Relationship between locomotive syndrome and advanced glycation end products measured by skin autofluorescence in community-dwelling patients: the Yakumo Study.

Advanced glycation end products (AGEs) have been reported to be associated with osteoporosis, aging, sarcopenia, and frailty. This study aimed to investigate the association AGEs with locomotive syndrome (LS). Participants were Japanese individuals aged 39 years or older who participated in the Yakumo Study (n=230). AGEs were measured by skin autofluorescence (SAF) using an AGE reader. We investigated SAF values for each locomotive stage. Multivariate logistic regression models were used to calculate the odds ratios of LS-associated factors. The relationships between SAF and physical performance and bone mineral density (BMD) were investigated. A receiver operating characteristic (ROC) curves were generated to determine the optimal cut-off value of SAF for predicting LS. SAF values tended to increase correspondingly with LS severity. SAF was an independently explanatory factor for LS (odds ratio 2.70; 95% confidence interval [CI] 1.040-6.990). SAF was positively correlated with the 10-m walking speed, The Timed Up and Go test results, and was negatively correlated with BMD. ROC curve represented by SAF for the presence or absence of LS risk had an area under the curve of 0.648 (95% CI: 0.571-0.726). High SAF values were identified as an independent risk factor for LS. AGEs could be a potential screening tool for people for LS.

What Are the Sex-Based Differences of Acetabular Coverage Features in Hip Dysplasia?

BACKGROUND: Eccentric rotational acetabular osteotomy is performed to prevent osteoarthritis caused by developmental dysplasia of the hip (DDH). To achieve sufficient acetabular coverage, understanding the characteristics of acetabular coverage in DDH is necessary. However, the features of acetabular coverage in males with DDH remain unclear. We thought that the differences in acetabular coverage between females and males might be associated with the differences in pelvic morphology between the sexes. QUESTIONS/PURPOSES: (1) What are the differences in the acetabular coverage between females and males with DDH? (2) What are the differences in the rotations of the ilium and ischium between females and males with DDH? (3) What is the relationship between the rotation of the ilium and ischium and the acetabular coverage at each height in females and males with DDH? METHODS: Between 2016 and 2023, 114 patients (138 hips) underwent eccentric rotational acetabular osteotomy at our hospital. We excluded patients with Tönnis Grade 2 or higher, a lateral center-edge angle of 25º or more, and deformities of the pelvis or femur, resulting in 100 patients (122 hips) being included. For female patients (98 hips), the median (range) age was 40 years (10 to 58), and for the male patients (24 hips), it was 31 years (14 to 53). We used all patients' preoperative AP radiographs and CT data. The crossover sign, posterior wall sign, and pelvic width index were evaluated in AP radiographs. The rotation of the innominate bone in the axial plane was evaluated at two different heights, specifically at the slice passing through the anterior superior iliac spine and the slice through the pubic symphysis and ischial spine in CT data. Furthermore, we evaluated the anterior and posterior acetabular sector angles. Comparisons of variables related to innominate bone measurements and acetabular coverage measurements between females and males in each patient were performed. The correlations between pelvic morphology measurements and acetabular coverage were evaluated separately for females and males, and the results were subsequently compared to identify any sex-specific differences. For continuous variables, we used the Student t-test; for binary variables, we used the Fisher exact test. A p value less than 0.05 was considered statistically significant. RESULTS: In the evaluation of AP radiographs, an indicator of acetabular retroversion-the crossover sign-showed no differences between the sexes, whereas the posterior wall sign (females 46% [45 of 98] hips versus males 75% [18 of 24] hips, OR 3.50 [95% confidence interval (CI) 1.20 to 11.71]; p = 0.01) and pelvic width index less than 56% (females 1% [1 of 98] versus males 17% [4 of 24], OR 18.71 [95% CI 1.74 to 958.90]; p = 0.005) occurred more frequently in males than in females. There were no differences in the iliac rotation parameters, but the ischium showed more external rotation in males (females 30° ± 2° versus males 24° ± 1°; p < 0.001). Regarding acetabular coverage, no differences between females and males were observed in the anterior acetabular sector angles. In contrast, males showed smaller values than females for the posterior acetabular sector angles (85° ± 9° versus 91° ± 7°; p = 0.002). In females, a correlation was observed between iliac rotation and acetabular sector angles (anterior acetabular sector angles: r = -0.35 [95% CI -0.05 to 0.16]; p < 0.001, posterior acetabular sector angles: r = 0.42 [95% CI 0.24 to 0.57]; p < 0.001). Similarly, ischial rotation showed a correlation with both acetabular sector angles (anterior acetabular sector angles: r = -0.34 [95% CI -0.51 to -0.15]; p < 0.001 and posterior acetabular sector angles: r = 0.45 [95% CI 0.27 to 0.59]; p < 0.001). Thus, in females, we observed that external iliac rotation and ischial internal rotation correlated with increased anterior acetabular coverage and reduced posterior coverage. In contrast, although acetabular coverage in males showed a correlation with iliac rotation (anterior acetabular sector angles: r = -0.55 [95% CI -0.78 to -0.18]; p = 0.006 and posterior acetabular sector angles: r = 0.74 [95% CI 0.48 to 0.88]; p < 0.001), no correlation was observed with ischial rotation. CONCLUSION: In males, acetabular retroversion occurs more commonly than in females and is attributed to their reduced posterior acetabular coverage. In females, an increase in the posterior acetabular coverage was correlated with the external rotation angle of the ischium, whereas in males, no correlation was found between ischial rotation and posterior acetabular coverage. In treating males with DDH via eccentric rotational acetabular osteotomy, it is essential to adjust bone fragments to prevent inadequate posterior acetabular coverage. Future studies might need to investigate the differences in acetabular coverage between males and females in various limb positions and consider the direction of bone fragment rotation. CLINICAL RELEVANCE: Our findings suggest that males with DDH exhibit acetabular retroversion more frequently than females, which is attributed to the reduced posterior acetabular coverage observed in males. The smaller posterior acetabular coverage in males might be related to differences in ischial morphology between sexes. During eccentric rotational acetabular osteotomy for males with DDH, adequately rotating acetabular bone fragments might be beneficial to compensate for deficient posterior acetabular coverage.

