Lack of vitamin D signalling in mesenchymal progenitors causes fatty infiltration in muscle.

BACKGROUND: Recent studies have indicated the importance of muscle quality in addition to muscle quantity in sarcopenia pathophysiology. Intramuscular adipose tissue (IMAT), which originates from mesenchymal progenitors (MPs) in adult skeletal muscle, is a key factor affecting muscle quality in older adults, suggesting that controlling IMAT formation is a promising therapeutic strategy for sarcopenia. However, the molecular mechanism underlying IMAT formation in older adults has not been clarified. We recently found that the vitamin D receptor (VDR) is highly expressed in MPs in comparison to myotubes (P = 0.028, N = 3), indicating a potential role of vitamin D signalling in MPs. In this study, we aimed to clarify the role of vitamin D signalling in MP kinetics, with a focus on adipogenesis. METHODS: MPs isolated from mouse skeletal muscles were subjected to adipogenic differentiation conditions with or without vitamin D (1α,25(OH)2D3, 100 nM) for 7 days, and adipogenicity was evaluated based on adipogenic marker expression. For in vivo analysis, tamoxifen-inducible MP-specific VDR-deficient (VdrMPcKO) mice were newly developed to investigate whether lack of vitamin D signalling in MPs is involved in IMAT formation. To induce muscle atrophy, VdrMPcKO male mice were subjected to tenotomy of the gastrocnemius muscle, and then muscle weight, myofibre cross-sectional area, adipogenic marker expression, and fatty infiltration into the muscle were evaluated at 3 weeks after operation (N = 3-4). In addition, a vitamin D-deficient diet was provided to wild-type male mice (3 and 20 months of age, N = 5) for 3 months to investigate whether vitamin D deficiency causes IMAT formation. RESULTS: Vitamin D treatment nearly completely inhibited adipogenesis of MPs through Runx1-mediated transcriptional modifications of early adipogenic factors such as PPARγ (P = 0.0031) and C/EBPα (P = 0.0027), whereas VDR-deficient MPs derived from VdrMPcKO mice differentiated into adipocytes even in the presence of vitamin D (P = 0.0044, Oil-Red O+ area). In consistency with in-vitro findings, VdrMPcKO mice and mice fed a vitamin D-deficient diet exhibited fat deposition in atrophied (P = 0.0311) and aged (P = 0.0216) skeletal muscle, respectively. CONCLUSIONS: Vitamin D signalling is important to prevent fate decision of MPs towards the adipogenic lineage. As vitamin D levels decline with age, our data indicate that decreased vitamin D levels may be one of the causes of IMAT formation in older adults, and vitamin D signalling may be a novel therapeutic target for sarcopenia.

Moderating effect of age on the relationship between physical health loss and emotional distress post-acute care in Japanese older hospitalized patients.

BACKGROUND: At present, there are no consistent findings regarding the association between physical health loss and mental health in older adults. Some studies have shown that physical health loss is a risk factor for worsening of mental health. Other studies revealed that declining physical health does not worsen mental health. This study aimed to clarify whether the relationship between physical health loss and emotional distress varies with age in older inpatients post receiving acute care. METHODS: Data for this study were collected from 590 hospitalized patients aged ≥ 65 years immediately after their transfer from an acute care ward to a community-based integrated care ward. Emotional distress, post-acute care physical function, and cognitive function were assessed using established questionnaires and observations, whereas preadmission physical function was assessed by the family members of the patients. After conducting a one-way analysis of variance (ANOVA) and correlation analysis by age group for the main variables, a hierarchical multiple regression analysis was conducted with emotional distress as the dependent variable, physical function as the independent variable, age as the moderator variable, and cognitive and preadmission physical function as control variables. RESULTS: The mean GDS-15 score was found to be 6.7 ± 3.8. Emotional distress showed a significant negative correlation with physical function in younger age groups (65-79 and 80-84 years); however, no such association was found in older age groups (85-89, and ≥ 90 years). Age moderated the association between physical function and emotional distress. Poor physical function was associated with higher emotional distress in the younger patients; however, no such association was observed in the older patients. CONCLUSIONS: Age has a moderating effect on the relationship between physical health loss and increased emotional distress in older inpatients after acute care. It was suggested that even with the same degree of physical health loss, mental damage differed depending on age, with older patients experiencing less damage.

