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; ••: ••-••.

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.

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%.

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.

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).