Japanese Knee Osteoarthritis Research Articles

Variability of functional knee phenotype for coronal alignment in advanced varus knee osteoarthritis in the Japanese population.

New concept of functional knee phenotypes in Caucasians demonstrated the variability of coronal alignment in knee osteoarthritis (OA), but it remains unclear in Japanese. This study aims to analyze the knee phenotype in advanced varus knee OA for Japanese. In addition, the ethnical difference is discussed. This study analyzed 879 knees involving 186 males (74years) and 693 females (74years). The knee phenotypes were assessed by the definition in Hirschmann's group. The hip-knee-ankle angle (HKA), femoral mechanical angle (FMA) and tibial mechanical angle (TMA) were assessed in CT data according to the coordinate system. The neutral angle was 180° in HKA, 93° in FMA and 87° in TMA. The smaller angle means larger varus angles. The average angle (males, females) of the HKA (170.9 ± 4.3°, 169.4 ± 5.0°), FMA (91.5 ± 2.7°, 90.6 ± 3.0°), and TMA (82.4 ± 3.6°, 82.7 ± 3.7°) demonstrated varus angles with the sex difference (HKA, p < 0.001; FMA, p = 0.001). The phenotypes were 73 types in males and 150 types in females with a mild correlation between the HKA and the FMA or TMA. In 61.3% of males and 52.2% of females, the TMA was greater than the FMA, while the FMA was greater in 16.7% of males and 23.1% of females. There were many functional knee phenotypes with sex differences for advanced varus knee OA in Japanese, showing ethnical differences of larger varus angles compared to those for Caucasians in the previous report. IV.

Medial Meniscus Posterior Root Repair Using a Modified Mason-Allen Suture Can Prevent the Progression of Cartilage Degeneration on the Loading Surface of the Medial Compartment: A Second-Look Arthroscopic Evaluation.

The treatment of medial meniscus posterior root tears (MMPRTs) has evolved to include a variety of repair strategies. This study investigated the location of the articular cartilage degeneration during second-look arthroscopy after transtibial pullout repair with a modified Mason-Allen suture using FasT-Fix (F-MMA) in 22 patients with MMPRTs. Second-look arthroscopy was performed approximately 1 year postoperatively to eval-uate the healing status of the medial meniscus (MM). Articular cartilage degeneration was assessed using the International Cartilage Repair Society grade at primary surgery and again at second-look arthroscopy. Articular surfaces of the medial/lateral femoral condyles, the medial/lateral tibial plateaus, the patella and the trochlea were divided into several subcompartments (MF 1-9, LF 1-9, MT 1-5, LT 1-5, P 1-9, T 1-3). Clinical evaluations used the Japanese Knee Injury and Osteoarthritis Outcome, Lysholm, and International Knee Documentation Committee scores. Second-look arthroscopic findings showed complete healing of the MM posterior root in all patients. Significant differences between pullout repair and second-look arthroscopy were observed for MF 2 and 4, LF 7, and P 7. All clinical outcomes were improved. Our results indicate that this technique improves clinical outcomes postoperatively and may prevent the progression of cartilage degenera-tion on the loading surface of the medial knee compartment.

Survey of footwears in Japanese elderly with knee osteoarthritis

Improper footwear can lead to painful knee and functional limitations for knee osteoarthritis (OA) patients. This study aimed to examine the use of different footwear types in Japanese knee OA and no knee symptomatic control elderly. The participants answered questionnaires comprised of demographic data, knee function and footwear survey. In the footwear survey, they chose the type of footwear and answered wearing time with it. The knee OA was classified according to American College of Rheumatology criteria. A total of 219 elderly participants were selected of which 69 who did not satisfy the criteria were excluded and the remainder were grouped as knee OA (97) and control group (53). The OA had a significant relationship to categorize the number of footwears adjusted by gender. Most subjects in both group used more than 3 footwears regularly. Knee OA had a smaller number of footwears. Total time of wearing shoes in a day was significantly shorter in the knee OA group (4.95 hours) compared to 6.67 hours in the control group. Few knee OA participants used sandal/Flip flop than the control individuals (23.2% in knee OA and 45.3% in control) and the knee OA group had a shorter time wearing time. Therapists should ask the wearing shoe and provide the shoe intervention to multiple footwear depending on individual patients’ lifestyle.

