Serum branched-chain amino acid levels are associated with fracture risk in Japanese women.

AIM: Branched-chain amino acids (BCAAs) have been shown to exert beneficial effects on muscle and bone metabolism; however, no studies to date have investigated whether BCAAs have beneficial effects on bone fractures. Herein, we aim to prospectively investigate the relationship between serum BCAA concentrations and the occurrence of vertebral fractures (VFs) in Japanese women. METHODS: During the observation period (7.5 ± 6.1 years), 188 of 983 participants experienced VF. Kaplan-Meier analyses were conducted to examine time-dependent variations in the vertebral compression fracture occurrence rate. Patients were stratified into quartiles based on serum BCAA concentration for this analysis. RESULTS: The analysis results indicated that the group with the lowest BCAA level developed VFs significantly earlier and with a higher frequency than the other groups (P < 0.001). A Cox proportional hazards model showed that BCAA concentration was a significant risk factor for incident fracture, even after adjusting for possible confounding factors. A series of multiple regression analyses were performed to identify factors related to serum BCAA concentration, with the results identifying levels of glycated hemoglobin (P < 0.001), adiponectin (P < 0.001), and NOx (P = 0.011) as significant factors associated with serum BCAA. CONCLUSIONS: Overall, the present study revealed that a lower serum BCAA level was an independent risk factor for incident VF in postmenopausal women. Geriatr Gerontol Int 2024; ••: ••-••.

Prevalence and associated factors of locomotive syndrome in young Japanese adults: a cross-sectional study.

BACKGROUND: The onset of locomotive syndrome (LS) precedes that of frailty. Therefore, the first step in extending healthy life expectancy is to implement measures against LS in young adults. The aim of this study was to investigate the prevalence of LS and its associated factors in young adults for early detection and prevention of LS. METHODS: The participants of this study comprised 413 university students specializing in health sciences (192 males and 221 females) with an average age of 19.1 ± 1.2 years. All participants voluntarily participated in the study and reported no serious health problems. The presence or absence of LS was evaluated using the stand-up test, two-step test, and the 25-question Geriatric Locomotive Function Scale. Additionally, musculoskeletal assessment (one-leg standing, squatting, shoulder elevation, and standing forward bend), body composition analysis (weight, body mass index, body fat mass, body fat percentage, skeletal muscle mass index (SMI), and phase angle), handgrip strength test, physical activity assessment, and nutritional assessment were conducted. Sex-stratified analyses were performed, comparing groups with and without LS. Factors associated with LS were explored using binomial logistic regression. RESULTS: Of the 413 young adults studied, 86 individuals (20.8%) were found to have LS. When stratified by sex, LS was observed to have a considerably higher prevalence in females (55, 24.9%) than in males (31, 16.1%). In males, the notable differences between the groups with and without LS were observed in one-leg standing and phase angle, whereas in females, differences were identified in body fat mass, body fat percentage, SMI, musculoskeletal pain, and handgrip strength. Two types of binomial logistic regression analysis revealed that the inability to perform one-leg standing was associated with LS in males, while the presence of musculoskeletal pain and a high body fat percentage were identified as factors associated with LS in females. CONCLUSIONS: One in five young adults were found to have LS in this study, underscoring the necessity for early intervention and LS health education. Furthermore, effective management of musculoskeletal pain is also crucial.

Nutritional and inflammation factors associated with current frailty level and effect of co-morbidities on the progression of frailty.

