 â€‹mm) was present in 16.7% and 26.7% of the patients before and after surgery, respectively, and MME was significantly increased after surgery (2.4 â€‹± â€‹1.3 â€‹mm) than before surgery (1.9 â€‹± â€‹1.2 â€‹mm) (p â€‹< â€‹0.0001). Full-length tibial osteophyte width measured by T2 mapping MRI was significantly increased after surgery (1.9 â€‹± â€‹0.7 â€‹mm) than before surgery (1.4 â€‹± â€‹0.6 â€‹mm) (p â€‹< â€‹0.0001). Among OA structural changes, only medial tibial osteophyte width directly correlated with MME before surgery (ߠ​= â€‹0.962) (p â€‹< â€‹0.001) and after surgery (ߠ​= â€‹0.928) (p â€‹= â€‹0.001). All the patients with MME had medial tibial osteophyte before and after surgery. A direct correlation was observed between changes of MME and those of medial tibial osteophyte width before and after surgery (r â€‹= â€‹0.63) (p â€‹< â€‹0.0001). Conclusion: MME and medial tibial osteophyte were simultaneously increased after surgery. In addition to close correlation between MME and medial tibial osteophyte width, changes of MME and medial tibial osteophyte width before and after surgery were directly correlated.

Medial meniscus extrusion is a determinant factor for the gait speed among MRI-detected structural alterations of knee osteoarthritis.

Objective: Knee osteoarthritis (OA) is one of the most common causes for reduction in gait speed. Research into the mechanism of underlying knee OA pain and other symptoms such as the reduction in the gait speed is essential to development of disease-modifying treatments for knee OA. We examined the magnetic resonance imaging (MRI)-detected structural alterations in knee joints those were associated with gait speed in knee OA patients. Design: In this cross-sectional study, structural alterations in knee joints of 74 knee OA patients (51 females; mean 72.2 years old) were evaluated by MRI, and subjects' gait speed was measured. Results: The mean self-selected gait speed of the subjects was 0.73 â€‹± â€‹0.21 â€‹m/s. A simple linear regression analysis revealed that MME was only correlated with the gait speed of the subjects with knee OA, while cartilage lesion, bone marrow lesion, subchondral bone cyst, subchondral cyst, osteophytes and meniscal pathology were not. A multiple regression analysis revealed that only MME was associated with gait speed (R2 â€‹= â€‹0.484, p â€‹< â€‹0.001). The area under the receiver operating characteristic curve for determining <0.8 â€‹m/s of gait speed as evaluated by MME were 0.72 (95% confidence interval: 0.60-0.84). The relative risks at a cut-off <0.8 â€‹m/s for gait speed as evaluated by MME at 6.2 â€‹mm were 2.19 (1.28-3.46, p â€‹= â€‹0.01). Conclusions: MME was associated with and the determinant for gait speed among MRI-detected structural alterations in patients with knee OA, suggesting the importance for elucidating the etiology of MME for developing a disease-modifying treatment for knee OA.

Physiologic Leg Bowing is not a Physiologic Condition but Instead is Associated with Vitamin D Disorders in Toddlers.

When children around 2-year-old show leg bowing without lower-limb radiographic abnormalities for rickets, the leg bowing is classified as "physiologic" genu varum without conducting a blood test. However, it has recently been suggested that toddlers who are diagnosed with physiologic genu varum may in fact have some form of bone metabolic disorder. In this 1:2 case-control study, blood samples were obtained from 33 toddlers with genu varum without radiographic abnormalities for rickets and 66 age- and gender-matched healthy children. Serum alkaline phosphatase (sALP), intact parathyroid hormone (siPTH), 25-hydroxy vitamin D [s25(OH)D], calcium (sCa), and inorganic phosphate (sP) were measured. s25(OH)D of the subjects with genu varum (24.8 ng/ml) were significantly lower than those of the control (33.6 ng/ml) (p < 0.001). The frequency of vitamin D insufficiency/deficiency (< 20 ng/ml) of the subjects with genu varum (39%) was significantly higher than that in the control (14%) (p = 0.004) (odds ratio by vitamin D insufficiency/deficiency: 4.1 [1.5-11.1, p = 0.004]). sCa in subjects with genu varum (10.2 ng/ml) were significantly higher than in control (9.8 ng/ml) (p < 0.001), as were sALP (1057 IU/l) and siPTH (28.4 pg/ml) (740 IU/l and 8.8 pg/ml in control, respectively; p < 0.001). siPTH levels were associated with s25(OH)D levels in subjects with genu varum (r = - 0.57, p < 0.001), while no association was observed in the control (r = 0.11, p = 0.36). Genu varum without radiographic abnormalities of rickets was associated with both vitamin D and bone-metabolic disorders in toddlers, indicating that physiologic genu varum is not a physiologic condition in toddlers.