Identification of potential blood-based biomarkers for frailty by using an integrative approach.

INTRODUCTION: Although frailty is a geriatric syndrome that is associated with disability, hospitalization, and mortality, it can be reversible and preventable with the appropriate interventions. Additionally, as the current diagnostic criteria for frailty include only physical, psychological, cognitive and social measurements, there is a need for promising blood-based molecular biomarkers to aid in the diagnosis of frailty. METHODS: To identify candidate blood-based biomarkers that can enhance current diagnosis of frailty, we conducted a comprehensive analysis of clinical data, messenger RNA sequencing (RNA-seq), and aging-related factors using a total of 104 older adults aged 65-90 years (61 frail subjects and 43 robust subjects) in a cross-sectional case-control study. RESULTS: We identified two candidate biomarkers of frailty from the clinical data analysis, nine from the RNA-seq analysis, and six from the aging-related factors analysis. By using combinations of the candidate biomarkers and clinical information, we constructed risk-prediction models. The best models used combinations that included skeletal muscle mass index measured by dual-energy X-ray absorptiometry (adjusted p = 0.026), GDF15 (adjusted p = 1.46E-03), Adiponectin (adjusted p = 0.012), CXCL9 (adjusted p = 0.011), or Apelin (adjusted p = 0.020) as the biomarker. These models achieved a high area under the curve of 0.95 in an independent validation cohort (95% confidence interval: 0.79-0.97). Our risk prediction models showed significantly higher areas under the curve than did models constructed using only basic clinical information (Welch's t-test p < 0.001). CONCLUSION: All five biomarkers showed statistically significant correlations with components of the frailty diagnostic criteria. We discovered several potential biomarkers for the diagnosis of frailty. Further refinement may lead to their future clinical use.

Longitudinal association between muscle and bone loss: Results of US and Japanese cohort studies.

BACKGROUND: Muscle and bone are physiologically interconnected, but joint changes of muscle and bone with aging, and whether the muscle-bone changes are different by sex and by country has been little studied. We examined longitudinal associations of bone mineral density (BMD) and muscle mass or muscle strength in community-dwelling 65 years or older in the United States and Japan. METHODS: The present analytic sample included 1129 women and men from the Baltimore Longitudinal Study of Aging (BLSA) (mean age, 74.5 ± 7.5 years; women, 49.8%) and 1998 women and men from the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA) (mean age, 70.0 ± 4.5 years; women, 51.4%). Median follow-up was 4.6 (min-max, 0-15.4) years in the BLSA and 4.0 (min-max, 0-13.4) years in the NILS-LSA. We selected visits at which participants had BMD (whole body, pelvic, femoral neck, trochanter, and Ward's triangle BMDs) and muscle mass [appendicular lean mass, (ALM)] measured by DXA scan. In each bone site, we ran cohort-specific bivariate linear mixed-effects models adjusted for baseline age, sex, body height, body weight, fat mass, education year, and smoking status. Race was an additional adjustment in the BLSA. Additionally, we performed sex-specific analyses. RESULTS: In the BLSA, the rate of change in ALM positively correlated with the rate of change in the whole body (rho = 0.30, P < 0.0001) and pelvic BMD (rho = 0.24, P < 0.0001), but not in trochanter, femoral neck, or Ward's triangle BMD (P > 0.05). In the NILS-LSA, ALM positively correlated with the rate of change in all bone sites (rho ranged from 0.20 to 0.71, P < 0.01). In women, ALM positively correlated with the rate of change in all bone sites in both cohorts (in the NILS-LSA, rho ranged from 0.35 to 0.91, P < 0.01; in the BLSA, rho ranged from 0.26 to 0.56, P < 0.05) except for femoral neck BMD in the BLSA. In men, ALM positively correlated with pelvic, trochanter, and Ward's triangle BMD in the NILS-LSA (rho ranged from 0.45 to 0.68, P < 0.0001), and whole body and trochanter BMD in the BLSA (both, rho = 0.20, P < 0.05). CONCLUSIONS: Muscle loss co-occurred with bone loss in both cohorts, but the association in the NILS-LSA tended to be stronger than in the BLSA, and the association was higher in women than in men, implying that the association may differ by sex and country.

