Lower bone mineral density can be a risk for an enlarging bone marrow lesion: A longitudinal cohort study of Japanese women without radiographic knee osteoarthritis.

OBJECTIVES: The aim is to elucidate the relationship between bone mineral density (BMD) at baseline and the change of bone marrow lesion (BML) during a 2-year follow-up (2YFU) period. METHODS: Seventy-eight female participants (mean age: 54.9 ± 9.6 years) without radiographic knee osteoarthritis were eligible. Based on right-knee magnetic resonance imaging, maximum BML area (BMLa) was calculated by tracing the BML border. The change in BMLa was defined using the following formula: [2YFU] - [Baseline] = ΔBMLa. Positive ΔBMLa was defined as enlarged; negative ΔBMLa was defined as regressed. Dual-energy X-ray absorptiometry was performed to measure the BMD of distal radius. Young adult mean [YAM (%)] of the BMD was used for statistical analysis. Linear regression analysis was conducted with ΔBMLa as the dependent variable and YAM as the independent variable. Receiver operating characteristic curve and logistic regression analyses were conducted for YAM to predict the prevalence of BML enlargement or regression. RESULTS: Twenty-six (33.3%) patients had enlarged BMLa, 12 (15.4%) participants showed regressing BMLa, and 40 (51.3%) patients remained stable. YAM was negatively associated with ΔBMLa (ß: - 0.375, P = 0.046). The best predictor of BML enlargement risk was 85% (odds ratio: 8.383, P = 0.025). CONCLUSIONS: Lower BMD could predict BML enlargement during a 2YFU period.

Effusion detected by ultrasonography and overweight may predict the risk of knee osteoarthritis in females with early knee osteoarthritis: a retrospective analysis of Iwaki cohort data.

BACKGROUND: Knee osteoarthritis (OA) has enormous medical and socioeconomic burdens, which early diagnosis and intervention can reduce. We investigated the influence of knee effusion on the progression of knee OA in patients with early knee OA. METHODS: A total of 404 participants without radiographic knee OA were assessed from a 3-year longitudinal analysis. Participants were classified into non-OA and early knee OA groups. The effusion area (mm2) was quantified using ultrasonography. Receiver operating characteristic and logistic regression analyses were performed. RESULTS: At the 3-year follow-up, 114 of 349 knees (32%) had progressed from non-OA and 32 of 55 knees (58%) had progressed from early knee OA to radiographic knee OA. Logistic regression analysis showed that female sex (odds ratio [OR] 3.36, 95% confidence interval [CIs] 2.98-5.42), early knee OA (OR 2.02, 95% CI 1.08-3.75), body mass index (OR 1.11, 95% CI 1.02-1.19), and effusion area (OR 1.01, 95% CI 1.01-1.02) were significantly correlated with knee OA progression. Women who were overweight (body mass index ≥ 25 kg/m2) with more severe effusion had a higher risk of OA progression (area under the curve = 0.691, OR = 6.00) compared to those not overweight (area under the curve = 0.568, OR = 1.91). CONCLUSION: Knee effusion may be an indicator of the progression of early-stage knee OA.

Bone marrow lesion severity was associated with proximal tibial inclination in early knee osteoarthritis.

PURPOSE: This study aimed to investigate the effect of tibial plateau (TP) inclination and serum bone metabolic markers on bone marrow lesion (BML) in the general Japanese population with early knee osteoarthritis (EKOA). METHODS: A total of 441 female volunteers who participated in the Iwaki Health Promotion Project in 2017 were enrolled. Participants without radiographic abnormalities were divided into normal and EKOA groups according to the Luyten's classification criteria for EKOA. The medial proximal tibial angle (MPTA), growth plate-TP angle, and growth plate-medial tibial plateau (MTP) angle were measured on standing anteroposterior radiographs of the knees. BML severity on T2-weighted fat-suppressed magnetic resonance imaging (MRI) was scored using the Whole-Organ MRI Score method. Serum levels of N-telopeptide of type I collagen, tartrate-resistant acid phosphatase-5b (TRACP-5b), bone-specific alkaline phosphatase, procollagen type I N-terminal propeptide, pentosidine, and homocysteine were assessed. Linear regression analysis was conducted to investigate the relationship between proximal tibial inclination, BML, and serum bone metabolic markers. RESULTS: The growth plate was observed in 309 (70%) participants, and 48 (16%) participants had EKOA. The mean MPTA, growth plate-TP angle, and growth plate-MTP angle were 86.1 ± 5.9°, 3.6 ± 1.1°, and 9.9 ± 2.6°, respectively. The MPTA was negatively correlated with the growth plate-TP and growth plate-MTP angles (p = 0.006, p < 0.001). Participants with EKOA who had BML exhibited greater growth plate-MTP angle than those who did not (p = 0.018). Regression analysis revealed that BML severity was positively associated with MPTA (p = 0.036) and a bone formation marker (p = 0.045). CONCLUSION: BML severity was positively associated with proximal tibial inclination and serum TRACP-5b level in participants with EKOA and normal knees, respectively. Assessment of proximal tibial inclination may provide insight into potential BML risk. Residual medial tibial inclination may potentially result in knee pain and symptoms in EKOA. LEVEL OF EVIDENCE: III.

The effect of low back pain and neck-shoulder stiffness on health-related quality of life: a cross-sectional population-based study.

BACKGROUND: This cross-sectional study sought to determine the neck-shoulder stiffness/low back pain (NSS/LBP) comorbidity rate in a Japanese community population and to compare the quality of life (QOL) in individuals with comorbid NSS/LBP, asymptomatic individuals, and those with symptoms of NSS or LBP alone. METHODS: The sample included 1122 subjects (426 men; 696 women) with NSS and LBP symptoms in the previous 3 months, and were grouped according to NSS, LBP, comorbid NSS and LBP symptoms (Comorbid), or no symptoms (NP). They completed the MOS 36-Item Short-Form Health Survey (SF-36). Health QOL was evaluated by the eight domain scores and the Physical Component Summary (PCS) and Mental Component Summary (MCS) scores after adjusting for age. The primary outcome was to examine the association between NSS/LBP, NSS, or LBP and bodily pain of the eight domains of SF-36. Secondary outcome was to compare health-related QOL among the four groups. RESULTS: Morbidity was 45.6% for NSS and 51.9% for LBP. Comorbidity affected 23% of men and 33% of women. Comorbid NSS/LBP, NSS, and LBP alone were independently associated with bodily pain after adjusting for potential confounders. Men who exhibited comorbidity had significantly lower MCS scores than asymptomatic men. Women who exhibited comorbidity and LBP had significantly lower MCS scores than those with no symptoms or NSS alone. Women who exhibited comorbidity had significantly lower MCS scores than those with no symptoms or LBP alone. CONCLUSIONS: Comorbidity of the two diseases is prevalent in 23% of the men and 33% of women in the Japanese sample. Although NSS, LBP, and comorbidity were independently associated with QOL in terms of pain, QOL was worse in individuals who exhibited comorbidity than in those without symptoms or with NSS alone.

Prevalence and associated factors of radiographic vertebral fractures in men: Rural population cross-sectional observation study in Japan.

BACKGROUND: Osteoporotic fractures constitute a major health concern in both women and men, particularly with the aging population. Many potential risk factors of vertebral fractures (VFx) have been identified in women, but not in men. Several reports have focused on the quality of life (QOL) of clinically diagnosed VFx, but not much has been reported on quantified QOL scores of incidental radiographic VFx in men. This cross-sectional study aimed to investigate the associated factors and the influence of incident radiographic VFx on QOL of men. METHODS: A total of 401 volunteer men aged 40 years or older (40-92 years) participated in this study. The mean age was 60.5 ± 11.8 years. Prevalent VFx were identified on the lateral lumbar spinal radiographs using the semiquantitative method. Bone mineral density, body composition, smoking, alcohol intake, past medical history, Mini-Mental State Examination, grip strength, gait speed, and biochemical markers were examined. QOL was evaluated using the 36-Item Short-Form Health Survey and the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire. RESULTS: Of the 401 subjects, 35 men (8.7%) had the prevalence of VFx. After adjustment for age, the presence of VFx was significantly associated with IGF-1 (odds ratio 0.985; p = 0.02). QOL scores were not significantly associated with VFx after adjustment for age. CONCLUSIONS: IGF-1 is the mediator of growth hormone, and IGF-1 stimulates the proliferation, differentiation, and mineralization of osteoblastic cells. The prevalence of VFx in men was 8.7%, and IGF-1 was significantly lower in the VFx group than in the non-VFx group.

