A genome-wide association study identifies a locus associated with knee extension strength in older Japanese individuals.

Sarcopenia is a common skeletal muscle disease in older people. Lower limb muscle strength is a good predictive value for sarcopenia; however, little is known about its genetic components. Here, we conducted a genome-wide association study (GWAS) for knee extension strength in a total of 3452 Japanese aged 60 years or older from two independent cohorts. We identified a significant locus, rs10749438 which is an intronic variant in TACC2 (transforming acidic coiled-coil-containing 2) (P = 4.2 × 10-8). TACC2, encoding a cytoskeleton-related protein, is highly expressed in skeletal muscle, and is reported as a target of myotonic dystrophy 1-associated splicing alterations. These suggest that changes in TACC2 expression are associated with variations in muscle strength in older people. The association was consistently observed in young and middle-aged subjects. Our findings would shed light on genetic components of lower limb muscle strength and indicate TACC2 as a potential therapeutic target for sarcopenia.

Genotypes of Stim1 and the proximal region on chromosome 1 exert opposite effects on stroke susceptibility in stroke-prone spontaneously hypertensive rat.

BACKGROUND: The stroke-prone spontaneously hypertensive rat (SHRSP) is a genetic model for cerebral stroke. Although a recent study on a congenic SHRSP suggested that a nonsense mutation in stromal interaction molecule 1 ( Stim1 ) encoding a major component of store-operated Ca 2+ entry was a causal variant for stroke in SHRSP, this was not conclusive because the congenic region including Stim1 in that rat was too wide. On the other hand, we demonstrated that the Wistar-Kyoto (WKY)-derived congenic fragment adjacent to Stim1 exacerbated stroke susceptibility in a congenic SHRSP called SPwch1.71. In the present study, we directly examined the effects of the Stim1 genotype on stroke susceptibility using SHRSP in which wild-type Stim1 was knocked in (called Stim1 -KI SHRSP). The combined effects of Stim1 and the congenic fragment of SPwch1.71 were also investigated. METHODS: Stroke susceptibility was assessed by the stroke symptom-free and survival periods based on observations of behavioral symptoms and reductions in body weight. RESULTS: Stim1 -KI SHRSP was more resistant to, while SPwch1.71 was more susceptible to stroke than the original SHRSP. Introgression of the wild-type Stim1 of Stim1 -KI SHRSP into SPwch1.71 by the generation of F1 rats ameliorated stroke susceptibility in SPwch1.71. Gene expression, whole-genome sequencing, and biochemical analyses identified Art2b , Folr1 , and Pde2a as possible candidate genes accelerating stroke in SPwch1.71. CONCLUSION: The substitution of SHRSP-type Stim1 to wild-type Stim1 ameliorated stroke susceptibility in both SHRSP and SPwch1.71, indicating that the nonsense mutation in Stim1 is causally related to stroke susceptibility in SHRSP.

Association of lysophosphatidic acid molecules with liver fibrosis: different roles indicated.

Lysophosphatidic acid is composed of lysophosphatidic acid (LPA) molecules with varied chemical forms. The present cross-sectional study was conducted to investigate the associations of various LPA molecules with liver fibrosis. Forty-six patients affected by various types of liver disease who underwent an ultrasound-guided liver biopsy were recruited for this study. Liver fibrosis was evaluated using histological grading, as well as shear wave velocity (Vs) and serum level of type IV collagen 7S (T4c7s). Serum levels of LPA molecules were determined using liquid-chromatography tandem mass-spectrometry (LC-MSMS). Total LPA showed a significant positive association with fibrosis severity evaluated based on histological grading, Vs, and T4c7s used as parameters, following adjustment for other confounding factors, including disease type, age, gender, body mass index, and high-sensitivity C-reactive protein. This association was replicated when 16:0-LPA was substituted for total LPA. In contrast, when 20:4-LPA was substituted for total LPA, no significant association with liver fibrosis was observed. In conclusion, the degree of association varied among the different LPA molecule chemical forms, suggesting different pathophysiological roles of individual LPA molecules, although total LPA concentration was shown to be associated with liver fibrosis.

Associations between dairy consumption and the physical function in Japanese community-dwelling older adults: The Shimane CoHRE study.