Association between Circulating Levels of CXCL9 and CXCL10 and Physical Frailty in Older Adults.

INTRODUCTION: Dysregulation of pro-inflammatory chemokines is considered a potential mechanism for the development of age-related medical conditions such as frailty. However, evidence linking circulating chemokines with frailty remains lacking. MATERIALS AND METHODS: We performed a case-control study including 48 cases and 48 controls aged 65-90 years, using the National Center for Geriatrics and Gerontology outpatient registry data. Cases were outpatients with physical frailty and low habitual daily activity. Controls were robust outpatients who performed habitual daily activities. The Japanese version of the Cardiovascular Health Study criteria was used to diagnose physical frailty, and the modified Baecke questionnaire was used to evaluate habitual daily activities. Serum CXCL9 and CXCL10 levels were measured using enzyme-linked immunosorbent assay. RESULTS: The median age (interquartile range) in cases and controls was 78 (73-83) and 76 (72-80) years, with the proportions of men were 47.9% and 43.8%, respectively. In the logistic regression model with adjustment for age, sex, and other confounding factors, the multivariable odds ratios (95% confidence intervals) for the highest versus lowest tertile of CXCL9 and CXCL10 levels were 7.90 (1.61-49.80) and 1.61 (0.42-6.30), respectively. However, we did not observe a linear association between CXCL9 levels and physical frailty components. DISCUSSION/CONCLUSION: Our preliminary data exhibit that circulating CXCL9 levels were positively associated with the odds of physical frailty. However, these findings lack evidence of a dose-response relationship between CXCL9 levels and physical frailty components. Further research with a larger sample size is required to confirm these findings.

Relationship between quadriceps muscle computed tomography measurement and motor function, muscle mass, and sarcopenia diagnosis.

Background: The quadriceps muscle is one of the human body's largest and most clinically important muscles and is evaluated using mid-thigh computed tomography (CT); however, its relationship with motor function and sarcopenia remains unclear. Herein, we investigated the relationship between the cross-sectional area (CSA) of the quadriceps muscle, CT attenuation value (CTV), dual-energy X-ray absorptiometry muscle mass measurements, and muscle strength and motor function to evaluate the relationship between muscle mass loss and motor function decline, determine the diagnostic ability for sarcopenia, and confirm the usefulness of quadriceps muscle CT evaluation. Methods: A total of 472 middle-aged and older community dwellers (254 men and 218 women) aged ≥40 years (mean age: 62.3 years) were included in this study. The quantity and quality of the quadriceps muscle were assessed using CSA and CTV (CSA×CTV) as a composite index multiplied by quality and quantity. Age-adjusted partial correlations by sex with eight motor functions (knee extension muscle strength, power, normal walking speed, fast walking speed, grip strength, sit-up ability, balance ability, and reaction time) were evaluated, including correction methods for height, weight, and body mass index (BMI). Further, the accuracy of sarcopenia diagnosis was evaluated using appendicular muscle mass with dual-energy X-ray absorptiometry measurements, grip strength, and walking speed as the gold standard, and receiver operating characteristic curves were plotted to evaluate diagnostic performance. Results: In men, CSA and CSA×CTV were significantly associated with seven of the eight motor functions (p<0.05), excluding only balance ability. BMI-corrected CSA was significantly correlated with all eight motor functions in men and women (p<0.05). In the diagnosis of sarcopenia based on skeletal muscle index, CSA (area under the curve (AUC) 0.935) and CSA×CTV (AUC 0.936) and their correction by height (CSA/height (AUC 0.917) and CSA×CTV/height (AUC 0.920)) were highly accurate and useful for diagnosis in men but moderately accurate in women (CSA (AUC 0.809), CSA×CTV (AUC 0.824), CSA/height (AUC 0.799), CSA×CTV/height (AUC 0.814)). Conclusion: The present results showed that a single CT image of the quadriceps muscle at the mid-thigh is useful for diagnosing sarcopenic changes, such as loss of muscle mass, muscle weakness, and muscle function.