Factors related to collapse progression in Japanese Investigation Committee classification type B osteonecrosis of the femoral head.

PURPOSE: This study aimed to identify factors related to collapse progression in Japanese Investigation Committee classification type B osteonecrosis of the femoral head (ONFH) and to identify patients who would benefit from surgical treatment. METHODS: This study included 41 patients (56 hips) with type B ONFH with a minimum follow-up of three years. Based on a ≥ 3 mm collapse progression in ONFH, we categorised patients into two groups: collapse progression and no collapse progression. Sagittal and coronal computed tomography images were used to measure the necrotic region relative to the intact femoral head diameter. The ratios of the necrotic regions of transverse and vertical diameter in coronal and sagittal images are defined as mediolateral transverse and mediolateral vertical, anteroposterior transverse and anteroposterior vertical, respectively. Demographic data and these imaging findings were compared between the two groups. We established a cut-off value for predicting collapse progression through receiver operating characteristic analysis and determined survival rates. RESULTS: Type B ONFH had a 17.8% collapse progression rate. The mediolateral transverse, mediolateral vertical, anteroposterior transverse, and anteroposterior vertical were significantly higher in the collapse progression group (P < 0.01). Mediolateral transverse was an independent risk factor of collapse progression (hazard ratio, 1.27; 95% confidence interval, 1.03-1.57; P = 0.03), with an optimal cut-off of 45.6%. The 5-year survival rates with collapse progression as the endpoints were 57.0 and 94.9% in the mediolateral transverse of ≥ 45.6 and < 45.6%, respectively. CONCLUSION: A mediolateral transverse of ≥ 45.6% predicts collapse progression in patients with type B ONFH.