AIM: Frailty is defined as extreme vulnerability, a syndrome that exposes the individual to a higher risk of disability. While risk factors for frailty have been gradually uncovered, the full identification of biochemical factors and co-morbidities influencing frailty remains incomplete. METHODS: Cross-sectional and longitudinal analyses were performed to elucidate the risk factors for the prevalence and progression of frailty. The study included 1035 Japanese female outpatients. At baseline, biochemical markers were measured. Co-morbidities included diabetes mellitus, dyslipidemia, hypertension, vertebral osteoarthritis, and osteoporosis. Frailty levels were assessed using frailty scores ranging from 0 to 5. Prevalence of frailty was judged by a score of 3 or above, and progression was judged by an increase in the frailty score during the observation period. Multiple regression analysis was used for the cross-sectional analysis, and the Cox hazard model was used for the longitudinal analysis. RESULTS: Of the 1035 selected participants, 212 were diagnosed with frailty. Advanced age and log IL-6 and branched-chain amino acids (BCAA) levels were significant independent risk factors for frailty. Subjects were followed for 7.7 ± 5.9 years and progression was observed in 130 subjects. Older age, the absence of hyperlipidemia, the presence of osteoporosis, and lower frailty scores were identified as significant risk factors for frailty progression. CONCLUSIONS: Inflammatory and nutritional markers exhibited significant associations with the current frailty status, whereas co-morbidities such as osteoporosis or hyperlipidemia emerged as independent risk or protective factors of future frailty progression. Geriatr Gerontol Int 2024; ••: ••-••.

Spinal osteoarthritis is a risk of vertebral fractures in postmenopausal women.

Recent studies have revealed that despite high bone mineral density (BMD), osteoarthritis (OA) is a risk factor for osteoporotic fractures. However, the relationship between spinal OA and vertebral fractures has not yet been fully investigated. This longitudinal analysis used a subset of ongoing cohort study consist with Japanese postmenopausal women. The prevalence of spinal OA was determined using Kellgren-Lawrence grading method. The incidence of vertebral fractures were determined by semiquantitative analysis of spinal X-ray films. The relationship between the presence of spinal OA and incidence of vertebral fractures was evaluated using the Cox regression analysis. In total, 1480 women were followed up for 8.1 ± 6.4 years. Among them, 923 were diagnosed with spinal OA, and incident vertebral fractures were observed in 473 participants. After adjusting for confounding variables, the spinal OA (≥ grade 2) was a significant predictor of incident vertebral fractures (hazard ratio, 1.52; 95% confidence interval: 1.19-1.93, p = 0.001). Using ROC analysis, the thresholds of lumbar BMD for incident vertebral fractures were 0.952 g/cm2 for patients with spinal OA and 0.753 g/cm2 for patients without spinal OA. The presence of spinal OA is a risk factor for incident vertebral fractures despite high lumbar BMD.

Neck circumference is a highly reliable anthropometric measure in older adults requiring long-term care.

The reliability of neck circumference measurement as an assessment tool for older adults requiring long-term care remains unknown. This study aimed to evaluate the reliability of neck circumference measurement in older adults requiring long-term care, and the effect of edema on measurement error. Two physical therapists measured the neck circumference. Intraclass correlation coefficient (ICC) and Bland-Altman analyses were performed to examine the reliability of neck circumference measurement. Correlation analysis was used to evaluate the relationship between edema values (extracellular water/total body water) and neck circumference measurement difference. For inter-rater reliability of neck circumference measurement, the overall ICC (2,1) was 0.98. The upper and lower limits of the difference between examiners ranged from -0.9 to 1.2 cm. There was no association between edema values and neck circumference measurement error. Thus, measurement of the neck circumference in older adults requiring long-term care is a reliable assessment tool, with a low error rate, even in older adults with edema.

Prevalence and factors associated with changes in frailty among community-dwelling older adults in Japan during the COVID-19 pandemic: A prospective cohort study from 2020 to 2022.