The increase in bone mineral density by bisphosphonate with active vitamin D analog is associated with the serum calcium level within the reference interval in postmenopausal osteoporosis.

OBJECTIVES: To examine the factors associated with increase in lumbar spine bone mineral density (LS-BMD) by bisphosphonates (BPs) with active vitamin D analog (aVD). METHODS: Two independent postmenopausal osteoporotic patients treated by BPs with aVD for 24 months (Study 1: n = 93, Study 2: n = 99) were retrospectively analyzed. RESULTS: In Study 1, LS-BMD of the patients significantly increased for 24 m (5.4%, p < .001). A multiple regression analysis among baseline characteristics revealed that serum calcium (sCa: 8.5-10.5 mg/dL) was associated with an increased LS-BMD by treatment (r2: 0.088, p = .02). While average sCa of the patients was 9.2 mg/dL before treatment, it increased time-dependently to 9.6 mg/dL for 24 m by treatment. As each patient had their LS-BMD five times during the study, there were four instances of %LS-BMD in each patient, resulting in 372 instances of %LS-BMD in Study 1. The smallest Akaike's information criterion value for the most appropriate cut-off levels of sCa for %LS-BMD by treatment every 6 m was 9.3 mg/dL. The %LS-BMD by treatment for 6 m during 24 m period in patients with sCa ≥9.3 mg/dL (1.5%) was significantly higher than that in patients with sCa <9.3 mg/dL (0.8%, p = .038). The results of Study 2 were similar to those of Study 1, confirming the phenomena observed. CONCLUSION: sCa was associated with an increased LS-BMD by BPs with aVD.

Bone marrow lesion is associated with disability for activities of daily living in patients with early stage knee osteoarthritis.

Osteoarthritis of the knee (knee OA) induces pain, loss of mobility and diminished activities of daily living (ADL). Although an understanding of the pathophysiology of early stage knee OA has been developed, the structural changes associated with disability for ADL in early stage knee OA are still unclear. The aim of the present study was to examine magnetic resonance imaging (MRI)-detected changes associated with disability for ADL in patients with early stage knee OA. One hundred and thirty-two patients with early stage medial knee OA (Kellgren-Lawrence grade ≤ 2) who first visited the outpatient clinic at our university hospital were included. They were also examined by 3.0-Tesla knee MRI. The OA-associated structural changes were scored using the Whole-Organ Magnetic Resonance Imaging Score (WORMS), and clinical manifestations were evaluated by the Japanese Knee Osteoarthritis Measure (JKOM). Median quartile regression was used for the analysis. Cartilage lesion, subchondral bone attrition and osteophytes were observed in all patients. Bone marrow lesions (BMLs) and synovitis were observed in 60% and 55% of the patients, respectively. Subchondral cysts and ligament changes were observed in 6% and 17% of the patients, respectively. Pain severity of the patients was associated with medial cartilage lesions (coefficient 2.50, 95% confidence interval 0.61-4.40, p < 0.01). Disability for ADL of the patients was associated with BMLs in the medial side of the knee joint (0.82, 0.21-1.02, p = 0.04). BMLs in the medial side of the knee joint were associated with disability for ADL of patients with early stage medial knee OA.

Association between leg bowing and serum alkaline phosphatase level regardless of the presence of a radiographic growth plate abnormality in pediatric patients with genu varum.