Association between advanced glycation end-products and fall risk in older adults: The Yakumo Study.

AIM: Advanced glycation end-products (AGEs) are irreversibly and heterogeneously formed compounds during the non-enzymatic modification of macromolecules, such as proteins. Aging and lifestyle habits, such as high-fat and high-protein diets, and smoking, promote AGEs accumulation. This study aimed to investigate the relationship between fall risk and AGEs in community-dwelling older adults. METHODS: This cross-sectional study included patients from the 2022 Yakumo Study who were evaluated for fall risk index 5-items version, locomotive syndrome stage and AGEs. AGEs were evaluated using Skin autofluorescence (SAF) measured by the AGE reader (DiagnOptics Technologies BV, Groningen, the Netherlands). We divided the participants into two groups according to the presence or absence of fall risk (fall risk index 5-items version ≥6 or not), and investigated the factors associated with fall risk. RESULTS: The fall risk group had a higher age and SAF, and a higher proportion of locomotive syndrome stage >2 than the without fall risk group in patients aged ≥65 years (P < 0.01). The multivariate logistic regression analysis after adjustment of age, sex and body mass index showed that locomotive syndrome stage ≥2 and SAF were independent associators of fall risk in older adults (odds ratio 3.26, P < 0.01, odds ratio 2.96, P < 0.05, respectively). The optimal cutoff value of the SAF for fall risk was 2.4 (area under the curve 0.631; 95% CI 0.53-0.733; sensitivity 0.415; specificity 0.814; P < 0.05). CONCLUSION: The accumulation of AGEs in skin tissues can be used to screen for fall risk comprehensively. Geriatr Gerontol Int 2024; 24: 517-522.

Association of mid-thigh quadriceps muscle quality with postoperative outcomes in patients with hip osteoarthritis undergoing total hip arthroplasty: a retrospective cohort study.

PURPOSE: Muscle quality is more important than muscle mass for assessing physical function. Computed tomography (CT) is used to evaluate intramuscular fatty infiltration. The mid-thigh quadriceps CT attenuation values (CTV) expressed in Hounsfield units (HU) negatively correlate with physical function. Patients with hip osteoarthritis (HOA) have lower extremity muscle atrophy, including decreased cross-sectional area (CSA), CTV, and muscle strength. Using preoperative CT images, we investigated the association between mid-thigh quadriceps CSA, CTV, and postoperative outcomes in patients with HOA. METHODS: This study included 62 patients who had unilateral HOA (62 hips) and underwent total hip arthroplasty (THA). We investigated the association between preoperative and postoperative Japanese Orthopaedic Association (JOA) hip scores, 12-item Short Form survey (SF-12), mid-thigh quadriceps CSA, and CTV. RESULTS: The mean age was 64.7 ± 10.1 years, with 15 men (24.2%), and the mean body mass index was 24.3 ± 4.3 kg/m2. Secondary HOA was present in 79.0% of patients. The mean CSA and CTV of the mid-thigh quadriceps on the operative side were 38.8 ± 9.8 cm2 and 40.3 ± 7.8 HU, respectively. Multiple regression analyses adjusted for age and sex showed that preoperative mid-thigh quadriceps CSA was not associated with preoperative and postoperative JOA hip scores or SF-12. The preoperative mid-thigh quadriceps CTV was associated with the postoperative JOA hip score in the gait ability domain and SF-12 in the physical component summary domain. CONCLUSION: Preoperative muscle quality is associated with postoperative outcomes in patients who have HOA regardless of age and sex.

Anti-sclerostin antibody therapy prevents post-ischemic osteonecrosis bone collapse via interleukin-6 association.