RNA-Sequencing Analysis Identification of Potential Biomarkers for Diagnosis of Sarcopenia.

Sarcopenia is a geriatric disease associated with increased mortality and disability. Early diagnosis and intervention are required to prevent it. This study investigated biomarkers for sarcopenia by using a combination of comprehensive clinical data and messenger RNA-sequencing (RNA-seq) analysis obtained from peripheral blood mononuclear cells. We enrolled a total of 114 older adults aged 66-94 years (52 sarcopenia diagnosed according to the Asian Working Group for Sarcopenia 2019 consensus and 62 normal older people). We used clinical data which were not included diagnosis criteria of sarcopenia, and stride length showed significance by logistic regression analysis (Bonferroni corrected p = .012, odds ratio = 0.14, 95% confidence interval [CI]: 0.05-0.40). RNA-seq analysis detected 6 differential expressed genes (FAR1, GNL2, HERC5, MRPL47, NUBP2, and S100A11). We also performed gene-set enrichment analysis and detected 2 functional modules (ie, hub genes, MYH9, and FLNA). By using any combination of the 9 candidates and basic information (age and sex), risk-prediction models were constructed. The best model by using a combination of stride length, HERC5, S100A11, and FLNA, achieved a high area under the curve (AUC) of 0.91 in a validation cohort (95% CI: 0.78-0.95). The quantitative PCR results of the 3 genes were consistent with the trend observed in the RNA-seq results. When BMI was added, the model achieved a high AUC of 0.95 (95% CI: 0.84-0.99). We have discovered potential biomarkers for the diagnosis of sarcopenia. Further refinement may lead to their future practical use in clinical use.

Serum levels of dehydroepiandrosterone sulfate are associated with a lower risk of mobility-subtype frailty in older Japanese community-dwellers.

PURPOSE: Previous studies suggest that lower serum levels of dehydroepiandrosterone sulfate (DHEA-S) are associated with physical frailty. Associations with subtypes of physical frailty have not been studied. This study aimed to investigate associations between serum DHEA-S levels and physical frailty and its subtypes in older Japanese community-dwellers using panel data. METHODS: This study was conducted within the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA). Repeated measurement data were collected from 1,886 older community-dwellers (60-91 years). Frailty was identified according to modified Cardiovascular Health Study criteria (weight loss, weakness, slowness, exhaustion, low physical activity) and was classified into following subtypes: mobility (weakness/slowness), non-mobility (weight loss/exhaustion), and low physical activity. Associations with serum DHEA-S (sex-specific tertiles [T1-T3]) were estimated by random-effects logistic regression models adjusting for age, sex, education, disease history (stroke, hypertension, heart disease, diabetes), smoking status, depressive symptoms, and survey wave. RESULTS: We found an average prevalence of 6.0% for frailty (mobility subtype, 7.0%; non-mobility subtype, 34.8%; low physical activity subtype, 9.4%) across survey waves. Mean (SD) sex-specific DHEA-S levels (µg/dL) at T1, T2, and T3 were 46.8 (20.8), 88.7 (28.4), and 158.0 (58.9), respectively. Compared with T1, the adjusted ORs (95% CIs) for frailty were 0.69 (0.44, 1.08) for T2 and 0.50 (0.30, 0.83) for T3 (P trend = 0.007). The corresponding values for mobility subtype were 0.80 (0.51, 1.24) for T2 and 0.55 (0.33, 0.90) for T3. CONCLUSION: Higher serum DHEA-S levels were associated with lower risk of frailty, especially mobility-subtype frailty, in older community-dwellers.

Relationship between sarcopenia classification and thigh muscle mass, fat area, muscle CT value and osteoporosis in middle-aged and older Japanese adults.