Manual labor occupations increase the short-term incidence of knee osteoarthritis in japanese, but not caucasian subjects

s / Osteoarthritis and Cartilage 22 (2014) S57–S489 S398 matrix remodeling process induced by an inflammatory microenvironment suggested by the presence of synovial hypervascularization. Figure 1. Prolidase protein expression: A) Hipertrophy synovial of patient with OA B) Normal synovium 710 MANUAL LABOR OCCUPATIONS INCREASE THE SHORT-TERM INCIDENCE OF KNEE OSTEOARTHRITIS IN JAPANESE, BUT NOT CAUCASIAN SUBJECTS K.M. Leyland y, M.T. Sanchez-Santos y, S. Muraki z, A. Judge y, T.D. Spector x, D.J. Hart x, J. Newton y, C. Cooper ky, N. Yoshimura z, N.K. Arden yk. yUniv. of Oxford, Oxford, United Kingdom; zUniv. of Tokyo, Tokyo, Japan; x St. Thomas’ Hosp., London, United Kingdom; kUniv. of Southampton, Southampton, United Kingdom Purpose: To determine the interacting role of occupation and obesity on the risk of incident knee osteoarthritis (OA) among Caucasian and Japanese women. Methods: We used data from women in two prospective communitybased cohorts, the UK based Chingford study and the Japanese Research on Osteoarthritis/osteoporosis Against Disability (ROAD) study. Incident radiographic knee osteoarthritis (RKOA) was defined as having Kellgren and Lawrence (K/L) grade 0 or 1 in both knees at baseline and a K/L grade 2 or greater at follow up. Follow-up x-rays were taken after a median of 4 years after baseline for Chingford and 3 years in ROAD. The cut-off for a normal BMI was 25 kg/m2 for the Caucasian subjects and 23 kg/m2 for the Japanese subjects. Occupation was divided into manual versus non-manual (i.e. sedentary/moderate activity) for both populations based on self-assessment. Multivariable logistic regression models assessed of risk of obesity, occupation and their interaction on incident RKOA, controlling for age, hand grip strength, walking distance, smoking and alcohol intake. Results: 12.4% of Caucasian and 14.5% of Japanese women developed incident RKOA in at least one knee. Being overweight/obese was associated with an increased risk of incident RKOA in both populations (Caucasian OR 1.7 [95% CI 1.0, 2.8]; Japanese OR 2.5 [95% CI 1.3, 4.9]), however having a manual labour occupation was only significantly associated with incident RKOA in the Japanese subjects (OR 2.8 [95% CI 1.3, 5.8]). No significant interaction between BMI category and occupation was found for either population (Chingford p1⁄40.070; ROAD p1⁄40.291), however the Japanese population showed a slight increase in risk for manual labour occupations in the overweight/obese category Table 1 Profile of Participants by presence or absence of back pain

Effect of nonsteroidal anti-inflammatory drug plasters for knee osteoarthritis in Japanese: a randomized controlled trial

The objective of this study was to examine the effect of a nonsteroidal anti-inflammatory drug (NSAID) plaster for knee osteoarthritis among Japanese patients. An open-labeled, randomized, controlled, multiclinic trial was performed involving outpatient clinic groups. Two comparative groups—plaster NSAIDs and oral NSAIDs—were randomly allocated. The drugs used were limited to the current top three in both groups in Japan. Treatments were assessed after four weeks and compared with the baseline scores. Outcomes were evaluated by two psychometric measures: Japanese knee osteoarthritis measure, and pain with the visual analogue scale. The total number of patients included in the final evaluation was 165 (87 for the plaster group and 78 for the oral group). Between these two groups there were no significant differences in gender, age, body height and weight, body mass index, and X-ray grading. The subjects in both groups showed improvements in both scores at the end of intervention. The differences in the improvements in scores between the two groups were not significant, though the mean rank score and the 95% CI of the plaster group were slightly better than those of the oral group. In conclusion, the local application of a plaster with NSAIDs leads to the same level of improvement in knee osteoarthritis as oral NSAIDs.