AIM: This study aimed to ascertain the prevalence of frailty during the pandemic and to determine factors associated with changes in frailty status. METHODS: In May-June of 2020-2022, we assessed the frailty of 549 participants using the Kihon Checklist. Furthermore, we classified participant residences as urban, suburban, and rural and investigated participants' engagement in hobbies and community activities in 2020 and 2022. Cochran's Q test was used to analyze the proportions of frailty status. Subsequently, we conducted a binomial logistic regression analysis with the improvement/deterioration of frailty status from 2020 to 2022 as the dependent variable, and engagement in hobbies and community activities as the independent variables. RESULTS: Significant changes were observed among participants in urban areas, where an increase in pre-frailty and a decrease in robust individuals from 2020 to 2021 were noted. Focusing on item no. 17 (going out), the decreasing frequency had recovered by 2022 in the group of all groups. Continued engagement in only hobbies or only community activities, and continued engagement in both were associated with remained robust/frailty-status improvement. Moreover, not engaging in either hobbies or community activities was associated with remained frail/frailty-status deterioration. CONCLUSIONS: During the early stages, the COVID-19 pandemic impacted the frailty of older adults in densely populated areas. The results also suggest an attenuation in the decline in older adult activity in 2022. Continuous engagement in hobbies and community activities was crucial for improving and preventing deterioration in frailty status during the COVID-19 pandemic. Geriatr Gerontol Int 2024; 24: 40-47.

Increased Risk of Tooth Loss in Postmenopausal Women With Prevalent Vertebral Fractures: An Observational Study.

The association between prevalent fractures and tooth loss in postmenopausal women remains unclear. Herein, we investigated the association between prevalent vertebral and nonvertebral fractures, the number of teeth present at baseline, and the number of teeth lost during follow-up in postmenopausal Japanese women. This cross-sectional study enrolled 843 participants (mean age 68.3 years). The number of teeth at follow-up was evaluated in 655 women in this longitudinal study. The participants were divided into four groups according to their prevalent fracture status: no fractures, vertebral fractures alone, nonvertebral fractures alone, and both fracture types. After adjusting for covariates, Poisson regression analyses were performed to investigate differences in the number of teeth at baseline and that lost during the follow-up period among the four groups. Participants with prevalent vertebral fractures alone had significantly fewer teeth at baseline than those in participants without fractures or nonvertebral fractures alone (p < 0.001 for both). Furthermore, they lost more teeth during the follow-up period than did those with no fractures (p = 0.021) and tended to lose more teeth than did those with nonvertebral fractures alone or both prevalent fracture types. We observed no significant difference in the number of teeth lost between the participants with nonvertebral fractures alone and those with no fractures. Postmenopausal women with prevalent vertebral fractures may be at a higher risk of tooth loss. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Minimal Detectable Changes in the Five Times Sit-to-Stand Test in Older Japanese Adults with Sarcopenia Requiring Long-Term Care.

Background and Objectives: Although the importance of sarcopenia control has been suggested, there are no minimal detectable change (MDC) studies of older adults with sarcopenia, to our knowledge, and the criteria for determining the effectiveness of interventions are unknown. The purpose of this study was to calculate the MDC in the five times sit-to-stand test (FTSST) in older Japanese adults with sarcopenia and use it as an index to determine the effectiveness of future interventions. Materials and Methods: This was a cross-sectional study conducted in January and February 2023. The participants of this study were older Japanese adults using daycare rehabilitation. Thirty-eight participants performed the FTSST twice a week. Grip strength, walking speed, and skeletal muscle mass were measured to determine the presence of sarcopenia. The diagnosis of sarcopenia was defined as low skeletal muscle mass and low muscle strength and/or low physical function, based on the Asian Working Group for Sarcopenia 2019 diagnostic criteria. Participants were further classified as sarcopenic or non-sarcopenic. Intraclass correlation coefficients (ICCs) and MDCs were calculated for the overall, sarcopenia, and non-sarcopenia groups using the two FTSST measures. The average and difference of the two variables were used to calculate the MDC. Results: Overall, the ICC (1,1) was 0.94, MDC was 2.87 s, and MDC% was 23.3%. The sarcopenia group had an ICC (1,1) of 0.93, MDC of 3.12 s, and MDC% of 24.0%. The non-sarcopenia group had an ICC (1,1) of 0.95, MDC of 2.25 s, and MDC% of 19.2%. Conclusions: Despite the limitation of the data being only from this study population, we found that a change of ≥3.12 s or ≥24.0% in the FTSST of older adults with sarcopenia was clinically meaningful and may help to determine the effectiveness of sarcopenia treatment. The improvement or decline in older Japanese adults with sarcopenia should be determined by changes in the FTSST over a longer period of time than that for other conditions.