Sarcopenia is one of the most important health issues in today's ageing society. As an evaluation method, computed tomography (CT) is an effective means of assessing not only the quantity but also the quality of skeletal muscle. We aimed to examine the relationship between sarcopenia severity and muscle/fat area, and osteoporosis. 321 patients (116 men and 205 women, mean age 77.2 ± 7.1 years, age range 53-96 years) who visited the Integrated Healthy Aging Clinic from 2016 to 2017 were included in this study. Based on the Asia Working Group for Sarcopenia2019 criteria, patients were divided into four groups: normal group, low-functional group (with normal skeletal muscle mass, but reduced muscle strength or physical function), sarcopenia group, and severe sarcopenia group. We measured the skeletal muscle (SM), intermuscular adipose tissue (IMAT), and subcutaneous adipose tissue (SAT) areas and the CT attenuation values (CTV) using cross sections of the mid-thigh CT. We also measured bone mineral density. Then, we compared each result among the four groups. We found a significant decrease in SM area in both men and women with sarcopenia (p < 0.001 for both sexes). In women, a decrease in SAT area was observed in the sarcopenia group (p < 0.001), and an increase in IMAT was observed in the low functional group (p < 0.001). The CTV decreased in men with sarcopenia and severe sarcopenia; similarly, women in the low functional and severe sarcopenia groups had decreased CTV (p < 0.001 for both sexes). An association between sarcopenia and osteoporosis in men was detected (p = 0.004). By using not only muscle mass but also fat mass and CTV, we were able to better examine the pathogenesis of sarcopenia and differences between men and women in Japanese middle-aged and older adults.

Sarcopenia affects conservative treatment of osteoporotic vertebral fracture.

OBJECTIVES: Sarcopenia and osteoporosis affects activities of daily living and quality of elderly people. However, little is known about its impact on elderly locomotor diseases, such as osteoporotic vertebral fracture (OVF). There is no report investigating the influence of both sarcopenia and osteoporosis on outcomes of OVF. This study aimed to evaluate the clinical outcomes of OVF in elderly patients from sarcopenic perspectives. METHODS: This prospective study was conducted with 396 patients, aged 65 years or more, hospitalized for the treatment of OVF (mean age, 81.9 ±â€¯7.1 years; 111 males, 285 females). The primary outcome was the Japanese Orthopaedic Association (JOA) score for lumbar disease (at first visit, hospital discharge, and 1 year after treatment) and Barthel index (at the same time and before hospitalization). The second outcome was living place after discharge. Susceptibility to sarcopenia and osteoporosis were evaluated and clinical results of conservative treatment were compared. RESULTS: Sarcopenia significantly affected Barthel index at first visit and discharge. Sarcopenia patients had significantly higher rate for discharge to nursing home and living in nursing home after 1 year than patients without sarcopenia. Osteoporosis significantly affected the JOA score at the first visit and the Barthel index before hospitalization, at the first visit, discharge, and after 1 year. Osteoporosis did not affect the living place at discharge and after 1 year. CONCLUSIONS: Sarcopenia and osteoporosis affected outcomes of conservative treatment for OVF; moreover, sarcopenia affected the living place of OVF patients at discharge and after 1 year.

Haloperidol prophylaxis for preventing aggravation of postoperative delirium in elderly patients: a randomized, open-label prospective trial.

PURPOSES: The aim of this study was to evaluate the safety and efficacy of the early administration haloperidol in preventing the aggravation of postoperative delirium in elderly patients. METHODS: A total of 201 patients (age ≥75 years) who underwent elective surgery were enrolled. The patients were divided into two groups: the intervention group (n = 101) received prophylactic haloperidol (5 mg); the control group (n = 100) did not. Haloperidol was administered daily during postoperative days 0-5 to the patients who presented with NEECHAM scores of 20-24 when measured at 18:00. The primary endpoint was the incidence of severe postoperative delirium. RESULTS: The incidence of severe postoperative delirium in all patients was 25.1%. The incidence of severe postoperative delirium in the intervention group (18.2%) was significantly lower than that in the control group (32.0%) (p = 0.02). The difference between the two groups was larger when the analysis was limited to the 70 patients who had NEECHAM scores of 20-24 for at least one day during postoperative days 0-5. No adverse effects of the haloperidol were observed. CONCLUSION: The prophylactic administration of haloperidol at the early stage of delirium significantly reduced the incidence of severe postoperative delirium in elderly patients. Clinical Trial Registration UMIN000007204.