Osteonecrosis of the femoral head (ONFH) is a debilitating condition characterized by subchondral bone necrosis, which frequently culminates in joint destruction. Although total hip arthroplasty is conventionally practiced to remediate ONFH, for patients under the age of 60, the outcomes can be suboptimal. Chronic inflammation, particularly that mediated by interleukin-6 (IL-6), has been conjectured to be a potential mechanism underlying the etiology of ONFH. This study aimed at exploring the interplay between IL-6, the canonical Wnt signaling pathway, and ONFH to provide insights for potential therapeutic interventions. Human ONFH specimens depicted an elevation in ß-catenin expression in the transitional layer, while IL-6 levels were pronounced in the same region. Subsequently, mouse models of ischemic osteonecrosis were treated with an anti-sclerostin antibody to assess its effects on bone metabolism and cellular processes. Histological analysis revealed that the administration of anti-sclerostin antibodies effectuated early recovery from bone necrosis, reduced empty lacunae, and suppressed IL-6 expression. The treatment evidently initiated the activation of the Wnt/ß-catenin signaling pathway, presenting a potential mechanism associated with IL-6-mediated inflammation. Furthermore, the antibody upregulated osteoblast formation, downregulated osteoclast formation, and increased bone volume. Micro-CT imaging demonstrated increased bone volume, prevented epiphyseal deformity, and improved compression strength. Therefore, this study yields significant findings, indicating the potency of anti-sclerostin antibodies in effectively modulating the Wnt/ß-catenin pathway, associating with IL-6 expression, and preventing post-ONFH bone collapse. Additionally, this preclinical investigation in mouse models offers an avenue for prospective research on potential therapeutic interventions against human ONFH.

Computer simulation study of cementless cup placement for dysplastic hip osteoarthritis using subluxation percentage of Crowe classification.

It is often difficult to achieve adequate bone coverage of the cup in total hip arthroplasty in cases of severe developmental dysplasia of the hip (DDH). This study aimed to evaluate the relationship between subluxation percentage of Crowe classification and cup center-edge (cup-CE) angle to investigate whether subluxation percentage according to the Crowe classification is a useful indicator for cementless cup placement. Cementless cup placement was simulated in 77 women with DDH in 91 hips (Crowe I, 35 hips; Crowe II, 35 hips; and Crowe III, 21 hips) using computed tomography-based computer simulation software. The cups were placed at the anatomic hip center (AHC) and 10-mm high hip center (HHC). The relationship between the subluxation percentage and cup-CE angle was evaluated using Spearman's rank correlation coefficient. In addition, the cutoff values for the subluxation percentage that satisfied a cup-CE angle ≥0° were determined using the receiving operating characteristic curve. The cup-CE angle was negatively correlated with the subluxation percentage in both AHC and 10-mm HHC (correlation coefficient ρ = -0.542 [p < 0.01] and -0.704 [p < 0.01], respectively). The cutoff values for subluxation percentage that satisfied a cup-CE angle ≥0° were 56.1% and 73.6% for AHC and 10-mm HHC, respectively. Cementless cup placement in AHC is difficult in cases with the subluxation percentage ≥56.1%, and HHC reconstruction or femoral structural autograft technique should be considered as an alternative. Moreover, placement at 10 mm above AHC is difficult in cases with subluxation percentage ≥73.6%.

Analysis of Dynamic Factors and Spinal Sagittal Alignment in Patients with Thoracic Spondylotic Myelopathy.

Introduction: Although thoracic spondylotic myelopathy (TSM) without ossification or disc disorder has been associated with some dynamic factors in the thoracolumbar area, a detailed investigation is yet to be published. Thus, in this study, we investigated the segmental motion and sagittal alignment of the thoracolumbar area in patients with and without TSM. Methods: Patients with TSM who were treated from 2013 to 2020 were enrolled in this study. The non-TSM group consisted of sex- and age-matched patients with spinal disorders other than TSM. Segmental mobility from T10-L2 during passive maximum flexion and extension following myelography and the sagittal cobb angles of T10-L1 and L1-L5 in the standing position were measured using multidetector computed tomography (CT). The mobility of each segment was set as the difference in the angles between the two positions. Results: In total, 10 patients (8 males and 2 females, mean age 65.8 years) with TSM and 20 without TSM were enrolled. The most stenotic level was observed at T10-T11 in four cases and T11-T12 in six. The average mobility at this segment in the TSM group (5.8°) was significantly greater than that in the non-TSM group (2.1°) (p<0.001). In the TSM group, the cobb angles of T10-L1 and L1-L5 were 2.3° and 17.4° of lordosis, respectively, which differed significantly from those in the non-TSM group, which were 8° of kyphosis and 32.2° of lordosis, respectively (p<0.001 and p=0.001, respectively). Conclusions: Compared with those without TSM, patients with TSM were found to have greater segmental mobility at the most stenotic level, thoracolumbar lordosis, and decreased lumbar lordosis.