Association between decreased neck circumference and impaired activities of daily living among older adults in long-term care.

AIM: Assessment interventions for the decline of activities of daily living (ADLs) in older adults are crucial, as ADL decline increases hospitalization duration and mortality risk. Decreased neck circumference may result in various physical dysfunctions, including malnutrition. However, the association between neck circumference and ADLs has not been fully clarified. This study aimed to determine the association between decreased neck circumference and ADLs in older adults requiring long-term care. METHODS: The study included 152 older adults deemed to require support or care under Japan's long-term care insurance system. Neck circumference was measured just below the thyroid cartilage with a measuring tape. The Barthel index was used to evaluate ADLs, and skeletal muscle mass and nutritional status were assessed by bioelectrical impedance analysis instruments. A multivariate analysis was conducted to investigate the association between neck circumference and ADLs. RESULTS: Neck circumference demonstrated a significant inverse correlation with age and a significant positive correlation with body mass index, skeletal muscle mass index, phase angle, and Barthel index. In the multivariate analysis, ADLs was significantly associated with neck circumference (odds ratio [OR] = 0.51, P = 0.002) and phase angle (OR = 0.04, P < 0.001). CONCLUSIONS: Neck circumference is associated with age, skeletal muscle mass, and nutritional status. Furthermore, a decrease in neck circumference is suggested as an independent risk factor for ADL decline in older adults requiring long-term care. Geriatr Gerontol Int 2023; 23: 906-911.

Sarcopenia with Depression Presents a More Severe Disability Than Only Sarcopenia among Japanese Older Adults in Need of Long-Term Care.

Background and objectives: The combination of depression and sarcopenia, a condition prevalent worldwide, may cause dis-tinct problems that should not be underestimated. However, to the best of our knowledge, no reports have investigated the combined effects of depression and sarcopenia. In this study, we compared physical function, nutritional status, and daily functioning among older adults with only depression (OD), those with only sarcopenia (OS), and those with sarcopenia with depression (SD) to examine the effects of the combination of depression and sarcopenia. Materials and Methods: The participants were 186 communi-ty-dwelling older individuals who required support or care. The participants were classified into four groups based on the presence or absence of sarcopenia and depression: Control, OD, OS, and SD. The following parameters were evaluated in the four groups: grip strength, walking speed, skeletal muscle mass index (SMI), Mini Nutritional Assessment Short-Form (MNA-sf), and long-term care certification level. In addition, univariate and multivariate analyses of the survey results were performed to identify risk factors leading from OS to SD. Results: We found that 31.2% of older participants who needed support or nursing care had SD, which had more pronounced adverse effects on grip strength, walking speed, SMI, MNA-sf, and level of nursing care than OD or OS. Furthermore, multivariate analysis of SD vs. OS showed that decreased grip strength and worsening MNA-sf were independent risk factors. Conclusions: SD is common among older individuals living in the community. Patients with SD require support and care, and the condition has a greater impact on physical function, nutritional status, and decline in life function compared to OD and OS. Therefore, it is desirable to elucidate the process leading to SD and investigate the risk factors and prognosis. It is expected that sarcopenia with depression will be investigated worldwide in the future.

Leg skeletal muscle mass asymmetry is independently associated with gait speed in older adults requiring long-term care.