Does the Q - H index show a stronger relationship than the H:Q ratio in regard to knee pain during daily activities in patients with knee osteoarthritis?

[Purpose] The purpose of this study was to elucidate the relationship between knee muscle strength and knee pain in activities of daily living, based on consideration of the difference between extension and flexion strength (Q - H) and the hamstring:quadriceps (H:Q) ratio in patients with knee osteoarthritis. [Subjects and Methods] The participants were 78 females with knee osteoarthritis, and a total of 133 knees that had not been treated surgically were the targets of this research. The legs were divided according to dominance. Isometric knee extension and flexion muscle strength and knee pain during activities of daily living were measured. The H:Q ratio (flexion/extension muscle strength) and the difference between extension and flexion strength, (extension muscle strength/weight) minus (flexion muscle strength/weight), that is, Q - H, were calculated. The correlation between these indices and the knee pain score during activities of daily living was investigated. [Results] Greater knee pain during activities of daily living was related to lower knee extension muscle strength and Q - H in both the dominant and nondominant legs. Knee flexion muscle strength and the H:Q ratio were not significantly correlated with knee pain during any activities of daily living. [Conclusion] Knee extension muscle strength and Q - H were found to be significantly correlated with knee pain during activities of daily living, whereas the H:Q ratio was not.

Sarcopenia and sarcopenic leg as potential risk factors for acute osteoporotic vertebral fracture among older women.

PURPOSE: Sarcopenia-related falls and fractures among women with osteoporosis are becoming an emerging problem because of rapid aging worldwide. We aimed to investigate the association between sarcopenia, given by the muscle mass of the arms and legs, and osteoporotic vertebral fracture (OVF) among female patients. METHODS: This cross-sectional study examined 216 women with fresh OVF (OVF group) diagnosed by magnetic resonance imaging and 1,608 women from an outpatient clinic who did not have a OVF [non-fracture (NF) group]. We performed whole-body dual-energy X-ray absorptiometry to analyze body composition, including skeletal muscle mass index (SMI; lean mass/height2) and bone mineral density (BMD). We used stepwise logistic regression analysis to determine the risk factors associated with OVF. RESULTS: After controlling for age, the OVF group showed lower appendicular SMI (5.62 vs. 5.97 kg/m2, P < 0.001), lower arm SMI (1.36 vs. 1.42 kg/m2, P = 0.004), lower leg SMI (4.27 vs. 4.55 kg/m2, P < 0.001), and higher prevalence of sarcopenia (42.3 vs. 25.9 %, P < 0.001), compared with the NF group. Reduced leg muscle mass and presence of sarcopenia were independent risk factors for acute OVF in multivariate analysis (odds ratio = 1.4, P = 0.002; odds ratio = 1.96, P < 0.001, respectively). CONCLUSIONS: We found higher prevalence of sarcopenia and lower leg muscle mass among patients with acute OVF compared with patients who did not have an OVF. These results suggest that sarcopenia may be a risk factor for OVF.

Sex- and age-related differences in mid-thigh composition and muscle quality determined by computed tomography in middle-aged and elderly Japanese.

AIM: Sex- and age-related differences in mid-thigh composition and muscle quality remain unclear. The present study aimed to clarify these differences using computed tomography in middle-aged and elderly Japanese. METHODS: A total of 2310 participants (age 40-89 years), who were randomly selected from the local residents, underwent computed tomography examination of the right mid-thigh. Thigh circumference and cross-sectional areas of the thigh, muscle, quadriceps, non-quadriceps, fat, and bone were measured. Knee extension strength and muscle quality index (knee extension strength/quadriceps cross-sectional area) were also assessed. Sex- and age-related differences in these indices were analyzed. RESULTS: The thigh cross-sectional area in men and women decreased by 0.6% and 0.5%/year, respectively, because of a decrease in muscle cross-sectional area (men 75.2%, women 40.6%), fat cross-sectional area (men 24.4%, women 59.6%) and bone cross-sectional area (men 0.5%, women -0.2%). Muscle cross-sectional area in men and women decreased by 0.6% and 0.4%/year, respectively, because of a decrease in quadriceps cross-sectional area (men 65.6%, women 81.6%) and non-quadriceps cross-sectional area (men 34.4%, women 18.4%). Muscle quality in men and women decreased by 0.4% and 0.3%/year, respectively. CONCLUSION: Thigh cross-sectional area decreased with age mainly because of a decrease in muscle cross-sectional area in men and fat cross-sectional area in women. The rate of decrease in muscle cross-sectional area was 1.5-fold higher in men than in women. Muscle cross-sectional area decreased with age mainly because of a decrease in quadriceps cross-sectional area, especially in women. Decrease in muscle quality with age was similar in both sexes.