OBJECTIVES: We investigated sex differences in the associations between dairy consumption and the physical function among community-dwelling older adults. METHODS: Six hundred and fifty-six older adults (75.6 ± 6.4 years old) participated in this study. Dairy consumption (5-item Likert score) and the physical function (gait speed, handgrip strength, and skeletal muscle mass) were measured. The linear and quadratic associations between dairy consumption and the physical function measures were examined by a multiple linear regression analysis adjusted for covariates. RESULTS: Among women, an increased dairy consumption was significantly linearly associated with greater hand-grip strength and faster gait speed (both p<0.05) after adjusting for covariates. Among men, dairy consumption was not associated with the physical function measures. Dairy consumption was not associated with the muscle mass in either sex. CONCLUSIONS: Increased dairy consumption was associated with a superior physical function in older women.

Association between flexibility activity and blood-pressure change among older adults in Japan: A 5-year longitudinal study.

This longitudinal study examined the relationship between flexibility-activity and blood-pressure (BP) change among older adults in Japan. Our study included 452 older adults who took part in our survey in both 2012/2013 and 2017/2018. The seated systolic blood pressure (SBP) and diastolic BP (DBP) were measured both at baseline and at the 5 years follow-up. The frequencies of the different physical activities at baseline were assessed using a questionnaire. A generalized linear mixed model was used to estimate the non-standardized coefficient (B) of BP change associated with flexibility activity, after adjustments for sex, age, body mass index, smoking status, alcohol consumption, antihypertensive medication use, history of heart disease, walking time, and muscle-strengthening activity as a fixed-effect, and area of residence as a random-effect. Higher flexibility-activity frequency was significantly associated with reduced SBP (B = -0.77 [95% confidence intervals = -1.36, -0.18], p for linear trend = 0.01, p for quadratic trend = 0.85) and DBP (-0.33 [-0.71, 0.05], p for linear trend = 0.09, p for quadratic trend = 0.04). Engaging in flexibility activity for 3 days per week was significantly associated with a reduction in DBP (B = -4.16, 95% CI [-7.53, -0.79], p = 0.02) compared with that in the reference group (0 days per week). Interaction tests were not significant between basic variables (sex, age, BMI, and antihypertensive medication) and flexibility. In conclusion, higher flexibility activity frequency was associated with a reduction in BP in older adults. Future longitudinal and interventional studies should examine the effects of flexibility activity on cardiovascular disease prevention.

Changes in masticatory performance and the new onset of diabetes mellitus in older adults: a 5-year longitudinal study.

Objective: Although masticatory performance is affected by age-related reduction in number of teeth (or treatment), the relationship between longitudinal changes in masticatory performance and diabetes mellitus is unknown. This longitudinal study investigated the association between changes in masticatory performance and new-onset diabetes mellitus among community-dwelling Japanese older adults. Methods: The data of 214 older adults living in Ohnan Town, Shimane, Japan, who participated in two surveys conducted between 2012 and 2017 were analyzed. Diabetes mellitus was defined as a hemoglobin A1c level ≥ 6.5% or self-reported diabetes mellitus. The masticatory performance (measured by number of gummy jelly pieces collected after chewing) was evaluated by dental hygienists. Masticatory performance was categorized into two groups (high or low) based on the median in each survey; further, four groups (Group A: remained consistently high, Group B: changed from low to high, Group C: remained consistently low, Group D: changed from high to low) were used to determine longitudinal changes in masticatory performance. Logistic regression was used to analyze the association between changes in masticatory performance and new-onset diabetes mellitus. Results: Overall, 10.3% of participants had diabetes mellitus at the follow-up survey. Multivariate analysis showed that Group D (odds ratio 8.69, 95% confidence interval 1.98-38.22) was positively associated with the development of diabetes mellitus compared with Group A after adjusting for sex, age, body mass index, alcohol consumption, physical activity, and eating speed. Conclusions: Deteriorating masticatory performance for 5 years may cause diabetes mellitus among older adults.

Apolipoprotein E-depletion accelerates arterial fat deposition in the spontaneously hypertensive rat.