US detection of medial meniscus extrusion can predict the risk of developing radiographic knee osteoarthritis: a 5-year cohort study.

OBJECTIVES: To clarify the relationship between the baseline value of medial meniscus extrusion (MME) and the radiographic change of knee osteoarthritis (KOA) through a 5-year follow-up. METHODS: Overall, 472 participants and 944 knees were eligible. MME (mm) was measured at the baseline, and KOA was radiographically evaluated at both baseline and 5-year follow-up by Kellgren-Lawrence grade (KLG). Radiographic KOA (ROA) was defined as the knee showing KLG ≥ 2. Incident ROA (iROA) was defined if the baseline KLG of 0-1 increased to KLG ≥ 2 in 5 years. Progressive ROA (pROA) was defined if the baseline KLG of 2-3 worsened to a higher grade in 5 years. Receiver operating characteristic (ROC) curve and generalized estimating equations were used for analysis. RESULTS: Of 574 non-ROA knees at the baseline, 43 knees (7.5%) developed iROA; of 370 ROA knees, 47 knees (12.7%) developed pROA. Based on the ROC curves, 4 mm was the optimal cutoff to detect the risk of iROA (area under curve [AUC] 0.639 [right knee]; AUC 0.641 [left knee]) and that of pROA (AUC 0.750 [right knee]; AUC 0.863 [left knee]). Multiple regression analysis showed that the 4-mm cutoff of MME was significantly associated with both the prevalence of iROA (regression coefficient [B] 1.909; p ≤ 0.001; adjusted odds ratio [aOR] 6.746) and that of pROA (B 1.791; p ≤ 0.001; aOR 5.993). CONCLUSIONS: On ultrasonography, the participants with more extruded medial meniscus showed a higher prevalence of both iROA and pROA. Ultrasonography could identify patients who had a risk of developing KOA. KEY POINTS: • Through a 5-year follow-up, the current cohort study was conducted to clarify the relationship between the baseline value of medial meniscus extrusion (MME) and the radiographic change of knee osteoarthritis (KOA). • More extruded medial meniscus evaluated by ultrasonography was associated with the development of radiographic KOA. • Ultrasonography could identify the patients who had a risk of developing KOA, and the 4-mm cutoff of MME was optimal to detect this risk.

Early knee osteoarthritis prevalence is highest among middle-aged adult females with obesity based on new set of diagnostic criteria from a large sample cohort study in the Japanese general population.

PURPOSE: A few new criteria for early detection and prevention of early knee osteoarthritis (EKOA) have been proposed. However, its prevalence, risk factors, relationship with function and prognosis have not been clarified. The purpose of this study was to investigate the prevalence of EKOA and its risk factors in the Japanese general population. METHODS: A total of 1104 volunteers (443 males, 661 females) who participated in the Iwaki cohort study in Japan were enrolled in this cross-sectional study. Their bilateral weight-bearing anterior-posterior knee radiographs were classified by Kellgren-Lawrence (KL) grade. EKOA (KL grade 0/1) was defined according to the following criteria: knee injury and osteoarthritis outcome score < 85%, joint line tenderness, and crepitus and its prevalence among age-sex groups was calculated. Logistic regression analyses were performed to determine the risk factors for EKOA. RESULTS: Eight hundred and twenty-two participants had KL grade 0/1, and the EKOA prevalence was 9.5% in males and 15.0% in females (p = 0.011). The prevalence of EKOA increased with age. The highest prevalence was noted in females aged 50-59 years. Logistic regression analysis showed that the risk factors for EKOA were age (p < 0.001, odds ratio (OR) 1.1), female sex (p = 0.002, OR 2.5), high body mass index (p < 0.001, OR 1.2), and history of knee injury (p < 0.001, OR 21.7). CONCLUSIONS: The highest EKOA prevalence was observed in middle adult females (50-59 years old). The risk factors for EKOA were female sex, ageing, obesity and knee injury history, which were extremely similar to those of definitive knee osteoarthritis. LEVEL OF EVIDENCE: Level I in diagnostic studies-investigating a diagnostic test.

Prevalence of cervical canal stenosis in farmers: Epidemiological study based on radiographic parameter of spinal cord injury patients.

BACKGROUND: Farming is one of the effective community activities for preventing the need for new long-term care insurance services. This study was conducted to compare spinal canal diameters between patients injured during orchard work (i.e., cultivating apples) and other situations that lead to cervical spinal cord injury without major fracture or dislocation and to investigate the frequency of cervical spinal canal stenosis among farmers in a Japanese community. METHODS: Subjects were 23 patients with cervical spinal cord injury without major fracture and dislocation. Charts and radiographs of these patients were retrospectively reviewed to evaluate the characteristics of the spinal cord injury. The spinal canal diameter at the injury level in the mid-sagittal plane of magnetic resonance imaging (MRI) and mechanism of injury were compared between patients injured by orchard work and other situations. Moreover, 358 Japanese general residents were evaluated for the prevalence of cervical canal stenosis using MRI and comparisons were made between farmers group and non-farmers group. RESULTS: Spinal canal diameters at the injury level were 5.8 ± 1.4 mm in patients injured during orchard work and 5.6 ± 1.0 mm in those injured in other situations; there were no differences between the two groups. Head contusion as mechanism of injury was more frequent in the orchard work group than in other situations group. Among farmers, the rate of spinal canal stenosis increased with age, and it was 62.3% in men and 66.2% in women. CONCLUSIONS: The frequency of cervical spinal canal stenosis was high with age regardless of farming work. In addition, head contusion might be a characteristic mechanism that causes spinal cord injury during orchard work. Therefore, screening of cervical degenerative conditions among farmers and education for prevention of cervical spinal cord injury during farming work are necessary.

Predicting radiological vertebral fractures with a combined physical function and body composition scoring system.

The objective of this study was to investigate the incidence of vertebral fractures (VFx) and the value of physical function (PF) and body composition (BC) for predicting VFx in a Japanese population. This study included 307 subjects (113 men, 194 women) at least 40 years of age who were assessed at community health check-ups in 2008 and 2016. PF was assessed by grip strength and by single-leg stance, timed up-and-go, and 30-s chair stand tests, each scored from 0 to 3 for a possible total of 12 points (higher scores reflect lower function). BC was scored on bioelectrical impedance measurements of trunk and appendage muscle volume, with 6 possible points. We diagnosed radiological VFx semiquantitatively on lateral views of the lumbar spine, and measured bone mineral status by quantitative ultrasound (QUS) of the calcaneus. We conducted logistic regression analysis with VFx as the dependent variable and age, sex, BMI, QUS, PF score, and BC score as independent variables. In 8 years, 36 participants (12%) sustained new VFx. After correcting for age, sex, BMI, and QUS, the odds of VFx increased with a PF score ≥ 8 (OR 5.6; 95% CI 1.21-25.90; P = 0.028) and increased further with a PF + BC score ≥ 9 (OR 8.1; 95% CI 1.80-36.00; P < 0.01). Both PF and BC are important for predicting fragility fractures. The scoring system used here may reflect small differences better than categorical (single cutoff) definitions of poor function.

A study of the factors associated with cervical spinal disc degeneration, with a focus on bone metabolism and amino acids, in the Japanese population: a cross sectional study.

BACKGROUND: The physical and biochemical factors responsible for cervical disc degeneration, and resulting in various spinal disorders, remain unclear. This study aimed to evaluate the correlation between cervical spinal canal stenosis and degeneration of intervertebral discs, and to analyze the factors related to disc degeneration in the Japanese population. METHODS: Three hundred and forty-four Japanese general residents underwent investigations, including magnetic resonance imaging of the cervical spine, in our health check project. We measured anteroposterior diameters at the levels of the cervical spinal disc in mid sagittal plane magnetic resonance imaging and evaluated disc degeneration. Spearman correlation coefficient was used to evaluate whether the diameters were correlated with disc degenerative scores. Stepwise multiple linear regression analysis was conducted with the score of disc degeneration as the dependent variable; and age, physical measurement values, bone mineral density of the forearm, and the value of serum bone metabolic markers and amino acids as the independent variables for each sex. RESULTS: As the age increased, the anteroposterior diameters decreased in both sexes. The minimum anteroposterior diameters were correlated with the disc degenerative scores (Spearman r = - 0.59, p < 0.001 in men, Spearman r = - 0.53, p < 0.001 in women). In multiple linear regression analysis, age, cross-linked N-telopeptide of type 1 collagen and isoleucine were significantly correlated with the cervical disc degenerative score in men (R2 = 0.47), and age and lysine were significantly correlated with the degenerative score in women (R2 = 0.50). CONCLUSION: The factors responsible for cervical disc degeneration differed between men and women. Whether modifying these significant factors is possible, or whether this intervention would contribute to prevention of disc degeneration requires future studies.

Associations between neck symptoms and LDL cholesterol in a cross-sectional population-based study.

BACKGROUND: Studies have reported associations between neck pain and degenerative changes in the cervical spine in women, and between neck pain and obesity or metabolic syndrome. The present study investigated associations between neck pain or stiffness and lipid profiles in subjects recruited from the general population of a Japanese community. METHODS: The 1122 volunteers who participated in this study included 426 men (age 52.6 ± 15.5 years; body mass index 23.6 ± 3.2) and 696 women (age 55.3 ± 15.3 years; body mass index 22.2 ± 3.4). Each subject filled out a questionnaire about any neck pain or neck-shoulder stiffness experienced in the previous 3 months. We recorded the following laboratory results related to metabolic factors, including lipid profiles: total cholesterol, LDL and HDL cholesterol, triglycerides, free fatty acids, glucose, and hemoglobin A1c. We conducted logistic and linear regression analyses using the prevalence of neck pain or neck-shoulder stiffness as the dependent variable and age, sex, body mass index, and laboratory data as independent variables. RESULTS: There was no significant difference in the prevalence of neck pain between men (20.5%) and women (21.5%). However, the prevalence of neck and shoulder stiffness was significantly higher in women (60.3%) than in men (38.0%; P < 0.05). Logistic and linear regression analyses showed a significant negative correlation between the prevalence of neck pain and LDL cholesterol (odds ratio [OR], 0.958; 95% CI, 0.921-0.997), and between the prevalence of neck-shoulder stiffness and age (OR, 1.025; 95% CI, 1.013-1.038) and gender (OR, 0.362; 95% CI, 0.25-0.494). CONCLUSION: LDL cholesterol was correlated with neck pain in this cross-sectional population-based study.

Metabolomics with severity of radiographic knee osteoarthritis and early phase synovitis in middle-aged women from the Iwaki Health Promotion Project: a cross-sectional study.

BACKGROUND: Osteoarthritis (OA) is one of the costliest and most disabling forms of arthritis, and it poses a major public health burden; however, its detailed etiology, pathophysiology, and metabolism remain unclear. Therefore, the purpose of this study was to investigate the key plasma metabolites and metabolic pathways, especially focusing on radiographic OA severity and synovitis, from a large sample cohort study. METHODS: We recruited 596 female volunteers who participated in the Iwaki Health Promotion Project in 2017. Standing anterior-posterior radiographs of the knee were classified by the Kellgren-Lawrence (KL) grade. Radiographic OA was defined as a KL grade of ≥ 2. Individual effusion-synovitis was scored according to the Whole-Organ Magnetic Resonance Imaging Scoring System. Blood samples were collected, and metabolites were extracted from the plasma. Metabolome analysis was performed using capillary electrophoresis time-of-flight mass spectrometry. To investigate the relationships among metabolites, the KL grade, and effusion-synovitis scores, partial least squares with rank order of groups (PLS-ROG) analyses were performed. RESULTS: Among the 82 metabolites examined in this assay, PLS-ROG analysis identified 42 metabolites that correlated with OA severity. A subsequent metabolite set enrichment analysis using the significant metabolites showed the urea cycle and tricarboxylic acid cycle as key metabolic pathways. Moreover, further PLS-ROG analysis identified cystine (p = 0.009), uric acid (p = 0.024), and tyrosine (p = 0.048) as common metabolites associated with both OA severity and effusion-synovitis. Receiver operating characteristic analyses showed that cystine levels were moderately associated with radiographic OA (p < 0.001, area under the curve 0.714, odds ratio 3.7). CONCLUSION: Large sample metabolome analyses revealed that cystine, an amino acid associated with antioxidant activity and glutamate homeostasis, might be a potential metabolic biomarker for radiographic osteoarthritis and early phase synovitis.

Breathing Room: Restoring Free Rotation in a Schiff-Base Macrocycle through Endoperoxide Formation.

Macrocyclization is a popular method for preparing hosts, but it can have unintended effects, like limiting molecular free rotation to yield mixtures of inseparable isomers. We report a [3 + 3] Schiff-base macrocycle (1) with anthracene bridges. Restricted rotation about the phenyl-anthracene bonds leads 1 to exist as a mixture of conformations (1Cs and 1C3v). Macrocycle 1 was photooxidized to tris(endoperoxide) adduct 4, alleviating restricted rotation. These results were supported by spectroscopic, structural, and computational analyses.

Eosinophilic Granulomatosis with Polyangiitis that was Difficult to Distinguish from Peroneal Nerve Palsy and Lumbar Disc Herniation: A Case Report.

Introduction: Eosinophilic granulomatosis with polyangiitis (EGPA) patients with mononeuropathy multiplex often visit orthopedic clinics; however, orthopedic surgeons have limited experience in diagnosing EGPA because of its rarity. We report a case of EGPA that required 1 month to confirm the diagnosis. Case Report: A 48-year-old woman presented with acute onset numbness in the right lower extremity. She had muscle weakness of the right lower extremity; lumbar spine magnetic resonance imaging showed lumbar disc herniation. Despite conservative treatment, her symptoms worsened. Blood tests showed increased eosinophils and serum IgE. She was diagnosed with EGPA, which should be considered in case of atypical paralytic symptoms. Conclusion: EGPA is so difficult to diagnose. In our case, the symptoms worsened on the 30th day after the initial visit. She was diagnosed with EGPA by a blood test at the time of admission. If patients with bronchial asthma or a history of allergies develop lumbar radiculopathy or peroneal nerve palsy-like symptoms, EGPA should be considered, and steroid treatment should be initiated early.

Association Between Central Sensitization and Increasing Prevalence of Nocturnal Knee Pain in the General Population with Osteoarthritis from the Iwaki Cohort Study.

PURPOSE: Knee pain is associated with osteoarthritis (OA) and increases during this condition; however, its correlation with central sensitization (CS) in arthritis patients requires greater understanding. The present cross-sectional cohort study to explore the prevalence of knee OA, nocturnal knee pain and disability in general population and to examine the association of CS with sleep quality in Japanese general population. PATIENTS AND METHODS: From among 1056 community-dowelling volunteers, 942 were enrolled as participants in this study. Bilateral weight-bearing anterior-posterior knee radiographs were classified by the Kellgren-Lawrence grade. Nocturnal knee pain and disability were assessed with self-reported questionnaires. Using the CS inventory with nine items (CSI-9), CS was defined as 10 points or higher. Sleep quality was scored using the Pittsburgh Sleep Quality Index (PSQI). Linear regression analysis, adjusted by age, sex, body mass index, Kellgren-Lawrence grade, nocturnal knee pain, and lifestyle habits, was performed to investigate the association of CS with PSQI. RESULTS: The prevalence of OA, nocturnal knee pain, and disability was 37.9%, 7.6%, and 6.2%, respectively. The mean CSI-9 score was 4.9 ± 4.4, with a CS prevalence of 14.0%. The mean PSQI score was 3.9 ± 2.4, which was correlated with the CSI-9 value. CS was not correlated with OA severity; however, nocturnal knee pain prevalence increased from 13.3% to 25.5% in knee OA patients with CS. The CSI-9 value correlated with PSQI total score and subscales. CONCLUSION: Knee OA severity correlated with nocturnal pain and disability; however, its association with CS was unproven. The combined effect of knee OA and CS elevated nocturnal pain and disability, resulting in diminished sleep quality.

Relationship between abnormalities detected by magnetic resonance imaging and knee symptoms in early knee osteoarthritis.

We investigated the prevalence of magnetic resonance imaging (MRI) findings and their relationship with knee symptoms in women without radiographic evidence of knee osteoarthritis (KOA). This cross-sectional cohort study included 359 Japanese women without radiographic evidence of KOA (Kellgren‒Lawrence grade < 2). All participants underwent T2-weighted fat-suppressed MRI of their knees. Structural abnormalities (cartilage damage, bone marrow lesions [BMLs], subchondral cysts, bone attrition, osteophytes, meniscal lesions, and synovitis) were scored according to the whole-organ MRI score method. Knee symptoms were evaluated using the Knee Injury and Osteoarthritis Outcome Score. Participants were divided into early and non-KOA groups based on early KOA classification criteria. Logistic regression analysis was performed to evaluate the relationship between MRI abnormalities and knee symptoms. Cartilage damage was the most common abnormality (43.5%). The prevalences of cartilage damage, BMLs, subchondral cysts, bone attrition, meniscal lesions, and synovitis were higher in patients with early KOA than in those without. Synovitis (odds ratio [OR] 2.254, P = 0.002) and meniscal lesions (OR 1.479, P = 0.031) were positively associated with the presence of early KOA. Synovitis was most strongly associated with knee pain and might be a therapeutic target in patients with early KOA.

Reduced serum levels of anti-Mullerian hormone is a putative biomarker of early knee osteoarthritis in middle-aged females at menopausal transition.

A recent epidemiological study revealed that the highest prevalence of early knee osteoarthritis (OA) was observed in females aged ≥ 50 years. The major causal factor of early knee OA was sex. Despite the relevance of estrogen in evaluating chondral and bone metabolism in OA, it is not easily clinically monitored because irregular menstrual cycles induce unstable female hormone patterns during menopausal transitions. Anti-Mullerian hormone (AMH) has been found to be a new stable biomarker to predict menopause. This study aimed to investigate the association between menopausal transition and early knee OA by using serum biomarkers, with special focus on AMH. A total of 518 female volunteers who participated in the Iwaki cohort study were enrolled and divided into pre-menopause and post-menopause groups. Weight-bearing anterior-posterior knee radiographs were classified by Kellgren-Lawrence (KL) grade, and grade ≥ 2 was defined as radiographic knee OA. In participants with KL grades 0 and 1, early knee OA was defined by Luyten's criteria. AMH, luteinizing hormone, follicle-stimulating hormone, estradiol (pg/ml), prolactin, and testosterone were measured on the female hormones. Bone mineral density at a distal radius was measured. The predictive power of female hormones for early knee OA was estimated by ROC analysis (comparison of area under curve, AUC) and regression analysis. Fifty-two participants (10.0%) were diagnosed with early knee OA and 204 (39.4%) with radiographic knee OA. In 393 (75.9%) females, menopause began. From the ROC analysis in pre-menopausal females, cutoff value of AMH for detecting early knee OA was 0.08 ng/ml (area under curve (AUC), 0.712; 95% CI, 0.527-0.897; p value, 0.025; odds ratio, 8.28). AUCs of other female hormones did not reach the level of AMH (range, 0.513 of prolactine to 0.636 of estradiol). Logistic regression analysis focusing on AMH reduction at menopausal transition showed that the related AMH below 0.08 ng/ml was significantly related to the presence of early knee OA (p = 0.035; odds ratio, 5.55). Reduced serum levels of AMH in middle-aged females were correlated with the presence of early knee OA, which might be a useful serum biomarker.

Usefulness of serum hyaluronic acid levels as a predictor of incidence of hand osteoarthritis analyzed by longitudinal analysis from the Iwaki cohort.