Use of alfacalcidol in osteoporotic patients with low muscle mass might increase muscle mass: an investigation using a patient database.

AIM: Sarcopenia causes a decline in physical performance and decreased quality of life. However, there is little evidence for effective treatments. Because of the similarities between osteoporosis and sarcopenia, alfacalcidol used for osteoporosis might be beneficial for low muscle mass. Therefore, we investigated the effect of alfacalcidol on muscle mass in patients with low muscle mass. METHODS: In this retrospective cohort analysis, patients from an osteoporosis database were divided into two groups: alfacalcidol-treated patients (vitamin D group; n = 156) and a control group without drug treatment (n = 233). Muscle mass was evaluated in terms of the skeletal muscle index (SMI; kg/m(2)) obtained from dual-energy X-ray absorptiometry measurements that were taken at the start and end of a 1-year period. Low muscle mass was determined using specific SMI cut-offs for Japanese individuals. RESULTS: Both the vitamin D group (mean age 73.7 ± 9.8 years) and the control group (mean age 72.3 ± 11.9 years) were primarily women (n = 141, 90.4%; n = 189, 81.1%, respectively). Low muscle mass was identified in 32.7% (n = 51) of the vitamin D group and 32.2% (n = 75) of the control group. The mean appendicular SMI in the vitamin D group did not change significantly over the 1-year period. The change was significant among the patients with low muscle mass (5.30 kg/m(2) vs 5.49 kg/m(2)). The mean appendicular SMI in the control group decreased significantly over the 1-year period (6.09 kg/m(2) vs 5.99 kg/m(2)). The change in the patients with low muscle mass was not significant. CONCLUSIONS: The vitamin D group maintained muscle mass, and the SMI increased in patients with low muscle mass. Thus, the use of alfacalcidol might be effective in osteoporotic patients with low muscle mass.

Effects of knee extensor muscle strength on the incidence of osteopenia and osteoporosis after 6 years.

The association of knee extensor muscle strength with bone mineral density (BMD) has been reported in cross-sectional epidemiological studies, but it remains unclear whether or not this is the case with longitudinal change. Thus, we investigated whether or not the knee extension strength can predict the incidence of osteopenia or osteoporosis after 6 years, then compared the difference between sexes. Subjects were 1255 community-dwelling Japanese men and menopaused women, aged 40-81 years. BMD of lumbar spine and femoral neck was assessed by dual-energy X-ray absorptiometry twice at 6-year intervals. Subjects were divided into three groups, normal, osteopenia, and osteoporosis, depending on their young adult mean BMD % value. In the cross-sectional analysis the correlations between the knee extension strength and BMD of the two regions were examined, using Pearson's correlation coefficient. Longitudinal analyses were then conducted to determine the odds ratio, controlled for age and BMI, given that those who were normal in the initial stage developed osteopenia or osteoporosis after 6 years, for every 1 SD decrease in knee extension strength, as well as those who first had normal or osteopenia and then developed osteoporosis. Cross-sectional analysis showed a statistically significant relation between knee extensor muscle strength and BMD at both the lumbar spine (p = 0.02) and the femoral neck (p < 0.0001) only in men. The longitudinal analysis showed the significant effect of muscle strength on the loss of femoral neck BMD from normal to osteopenia or osteoporosis both in men (OR 1.84, 95 % CI 1.36-2.48, p < 0.0001) and in women (OR 1.29, 95 % CI 1.002-1.65, p < 0.05), as well as on the loss of spinal BMD from normal or osteopenia to osteoporosis only in men (OR 2.97, 95 % CI 1.07-8.23, p < 0.05). The results suggest the importance of knee extension strength to maintain the bone health of the proximal femur and spine in aging particularly in men.