Hypertension and atherosclerosis are often found in one patient causing serious cardiovascular events. An animal model simultaneously expressing hypertension and atherosclerosis would be useful to study such a complex risk status. We therefore attempted to introduce a null mutation of the apolipoprotein E (ApoE) gene into the spontaneously hypertensive rat (SHR) using CRISPR/Cas9 to establish a genetic model for atherosclerosis with hypertension. We successfully established SHRApoE(-/-) having a 13-bps deletion in the 5'-end of ApoE gene. Deletion of ApoE protein was confirmed by Western blotting. Blood pressure of SHRApoE(-/-) was comparable to that of SHR. Feeding the rats with high fat high cholesterol diet (HFD) caused a significant increase in LDL cholesterol as well as in triglyceride in SHRApoE(-/-). After 8 weeks of HFD loading, superficial fat deposition was observed both in the aorta and the mesenteric arteries of SHRApoE(-/-) instead of mature atheromatous lesions found in humans. In addition, a null mutation of peroxiredoxin 2 (Prdx2) was introduced into SHRApoE(-/-) to examine the effect of increased oxidative stress on the development of atherosclerosis. SHR with the double depletion of ApoE and Prdx2 did not show mature atheroma either. Further, salt loading did not promote development of atheroma although it accelerated the development of fat deposition. These results indicated that when compared with ApoE-knockout mice, SHRApoE(-/-) was more resistant to atherosclerosis even though they have severe hypertension.

Neither Trimethylamine-N-Oxide nor Trimethyllysine Is Associated with Atherosclerosis: A Cross-Sectional Study in Older Japanese Adults.

Recent evidence suggests that trimethylamine-N-oxide (TMAO), a metabolite of L-carnitine and choline, is linked to atherosclerosis and cardiovascular diseases. As TMAO content is very high in fish, we raised the following question: why do Japanese people, who consume lots of fish, show a low risk of atherosclerosis? To address this question, we investigated the effects of TMAO and other L-carnitine-related metabolites on carotid intima-media thickness (IMT). Participants were recruited from a small island and a mountainous region. Plasma L-carnitine, γ-butyrobetaine (γBB), TMAO, trimethyllysine (TML), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) levels were measured using liquid or gas chromatography-mass spectrometry. Plasma L-carnitine concentration was higher in men than in women. TMAO and TML were significantly higher in the residents of the island than in the mountainous people. In multiple linear regression analyses in all participants, TML showed a significant inverse association with max-IMT and plaque score (PS), whereas TMAO did not show any associations. In women, L-carnitine was positively associated with max-IMT and PS. TMAO was correlated with both EPA and DHA levels, implying that fish is a major dietary source of TMAO in Japanese people. Our study found that plasma TMAO was not an apparent risk factor for atherosclerosis in elderly Japanese people, whereas a low level of TML might be a potential risk. L-carnitine may be a marker for atherosclerosis in women.

Effectiveness of Intergenerational Interaction on Older Adults Depends on Children's Developmental Stages; Observational Evaluation in Facilities for Geriatric Health Service.

The demand for intergenerational exchange is growing in the world, where the size of a family is becoming smaller. To promote intergenerational exchange, it is important to know whether different stages of child age have different effects. This study aimed to examine effects of intergenerational exchange using children at different developmental stages through a questionnaire survey. The subjects were 296 employees of 116 facilities for geriatric health services that routinely conduct intergenerational exchanges. A questionnaire was designed to ask the employees what effects were observed on old adults and on the employees themselves after intergenerational exchanges were conducted. The results indicated that younger children caused better effects both for older adults and for the employees regarding some of the items, while older children caused equal or lesser effects for all items. It was suggested that the developmental stage of children should be considered according to the purpose of intergenerational exchange.

Associations between physical frailty and living arrangements in Japanese older adults living in a rural remote island: The Shimane CoHRE study.

Background: Living arrangements have been known to be associated with physical frailty. However, the prevalence of frailty and its risk factors in remote islands is not understood. We examined the association between living arrangements and objectively measured frailty among older adults living in a remote island of Japan. Methods: Among older people living in Okinoshima, 656 older adults (75.6 ± 6.4 years) were analyzed. Physical frailty (robust, prefrailty, or frailty) was assessed using the 5-item frailty phenotype (unintentional weight loss, self-reported exhaustion, weakness, slow walking speed, and low physical activity). Physical functions (muscle mass, gait speed, and grip strength) were measured objectively. Results: The prevalence of frailty and prefrailty was 6.6% and 43.8%, respectively. Living with a spouse resulted in a significantly lower prevalence of frailty (p < 0.001) compared with other living arrangements. All objectively measured physical functions among those who lived with a spouse were significantly superior to those who lived with family or alone (p < 0.001). Multinomial logistic regression showed that living alone was significantly associated with frailty (odds ratio [OR] 2.36, 95% confidence interval [CI] 1.07-5.24) and prefrailty (OR 1.75, 95% CI 1.14-2.69) after adjusting for all covariates. Conclusion: The prevalence of frailty on remote islands seemed similar to that in urban areas. Older people living in remote islands might be able to maintain their physical health. Furthermore, living alone may correlate with increased risks of frailty and prefrailty. Among elderly individuals on remote islands, living with a spouse might be desirable to prevent (pre)frailty.