When children around 2 years of age show leg bowing and diseases are ruled out based on radiographic findings without conducting blood tests, they are classified as "physiologic" genu varum. Since whether or not physiologic genu varum is associated with bone metabolism is unclear, this study was conducted to clarify the association between genu varum and bone metabolism in children. Thirty-five pediatric patients with genu varm who visited our out-patient clinic were enrolled. While two of the 35 children had nutritional rickets, showing abnormalities on both blood test (ALP, ≥1000 IU/L; iPTH, >65 pg/mL and 25(OH)D, ≤20 ng/mL) and radiographs (such as cupping, fraying or splaying), five of 35 children showed abnormalities on blood tests but not radiographs. While metaphyseal-diaphyseal angle (MDA) correlated with serum 25-hydroxy vitamin D (r = -0.35, p = 0.04) and magnesium (r = -0.36, p = 0.04), MDA and femorotibial angle (FTA) correlated with alkaline phosphatase (r = 0.43, p = 0.01 and r = 0.51, p = 0.006, respectively). A ridge regression analysis adjusted for age and body mass index indicated that ALP was associated with MDA and FTA. A logistic regression analysis adjusted for age and BMI indicated that higher ALP influenced an MDA >11°, which indicates the risk for the progression of genu varum (odds ratio 1.002, 95% confidence interval 1.0003-1.003, p = 0.021). The higher ALP (+100 IU), the higher risk of an MDA >11° (odds ratio 1.22). In conclusion, genu varum is associated with the alkaline phosphatase level regardless of the presence of radiographic abnormalities in the growth plate in children.

Association of medial meniscal extrusion with medial tibial osteophyte distance detected by T2 mapping MRI in patients with early-stage knee osteoarthritis.

BACKGROUND: Medial meniscal extrusion (MME) is associated with progression of medial knee osteoarthritis (OA), but no or little information is available for relationships between MME and osteophytes, which are found in cartilage and bone parts. Because of the limitation in detectability of the cartilage part of osteophytes by radiography or conventional magnetic resonance imaging (MRI), the rate of development and size of osteophytes appear to have been underestimated. Because T2 mapping MRI may enable us to evaluate the cartilage part of osteophytes, we aimed to examine the association between MME and OA-related changes, including osteophytes, by using conventional and T2 mapping MRI. METHODS: Patients with early-stage knee OA (n = 50) were examined. MRI-detected OA-related changes, in addition to MME, were evaluated according to the Whole-Organ Magnetic Resonance Imaging Score. T2 values of the medial meniscus and osteophytes were measured on T2 mapping images. Osteophytes surgically removed from patients with end-stage knee OA were histologically analyzed and compared with findings derived by radiography and MRI. RESULTS: Medial side osteophytes were detected by T2 mapping MRI in 98% of patients with early-stage knee OA, although the detection rate was 48% by conventional MRI and 40% by radiography. Among the OA-related changes, medial tibial osteophyte distance was most closely associated with MME, as determined by multiple logistic regression analysis, in the patients with early-stage knee OA (ß = 0.711, p < 0.001). T2 values of the medial meniscus were directly correlated with MME in patients with early-stage knee OA, who showed ≥ 3 mm of MME (r = 0.58, p = 0.003). The accuracy of osteophyte evaluation by T2 mapping MRI was confirmed by histological analysis of the osteophytes removed from patients with end-stage knee OA. CONCLUSIONS: Our study demonstrates that medial tibial osteophyte evaluated by T2 mapping MRI is frequently observed in the patients with early-stage knee OA, showing close association with MME, and that MME is positively correlated with the meniscal degeneration.

Serum interleukin 6 levels are associated with depressive state of the patients with knee osteoarthritis irrespective of disease severity.

This cross-sectional study investigated the prevalence of depressive state and association between depressive state and serum interleukin (IL)-6 levels in knee osteoarthritis (OA) patients. A total of 115 painful knee OA patients were enrolled and divided into two groups according to the radiographic OA severity. Pain was evaluated using a visual analog scale (VAS). Depressive state was assessed by the self-rating depression scale (SDS). Serum IL-6 levels were also measured. Pearson's correlation coefficient was used to assess the correlation between the variants tested, and logistic regression analysis was used to identify factors associated with the depressive state. Fifty-two percent of the patients had an SDS score of ≥ 40, which is indicative of the depressive state. The pain VAS score (r = 0.22, p = 0.02) and serum IL-6 level (r = 0.31, p < 0.01) were independently associated with the SDS score of all early-stage knee OA patients (Kellgren-Lawrence [K/L] grade 2). However, only the serum IL-6 level was independently associated with the SDS scores of advanced-stage knee OA patients (K/L grades 3 and 4, r = 0.36, p < 0.01). A logistic regression analysis revealed that serum IL-6 level was the variable for the SDS score [odds ratio 1.41 (95% confidence interval 1.03-1.94, p < 0.03)]. Approximately half of the knee OA patients were found to be in the depressive state, and their serum IL-6 levels to be associated with the depressive state, irrespective of OA severity.

Preoperative timed single leg standing time is associated with the postoperative activity of daily living in aged disabled patients with end-stage knee osteoarthritis at six-months after undergoing total knee arthroplasty.