The factors predicting hand osteoarthritis (HOA) in patients remain unknown. We aimed to investigate the usefulness of serum hyaluronic acid (sHA) levels in predicting HOA progression from a 6-year longitudinal epidemiological study. A total of 417 participants in the Iwaki cohort were followed-up over 6 years. Hand and knee radiographs taken at baseline and follow-up were scored according to Kellgren-Lawrence grades and Kallman score. Participants were classified into the HOA group and the non-HOA group. sHA levels at baseline were determined by ELISA. Correlations between sHA levels, the number of involved joints, and Kallman score were estimated. Factors related to the incidence or progression of HOA over 6 years were analyzed. The prevalence of HOA was 19.9% at baseline, and 3.6 ± 2.1 joints were involved. sHA levels in the HOA group at baseline were significantly higher than in the non-HOA group (p < 0.001) and correlated with the number of involved joints (r = 0.399, p < 0.001) and Kallman score (r = 0.540, p < 0.001). The incidence rate was 14.5%, and the progression rate was 46.1% over 6 years. Higher sHA levels at baseline were the risk factor of HOA incidence. Thus, sHA levels predicted the incidence of HOA over 6 years.

Knee effusion evaluated by ultrasonography warns knee osteoarthritis patients to develop their muscle atrophy: a three-year cohort study.

This study aimed to elucidate the relationship between the quantitative value of suprapatellar effusion and the longitudinal changes in lower-extremity muscle mass (MM) in a cohort with knee osteoarthritis (KOA). Fifty-three subjects (106 legs) with bilateral radiographic KOA at baseline (BL) were enrolled. MM was calculated by bioimpedance analysis three times at BL, and at the one-year (1Y) and three-year (3Y) follow-ups. The longitudinal change in the lower-extremity MM was calculated by subtracting MMBL from MM1Y, and MM1Y from MM3Y. Subjects with ≥1.0 z-score loss were defined as having severe MM loss (SMML). Effusion was evaluated as the sagittal area of suprapatellar pouch (mm2) by ultrasonography. The ROC curve was drawn to determine the cut-off of effusion area. General estimating equations (GEEs) were conducted with the prevalence of SMML as the dependent variable and with the cut-off of effusion area as the independent variable. Sixteen legs (15.1%) demonstrated SMMLBL-1Y and another sixteen legs demonstrated SMML1Y-3Y. GEEs revealed that individuals with ≥90 mm2 effusion had significantly higher odds of SMMLBL-1Y prevalence (Odds ratio: 21.561; P-value: 0.003). Individuals with leachate knee effusion at BL had a significant risk of losing MM through the first year of the initial knee effusion assessment.

Detection of synovitis in early knee osteoarthritis by MRI and serum biomarkers in Japanese general population.

To investigate synovitis' influence on early knee osteoarthritis (EKOA) by serum biomarkers and magnetic resonance imaging (MRI) findings in Japanese women. We enrolled 255 women aged 30-70 without radiographic abnormalities (Kellgren-Lawrence grade ≥ 2). Knee injury, OA outcome scores (KOOS), clinical examinations, and standing radiograph were used for classification criteria of EKOA. Participants were classified into normal knee group and EKOA group. All participants underwent MRIs of their right knee. The amount of effusion-synovitis volume was quantified. We compared serum matrix metalloproteinases-3 levels (MMP-3), high-sensitivity C-reactive protein, interleukin-6, and adiponectin between the groups. The relationship between synovitis and EOKA was investigated using multiple linear regression. Fifty-four participants (21%) were classified as EKOA. Serum MMP-3 concentration and effusion-synovitis volume were higher in patients with EKOA (p = 0.025 and p = 0.001, respectively). Effusion-synovitis volume negatively correlated with all KOOS subscales and positively correlated with serum MMP-3 concentration. Serum MMP-3 concentration was associated with effusion-synovitis volume ß = 0.60, p < 0.001). There was mildly active but definitive synovitis in EKOA. This was an observational study so that no conclusions can be drawn regarding cause-effect for synovitis and symptoms. Future studies should conduct follow-up of participants with synovitis to assess the progression of knee OA.