Genetic Modifications to Alter Blood Pressure Level.

Genetic manipulation is one of the indispensable techniques to examine gene functions both in vitro and in vivo. In particular, cardiovascular phenotypes such as blood pressure cannot be evaluated in vitro system, necessitating the creation of transgenic or gene-targeted knock-out and knock-in experimental animals to understand the pathophysiological roles of specific genes on the disease conditions. Although genome-wide association studies (GWAS) in various human populations have identified multiple genetic variations associated with increased risk for hypertension and/or its complications, the causal links remain unresolved. Genome-editing technologies can be applied to many different types of cells and organisms for creation of knock-out/knock-in models. In the post-GWAS era, it may be more worthwhile to validate pathophysiological implications of the risk variants and/or candidate genes by creating genome-edited organisms.

Reduced masticatory performance and not using dentures are associated with hypertension in older adults with tooth loss: the Shimane CoHRE study.

The relationship between masticatory performance and hypertension has seldom been studied. The association between hypertension and tooth loss with/without denture use is unclear. This cross-sectional study examined the relationship between hypertension and masticatory performance and whether the relationship between hypertension and the number of teeth varied with denture use among older Japanese adults. Hypertension was defined as a systolic or diastolic blood pressure ≥140 or ≥90 mm Hg, respectively, or the use of antihypertensive medications. Masticatory performance was assessed using a chewable gummy jelly. The number of teeth and denture use were visually assessed by a trained dental hygienist. Poisson regression analyses were carried out to estimate the prevalence ratio and 95% confidence interval (CI) of hypertension with the number of teeth (≥28, 20-27, or 0-19 teeth), quartiles of masticatory performance (Q1: highest [reference] to Q4: lowest), and tooth loss with/without denture use. Hypertension was significantly associated with masticatory performance in participants in Q3 (prevalence ratio = 1.35; 95% CI = 1.07, 1.72) and Q4 (prevalence ratio = 1.31; 95% CI = 1.01, 1.69). There was no association between tooth loss and hypertension. Compared to participants with >28 teeth, the prevalence ratios and 95% CIs of those without dentures and those with 20-27 teeth were 1.33 (95% CI = 1.06, 1.68) and 1.69 (95% CI = 1.21, 2.37), respectively, in those with 0-19 teeth. Masticatory performance was inversely associated with hypertension, and tooth loss without the use of dentures was related to hypertension. Therefore, masticatory function may be important for preventing hypertension among older adults.

Combined association of oral and skeletal muscle health with type 2 diabetes mellitus among community-dwelling older adults in Japan: a cross-sectional study.

Objective: Although oral health and skeletal muscle status are known to be risk factors for type 2 diabetes mellitus (T2DM), there is limited information on their combined effects among community-dwelling older adults. The purpose of this study was to investigate the association between oral health and skeletal muscle status among older adults with T2DM in Japan. Participants and Methods: This cross-sectional study included data from individuals aged ≥60 years. T2DM was defined as a glycosylated hemoglobin A1c level ≥48 mmol/mol (≥6.5%) or the use of hypoglycemic agents. For oral health status, dental hygienists assessed the number of teeth (NT) and masticatory function (MF). Skeletal muscle status was assessed using skeletal muscle mass index (SMI) and handgrip strength (HGS). Logistic regression analysis examined T2DM in nine-category combinations of oral health status (each of the three categories in NT and MF) and skeletal status (each of the three categories in SMI and HGS). Results: T2DM was prevalent in 83 participants (16.4%) and was significantly associated with low NT and SMI (odds ratio [OR] = 5.93, 95% confidence interval [CI]: 1.37-25.73) and low MF and SMI (OR = 4.48, 95% CI: 1.23-16.35) compared to high NT and SMI and high MF and SMI, respectively. Conclusion: Our findings indicate that low muscle mass with tooth loss or masticatory dysfunction is associated with T2DM among community-dwelling older adults. This suggests that maintaining oral health and muscle mass may be an effective strategy for the prevention of T2DM.

Milk Fermented with Mushrooms Prevents Stroke in the Stroke-Prone Spontaneously Hypertensive Rats Independently of Blood Pressure.