OBJECTIVES: The aim of the present study was to investigate the effect size (ES) of total knee arthroplasty (TKA) for the symptoms and lower limb function and identify preoperative factor(s) associated with the post-operative activity of daily living (ADL) in aged patients with end-stage knee OA undergoing TKA. METHODS: Fifty-nine aged patients with end-stage knee OA (mean age: 74.6 years) were enrolled in this study. The symptoms and lower limb function of the patients were evaluated using the Japanese Knee Osteoarthritis Measure (JKOM), the timed up and go (TUG) test and timed single-legged stance test with eyes open (TSLS) before and after six months from the operation. RESULTS: While the ES of TKA for the improvement of pain was 2.83, the ES of TKA for the improvement of ADL, TUG and TSLS were 1.30, 0.59, and 0.49, respectively. While the post-operative ADL score was not associated with the preoperative ADL or pain scores, it was associated with the preoperative TUG and TSLS scores. A multiple regression analysis revealed that the one preoperative factor associated with the postoperative ADL was the TSLS. CONCLUSION: The preoperative TSLS is associated with the postoperative ADL in aged disabled patients with end-stage knee OA.

The MRI-detected osteophyte score is a predictor for undergoing joint replacement in patients with end-stage knee osteoarthritis.

OBJECTIVES: The aim of this prospective cohort study was to examine whether MRI-detected osteoarthritis (OA)-structural changes at baseline could predict knee OA patients who would undergo total knee arthroplasty (TKA). METHODS: In total, 128 end-stage medial-type knee OA patients were enrolled and followed up for 6 months. MRI using the whole-organ MRI scoring (WORMS) method, radiographic findings, visual analog scale (VAS) for pain and a patient-oriented outcome measure, and the Japanese Knee Osteoarthritis Measure (JKOM) were recorded at baseline. The area under the curve (AUC) was estimated to determine the discriminative value of the prediction models. RESULTS: While 74 patients (57.8%) did not undergo TKA, the remaining 54 patients (42.2%) underwent TKA during this period. The AUCs of the receiver operating characteristic (ROC) curve for the activities of daily living (ADL) score evaluated by the JKOM ADL score [0.70 (95% CI: 0.60-0.79)] and osteophyte score [0.72 (0.64-0.81)] were 0.70 or greater. The JKOM ADL score (17/40) and the osteophyte score (30/98) showed relative risks (RR) of 2.61 (1.32-5.15) and 3.01 (1.39-6.52) for undergoing TKA, respectively. CONCLUSION: The osteophyte score detected by MRI, in addition to ADL score, was found to be an important factor in determining whether the patient should undergo TKA.

The incidence of and risk factors for developing atypical femoral fractures in Japan.

The long-term treatment with anti-resorptive drugs for osteoporotic patients is suggested to be associated with an increase in atypical femoral fractures (AFFs). However, their incidence, patient characteristics, and risk factors have not been fully elucidated especially in Asian countries. This retrospective observational cohort study found fourteen AFFs in ten patients (four bilateral fractures) among 2,238 hip and femoral shaft fractures treated in our associated hospitals between 2005 and 2010; this incidence (0.63%) was similar to Caucasians. Of the ten patients with AFFs, nine (90%) and six (60%) were using bisphosphonates (BPs) and glucocorticoids (GCs), respectively, compared to 14.3 and 8.6% for patients with typical femoral fractures who were using these agents. As comorbid conditions, five patients had collagen disease (CD) and two had diabetes. A fracture location-, age- and gender-matched (1:3) case-control study revealed that administration of BPs, GCs, and suffering from collagen disease (CD) were significant risk factors for developing AFFs [odds ratios 36.0 (95% confidence intervals 3.8-342.2), 13.0 (2.3-74.1) and 9.0 (1.6-50.3), respectively]. Interestingly, all of the patients with atypical subtrochanteric femoral fractures, defined as those within 5 cm of the lesser trochanter, were taking GCs due to CD, and the age of these patients (average of 54.8 years) was significantly younger than those with atypical diaphyseal femoral fractures (average of 77.2 years, p < 0.05). In conclusion, the incidence of AFFs in the Japanese population was similar to that of Caucasians, and taking BPs and GCs and suffering from CD were risk factors for developing AFFs.

The fracture sites of atypical femoral fractures are associated with the weight-bearing lower limb alignment.