AIM: Decreased gait speed in older adults has been associated with incident disability, cognitive impairment, institutionalization, falls, deterioration in level of care, and mortality. Gait speed has been reported to be related to leg asymmetry. However, the relationship between gait speed and leg skeletal muscle mass asymmetry in older adults requiring long-term care has not been clarified. In this study, we examined the association between gait speed and leg skeletal muscle mass asymmetry and the cutoff values of leg skeletal muscle mass asymmetry that may affect gait speed. METHODS: The asymmetry index of leg skeletal muscle mass was measured in 230 older adults under the Japanese long-term care insurance system using bioelectrical impedance analysis. This cross-sectional study used multiple regression analysis and receiver operating characteristic (ROC) curve analysis to determine the relationship between gait speed and the asymmetry index of leg skeletal muscle mass. RESULTS: Multiple regression analysis revealed that the asymmetry index of leg skeletal muscle mass (ß = -0.19, P = 0.002, R2 = 0.261) was independently and significantly associated with gait speed. Furthermore, ROC analysis showed that the cutoff value of the asymmetry index of leg skeletal muscle mass that identified reduced gait speed (<1.0 m/s) was 3.02% (Area under the curve = 0.62, sensitivity 47.3%, specificity 81.0%, P = 0.014). CONCLUSIONS: The asymmetry index of leg skeletal muscle mass was associated with gait speed in older adults requiring long-term care. Future assessment and interventions directed towards symmetry of leg skeletal muscle mass may help to improve gait speed in older adults. Geriatr Gerontol Int 2023; 23: 371-375.

Indicators predicting the development and improvement of sarcopenia in older adults requiring long-term care.

[Purpose] This study aimed to identify factors associated with sarcopenia development and improvement among older adults requiring long-term care. [Participants and Methods] This prospective observational study included 118 older adults requiring long-term care in a single facility. Sarcopenia was assessed according to the 2019 diagnostic criteria of the Asian Working Group for Sarcopenia at baseline and after 6 months. Nutritional status was measured using calf circumference and the Mini Nutritional Assessment-Short Form to examine the association between sarcopenia onset and improvement. [Results] Risk of malnutrition and lower calf circumference at baseline were significantly associated with sarcopenia development. The study also showed that a non-risk of malnutrition, higher calf circumference, and higher skeletal muscle mass index were significantly associated with improved sarcopenia. [Conclusion] The Mini Nutritional Assessment-Short Form and calf circumference were able to predict sarcopenia development and improvement in older adults requiring long-term care.

p57Kip2 is an essential regulator of vitamin D receptor-dependent mechanisms.

A cyclin-dependent kinase (CDK) inhibitor, p57Kip2, is an important molecule involved in bone development; p57Kip2-deficient (p57-/-) mice display neonatal lethality resulting from abnormal bone formation and cleft palate. The modulator 1α,25-dihydroxyvitamin D3 (l,25-(OH)2VD3) has shown the potential to suppress the proliferation and induce the differentiation of normal and tumor cells. The current study assessed the role of p57Kip2 in the 1,25-(OH)2VD3-regulated differentiation of osteoblasts because p57Kip2 is associated with the vitamin D receptor (VDR). Additionally, 1,25-(OH)2VD3 treatment increased p57KIP2 expression and induced the colocalization of p57KIP2 with VDR in the osteoblast nucleus. Primary p57-/- osteoblasts exhibited higher proliferation rates with Cdk activation than p57+/+ cells. A lower level of nodule mineralization was observed in p57-/- osteoblasts than in p57+/+ cells. In p57+/+ osteoblasts, 1,25-(OH)2VD3 upregulated the p57Kip2 and opn mRNA expression levels, while the opn expression levels were significantly decreased in p57-/- cells. The osteoclastogenesis assay performed using bone marrow cocultured with 1,25-(OH)2VD3-treated osteoblasts revealed a decreased efficiency of 1,25-(OH)2VD3-stimulated osteoclastogenesis in p57-/- cells. Based on these results, p57Kip2 might function as a mediator of 1,25-(OH)2VD3 signaling, thereby enabling sufficient VDR activation for osteoblast maturation.

Nitric oxide is associated with fracture risk in Japanese women.