OBJECTIVES: In a previous study, a mushroom was shown to digest milk protein to a mixture of oligopeptides and free amino acids. The aim of this study was to examine effects of this mixture, i.e., mushroom-fermented milk, on blood pressure and stroke susceptibility in the stroke-prone spontaneously hypertensive rats (SHRSP). MATERIALS AND METHODS: Rats were fed mushroom-fermented milk with or without 1 % salt water. Blood pressure was monitored either by the tail-cuff method or the telemetry system. Symptoms of stroke were examined every day to determine the stroke latency. RESULTS: Mushroom-fermented milk at 120 mg/Kg BW/day (estimated as a peptides/amino acids content) did not ameliorate hypertension in SHRSP. In contrast, mushroom-fermented milk significantly improved stroke susceptibility under salt-loading. The effects were replicated using milk fermented with three different mushrooms. To elucidate the effective components in mushroom-fermented milk, spermidine (3 mM), one of major components of mushroom-fermented milk, and a mixture of amino acids (0.8 g/L) was examined, both of which showed no significant effects on stroke susceptibility. Intake of mushroom-fermented milk did not affect sodium content significantly either in feces or in urine of the rats given 1% salt water. This observation indicated sodium absorption by the digestive system was not inhibited by intake of mushroom-fermented milk. CONCLUSION: Despite that the mechanisms were not elucidated, intake of mushroom-fermented milk effectively prevented stroke in SHRSP. Mushroom-fermented milk would be a new candidate for a supplemental nutrient supporting the cardiovascular health.

A 3-Mbp fragment on rat chromosome 1 affects susceptibility both to stroke and kidney injury under salt loading in the stroke-prone spontaneously hypertensive rat: a genetic approach using multiple congenic strains.

We have previously reported that a major quantitative trait locus (QTL) responsible for susceptibility to salt-induced stroke in the stroke-prone spontaneously hypertensive rat (SHRSP) is located in a 3-Mbp region on chromosome 1 covered by SHRSP.SHR-(D1Rat23-D1Rat213)/Izm (termed Pr1.31), a congenic strain with segments from SHRSP/Izm introduced into the stroke-resistant SHR/Izm. Here, we attempted to narrow down the candidate region on chromosome 1 further through analyses of subcongenic strains constructed for the target region. Simultaneously, salt-induced kidney injury was evaluated through the measurement of urinary albumin and the gene expression of renal tubular injury markers (Kim-1 and Clu) to explore a possible mechanism leading to the onset of stroke. All subcongenic strains examined in this study showed lower susceptibility to salt-induced stroke than SHRSP. Interestingly, Pr1.31 had the lowest stroke susceptibility when compared with newly constructed subcongenic strains harboring fragments of the congenic sequence in Pr1.31. Although Kim-1 and Clu expression after 1 week of salt loading in Pr1.31 did not differ significantly from those in SHRSP, the urinary albumin level of Pr1.31 was significantly lower than those of the other subcongenic strains and that of SHRSP. The present results indicated that, although the congenic fragment in Pr1.31 harbored the gene(s) related to salt-induced organ damages, further genetic dissection of the candidate region was difficult due to multiple QTLs suggested in this region. Further analysis using Pr1.31 will unveil genetic and pathophysiological mechanisms underlying salt-induced end organ damages in SHRSP.

Defective Function of the Blood-Brain Barrier in a Stroke-Prone Spontaneously Hypertensive Rat: Evaluation in an In Vitro Cell Culture Model.

The blood-brain barrier (BBB) comprises three cell types: brain capillary endothelial cells (BECs), astrocytes, and pericytes. Abnormal interaction among these cells may induce BBB dysfunction and lead to cerebrovascular diseases. The stroke-prone spontaneously hypertensive rat (SHRSP) harbors a defective BBB, so we designed the present study to examine the role of these three cell types in a functional disorder of the BBB in SHRSP in order to elucidate the role of these cells in the BBB more generally. To this end, we employed a unique in vitro model of BBB, in which various combinations of the cells could be tested. The three types of cells were prepared from both SHRSPs and Wistar Kyoto rats (WKYs). They were then co-cultured in various combinations to construct in vitro BBB models. The barrier function of the models was estimated by measuring transendothelial electrical resistance and the permeability of the endothelial monolayer to sodium fluorescein. The in vitro models revealed that (1) BECs from SHRSPs had an inherent lower barrier function, (2) astrocytes of SHRSPs had an impaired ability to induce barrier function in BECs, although (3) both pericytes and astrocytes of SHRSPs and WKYs could potentiate the barrier function of BECs under co-culture conditions. Furthermore, we found that claudin-5 expression was consistently lower in models that used BECs and/or SHRSP astrocytes. These results suggested that defective interaction among BBB cells-especially BECs and astrocytes-was responsible for a functional disorder of the BBB in SHRSPs.