Effect of nonsteroidal anti-inflammatory drug plasters for knee osteoarthritis in Japanese: a randomized controlled trial

The objective of this study was to examine the effect of a nonsteroidal anti-inflammatory drug (NSAID) plaster for knee osteoarthritis among Japanese patients. An open-labeled, randomized, controlled, multiclinic trial was performed involving outpatient clinic groups. Two comparative groups-plaster NSAIDs and oral NSAIDs-were randomly allocated. The drugs used were limited to the current top three in both groups in Japan. Treatments were assessed after four weeks and compared with the baseline scores. Outcomes were evaluated by two psychometric measures: Japanese knee osteoarthritis measure, and pain with the visual analogue scale. The total number of patients included in the final evaluation was 165 (87 for the plaster group and 78 for the oral group). Between these two groups there were no significant differences in gender, age, body height and weight, body mass index, and X-ray grading. The subjects in both groups showed improvements in both scores at the end of intervention. The differences in the improvements in scores between the two groups were not significant, though the mean rank score and the 95% CI of the plaster group were slightly better than those of the oral group. In conclusion, the local application of a plaster with NSAIDs leads to the same level of improvement in knee osteoarthritis as oral NSAIDs.

The knee osteoarthritis susceptibility locus DVWA on chromosome 3p24.3 is the 5′ part of the split COL6A4 gene

In a recent study the DVWA gene located on human chromosome 3p24.3 was identified as a susceptibility locus for knee osteoarthritis in Japanese and Chinese patients (Miyamoto, Y., Shi, D., Nakajima, M., Ozaki, K., Sudo, A., Kotani, A., Uchida, A., Tanaka, T., Fukui, N., Tsunoda, T., Takahashi, A., Nakamura, Y., Jiang, Q., Ikegawa, S., 2008. Common variants in DVWA on chromosome 3p24.3 are associated with susceptibility to knee osteoarthritis. Nat. Genet. 40, 994–998). The authors concluded that DVWA codes for a novel protein containing two von Willebrand factor A (VWA) domains without a signal peptide sequence. The experimental data provided in this interesting study led to the suggestion of a mechanism for the etiology of the disease, based on an interaction between DVWA protein and β-tubulin. More recently, no significant association between DVWA and osteoarthritis was found in UK patient samples (Valdes, A.M., Spector, T.D., Doherty, S., Wheeler, M., Hart, D.J., Doherty, M., 2008. Association of the DVWA and GDF5 polymorphisms with osteoarthritis in UK populations. Ann. Rheum. Dis. Dec 3. [Epub ahead of print]), but a meta-analyses with data from individuals of white European descent from the Netherlands, the UK, Spain and Greece and the original Japanese and Chinese cohort provided evidence for a global association of one of the polymorphisms, a cysteine to tyrosine exchange (rs7639618) (Meulenbelt, I., Chapman, K., Dieguez-Gonzalez, R., Shi, D., Tsezou, A., Dai, J., Malizos, K.N., Kloppenburg, M., Carr, A., Nakajima, M., van der Breggen, R., Lakenberg, N., Gomez-Reino, J.J., Jiang, Q., Ikegawa, S., Gonzalez, A., Loughlin, J., Slagboom, E.P., 2009. Large replication study and meta-analyses of DVWA as an osteoarthritis susceptibility locus in European and Asian populations. Hum. Mol. Genet. 8, 1518–1523). However, there was no independent association with knee osteoarthritis in Europeans. Here we present information that the newly identified DVWA represents the human gene coding for the collagen VI α4 chain, which could point to a more complex disease mechanism.