PURPOSE: Atypical femoral fractures (AFFs) are stress-related fractures that are speculated to associate with long-term treatment with bisphosphonates for osteoporosis. A history of AFF is a high risk factor for the development of a subsequent AFF in the same location of the contralateral femur, suggesting that a patient's individual anatomical factor(s) are related to the fracture site of AFFs. In this study, we investigated the radiographs of fourteen AFFs (four bilateral fractures among ten patients) treated at six hospitals associated with our university between 2005 and 2010. The fracture site and standing femorotibial angle (FTA), which reflects the mechanical axis of the lower limb, were measured on weight-bearing lower limb radiographs. The fracture site and FTA of patients with typical femoral fractures (TFF) were compared to those of patients with AFFs. The correlations were examined using Spearman's rank correlation coefficients. The fracture locations in the femora were almost the same in the patients with bilateral AFFs. There was a positive correlation between the fracture site and the standing FTA in the patients with AFFs (r=0.82, 95% confidence interval; 0.49 to 0.94), indicating that the larger the standing FTA (varus alignment), the more distal the site of the fracture in the femur. The FTA of the patients with atypical diaphyseal femoral fracture were significantly larger compared to that of those with not only atypical subtrochanteric fractures but also TFFs. In conclusion, the fracture sites of AFFs are associated with the standing lower limb alignment, while those of TFFs are not.

Disability for daily living is a predictor for joint replacement in patients with end-stage knee osteoarthritis.

The objective indicators which reflect the past results of end-stage knee osteoarthritis (OA) patients who have already received total knee arthroplasty (TKA) could be helpful for physicians to discuss with patients who are considering TKA. The aim of this prospective cohort study was to examine whether we could predict the knee OA patients who would receive TKA in advance based on baseline data, and to set cut-off points for receiving TKA. The two-hundred and forty end-stage medial-type knee OA patients were enrolled and followed up for 6 months while performing therapeutic exercises. Radiographic findings, visual analog scale for pain and a patient-oriented outcome measure, the Japanese Knee Osteoarthritis Measure (JKOM), were recorded at baseline. Relative risks (RRs) using the area under the curve (AUC) for a receiver operating characteristic (ROC) curve were calculated to evaluate several scores for receiving TKA. While 119 patients (55.3 %) did not undergo TKA, the remaining 96 patients (44.7 %) underwent TKA during this period. The AUCs of the ROC curve for the JKOM total score [0.71 (95 % CI 0.64-0.79)] were higher than those for radiographic parameters. Among the JKOM subcategories, JKOM category III, which indicates the condition in daily life, showed the highest AUC of 0.72 (0.65-0.80). The JKOM total score (65/100) and JKOM category III score (17/40) showed RRs of 2.20 (1.33-3.63) and 1.95 (1.18-3.22) for receiving TKA, respectively. The presence of disability in daily living was found to be an important factor determining whether the patient should undergo TKA.

Reference intervals of serum hyaluronic acid corresponding to the radiographic severity of knee osteoarthritis in women.

BACKGROUND: While serum levels of hyarulonic acid (sHA) is known to be useful for a burden of disease biomarker in knee OA, it is far from practical. The reference intervals must be established for biomarkers to be useful for clinical interpretation. The aim of this study was to establish the reference intervals of sHA corresponding to the radiographic severity of knee OA for elucidating whether sHA can be useful as a burden of disease marker for individual patient with knee OA. METHODS: 372 women with Kellgren & Lawrence grade (K/L) 1 through 4 painful knee OA were enrolled in this study. The patients included 54 with K/L 1, 96 with K/L 2, 97 with K/L 3, and 118 with K/L 4. Serum samples were obtained from all subjects on the day that radiographs taken. A HA binding protein based latex agglutination assay that employed an ELISA format was used to measure sHA. Age and BMI adjusted one way ANOVA was used to set the reference intervals of sHA. RESULTS: The reference intervals for sHA corresponding to the patients with K/L 4 (49.6 - 66.5 ng/ml) was established without any overlap against to those with K/L 1, 2 and 3, while those with K/L 1, 2 and 3 showed considerable overlap. CONCLUSIONS: These results indicate that sHA can be available as a burden of disease marker for the individuals with severe knee OA (K/L 4), while it is not for those with primary to moderate knee OA (K/L 1-3).

Correlations between both the expression levels of inflammatory mediators and growth factor in medial perimeniscal synovial tissue and the severity of medial knee osteoarthritis.