Association between hilliness and walking speed in community-dwelling older Japanese adults: A cross-sectional study.

PURPOSE: This cross-sectional study investigated the association between hilliness and walking speed in community-dwelling older adults, and whether it varied according to their car-driving status. METHODS: Data were collected from 590 participants aged 65 and older living in Okinoshima Town, Shimane prefecture, Japan, in 2018. Comfortable walking speed (m/s) was objectively assessed. Hilliness was measured by the mean land slope (degree) within a 500-m or 1000-m network buffer around each participant's home using a geographic information system. A multiple linear regression examined whether the land slope was associated with walking speed, adjusted for sex, age, body mass index, smoking habits, alcohol consumption habits, exercise habits, chronic disease, and living arrangements. A stratified analysis by car-driving status was also conducted. RESULTS: After adjusting for all confounders, the land slope within the 500-m or 1000-m network buffer was negatively associated with walking speed (B = -0.007, 95% CI [-0.011, -0.002]; B = -0.007, 95% CI [-0.011, -0.003], respectively). The stratified analysis by car-driving status showed that living in a hilly area was negatively associated with walking speed among non-drivers in the 500-m or 1000-m network buffer (B = -0.011, 95% CI [-0.017, -0.004]; B = -0.012, 95% CI [-0.019, -0.006]), though there were no associations among drivers. CONCLUSIONS: A hilly environment is positively associated with slow walking speed in community-dwelling older adults in Japan. Moreover, car-driving status potentially modifies the relationship between living in a hilly environment and slow walking speed.

Relationship between Masticatory Function and Bone Mineral Density in Community-Dwelling Elderly: A Cross-Sectional Study.

The relationship between masticatory function and bone mineral density (BMD) is unclear. This cross-sectional study examined this relationship after adjusting for confounding factors. The subjects were 702 community-dwelling elderly adults (306 men, 396 women) who had been recruited for the Community-Based Healthcare Research and Education study in 2019. Objective masticatory function was assessed using the gummy jelly method. The median for each descriptive statistic was 69.0 years for age, 86.2% for the young adult mean, and 18.0 for masticatory function. Comparisons of the groups with good and poor masticatory function by sex revealed a significant difference in muscle mass and the tooth number for both sexes (p < 0.05). Men showed significant differences in age (p < 0.05) and salivary occult blood findings (p < 0.05). Multivariate analysis using propensity scores showed a significant association between masticatory function and BMD in both sexes (men: odds ratio 163.0, 95% confidence interval 1.36-19,610.55, p = 0.04; women: odds ratio 48.65, 95% confidence interval 1.52-1561.15, p = 0.03 in women). Masticatory function and BMD in the community-dwelling elderly may be related. However, other factors, including frailty and sarcopenia, may also be involved. Regular oral health care by dentists and dental hygienists may benefit this population.

Effect of Multimorbidity on Fragility Fractures in Community-Dwelling Older Adults: Shimane CoHRE Study.

Fragility fractures (FFxs), which are a common musculoskeletal injury in older adults, is associated with an increased frequency of falls. Both FFxs and falls may result from drugs, habits, and co-occurring diseases. We aimed to evaluate the effects of various diseases on the risk of FFx. This retrospective study included 1420 individuals aged ≥60 years. We evaluated the history of clinical FFx and diseases using a detailed questionnaire and a health examination. The risk of comorbidities was assessed using the Age-Adjusted Charlson Comorbidity (AAC) Index. We performed binary logistic regression analysis to determine the risk of FFx and falls after adjusting for covariates. In elderly men, the incidence of FFx positively correlated with rheumatoid arthritis and parent's hip fracture. For elderly women, the incidence of FFx positively correlated with rheumatoid arthritis and antihypertensive drugs but was inversely associated with dyslipidemia and antilipidemic drugs. The FFX risk of older adults with an AAC Index ≥6 was higher than those with an AAC Index of 1-3. In addition, the AAC Index and falls were independently and strongly associated with a higher risk of FFx. Taken together, multimorbidity increases the risk of clinical FFx independent of falls in the community-dwelling elderly population.