Large replication study and meta-analyses of DVWA as an osteoarthritis susceptibility locus in European and Asian populations

Recently, through a genome wide association study in Japanese knee osteoarthritis (OA) cases, a previously unknown gene, DVWA, was identified. The non-synonymous single nucleotide polymorphism (SNP) rs7639618 was subsequently found to be consistent and most significantly associated in Japanese and Han Chinese knee OA studies and functional relevant. Here, the association of the DVWA polymorphisms (rs7639618, rs11718863 and rs9864422) was genotyped in 1120 knee OA cases, 1482 hip OA cases and 2147 controls, all of white European descent from the Netherlands, the UK, Spain and Greece. Random effect DerSimonian and Laird meta-analyses were performed to assess the association in the different strata. To assess a more global effect, the original Japanese and Chinese data were included with the European. The meta-analyses provided evidence for global association of rs7639618 with knee OA with an odds ratio (OR) of 1.29, 95% confidence interval (CI) of 1.15-1.45 and a P-value of 2.70 x 10(-5). This effect, however, showed moderate heterogeneity, and rs7639618 was not independently associated with knee OA in Europeans, with an OR of 1.16, 95% CI of 0.99-1.35 and a P-value of 0.063. Furthermore, no association was observed with hip OA in Europeans, with a P-value of 0.851. Our results suggest that there may be global relevance for the DVWA SNP rs7639618 among knee OA cases, however, the apparent lower effect size in combination with the higher risk allele frequency in the European samples highlights again the ethnic differences in effects of discovered OA susceptibility genes.

A functional SNP in EDG2 increases susceptibility to knee osteoarthritis in Japanese

Osteoarthritis (OA) is the most common form of arthritis and is characterized by the gradual loss of articular cartilage. Several OA-susceptibility genes have been identified; however, there are few pharmaceutical targets that can be targeted with small-molecule compounds. To investigate whether a susceptibility gene for OA exists among G-protein-coupled receptors (GPCRs), we performed a stepwise association study for 167 single nucleotide polymorphisms (SNPs) in 44 GPCR genes that were present in cartilage. Through the stepwise association study, an SNP located in the promoter region of EDG2 [endothelial differentiation, lysophosphatidic acid (LPA) GPCR, 2] (-2,820G/A; rs10980705) showed significant association with knee OA in two independent populations (pooled P = 2.6 x 10(-5)). Luciferase and electrophoretic mobility shift assays indicate that this SNP exerts an allelic difference on transcriptional activity and DNA binding in synovial cells, with the susceptibility allele showing increased activity and binding. EDG2 encodes an LPA receptor dominantly expressed in the synovium. The LPA receptor increased the expression of inflammatory cytokines and matrix metalloproteases in synovial cells. Our findings suggest that the LPA-EDG2 signal is involved in the pathogenesis of OA via catabolic process.

A functional polymorphism in the 5′ UTR of GDF5 is associated with susceptibility to osteoarthritis

Osteoarthritis (MIM 165720), characterized by degeneration of articular cartilage, is the most common form of human arthritis and a major concern for aging societies worldwide. Epidemiological and genetic studies have shown that osteoarthritis is a polygenic disease. Here, we report that the gene encoding growth differentiation factor 5 (GDF5) is associated with osteoarthritis in Asian populations. A SNP in the 5' UTR of GDF5 (+104T/C; rs143383) showed significant association (P = 1.8 x 10(-13)) with hip osteoarthritis in two independent Japanese populations. This association was replicated for knee osteoarthritis in Japanese (P = 0.0021) and Han Chinese (P = 0.00028) populations. This SNP, located in the GDF5 core promoter, exerts allelic differences on transcriptional activity in chondrogenic cells, with the susceptibility allele showing reduced activity. Our findings implicate GDF5 as a susceptibility gene for osteoarthritis and suggest that decreased GDF5 expression is involved in the pathogenesis of osteoarthritis.