An enhanced expression of the inflammatory mediators in the perimeniscal synovium in knee osteoarthritis (OA) has been suggested to contribute to progressive cartilage degeneration. However, whether the expression levels of these molecules correlated with the severity of OA still remained unclear. Medial perimeniscal synovial samples were obtained from 23 patients with Kellgren-Lawrence (K/L) grades 2 to 4 of medial knee OA. Immunohistochemical analysis of the synovium revealed that the MMP-1, COX-2 and IL-1ß expression of the patients with K/L 4 to be significantly reduced in comparison to those with either K/L 2 or 3, while the TGF-ß expression showed the opposite. The synovial expression of MMP-1 and IL-1ß showed a significant negative correlation with the severity of OA, while that of TGF-ß again showed the opposite. In conclusion, although synovial inflammation remained active, the MMP-1, COX-2 and IL-1ß expression in synovium decreased depending upon the severity of OA, while the TGF-ß expression increased.

A longitudinal study of the relationship between the status of bone marrow abnormalities and progression of knee osteoarthritis.

BACKGROUND: Bone marrow abnormalities (BMAs) detected on magnetic resonance imaging (MRI) are suggested to be involved in the pathogenesis of osteoarthritis (OA), and the size of the BMAs is associated with the progression of OA. However, it still remains unclear as to whether the associations of BMA size and OA severity are observed equally or whether they differ from early to advanced stages of OA. In the present study we examined whether BMA enlargement and OA progression differed according to the severity of OA. METHODS: One hundred and eighty patients with knee OA were enrolled in the present study, and 122 of these patients completed this study. Radiography and knee MRI were done two times in all patients, at the baseline and 6 months or later at the time of patient follow-up. The severity of OA was evaluated by radiography using the Kellgren-Lawrence (K-L) grade. The patients who showed a deterioration in the K-L grade during the follow-up examination (59/122) were defined as the deterioration group. T2-weighted fat-suppressed MR images were used to score the size of the BMAs according to the whole-organ magnetic resonance imaging score (WORMS). A new scoring system, the spacial BMA score (s-score) was defined to assess the size of the BMAs three-dimensionally. RESULTS: In patients with K-L grade 2, the s-score changes during the follow-up period in the deterioration group were significantly increased in comparison to those in the no-change group (P = 0.04), and no significant s-score changes were observed in patients with either K-L grade 1 or 3 (P = 0.07 and 0.57) between the deterioration group and the no-change group during the follow-up examination. In patients with K-L grade 3, the s-score at the baseline in the deterioration group was higher than that in the no-change group (P = 0.05). CONCLUSIONS: The relationship between the size and enlargement of BMAs and the progression of OA changed depending upon the severity of OA.

Correlation between synovitis detected on enhanced-magnetic resonance imaging and a histological analysis with a patient-oriented outcome measure for Japanese patients with end-stage knee osteoarthritis receiving joint replacement surgery.

Osteoarthritis (OA) is a disease that primarily results in the degeneration and destruction of the articular cartilage. However, synovitis that occurs secondarily by this primary phenomenon is crucial for both the structural and symptomatic progression of the disease. The Japanese Knee Osteoarthritis Measure (JKOM) was created as an outcome measure for Japanese patients with knee OA. This study was conducted to determine whether synovitis in knee OA correlates with the current disability of patients with knee OA who required total knee arthroplasty (TKA). Thirty-four Japanese patients with end-stage knee OA who required TKA were included in this study. The visual analog scale (VAS, 0-100) for pain and the JKOM score, as well as the Western Ontario and McMaster Universities Arthritis Index (WOMAC), were examined before the operation. Synovial samples were taken at the time of the operation. A histological analysis and gadolinium-enhanced magnetic resonance imaging (Gd-MRI) were conducted to evaluate synovitis. Correlations between the synovitis score evaluated by histological analysis and Gd-MRI with either the pain VAS score or the JKOM score were examined using Spearman's rank correlation coefficient. Neither the synovitis scores evaluated by the histological analysis nor those by a Gd-MRI correlated with the pain VAS score (n = 34, r = 0.25, p = 0.18 and r = 0.08, p = 0.75, respectively) and WOMAC (n = 14, r = 0.35, p = 0.22 and r = 0.45, p = 0.16, respectively) of the patients. However, they significantly correlated with the JKOM score of the patients (n = 34, r = 0.55, p = 0.001 and r = 0.71, p = 0.001, respectively). The severity of synovitis in OA was closely correlated with the current functional impairment and disability of the patients receiving TKA with end-stage knee OA.