High prevalence of sarcopenia and reduced leg muscle mass in Japanese patients immediately after a hip fracture.

AIM: Sarcopenia-related falls and fractures are becoming an emerging problem as a result of rapid aging worldwide. We aimed to investigate the prevalence of sarcopenia by estimating the muscle mass of the arms and legs of patients with and without hip fracture. METHODS: This cross-sectional study examined 357 patients immediately after a hip fracture (the HF group) and in 2511 patients from an outpatient clinic who did not have a hip fracture (the NF group) at single institution in Japan. We carried out whole-body dual energy X-ray absorptiometry to analyze body composition with skeletal muscle mass index (SMI; lean mass/height(2)) and bone mineral density (BMD). We carried out stepwise logistic regression analysis to determine the factors associated with a hip fracture. RESULTS: Lower appendicular SMI (P < 0.001), leg SMI (P < 0.001), and higher prevalence of sarcopenia (P < 0.001) were observed in the HF group after controlling for age and sex. The arm SMI was similar in both groups (P > 0.95). In multivariate analysis, the presence of sarcopenia, older age and lower BMD were associated with the occurrence of a hip fracture (OR 1.476, P = 0.002; OR 1.103, P < 0.001; OR 0.082, P < 0.001; respectively). CONCLUSION: This study showed a higher prevalence of sarcopenia and more reduced leg muscle mass in patients after a hip fracture than in the outclinic patients who did not have hip fractures. The results imply sarcopenia can be a risk factor for a hip fracture.

Divergent Significance of Bone Mineral Density Changes in Aging Depending on Sites and Sex Revealed through Separate Analyses of Bone Mineral Content and Area.

Bone mineral density (aBMD) is equivalent to bone mineral content (BMC) divided by area. We rechecked the significance of aBMD changes in aging by examining BMC and area separately. Subjects were 1167 community-dwelling Japanese men and women, aged 40-79 years. ABMDs of femoral neck and lumbar spine were assessed by DXA twice, at 6-year intervals. The change rates of BMC and area, as well as aBMD, were calculated and described separately by the age stratum and by sex. In the femoral neck region, aBMDs were significantly decreased in all age strata by an increase in area as well as BMC loss in the same pattern in both sexes. In the lumbar spine region, aBMDs decreased until the age of 60 in women, caused by the significant BMC decrease accompanying the small area change. Very differently in men, aBMDs increased after their 50s due to BMC increase, accompanied by an area increase. Separate analyses of BMC and area change revealed that the significance of aBMD changes in aging was very divergent among sites and between sexes. This may explain in part the dissociation of aBMD change and bone strength, suggesting that we should be more cautious when interpreting the meaning of aBMD change.

The effect of impact direction on the fracture load of osteoporotic proximal femurs.

Hip fractures among the elderly are a worldwide problem. The objective of this study was (1) to confirm whether or not differences in bone strength are reflected in the proximal femur finite element (FE) model constructed from CT images of healthy subjects and osteoporosis patients, and (2) to investigate the effect of loading angle direction on bone fractures. The results from comparison of bone strength between the fracture group, fragile group (osteoporosis patients with no fracture after falling), and healthy group showed that differences in bone strength were definitely reflected in this FE model. Furthermore, the relationship between the loading direction and fracture load value was significant in all groups in the age-adjusted general linear model, and the model made from the trochanteric fracture patients was more sensitive to loading direction than those from cervical neck fracture. No significant differences were observed in the age-corrected comparison of DXA Neck BMD, Wards BMD, and total BMD in these two groups. The difference in the trochanteric BMD showed a trend of low bone density in the trochanteric fracture group. There is thus a possibility that the bone density at this location is implicated in the fragility under certain loading directions.