Although nitric oxide (NO) is a known factor that regulates the bone physiology, few and discordant results have been obtained in human studies evaluating the effect of nitrates on bone health. We investigated for the relationship between serum NOx level and incident osteoporotic fracture rate prospectively in a cohort consisting of Japanese women. A total of 871 subjects (67.5 ± 10.8 y/o) were analyzed. During the observation period (8.8 ± 7.2 yrs), incident osteoporotic fractures occurred in 267 participants (209 vertebral fractures, 57 long-bone fractures, and 1 both types). Hazard ratio, by the Cox proportional hazards model, of serum NOx for incident fracture was 0.64 (95% confidence interval 0.53-0.78, p < 0.001) after adjustment for baseline age (1.13, 1.06-1.21, p < 0.001), lumbar bone mineral density (L-BMD; 0.85, 0.78-0.92, p < 0.001), presence of prevalent fracture (3.27, 2.49-4.32, p < 0.001), and treatment of osteoporosis (0.70, 0.53-0.92, p = 0.010). The relationships between serum level of NOx and bone-related parameters were examined by multiple regression analysis; body mass index (p < 0.001) and L-BMD (p = 0.011) were significantly associated with serum NOx level. These results suggest that the low circulating NOx is one of the independent predictors for osteoporotic fracture occurrence in postmenopausal women.

Frailty under COVID-19 pandemic in Japan: Changes in prevalence of frailty from 2017 to 2021.

BACKGROUND: After the outbreak of the coronavirus disease 2019 (COVID-19), "pandemic-associated-frailty" or profound health deterioration, in older adults has been considered a health concern. In this study, we sought to demonstrate whether pandemic-associated-frailty is occurring in Japan, where the population is aging, by showing the prevalence of frailty before and during the COVID-19 outbreak, using the same method. METHODS: A total of 5222 older adults in Otawara City, Tochigi Prefecture, aged 70 and 75 were surveyed annually using a complete survey, excluding those who were certified as requiring long-term care. Frailty during 2017-2019 before the COVID-19 outbreak and during 2020-2021 during the COVID-19 outbreak was determined using the Kihon Checklist (KCL). Statistical analysis was performed using the χ2 test to compare annual frailty status and Kruskal-Wallis test to compare the scores. RESULTS: The frailty statuses over the five-year period showed a significant decrease in Robust and a significant increase in Pre-frailty and Frailty (p < 0.001). Frailty increased markedly during the second year of the pandemic. Based on the category, the scores deteriorated significantly for activities of daily living (p < 0.001), physical function (p = 0.003), oral function (p < 0.001), outdoor activity (p < 0.001), and depression (p < 0.001). Moreover, there was a significant deterioration in the total score for 25 items (p < 0.001). In addition, a significant deterioration was observed in the total score of 23 items, excluding the social withdrawal affected by self-restraint life (p < 0.001). CONCLUSIONS: The population prevalence of frailty in older adults increased steadily from the pre-pandemic year through the first and second years of the pandemic. Based on the 25 questions of the KCL, two aspects including visiting friends and going out less stood out. This suggests that pandemic-associated-frailty occurred in Japan.

Patterns of Changes in Respiratory Muscle Strength over 1 Year in Non-Sarcopenia, Sarcopenia, and Severe Sarcopenia.

In this prospective longitudinal cohort study, we explored the characteristics of older people with lower respiratory muscle strength, according to sarcopenia severity, over the course of 1 year. The maximum expiratory pressure (MEP), grip strength, walking speed, and skeletal muscle mass index of 58 participants (28 men, 30 women; mean age, 76.9 ± 7.7 years) were measured at baseline and at the 1-year follow-up. Participants were classified into a decreased MEP group (n = 29; MEP decreased by ≥10% after 1 year) and a non-decreased MEP group (n = 29; MEP decreased by <10%). Sarcopenia status in the mild direction at baseline was significantly associated with MEP decline after one year. Repeated two-way analysis of variance showed significant main effects of measurement time (p < 0.001) and severity of sarcopenia (p = 0.026), as well as a significant interaction effect (p = 0.006). Surprisingly, MEP decreased significantly in the non-sarcopenia and sarcopenia groups, but not in the severe sarcopenia group. Thus, individuals without sarcopenia and those with moderate sarcopenia at baseline are predisposed to MEP decline and should be closely monitored for signs of such decline and associated adverse events.