Spinal pseudoarthrosis following osteoporotic vertebral fracture: prevalence, risk factors, and influence on patients' activities of daily living 1 year after injury.

PURPOSE: To investigate the prevalence and risk factors and influence of pseudoarthrosis on activities of daily living (ADL) of patients with osteoporotic vertebral fracture (OVF). METHODS: Spinal pseudoarthrosis is defined as the presence of a cleft in the vertebral body on a lateral X-ray image in the sitting position at 1 year after admission. Of the total 684 patients treated for OVF between January 2012 and February 2019 at our institution, 551 patients (mean age, 81.9 years; a male-to-female ratio, 152:399) who could be followed up to 1 year were included in this study. Prevalence, risk factors, and influence of pseudoarthrosis on the ADL of patients as well as fracture type and location were investigated. Pseudoarthrosis was set as the objective variable. Total bone mineral density, skeletal muscle mass index, sex, age, history of osteoporosis treatment, presence of dementia, vertebral kyphosis angle, fracture type (presence of posterior wall injury), degree of independence before admission, history of steroid use, albumin level, renal function, presence of diabetes, and diffuse idiopathic skeletal hyperostosis were set as explanatory variables for multivariate analysis of the influence of pseudoarthrosis on the walking ability and ADL independence before and 1 year after OVF. RESULTS: In total, 54 (9.8%) patients were diagnosed with pseudarthrosis 1 year after injury (mean age, 81.3 ± 6.5 years; male-to-female ratio, 18:36). BKP was performed in nine patients who did not develop pseudoarthrosis after 1 year. In the multivariate analysis, only the presence of posterior wall injury was significantly correlated with the presence of pseudoarthrosis (OR = 2.059, p = 0.039). No significant difference was found between the pseudarthrosis group and the non-pseudarthrosis group in terms of walking ability and ADL independence at 1 year. CONCLUSIONS: The prevalence of pseudoarthrosis following OVF was 9.8%, and its risk factor was posterior wall injury. The BKP group was not included in the pseudoarthrosis group, which may have led to an underestimation of the prevalence of pseudoarthrosis. The prevalence, risk factors, and influence of spinal pseudoarthrosis on patients' ADL following osteoporotic vertebral fracture (OVF) were investigated. Pseudoarthrosis occurs in 9.8% 1 year after the injury in patients with OVF. Posterior wall injury was the risk factor of pseudoarthrosis.

Development of helix-stabilized antimicrobial peptides composed of lysine and hydrophobic α,α-disubstituted α-amino acid residues.

Lysine-based amphipathic nonapeptides, including homochiral peptides [Ac-(l-Lys-l-Lys-Xaa)3-NH2 (Xaa=Gly, Ala, Aib, Ac5c, or Ac6c) and Ac-(d-Lys-d-Lys-Aib)3-NH2], a heterochiral peptide [Ac-(l-Lys-d-Lys-Aib)3-NH2], and a racemic mixture of diastereomeric peptides [Ac-(rac-Lys-rac-Lys-Aib)3-NH2] were designed and synthesized to investigate the relationship between their preferred secondary structures and their antimicrobial activity. Peptide 5, [Ac-(l-Lys-l-Lys-Ac6c)3-NH2] formed a stable α-helical structure and exhibited strong activity against Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa).