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Importance: Identification of individuals at high risk for atherosclerotic cardiovascular disease within the population is important to inform primary prevention strategies., Objective: To evaluate the prognostic value of routinely available cardiovascular biomarkers when added to established risk factors., Design, Setting, and Participants: Individual-level analysis including data on cardiovascular biomarkers from 28 general population-based cohorts from 12 countries and 4 continents with assessments by participant age. The median follow-up was 11.8 years., Exposure: Measurement of high-sensitivity cardiac troponin I, high-sensitivity cardiac troponin T, N-terminal pro-B-type natriuretic peptide, B-type natriuretic peptide, or high-sensitivity C-reactive protein., Main Outcomes and Measures: The primary outcome was incident atherosclerotic cardiovascular disease, which included all fatal and nonfatal events. The secondary outcomes were all-cause mortality, heart failure, ischemic stroke, and myocardial infarction. Subdistribution hazard ratios (HRs) for the association of biomarkers and outcomes were calculated after adjustment for established risk factors. The additional predictive value of the biomarkers was assessed using the C statistic and reclassification analyses., Results: The analyses included 164 054 individuals (median age, 53.1 years [IQR, 42.7-62.9 years] and 52.4% were women). There were 17 211 incident atherosclerotic cardiovascular disease events. All biomarkers were significantly associated with incident atherosclerotic cardiovascular disease (subdistribution HR per 1-SD change, 1.13 [95% CI, 1.11-1.16] for high-sensitivity cardiac troponin I; 1.18 [95% CI, 1.12-1.23] for high-sensitivity cardiac troponin T; 1.21 [95% CI, 1.18-1.24] for N-terminal pro-B-type natriuretic peptide; 1.14 [95% CI, 1.08-1.22] for B-type natriuretic peptide; and 1.14 [95% CI, 1.12-1.16] for high-sensitivity C-reactive protein) and all secondary outcomes. The addition of each single biomarker to a model that included established risk factors improved the C statistic. For 10-year incident atherosclerotic cardiovascular disease in younger people (aged <65 years), the combination of high-sensitivity cardiac troponin I, N-terminal pro-B-type natriuretic peptide, and high-sensitivity C-reactive protein resulted in a C statistic improvement from 0.812 (95% CI, 0.8021-0.8208) to 0.8194 (95% CI, 0.8089-0.8277). The combination of these biomarkers also improved reclassification compared with the conventional model. Improvements in risk prediction were most pronounced for the secondary outcomes of heart failure and all-cause mortality. The incremental value of biomarkers was greater in people aged 65 years or older vs younger people., Conclusions and Relevance: Cardiovascular biomarkers were strongly associated with fatal and nonfatal cardiovascular events and mortality. The addition of biomarkers to established risk factors led to only a small improvement in risk prediction metrics for atherosclerotic cardiovascular disease, but was more favorable for heart failure and mortality.

Background and Aims: Assessing the relationship between vitamin K1 intakes, using region-specific food databases, with both all-cause, and cardiovascular disease (CVD) mortality warrants further investigation to inform future preventative strategies. Consequently, we examined the aforementioned associations in the Perth Longitudinal Study of Ageing Women (PLSAW)., Methods and Results: 1436 community-dwelling older Australian women (mean ± SD age 75.2 ± 2.7 years) completed a validated food frequency questionnaire at baseline (1998). Vitamin K1 intake was calculated based on an Australian vitamin K food database, supplemented with published data. All-cause and CVD mortality data was obtained from linked health records. Associations were examined using restricted cubic splines within Cox-proportional hazard models, adjusted for a range of cardiovascular and lifestyle related risk factors. Over 15 years of follow-up, 601 (41.9%) women died, with 236 deaths (16.4%) due to CVD. Compared to women with the lowest vitamin K1 intakes (Quartile 1, median 49.1 μg/day), those with the highest intakes (Quartile 4, median 119.3 μg/day) had lower relative hazards for all-cause mortality (HR 0.66 95%CI 0.51-0.86) and CVD mortality (HR 0.61 95%CI 0.41-0.92). A plateau in the inverse association was observed from vitamin K1 intakes of approximately ≥80 μg/day., Conclusion: Higher vitamin K1 intakes were associated with lower risk for both all-cause and CVD mortality in community-dwelling older women, independent of CVD related risk factors. A higher intake of vitamin K1 rich foods, such as leafy green vegetables, may support cardiovascular health., Competing Interests: Declaration of competing interest The authors have nothing to disclose., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Frailty is associated with declines in physiological capacity across sensory, neurological, and musculoskeletal systems. An underlying assumption is that the frailer an individual, the more likely they are to experience falls and fractures. We examined whether grades of frailty can assess the long-term risk of hospitalized falls, fractures, and all-cause mortality in 1261 community-dwelling older women (mean age [SD] of 75.1 [2.7] yr) over 14.5 yr. Frailty was operationalized using a frailty index (FI) of cumulative deficits from 33 variables across multiple health domains (physical, mental, comorbidities) at baseline. The total score across these variables was summed and divided by 33 to obtain the FI. Participants were graded as fit (FI ≤ 0.12), mildly frail (FI > 0.12-0.24), moderately frail (FI > 0.24-0.36), or severely frail (FI > 0.36). Fall-related (n = 498), any fracture-related (n = 347), and hip fracture-related hospitalizations (n = 137) and deaths (n = 482) were obtained from linked health records. Associations between FI grades and clinical outcomes were analyzed using multivariable-adjusted Cox-proportional hazard models including age, treatment (calcium/placebo), BMI, smoking history, socioeconomic status, plasma vitamin D (25OHD) status plus season obtained, physical activity, self-reported prevalent falls in the last 3 mo, and self-reported fractures since the age of 50 yr. At baseline, 713 (56.5%), 350 (27.8%), 163 (12.9%), and 35 (2.8%) of women were classified as fit, mildly frail, moderately frail, and severely frail, respectively. Women with mild, moderate, and severe frailty had significantly higher hazards (all P < .05) for a fall-related (46%, 104%, 168%), any fracture-related (88% for moderate, 193% for severe frailty), hip fracture-related hospitalizations (93%, 127%, 129%), and all-cause mortality (47%, 126%, 242%). The FI identified community-dwelling older women at risk for the most serious falls and fractures and may be incorporated into risk assessment tools to identify individuals with poorer clinical prognosis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Background: Abdominal aortic calcification (AAC), a marker of vascular disease, is associated with disease in other vascular beds including gastrointestinal arteries. We investigated whether AAC is related to rapid weight loss over 5 years and whether rapid weight loss is associated with 9.5-year all-cause mortality in community-dwelling older women., Methods: Lateral spine images from dual-energy x-ray absorptiometry (1998/1999) were used to assess AAC (24-point AAC scoring method) in 929 older women. Over 5 years, body weight was assessed at 12-month intervals. Rapid weight loss was defined as >5% decrease in body weight within any 12-month interval. Multivariable-adjusted logistic regression was used to assess AAC and rapid weight loss and Cox regression to assess the relationship between rapid weight loss and 9.5-year all-cause mortality., Results: Mean±SD age of women was 75.0±2.6 years. During the initial 5 years, 366 (39%) women presented with rapid weight loss. Compared with women with low AAC (24-point AAC score 0-1), those with moderate (24-point AAC score 2-5: odds ratio, 1.36 [95% CI, 1.00-1.85]) and extensive (24-point AAC score 6+: odds ratio, 1.59 [95% CI, 1.10-2.31]) AAC had higher odds for presenting with rapid weight loss. Results remained similar after further adjustment for dietary factors (alcohol, protein, fat, and carbohydrates), diet quality, blood pressure, and cholesterol measures. The estimates were similar in subgroups of women who met protein intake (n=599) and physical activity (n=735) recommendations (extensive AAC: odds ratios, 1.81 [95% CI, 1.12-2.92] and 1.58 [95% CI, 1.02-2.44], respectively). Rapid weight loss was associated with all-cause mortality over the next 9.5 years (hazard ratio, 1.49 [95% CI, 1.17-1.89]; P =0.001)., Conclusions: AAC extent was associated with greater risk for rapid weight loss over 5 years in older women, a risk for all-cause mortality. Since the association was unchanged after taking nutritional intakes into account, these data support the possibility that vascular disease may play a role in the maintenance of body weight., Competing Interests: Disclosures None.

Objective: To examine the association between high-sensitivity cardiac troponin I (hs-cTnI), a biomarker of myocardial injury, muscle function decline and 14.5-year fall-related hospitalisation risk in women aged over 70 years., Methods: 1179 ambulatory community-dwelling women aged over 70 years with subclinical levels of hs-cTnI (ie, <15.6 ng/L), who were followed up for 14.5 years, were included. Samples for hs-cTnI were obtained in 1998. Fall-related hospitalisations were retrieved from linked health records. Muscle function measures, including handgrip strength and the Timed-Up-and-Go (TUG) test, were assessed in 1998 and 2003., Results: Mean±SD age was 75.2±2.7 years. Over 14.5 years of follow-up, 40.4% (476 of 1179) experienced fall-related hospitalisation. Participants were categorised into four approximate hs-cTnI quartiles: quartile 1 (<3.6 ng/L), quartile 2 (3.6-4.4 ng/L), quartile 3 (4.5-5.8 ng/L) and quartile 4 (≥5.9 ng/L). Compared with those in Q1, women in Q4 were likely to experience fall-related hospitalisation (36.0% vs 42.8%). In a multivariable-adjusted model that accounted for CVD and fall risk factors, compared with women in Q1, those in Q4 had a 46% higher risk of fall-related hospitalisation (HR 1.46, 95% CI 1.08 to 1.98). Additionally, women in Q4 had slower TUG performance compared with those in Q1 (10.3 s vs 9.5 s, p=0.032)., Conclusion: Elevated level of hs-cTnI was associated with slower TUG performance and increased fall-related hospitalisation risk. This indicates subclinical level of hs-cTnI can identify clinically relevant falls, emphasising the need to consider cardiac health during fall assessment in women aged over 70 years., Trial Registration Number: ACTRN12617000640303., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Abdominal aortic calcification (AAC), a recognized measure of advanced vascular disease, is associated with higher cardiovascular risk and poorer long-term prognosis. AAC can be assessed on dual-energy X-ray absorptiometry (DXA)-derived lateral spine images used for vertebral fracture assessment at the time of bone density screening using a validated 24-point scoring method (AAC-24). Previous studies have identified robust associations between AAC-24 score, incident falls, and fractures. However, a major limitation of manual AAC assessment is that it requires a trained expert. Hence, we have developed an automated machine-learning algorithm for assessing AAC-24 scores (ML-AAC24). In this prospective study, we evaluated the association between ML-AAC24 and long-term incident falls and fractures in 1023 community-dwelling older women (mean age, 75 ± 3 years) from the Perth Longitudinal Study of Ageing Women. Over 10 years of follow-up, 253 (24.7%) women experienced a clinical fracture identified via self-report every 4-6 months and verified by X-ray, and 169 (16.5%) women had a fracture hospitalization identified from linked hospital discharge data. Over 14.5 years, 393 (38.4%) women experienced an injurious fall requiring hospitalization identified from linked hospital discharge data. After adjusting for baseline fracture risk, women with moderate to extensive AAC (ML-AAC24 ≥ 2) had a greater risk of clinical fractures (hazard ratio [HR] 1.42; 95% confidence interval [CI], 1.10-1.85) and fall-related hospitalization (HR 1.35; 95% CI, 1.09-1.66), compared to those with low AAC (ML-AAC24 ≤ 1). Similar to manually assessed AAC-24, ML-AAC24 was not associated with fracture hospitalizations. The relative hazard estimates obtained using machine learning were similar to those using manually assessed AAC-24 scores. In conclusion, this novel automated method for assessing AAC, that can be easily and seamlessly captured at the time of bone density testing, has robust associations with long-term incident clinical fractures and injurious falls. However, the performance of the ML-AAC24 algorithm needs to be verified in independent cohorts. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Lipocalin-2 (LCN2) is released by several cell types including osteoblasts and adipocytes and has been suggested as a marker of renal dysfunction, metabolic syndrome (MetS) and type 2 diabetes (T2D). Whether LCN2 is linked to these diseases in older women remains unknown. This study investigated whether LCN2 is related to features of MetS and T2D in older women. This cross-sectional study included 705 non-diabetic women (mean age 75.1 ± 2.6 years) for MetS analysis and 76 women (mean age 75.4 ± 2.8 years) with T2D. Total circulating LCN2 levels were analysed using a two-step chemiluminescent microparticle monoclonal immunoassay. MetS was determined by a modified National Cholesterol Education Program Adult Treatment Panel III classification. Multivariable-adjusted logistic regression analysis was used to assess odds ratios between LCN2 quartiles and MetS. Women in the highest LCN2 quartile had approximately 3 times greater risk for MetS compared to women in the lowest quartile (OR 3.05; 95%CI 1.86-5.02). Women with T2D or MetS scores of ≥ 3 had higher LCN2 levels compared to women with a MetS score of 0 (p < 0.05). Higher LCN2 correlated with higher body mass index, fat mass, triglycerides and glycated haemoglobin and lower high-density lipoprotein cholesterol and estimated glomerular filtration rate (p < 0.05). Higher circulating levels of LCN2 are associated with worsened cardio-metabolic risk factors and increased odds of MetS and T2D in older women. Whether it can be used as a biomarker for identifying those at risk for MetS and T2D should be explored further., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Lateral spine images for vertebral fracture assessment can be easily obtained on modern bone density machines. Abdominal aortic calcification (AAC) can be scored on these images by trained imaging specialists to assess cardiovascular disease risk. However, this process is laborious and requires careful training., Methods: Training and testing of model performance of the convolutional neural network (CNN) algorithm for automated AAC-24 scoring utilised 5012 lateral spine images (2 manufacturers, 4 models of bone density machines), with trained imaging specialist AAC scores. Validation occurred in a registry-based cohort study of 8565 older men and women with images captured as part of routine clinical practice for fracture risk assessment. Cox proportional hazards models were used to estimate the association between machine-learning AAC (ML-AAC-24) scores with future incident Major Adverse Cardiovascular Events (MACE) that including death, hospitalised acute myocardial infarction or ischemic cerebrovascular disease ascertained from linked healthcare data., Findings: The average intraclass correlation coefficient between imaging specialist and ML-AAC-24 scores for 5012 images was 0.84 (95% CI 0.83, 0.84) with classification accuracy of 80% for established AAC groups. During a mean follow-up 4 years in the registry-based cohort, MACE outcomes were reported in 1177 people (13.7%). With increasing ML-AAC-24 scores there was an increasing proportion of people with MACE (low 7.9%, moderate 14.5%, high 21.2%), as well as individual MACE components (all p-trend <0.001). After multivariable adjustment, moderate and high ML-AAC-24 groups remained significantly associated with MACE (HR 1.54, 95% CI 1.31-1.80 & HR 2.06, 95% CI 1.75-2.42, respectively), compared to those with low ML-AAC-24., Interpretation: The ML-AAC-24 scores had substantial levels of agreement with trained imaging specialists, and was associated with a substantial gradient of risk for cardiovascular events in a real-world setting. This approach could be readily implemented into these clinical settings to improve identification of people at high CVD risk., Funding: The study was supported by a National Health and Medical Research Council of Australia Ideas grant and the Rady Innovation Fund, Rady Faculty of Health Sciences, University of Manitoba., Competing Interests: Declaration of interests DPK has received a grant from Solarea Bio and royalties from Wolters Kluwer. DPK sits on the Scientific Advisory Boards of Solarea Bio, Pfizer and Reneo and has participated on the Data Safety Monitoring Board for the AgNovos Healthcare osteoporosis treatment trial. All other authors have no disclosures to declare., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Abdominal aortic calcification (AAC) has been inconsistently associated with skeletal health. We aimed to investigate the association of AAC with bone mineral density (BMD) and fracture risk by pooling the findings of observational studies., Methods: MEDLINE, EMBASE, Web of Science, and Google Scholar were searched (August 2021). All clinical studies that assessed the association between AAC and BMD or fracture were included. AAC was categorized into any/advanced (all higher reported groups) versus no/less advanced (lowest reported group). Pooled standardized mean differences (SMDs) and risk ratios (RRs) with 95% confidence intervals (CI) were determined for BMD and fracture, respectively, using random-effects models., Results: Of 2 192 articles screened, 86 (61 553 participants) were included in the review, while 42 provided data for meta-analysis. AAC was associated with lower BMD at the total hip (SMD = -1.05 [95%CI: -1.47 to -0.63]; 16 studies), femoral neck (-0.25 [-0.46 to-0.04]; 10), and lumbar spine (-0.67 [-1.21 to -0.12]; 20). AAC was associated with a greater risk of any fracture (RR = 1.73 [95%CI: 1.48-2.02]; 27). AAC was also associated with vertebral, non-vertebral, and hip fractures. In dose-response analysis, the highest AAC group had greater risks of any, vertebral and non-vertebral fractures., Conclusions: AAC is associated with lower BMD and increased fracture risk at multiple sites, underscoring the potential importance of vascular disease on skeletal health. Detection of AAC at the time of BMD testing may provide clinicians with prognostic information about bone health to enhance osteoporosis screening programs and fracture risk prediction., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Impaired muscle function has been identified as a risk factor for declining cognitive function and cardiovascular health, both of which are risk factors for late-life dementia (after 80 years of age). We examined whether hand grip strength and timed-up-and-go (TUG) performance, including their change over 5 years, were associated with late-life dementia events in older women and whether any associations provided independent information to Apolipoprotein E ℇ 4 (APOE ℇ 4) genotype., Methods: Grip strength and TUG were assessed in community-dwelling older women (mean ± SD; age 75.0 ± 2.6 years) at baseline (n = 1225) and 5 years (n = 1052). Incident 14.5-year late-life dementia events (dementia-related hospitalization/death) were obtained from linked health records. Cardiovascular risk factors (Framingham Risk Score), APOE genotyping, prevalent atherosclerotic vascular disease and cardiovascular-related medications were evaluated at baseline. These were included in multivariable-adjusted Cox-proportional hazards models assessing the relationship between muscle function measures and late-life-dementia events., Results: Over follow-up, 207 (16.9%) women had a late-life dementia event. Compared with women with the highest grip strength (Quartile [Q] 4, 25.8 kg), those with the lowest grip strength (Q1, 16.0 kg) had greater hazard for a late-life dementia event (HR 2.27 95% CI 1.54-3.35, P < 0.001). For TUG, the slowest women (Q4, 12.4 vs. Q1, 7.4 s) also recorded a greater hazard for a late-life dementia event (HR 2.10 95% CI 1.42-3.10, P = 002). Weak hand grip (<22 kg) or slow TUG (>10.2 s) provided independent information to the presence of an APOE ℇ 4 allele (n = 280, 22.9%). Compared with women with no weakness and no APOE ℇ 4 allele, those with weakness and APOE ℇ 4 allele had a greater hazard (HR 3.19 95% CI 2.09-4.88, P < 0.001) for a late-life dementia event. Women presenting with slowness and the APOE ℇ 4 allele also recorded a greater hazard for a late-life dementia event (HR 2.59 95% CI 1.64-4.09, P < 0.001). For 5-year muscle function changes, compared with women with the lowest performance decrement (Q1), those with the largest decrement (Q4) had higher hazards for a late-life dementia event (grip strength HR 1.94 95% CI 1.22-3.08, P = 0.006; TUG HR 2.52 95% CI 1.59-3.98, P < 0.001) over the next 9.5 years., Conclusions: Weaker grip strength and slower TUG, and a greater decline over 5 years, were significant risk factors for a late-life-dementia event in community-dwelling older women, independent of lifestyle and genetic risk factors. Incorporating muscle function measures as part of dementia screening appears useful to identify high-risk individuals who might benefit from primary prevention programmes., (© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Background: A few cross-sectional studies have highlighted inconsistent associations between cardiovascular disease (CVD) and musculoskeletal conditions. We sought to investigate the relationship between clinical CVD including subtypes, compromised muscle function, as well as incident self-reported and injurious falls in older women., Materials and Methods: 1431 community-dwelling older women (mean age ± SD; 75.2 ± 2.7 years) were included in over 14.5 years of a prospective study, the Perth Longitudinal Study of Ageing in Women. CVD (up to 18-years prior to the baseline visit) and injurious fall hospitalizations over 14.5 years were obtained from linked health records. Self-reported falls for five years were obtained via a written adverse event diary posted every four months. Timed-Up-and-Go (TUG) test and hand grip strength were used to assess mobility and muscle strength, respectively. Mobility impairment was defined as TUG performance >10.2 sec and muscle weakness characterized as grip strength <22 kg., Results: Over 5-years, 411 (28.7%) women reported a falls, while 567 (39.6%) were hospitalized due to an injurious fall over 14.5 years. Prior CVD events were associated with 32% (HR 1.32 95%CI, 1.06-1.64) and 29% (HR 1.29 95%CI, 1.07-1.56) increased risk of self-reported and injurious falls, respectively, in multivariable-adjusted models. When considering subtypes of CVD, only cerebrovascular disease was related to self-reported (HR 1.77; 95%CI, 1.15-2.72) and injurious falls requiring hospitalization (HR 1.51; 95%CI, 1.00-2.27). CVD was also associated with cross-sectional and prospective mobility impairments. However, no evidence for such relationships was observed for muscle weakness., Conclusions: Prevalent CVD events, particularly cerebrovascular disease, are related to an increased risk of long-term falls. These findings highlight the need to recognize increased falls risk in patients with CVD. Further, there is a need to understand whether incorporating prevalent CVD into falls screening tools improves risk stratification or affects model calibration., Competing Interests: Conflict of interest None of authors have any conflicts of interest to disclose., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: In recent years, a potential beneficial role of Vitamin K in neuromuscular function has been recognised. However, the optimal dietary intake of Vitamin K to support muscle function in the context of falls prevention remains unknown., Objective: To examine the relationship of dietary Vitamin K1 and K2 with muscle function and long-term injurious fall-related hospitalisations in older women., Design: Cohort study., Participants: 1347 community-dwelling older Australian women ≥70 years., Measurements: A new Australian Vitamin K nutrient database, supplemented with published data, was used to calculate Vitamin K1 and K2 intake from a validated food frequency questionnaire at baseline (1998). Muscle function (grip strength and timed-up-and-go; TUG) as well plasma Vitamin D status (25OHD) were also assessed at baseline. Fall-related hospitalisations over 14.5 years were obtained from linked health records. Multivariable-adjusted logistic regression and Cox-proportional hazard models were used to analyse the data., Results: Over 14.5 years of follow-up (14,774 person-years), 535 (39.7%) women experienced a fall-related hospitalisation. Compared to women with the lowest Vitamin K1 intake (Quartile 1, median 49 µg/d), those with the highest intake (Quartile 4, median 120 µg/d) had 29% lower odds (OR 0.71 95%CI 0.52-0.97) for slow TUG performance (>10.2 s), and 26% lower relative hazards of a fall-related hospitalisation (HR 0.74 95%CI 0.59-0.93) after multivariable adjustment. These associations were non-linear and plateaued at moderate intakes of ~70-100 µg/d. There was no relation to grip strength. Vitamin K2 intakes were not associated with muscle function or falls., Conclusion: A higher habitual Vitamin K1 intake was associated with better physical function and lower long-term injurious falls risk in community-dwelling older women. In the context of musculoskeletal health, Vitamin K1 found abundantly in green leafy vegetables should be promoted., Competing Interests: All authors declare no conflicts of interest.

Background and Aims: We and others have identified links between cardiovascular conditions and poor musculoskeletal health. However, the relationship between measures of carotid atherosclerosis such as focal carotid plaque and common carotid intima media thickness (CCA-IMT) and falls remains understudied. This study examined the association between measures of carotid atherosclerosis and fall-related hospitalization over 11.5 years in community dwelling older women., Methods and Results: 1116 older women recruited in 1998 to a five-year randomized controlled trial to examine the effect of calcium supplementation in preventing fracture and who had undertaken B-mode ultrasound in 2001 (three years after the baseline clinical visit) were included in this study. The participants were followed for over 11.5 years as Perth Longitudinal Study of Ageing Women (PLSAW). Over the follow up period, 428 (38.4%) women experienced a fall-related hospitalization. Older women with carotid plaque had 44% a higher relative hazard for fall-related hospitalization (HR 1.44; 95%CI, 1.18 to 1.76) compared to those without carotid plaque. The association persisted after adjustment for established falls risk factors such as measures of muscle strength and physical function.Each SD increase in the mean and maximum CCA-IMT was also associated with a higher risk of fall-related hospitalizations (HR 1.10; 95%CI, 1.00 to 1.21 and HR 1.11; 95%CI, 1.01 to 1.22, respectively)., Conclusions: Measures of carotid atherosclerosis are associated with a higher risk of fall-related hospitalization independent of established falls risk factors. These findings suggest the importance of vascular health when considering falls risk., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: The extent of abdominal aortic calcification (AAC) is a major predictor of vascular disease events. We have previously found regular apple intake, a major source of dietary flavonoids, associates with lower AAC. Whether total dietary flavonoid intake impacts AAC remains unknown. Here, we extend our observations to habitual intakes of total flavonoids, flavonoid subclasses, and specific flavonoid-containing foods, with the odds of extensive AAC., Methods: We conducted cross-sectional analyses on 881 females (median [interquartile range] age, 80 [78-82] years; body mass index, 27 [24-30] kg/m 2 ) from the PLSAW (Perth Longitudinal Study of Ageing Women). Flavonoid intake was calculated from food-frequency questionnaires. Calcifications of the abdominal aorta were assessed on lateral lumbar spine images and categorized as less extensive or extensive. Logistic regression was used to investigate associations., Results: After adjusting for demographic, lifestyle and dietary confounders, participants with higher (Q4), compared with lower (Q1) intakes, of total flavonoids, flavan-3-ols, and flavonols had 36% (odds ratio [95% CI], 0.64 [0.43-0.95]), 39% (0.61 [0.40-0.93]) and 38% (0.62 [0.42-0.92]) lower odds of extensive AAC, respectively. In food-based analyses, higher black tea intake, the main source of total flavonoids (75.9%), associated with significantly lower odds of extensive AAC (2-6 cups/d had 16%-42% lower odds compared with 0 daily intake). In a subset of nonconsumers of black tea, the association of total flavonoid intake with AAC remained (Q4 versus Q1 odds ratio [95% CI], 0.11 [0.02-0.54])., Conclusions: In older women, greater habitual dietary flavonoid intake associates with less extensive AAC.

We have previously shown that abdominal aortic calcification (AAC), a marker of advanced atherosclerotic disease, is weakly associated with reduced hip areal bone mineral density (aBMD). To better understand the vascular-bone health relationship, we explored this association with other key determinants of whole-bone strength and fracture risk at peripheral skeletal sites. This study examined associations of AAC with peripheral quantitative computed tomography (pQCT)-assessed total, cortical and trabecular volumetric BMD (vBMD), bone structure and strength of the radius and tibia among 648 community-dwelling older women (mean ± SD age 79.7 ± 2.5 years). We assessed associations between cross-sectional (2003) and longitudinal (progression from 1998/1999-2003) AAC assessed on lateral dual-energy X-ray absorptiometry (DXA) images with cross-sectional (2003) and longitudinal (change from 2003 to 2005) pQCT bone measures at the 4% radius and tibia, and 15% radius. Partial Spearman correlations (adjusted for age, BMI, calcium treatment) revealed no cross-sectional associations between AAC and any pQCT bone measures. AAC progression was not associated with any bone measure after adjusting for multiple comparisons, despite trends for inverse correlations with total bone area at the 4% radius (r s  =  - 0.088, p = 0.044), 4% tibia (r s  =  - 0.085, p = 0.052) and 15% radius (r s  =  - 0.101, p = 0.059). Neither AAC in 2003 nor AAC progression were associated with subsequent 2-year pQCT bone changes. ANCOVA showed no differences in bone measures between women with and without AAC or AAC progression, nor across categories of AAC extent. Collectively, these finding suggest that peripheral bone density and structure, or its changes with age, are not associated with central vascular calcification in older women., (© 2022. The Author(s).)

This study examined the association between dietary Vitamin K1 intake with fracture-related hospitalizations over 14.5 years in community-dwelling older Australian women ( n = 1373, ≥70 years). Dietary Vitamin K1 intake at baseline (1998) was estimated using a validated food frequency questionnaire and a new Australian Vitamin K nutrient database, which was supplemented with published data. Over 14.5 years, any fracture ( n = 404, 28.3%) and hip fracture ( n = 153, 10.7%) related hospitalizations were captured using linked health data. Plasma Vitamin D status (25OHD) and the ratio of undercarboxylated osteocalcin (ucOC) to total osteocalcin (tOC) from serum was assessed at baseline. Estimates of dietary Vitamin K1 intake were supported by a significant inverse association with ucOC : tOC; a marker of Vitamin K status ( r = -0.12, p < 0.001). Compared to women with the lowest Vitamin K1 intake (Quartile 1, <61 μg d -1 ), women with the highest Vitamin K1 intake (Quartile 4, ≥99 μg d -1 ) had lower hazards for any fracture- (HR 0.69 95%CI 0.52-0.91, p < 0.001) and hip fracture-related hospitalization (HR 0.51 95%CI 0.32-0.79, p < 0.001), independent of 25OHD levels, as part of multivariable-adjusted analysis. Spline analysis suggested a nadir in the relative hazard for any fracture-related hospitalizations at a Vitamin K1 intake of approximately 100 μg day -1 . For hip fractures, a similar relationship was apparent. Higher dietary Vitamin K1 is associated with lower long-term risk for any fracture- and hip fracture-related hospitalizations in community-dwelling older women.

Objective: Examine if two inexpensive measures of atherosclerotic vascular diseases (ASVD), abdominal aortic calcification (AAC) and high-sensitivity cardiac troponin I (hs-cTnI) provide complementary information for 10-year ASVD mortality and all-cause mortality risk in older women., Methods: 908 community-dwelling women without prevalent ASVD (≥75 years) were followed-up between 2003 and 2013. AAC and plasma hs-cTnI measures were obtained in 2003. AAC was assessed on lateral spine images using a semiquantitative method (AAC24). Linked health records were used for mortality outcomes., Results: Mean±SD age was 79.9±2.6 years. 276 (30.4%) women died during follow-up, including 138 (15.2%) ASVD-related deaths. AAC24 and hs-cTnI were independently associated with ASVD and all-cause mortality (p<0.001). The cohort was dichotomised into four groups: (1) low AAC24 (AAC24: 0 or 1) and 1) and

Background: The ratio of creatinine to cystatin C (Cr:Cyc) has been proposed as a biomarker of sarcopenia, as greater Cr:Cyc is typically associated with greater muscle mass. We examined the relationship between Cr:Cyc with individual sarcopenia measures, 5-year self-reported falls, and 12-year fall-related hospitalizations in a prospective cohort study of 1 118 community-dwelling older women (mean age 75.2 ± 2.7 years)., Methods: Serum Cr:Cyc, hand grip strength, and timed-up-and-go performance were assessed at baseline (1998), while dual-energy x-ray absorptiometry-derived appendicular lean mass (ALM)/height2 (m) was obtained in a subset of women at baseline and 1 year (n = 334). Incident 5-year self-reported falls and 12-year falls-related hospitalizations were considered., Results: In a multivariable-adjusted model, women with the lowest Cr:Cyc (Quartile [Q] 1) had 5% (1.0 kg) weaker grip strength, as well as 3.7% (0.22 kg/m2) and 5.5% (0.031) lower ALM adjusted for height2 or body mass index, respectively, compared to women in Q4 (all p < .05). 329 women reported an incident fall over 5 years, and 326 fall-related hospitalizations were recorded over 12 years. Women in Q1 of Cr:Cyc had a greater relative hazard for a fall over 5 years (hazard ratio [HR] 1.50; 95% confidence interval [CI] 1.11-2.01) and fall-related hospitalization over 12 years (HR 1.53; 95% CI 1.13-2.07) compared to Q4 in the multivariable-adjusted model., Conclusion: These findings support further investigation into the use of Cr:Cyc as a muscle biomarker to help clinicians identify individuals at risk of falls for early inclusion into evidence-based primary prevention programs targeting improvements to diet and exercise., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Osteoporosis has been linked with increased risk of cardiovascular disease previously. However, few studies have detailed bone and vascular information. In a prospective study of older women, we demonstrated heel quantitative ultrasound measures were associated with increased cardiovascular and all-cause mortality, independent of established cardiovascular risk factors., Introduction: Osteoporosis and low bone mineral density (BMD) have been previously linked to cardiovascular disease (CVD) and mortality. Calcaneal quantitative ultrasound (QUS) is used to evaluate bone material properties, especially in older women. However, it is uncertain whether it is related to risk of mortality. This study was aimed to investigate the association between calcaneal QUS measurements and 15-year all-cause and CVD mortality in 1404 older women (mean age 75.2 ± 2.7 years)., Methods: One thousand four hundred four older women, participants of Calcium Intake Fracture Outcome study (CAIFOS), had calcaneal bone measured at baseline (1998) and followed for 15 years. The primary outcomes, any deaths, and deaths attributable to cardiovascular causes ascertained by using linked data were obtained from Western Australia data linkage system., Results: Over the 15 years of follow-up (17,955 person years), 584 of the women died, and 223 from CVD. For every standard deviation (SD), reduction in broadband ultrasound attenuation (BUA) in minimally and multivariable-adjusted model including cardiovascular risk factors increased relative hazards for all-cause (multivariable-adjusted HR 1.15; 95%CI: 1.06-1.26, p = 0.001) and CVD mortality (multivariable-adjusted HR 1.20; 95%CI: 1.04-1.38, p = 0.010). Such relationships also persisted when hip BMD was included in the model (all-cause mortality HR 1.19; 95%CI: 1.07-1.33, p = 0.002; CVD mortality HR 1.28; 95%CI: 1.07-1.53, p = 0.008)., Conclusion: BUA is associated with all-cause and CVD mortality in older women independent of BMD and established CVD risk factors. Understanding why and how these are related may provide further insights about the bone-vascular nexus as well as therapeutic targets benefiting both systems., (© 2022. The Author(s).)

Background: Dementia after the age of 80 years (late-life) is increasingly common due to vascular and non-vascular risk factors. Identifying individuals at higher risk of late-life dementia remains a global priority., Methods: In prospective study of 958 ambulant community-dwelling older women (≥70 years), lateral spine images (LSI) captured in 1998 (baseline) from a bone density machine were used to assess abdominal aortic calcification (AAC). AAC was classified into established categories (low, moderate and extensive). Cardiovascular risk factors and apolipoprotein E ( APOE) genotyping were evaluated. Incident 14.5-year late-life dementia was identified from linked hospital and mortality records., Findings: At baseline women were 75.0 ± 2.6 years, 44.7% had low AAC, 36.4% had moderate AAC and 18.9% had extensive AAC. Over 14.5- years, 150 (15.7%) women had a late-life dementia hospitalisation ( n  = 132) and/or death ( n  = 58). Compared to those with low AAC, women with moderate and extensive AAC were more likely to suffer late-life dementia hospitalisations (9.3%, 15.5%, 18.3%, respectively) and deaths (2.8%, 8.3%, 9.4%, respectively). After adjustment for cardiovascular risk factors and APOE , women with moderate and extensive AAC had twice the relative hazards of late-life dementia (moderate, aHR 2.03 95%CI 1.38-2.97; extensive, aHR 2.10 95%CI 1.33-3.32), compared to women with low AAC., Interpretation: In community-dwelling older women, those with more advanced AAC had higher risk of late-life dementia, independent of cardiovascular risk factors and APOE genotype. Given the widespread use of bone density testing, simultaneously capturing AAC information may be a novel, non-invasive, scalable approach to identify older women at risk of late-life dementia., Funding: Kidney Health Australia, Healthway Health Promotion Foundation of Western Australia, Sir Charles Gairdner Hospital Research Advisory Committee Grant, National Health and Medical Research Council of Australia., Competing Interests: DPK has received a grant from Solarea Bio, Amgen and royalties from Wolters Kluwer. DPK sits on the Scientific Advisory Boards of Solarea Bio, Pfizer and Reneo and has participated on the Data Safety Monitoring Board for the AgNovos Healthcare osteoporosis treatment trial. All other authors declare no conflicts of interest., (© 2022 The Author(s).)

Background: The dose-response relationship of vitamin D status and the risk of serious falls requiring hospitalization in older women is unclear. We examined the association between plasma 25-hydroxyvitamin D (25OHD) with falls-related hospitalizations over 14.5 years in a large cohort of older women., Methods: In 1348 community-dwelling Australian women aged ≥70 years, plasma 25OHD concentrations were assessed at baseline (1998) using LC-MS/MS. Fall-related hospitalizations were obtained from linked data systems. Baseline grip strength and timed-up-and-go (TUG) were assessed as measures of muscle strength and physical function, respectively., Results: Mean plasma 25OHD was 66.9 ± 28.2 nmol/L. The number of women in the low (LOW; <50 nmol/L), medium (MED; 50 to <75 nmol/L), and higher 25OHD (HIGH; ≥75 nmol/L) categories were 384 (28.5%), 491 (36.4%), and 473 (35.1%), respectively. In the multivariable-adjusted analysis, compared to LOW, women in HIGH had significantly lower hazards for a falls-related hospitalization (HR 0.76 95%CI 0.61-0.95). Restricted cubic spline regression models highlight increasing gradient of risk for a falls-related hospitalization with decreasing 25OHD levels. Generalized additive modeling highlighted higher 25OHD to be associated with better TUG performance. Including TUG into the multivariable-adjusted models did not alter the relationship between 25OHD and injurious falls (HIGH vs. LOW HR 0.76 95%CI 0.60-0.95)., Conclusions: In community-dwelling older Australian women, maintaining plasma 25OHD at 75 nmol/L or above may confer benefits to muscle function and long-term prevention of injurious falls requiring hospitalization. This relationship appears to be independent of better physical function observed in women with higher 25OHD levels., (© 2021 The American Geriatrics Society.)

We have recently proposed a new approach to evaluate 2D femoral neck (FN) structure, named the Minimal Model (MM), that comprised FN areal bone mineral density (FNaBMD) and FNWidth and 2 new internal structural measures; (1) the standard deviation of normalized mineral mass projection profile distribution (FNSigma), and (2) the displacement between center-of-mineral mass and geometric center of mineral mass projection profile (FNDelta). The contralateral hip of 67 FN fracture Chinese male patients had a QCT scan shortly after fracture and was compared to 156 community participants without hip fracture. The QCT scans were analyzed using Mindways software to enable DXA-equivalent 2D images to be obtained; MM variables were calculated from these images. In FN fracture and nonfracture participants, the 4 MM variables as well as age, weight and height were compared. Compared to nonfracture, fracture participants were older, weighed less and were taller. After adjustment for these differences FN fracture participants compared to nonfracture had mean ± SD lower FNaBMD 0.54 ± 0.11 vs 0.70 ± 0.11 g/cm 2 (p < 0.001); larger FNSigma 1.05 ± 0.11 vs 0.98 ± 0.10 cm (p < 0.001); larger FNDelta 0.43 ± 0.09 vs 0.33 ± 0.09 cm (p < 0.001), however FNWidth did not differ 2.96 ± 0.35 vs 2.92 ± 0.34 cm. All variables except FNaBMD and FNWidth were correlated; however logistic regression identified increased age and height, reduced FNaBMD and increased FNSigma as independent contributors to differentiating participants with FN fracture from nonfracture. Area under ROC analysis identified significant improvement in discrimination with addition of FNSigma to the base model of Age and FNaBMD (C statistic 0.88 and 0.91, p = 0.019). These analyses identified important internal structural information available from 2D DXA imaging that contributes to discrimination of FN fracture in addition to low bone mass. This analytical approach may contribute to improved clinical FN fracture prediction, extending value of widely available DXA technology., (Copyright © 2021 The International Society for Clinical Densitometry. All rights reserved.)

Background: Many older women demonstrate an age-related accelerating rate of renal decline that is associated with increased rates of bone disease, cardiovascular disease and mortality. Population-based protein restriction has been studied principally in patients with reduced renal function. In this investigation, we examined the hypothesis of a differential effect of plant-derived protein compared with animal-derived protein on renal function in older women., Methods: We assessed dietary intake from a validated food frequency questionnaire and the estimated glomerular filtration rate (eGFR) (using the Chronic Kidney Disease Epidemiology Collaboration creatinine and cystatin C equation) at baseline, 5 and 10 years in the Longitudinal Study of Aging Women cohort. We tested the association between plant- and animal-sourced protein intake and kidney function using linear mixed modeling., Results: A total of 1374 Caucasian women [mean (standard deviation, SD) age = 75 years (2.7) and mean (SD) baseline eGFR = 65.6 mL/min/1.73 m2 (13.1)] contributed to the analysis. The average decline in eGFR was 0.64 mL/min/1.73 m2/year [95% confidence interval (CI) 0.56-0.72]. Higher intakes of plant-sourced protein were associated with slower declines in eGFR after adjusting for covariates including animal protein and energy intake (P = 0.03). For each 10 g of plant protein, the yearly decline in eGFR was reduced by 0.12 mL/min/1.73 m2 (95% CI 0.01-0.23), principally associated with fruit-, vegetable- and nut-derived protein. The intake of animal protein was not associated with eGFR decline (P = 0.84)., Conclusions: Older women consuming a diet that is richer in plant-sourced protein have a slower decline in kidney function. These data extend support for the health benefits of plant-rich diets in the general population to maintain kidney health., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Backgrounds and Aims: Abdominal aortic calcification (AAC) is associated with weaker grip strength, an established risk factor for fall-related hospitalizations. However, its association with long-term fall-related hospitalisations remains unknown. This study investigated the association between AAC and long-term fall-related hospitalizations in community-dwelling older women., Methods: Fall-related hospitalizations were obtained from linked data over 14.5-years in a prospective cohort of 1053 older women (mean age 75.0 ± 2.6 years). At baseline (1998/99), AAC was assessed from lateral spine images obtained using dual-energy X-ray absorptiometry, and scored using a semi-quantitative method (AAC24, range 0-24). The presence of any AAC was defined by AAC24 ≥ 1., Results: Over 14.5-years, 413 (39.2%) women experienced a fall-related hospitalization. In the multivariable-adjusted model, each unit increase in baseline AAC24 was associated with a 3% increase in relative hazards for a fall-related hospitalization (HR 1.03 95%CI, 1.01 to 1.07). Compared to women with no AAC, women with any AAC had a 40% (HR 1.40 95%CI, 1.11 to 1.76) and 39% (HR 1.39 95%CI, 1.10 to 1.76) greater risk for fall-related hospitalizations in the minimal and multivariable-adjusted models, respectively. This relationship was not attenuated by including measures of muscle function such as grip strength and timed-up-and-go., Conclusions: The presence of AAC is associated with long-term fall-related hospitalizations risk, independent of muscle function, in community-dwelling older women. Concurrent assessment of AAC may be a simple and cost-effective way to identify older women at higher risk of falling as part of routine osteoporosis screening., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background & Aims: Poor nutritional habits are linked to higher perceived stress, but the relationship between fruit and vegetable (FV) intake and stress is uncertain. The primary aim of this cross-sectional study was to explore the relationship between FV intake and perceived stress in a population-based cohort of men and women aged ≥25 years from the Australian Diabetes, Obesity and Lifestyle (AusDiab) Study. A secondary aim was to investigate the relationship between serum carotenoids, biomarkers of FV intake, and perceived stress., Methods: In Australian men and women, dietary intake was assessed using a Food Frequency Questionnaire in 1999-2000 (n = 8689). Perceived stress was assessed using a validated Perceived Stress Questionnaire [PSQ index values ranging from 0 (lowest) to 1 (highest)]. Serum carotenoids were measured in a subset of participants (n = 1187) using high-performance liquid chromatography. Multivariable-adjusted linear and logistic regression were performed to investigate the associations between FV intake and perceived stress., Results: Mean age of participants was 47.4 (SD 14.1) years (49.8% females). Participants with the highest intakes of FV had 10% lower PSQ index values than those with the lowest intake [Q4: 0.27 ± 0.004 vs. Q1: 0.30 ± 0.004 (mean ± SE), p = 0.004]. Similar associations were found for fruits and vegetables, analysed separately. In subgroup analyses higher FV intake was associated with lower perceived stress in the middle-aged adults [≥45-<65 years (p = 0.004)], but not in the younger (<45 years) and older participants (≥65 years). Higher FV intake was also significantly associated with lower perceived stress in men (p = 0.009) and women (p = 0.012), separately. Serum carotenoid levels were inversely associated with perceived stress before, but not after adjusting for age and other confounding factors., Conclusion: In Australian adults, higher FV intake was associated with lower perceived stress, particularly in the middle-aged adults. These findings support current recommendations that fruit and vegetables are essential for health and well-being., Competing Interests: Conflict of interest CPB and JMH report grants from FruitWest, and from Department of Agriculture and Food WA, outside the submitted work. DJM and JES report grants from Abbott Australasia Pty Ltd, Alphapharm Pty Ltd, AstraZeneca, Bristol-Myers Squibb, Eli Lilly Australia, GlaxoSmithKline, Janssen-Cilag, Merck Sharp & Dohme, Novartis Pharmaceuticals, Novo Nordisk Pharmaceuticals, Roche Diagnostics Australia, Sanofi Aventis and Sanofi-synthelabo, during the conduct of the study. RMD received a Primary Growth Partnership grant via the Ministry of Primary Industries in New Zealand with Fonterra Co-operative Group Ltd, outside the submitted work. All other authors have no potential conflicts of interest to report., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Evidence from animal models suggests that undercarboxylated osteocalcin (ucOC) is involved in muscle mass maintenance and strength. In humans, the ucOC to total (t)OC ratio may be related to muscle strength and perhaps physical function and falls risk, but data are limited. We tested the hypothesis that ucOC and ucOC/tOC ratio are associated with muscle function (muscle strength and physical function) in older women and 15-year falls-related hospitalizations. Serum tOC and ucOC were assessed in 1261 older women (mean age 75.2 ± 2.7 years) forming the Perth Longitudinal Study of Aging Women (1998 to 2013). Timed-up-and-go (TUG) and grip strength were assessed at baseline and at 5 years. Falls-related hospitalizations (14.5-year follow-up) were captured by the Hospital Morbidity Data Collection, via the Western Australian Data Linkage System. At baseline, women with higher ucOC/tOC ratio (quartile 4) had slower TUG performance compared with quartile 1 (~0.68 seconds, p < .01). Grip strength and 5-year change of TUG and grip were not different (p > .05) between quartiles. Fear of falling limiting house, outdoor, and combined activities was significantly different across quartiles (p < .05). Higher ucOC/tOC was significantly associated with poorer TUG performance at baseline and 5-year change in performance, increased walking aid use, and fear of falling (all p < .05). Higher ucOC was related to lower grip strength at baseline (p < .05) but not 5-year change in strength. Those with the highest ucOC/tOC had greater falls-related hospitalizations (unadjusted log rank, p = .004) remaining significant after adjusting for key variables (hazard ratio [HR] = 1.31, 95% confidence interval [CI] 1.09-1.57, p = .004). We identified a large proportion of older women with high ucOC/tOC ratio who had reduced physical function, including its long-term decline and increased risk of falls-related hospitalizations. Early identification of women at higher risk can enable prevention and intervention strategies to occur, reducing risk for injurious falls. © 2020 American Society for Bone and Mineral Research (ASBMR).., (© 2020 American Society for Bone and Mineral Research (ASBMR).)

We have previously shown that higher intake of cruciferous vegetables is inversely associated with carotid artery intima-media thickness. To further test the hypothesis that an increased consumption of cruciferous vegetables is associated with reduced indicators of structural vascular disease in other areas of the vascular tree, we aimed to investigate the cross-sectional association between cruciferous vegetable intake and extensive calcification in the abdominal aorta. Dietary intake was assessed, using a FFQ, in 684 older women from the Calcium Intake Fracture Outcome Study. Cruciferous vegetables included cabbage, Brussels sprouts, cauliflower and broccoli. Abdominal aortic calcification (AAC) was scored using the Kauppila AAC24 scale on dual-energy X-ray absorptiometry lateral spine images and was categorised as 'not extensive' (0-5) or 'extensive' (≥6). Mean age was 74·9 (sd 2·6) years, median cruciferous vegetable intake was 28·2 (interquartile range 15·0-44·7) g/d and 128/684 (18·7 %) women had extensive AAC scores. Those with higher intakes of cruciferous vegetables (>44·6 g/d) were associated with a 46 % lower odds of having extensive AAC in comparison with those with lower intakes (<15·0 g/d) after adjustment for lifestyle, dietary and CVD risk factors (ORQ4 v. Q1 0·54, 95 % CI 0·30, 0·97, P = 0·036). Total vegetable intake and each of the other vegetable types were not related to extensive AAC (P > 0·05 for all). This study strengthens the hypothesis that higher intake of cruciferous vegetables may protect against vascular calcification.

Background The prognostic importance of abdominal aortic calcification (AAC) viewed on noninvasive imaging modalities remains uncertain. Methods and Results We searched electronic databases (MEDLINE and Embase) until March 2018. Multiple reviewers identified prospective studies reporting AAC and incident cardiovascular events or all-cause mortality. Two independent reviewers assessed eligibility and risk of bias and extracted data. Summary risk ratios (RRs) were estimated using random-effects models comparing the higher AAC groups combined (any or more advanced AAC) to the lowest reported AAC group. We identified 52 studies (46 cohorts, 36 092 participants); only studies of patients with chronic kidney disease (57%) and the general older-elderly (median, 68 years; range, 60-80 years) populations (26%) had sufficient data to meta-analyze. People with any or more advanced AAC had higher risk of cardiovascular events (RR, 1.83; 95% CI, 1.40-2.39), fatal cardiovascular events (RR, 1.85; 95% CI, 1.44-2.39), and all-cause mortality (RR, 1.98; 95% CI, 1.55-2.53). Patients with chronic kidney disease with any or more advanced AAC had a higher risk of cardiovascular events (RR, 3.47; 95% CI, 2.21-5.45), fatal cardiovascular events (RR, 3.68; 95% CI, 2.32-5.84), and all-cause mortality (RR, 2.40; 95% CI, 1.95-2.97). Conclusions Higher-risk populations, such as the elderly and those with chronic kidney disease with AAC have substantially greater risk of future cardiovascular events and poorer prognosis. Providing information on AAC may help clinicians understand and manage patients' cardiovascular risk better.

Purpose: Chronic inflammation plays a role in the pathogenesis of age-related renal disease and the diet can moderate systemic inflammation. The primary objective of this study was to examine the associations between a dietary inflammatory index (DII ® ) score and renal function, the trajectory of renal function decline, and renal disease-related hospitalizations and/or mortality over 10 years., Methods: The study was conducted in 1422 Western Australian women without prevalent chronic kidney disease and aged ≥ 70 years. Baseline dietary data, obtained from a validated food frequency questionnaire, were used to calculate a DII score for each individual., Results: In this cohort, the mean [range] DII score was 0.19 [- 6.14 to 6.39]. A higher DII score was associated with poorer renal function at baseline and a greater renal function decline over 10 years; after multivariable adjustments, a one-unit higher DII score was associated with a 0.55 mL/min/1.73 m 2 lower eGFR at baseline (p = 0.01) and a 0.06 mL/min/1.73 m 2 greater annual decline in eGFR over 10 years (p = 0.05). Restricted cubic splines provide evidence of a non-linear association between baseline DII score and risk of a renal disease-related event. Compared to participants in the lowest quintile, those in the highest quintile of DII score were at a higher risk of experiencing a renal disease-related event (adjusted HR 2.06, 95% CI 0.97, 4.37)., Conclusion: Recommending an increased consumption of foods with a higher anti-inflammatory potential could form part of a multifaceted approach to reduce the risk of renal disease through diet and lifestyle changes.

Midkine (MDK), a heparin-binding growth factor cytokine, is involved in the pathogenesis of kidney diseases by augmenting leukocyte trafficking and activation. Animal models and small case control studies have implicated MDK as a pathological biomarker in chronic kidney diseases (CKD), however this is yet to be confirmed in prospective human studies. In a prospective study of 499 elderly, predominantly Caucasian women aged over 70 years the association between serum MDK collected in 1998, and renal function change and the risk of CKD-related hospitalisations and deaths at 5 and 14.5 years, respectively, was examined. Baseline serum MDK was not associated with 5-year change in estimated glomerular filtration rate using the CKD Epidemiology Collaboration creatinine and cystatin C equation (Standardised β = - 0.09, 95% confidence interval - 3.76-0.48, p = 0.129), 5-year rapid decline in renal function (odds ratio = 0.97, 95% confidence interval 0.46-2.02, p = 0.927) or the risk of 14.5-year CKD-related hospitalisations and deaths (hazard ratio = 1.27, 95% confidence interval .66-2.46, p = 0.470) before or after adjusting for major risk factors. In conclusion, in this cohort of elderly women with normal or mildly impaired renal function, serum MDK was not associated with renal function change or future CKD-related hospitalisations and deaths, suggesting that MDK may not be an early biomarker for progression of CKD.

Analyses using newly developed structural measures of minimal model (aBMD, W, Sigma, Delta) in a Chinese female age-matched cohort of femoral neck fracture patients and non-fracture community controls resulted in improved fracture prediction, suggesting the usefulness of new variables, extending the value of widely available DXA technology., Introduction: We have developed a new approach to evaluate 2D femoral neck (FN) structure, the minimal model (MM). This model includes FNaBMD and FNWidth with two new internal structural measures, the standard deviation of normalized mineral mass projection profile distribution (FNSigma) and the displacement between center of mineral (CoM) mass and geometric center of mineral mass projection profile (FNDelta)., Methods: Differences in these four structural measurements together with age, weight, and height were compared in the contralateral hip of 285 FN fracture Chinese female patients and 261 age-matched community controls. Structural variables were calculated from DXA equivalent 2D images obtained from QCT scans analyzed using Mindways Software., Results: Review of FN scanned profiles of fracture patients and controls identified substantial reduction in mineral mass in the superior segment of FN. Fracture participants were taller, weighed less, and had lower FNaBMD and larger FNDelta, due to a larger inferior displacement in the CoM, consistent with greater reduction in superior segment bone. Logistic regression identified increased height, reduced FNaBMD, increased FNDelta, and reduced FNSigma per SD as significant independent contributors to differentiating fracture from non-fracture. Area under ROC analysis identified significant improvement in discrimination with the addition of FNDelta and FNSigma to the model including age, height, weight, and FNaBMD (C statistic 0.87 and 0.84 respectively)., Conclusions: These data extend previous data that identified the benefit of 2D FN internal structural information in discriminating those at increased future fracture risk from recently fractured individuals. These data support continuing investigation of MM analysis as a straightforward analytical approach adding value to DXA hip aBMD in predicting fracture risk.

Background: High vegetable intake is associated with beneficial effects on bone. However, the mechanisms remain uncertain. Green leafy vegetables are a rich source of vitamin K1, which is known to have large effects on osteoblasts and osteocalcin (OC) metabolism., Objective: To examine the effects of consumption of two to three extra serves of green leafy vegetables daily on bone metabolism., Methods: Thirty individuals (mean age 61.8 ± 9.9 years, 67% male) completed three experimental phases in a randomised controlled crossover design, each lasting four weeks, with a washout period of four weeks between phases (clinical trial registration: ACTRN12615000194561). The three experimental phases were: (i) increased dietary vitamin K1 by consuming green leafy vegetables (H-K; ~200 g/d containing 164.3 [99.5-384.7] μg/d of vitamin K1); (ii) low vitamin K1 by consuming vitamin K1-poor vegetables (L-K; ~200 g/d containing 9.4 [7.7-11.6] μg/d of vitamin K1); and (iii) control (CON) where participants consumed an energy-matched non-vegetable control. OC forms, total OC (tOC), carboxylated OC (cOC) and undercarboxylated OC (ucOC), were measured in serum pre- and post-intervention for each experimental phase using a sandwich-electrochemiluminescence immunoassay., Results: Pre-intervention tOC, ucOC and ucOC:tOC levels were similar between phases ( P  > .05). Following H-K, but not L-K, tOC, ucOC and ucOC:tOC levels were significantly lower compared to pre-intervention levels ( P  ≤ .001) and compared to CON (~14%, 31% and 19%, respectively, all P  < .05), while cOC remained unchanged., Conclusions: In middle-aged healthy men and women, an easily achieved increase in dietary intake of vitamin K1-rich green leafy vegetables substantially reduces serum tOC and ucOC suggesting increased entry of OC into bone matrix, where it may improve the material property of bone. In conjunction with previous epidemiological and randomised controlled trial data, these findings suggest that interventions to increase vegetable intake over extended periods should include bone end points including fracture risk., (© 2020 The Authors.)

Purpose: Increasing vegetable intake and diversity are recommended to maintain better health. Evidence for the health benefits of vegetable diversity, separate from total intake, is scarce. We aimed to investigate the associations of vegetable diversity with subclinical measures of atherosclerosis and atherosclerotic vascular disease (ASVD) mortality., Methods: Vegetable diversity was assessed within a validated food frequency questionnaire using a single question, 'How many different vegetables do you usually consume each day (< 1 to ≥ 6 per day)'. Cox proportional hazards modelling was used to examine the association between vegetable diversity and ASVD mortality in 1226 women aged ≥ 70 years without clinical ASVD or diabetes mellitus at baseline (1998). In 2001, B-mode ultrasonography was used to measure common carotid artery intima-media thickness (CCA-IMT) (n = 954) and carotid plaque severity (n = 968)., Results: Over 15 years (15,947 person-years) of follow-up, 238 ASVD-related deaths were recorded. For each additional different vegetable consumed per day, there was 17% lower hazard for ASVD mortality (HR = 0.83, 95% CI 0.78, 0.93, P = 0.001); a 1.7% lower mean CCA-IMT (B ± SE: - 0.013 ± 0.004, P < 0.001); and a 1.8% lower maximum CCA-IMT (B ± SE: - 0.017 ± 0.004, P < 0.001). Further adjustment for total vegetable intake attenuated the association between vegetable diversity and ASVD mortality (P = 0.114), but not CCA-IMT (P = 0.024). No association was observed between vegetable diversity and carotid plaque severity (P > 0.05)., Conclusions: Vegetable diversity may contribute to benefits in lowering risk of ASVD in older women. The reduction in risk is partly explained by increased total vegetable consumption., Clinical Trial Registry: The Perth Longitudinal Study of Aging in Women (PLSAW) trial registration ID is ACTRN12617000640303. This study was retrospectively registered on the Australian New Zealand Clinical Trials Registry at http://www.anzctr.org.au.

Although a relationship between vascular disease and osteoporosis has been recognized, its clinical importance for fracture risk evaluation remains uncertain. Abdominal aortic calcification (AAC), a recognized measure of vascular disease detected on single-energy images performed for vertebral fracture assessment, may also identify increased osteoporosis risk. In a prospective 10-year study of 1024 older predominantly white women (mean age 75.0 ± 2.6 years) from the Perth Longitudinal Study of Aging cohort, we evaluated the association between AAC, skeletal structure, and fractures. AAC and spine fracture were assessed at the time of hip densitometry and heel quantitative ultrasound. AAC was scored 0 to 24 (AAC24) and categorized into low AAC (score 0 and 1, n = 459), moderate AAC (score 2 to 5, n = 373), and severe AAC (score >6, n = 192). Prevalent vertebral fractures were calculated using the Genant semiquantitative method. AAC24 scores were inversely related to hip BMD ( r s = -0.077, p = 0.013), heel broadband ultrasound attenuation ( r s = -0.074, p = 0.020), and the Stiffness Index ( r s = -0.073, p = 0.022). In cross-sectional analyses, women with moderate to severe AAC were more likely to have prevalent fracture and lumbar spine imaging-detected lumbar spine fractures, but not thoracic spine fractures (Mantel-Haenszel test of trend p < 0.05). For 10-year incident clinical fractures and fracture-related hospitalizations, women with moderate to severe AAC (AAC24 score >1) had increased fracture risk (HR 1.48; 95% CI, 1.15 to 1.91; p = 0.002; HR 1.46; 95% CI, 1.07 to 1.99; p = 0.019, respectively) compared with women with low AAC. This relationship remained significant after adjusting for age and hip BMD for clinical fractures (HR 1.40; 95% CI, 1.08 to 1.81; p = 0.010), but was attenuated for fracture-related hospitalizations (HR 1.33; 95% CI, 0.98 to 1.83; p = 0.073). In conclusion, older women with more marked AAC are at higher risk of fracture, not completely captured by bone structural predictors. These findings further support the concept that vascular calcification and bone pathology may share similar mechanisms of causation that remain to be fully elucidated © 2019 American Society for Bone and Mineral Research., (© 2019 American Society for Bone and Mineral Research.)

The vitamin D debate relates in part to ideal public health population levels of circulating 25-hydroxyvitamin D (25OHD) to maintain bone structure and reduce fracture. In a secondary analysis of 1348 women aged 70 to 85 years at baseline (1998) from the Perth Longitudinal Study of Aging in Women (a 5-year calcium supplementation trial followed by two 5-year extensions), we examined the dose-response relations of baseline plasma 25OHD with hip DXA BMD at year 1, lumbar spine BMD, and trabecular bone score (TBS) at year 5, and fracture-related hospitalizations over 14.5 years obtained by health record linkage. Mean baseline plasma 25OHD was 66.9 ± 28.2 nmol/L and 28.5%, 36.4%, and 35.1% of women had levels <50, 50 to 74.9, and ≥75 nmol/L, respectively. Generalized additive models showed that total hip and femoral neck BMD and TBS, but not spine BMD, were higher with increasing plasma 25OHD up to 100 nmol/L. Compared with those with 25OHD <50 nmol/L, women with 25OHD ≥75 nmol/L had significantly higher total hip and femoral neck BMD at year 1 (3.3% to 3.9%) and TBS at year 5 (2.0%), all P < 0.05. During the follow-up, 27.6% of women experienced any fracture-related hospitalization and 10.6% hip fracture-related hospitalization. Penalized spline regression models showed a decrease in risk with increased 25OHD levels up to 65 nmol/L and 75 nmol/L for hip fracture and any fracture-related hospitalization, respectively. Cox regression grouped analyses showed that compared with women with 25OHD <50 nmol/L, those with 25OHD levels 50 to 74.9 and ≥75 nmol/L had significantly lower risk for hip fracture [HR 0.60 (95% CI, 0.40 to 0.91) and 0.61 (95% CI, 0.40 to 0.92), respectively], and any fracture-related hospitalization [HR 0.77 (95% CI, 0.59 to 0.99) and 0.70 (95% CI, 0.54 to 0.91), respectively]. In older white women, 25OHD levels >50 nmol/L are a minimum public health target and 25OHD levels beyond 75 nmol/L may not have additional benefit to reduce fracture risk. © 2019 American Society for Bone and Mineral Research., (© 2019 American Society for Bone and Mineral Research.)

One year of calcium supplementation in older women led to modest reductions in total osteocalcin and undercarboxylated osteocalcin (ucOC), with no changes in muscle or fat mass, or glycated haemoglobin. Future studies should explore whether treatments with more profound effects of suppressing ucOC may lead to impaired glycaemic control., Introduction: Total osteocalcin (TOC) is a marker of bone turnover, while its undercarboxylated form has beneficial effects on glucose metabolism in mice. This post hoc analysis of a randomised double-blind, placebo-controlled trial examined whether 1 year of calcium supplementation affected circulating TOC, undercarboxylated osteocalcin (ucOC) or glycated haemoglobin (HbA1c) in 1368 older community-dwelling women (mean age 75.2 ± 2.7 years)., Methods: Women enrolled in the Calcium Intake Fracture Outcome Study trial (1998-2003) were supplemented with 1.2 g/d of elemental calcium (in the form of calcium carbonate) or placebo. Circulating TOC, ucOC and HbA1c was measured at 1 year (1999)., Results: After 1 year of calcium supplementation, TOC and ucOC levels were 17% and 22% lower compared with placebo (mean 22.7 ± 9.1 vs. 27.3 ± 10.9 μg/L and 11.1 ± 4.9 vs. 13.0 ± 5.7 μg/L, both P < 0.001). Carboxylated osteocalcin/ucOC was 6% lower after calcium supplementation (P < 0.05). Despite this, no differences in HbA1c were observed (calcium, 5.2 ± 0.6 vs. placebo, 5.3 ± 0.8%; P = 0.08). Calcium supplementation did not affect BMI, whole body lean or fat mass. In exploratory analyses, total calcium (dietary and supplemental) was inversely related to TOC and ucOC, indicating calcium intake is an important dietary determinant of osteocalcin levels., Conclusion: One year of calcium supplementation in older women led to modest reductions in TOC and ucOC, with no changes in muscle or fat mass, or HbA1c. Future studies should explore whether treatments with more profound effects of suppressing ucOC may lead to impaired glycaemic control.

Background: In younger individuals, dietary nitrate supplementation has been shown to improve short-term vascular and muscle function. The role of higher habitual nitrate intake as part of a typical diet on muscle function in ageing has not been investigated. A cross-sectional study of relationships between dietary nitrate and measures of muscle function in older community-dwelling Australian women (n = 1420, ≥70 years) was undertaken., Methods: Participants completed a semi-quantitative food frequency questionnaire assessing dietary intake over the previous year. Total nitrate from vegetables and non-vegetable sources was calculated from a validated instrument that quantified the nitrate content of food recorded within the food frequency questionnaire. Handgrip strength and timed-up-and-go (TUG) were assessed, representing muscle strength and physical function, respectively. Cut-points for weak grip strength (<22 kg) and slow TUG (>10.2 s) were selected due to their association with adverse outcomes. Linear and logistic regressions were used to examine the relationship between total nitrate intake and muscle function measures., Results: Mean ± standard deviation (SD) total nitrate intake was 79.5 ± 31.2 mg/day, of which 84.5% came from vegetables. Across the unadjusted tertiles of nitrate intake (<64.2 mg/day; 64.2 to <89.0 mg/day; ≥89.0 mg/day), women in the highest tertile had a 4% stronger grip strength and a 5% faster TUG performance compared with the lowest tertile. In multivariable-adjusted models, each SD higher nitrate intake (31.2 mg/day) was associated with stronger grip strength (per kilogram, β 0.31, P = 0.027) and faster TUG (per second, β -0.27, P = 0.001). The proportion of women with weak grip strength (<22 kg) or slow TUG (>10.2 s) was 61.0% and 36.9%, respectively. Each SD higher nitrate intake (31.2 mg/day) was associated with lower odds for weak grip strength (OR 0.84, 95% CI 0.74-0.95, P = 0.005) and slow TUG (OR 0.86, 95% CI 0.76-0.98, P = 0.021). Compared with women in the lowest tertile of nitrate intake, women in the highest nitrate intake tertile had lower odds for weak grip strength (OR 0.65, 95% CI 0.49-0.87, P trend= 0.004) and slow TUG (OR 0.72, 95% CI 0.53-0.97, P trend  = 0.044)., Conclusions: This investigation highlights potential benefits of nitrate-rich diets on muscle strength and physical function in a large cohort of older women. Considering poor muscle strength and physical function is associated with a range of adverse health outcomes such as falling, fractures, cardiovascular disease, and mortality, increasing dietary nitrate, especially though vegetable consumption may be an effective way to limit age-related declines in muscle function., (© 2019 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.)

Introduction: Abdominal aortic calcification (AAC) is associated with low bone mass and increased fracture risk. Two previous meta-analyses have investigated the association between AAC and fracture. However, these meta-analyses only identified articles until December 2016, undertook limited searches and did not explore potential sources of between-study heterogeneity. We aim to undertake a sensitive and comprehensive assessment of the relationship between AAC, bone mineral density (BMD) as well as prevalent and incident fractures., Methods: We will search MEDLINE, EMBASE, Web of Science core collection and Google Scholar (top 200 articles sorted by relevance) from their inception to 1 June 2018. Reference lists of included studies and previous systematic reviews will be hand searched for additional eligible studies. Retrospective and prospective cohort studies (cross-sectional, case-control and longitudinal) reporting the association between AAC, BMD and fracture at any site will be included. At least two investigators will independently: (A) evaluate study eligibility and extract data, with a third investigator to adjudicate when discrepancies occur, (B) assess study quality by the Newcastle-Ottawa Scale for each cohort/study. The meta-analysis will be reported in adherence to the Meta-analysis of Observational Studies in Epidemiology criteria. AAC will be grouped as either: (1) AAC present or absent, (2) AAC categorised as 'low' (referent-lowest reported group) versus 'high' (all other groups) or (3) dose-response when AAC was assessed in ≥3 groups. Where primary event data were reported in individual studies, pooled risk differences and risk ratios with 95% CI will be calculated, from which, a summary estimate will be determined using DerSimonian-Laird random effects models. For the AAC and BMD pooled analyses, estimates will be expressed as standardised mean difference with 95% CI. We will examine the likelihood of publication bias and where possible, investigate potential reasons for between-study heterogeneity using subgroup analyses and meta-regression., Ethics and Dissemination: The study will be submitted to a peer- reviewed journal and disseminated via research presentations., Prospero Registration Number: CRD42018088019., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This paper explores the effects of aging on femoral neck (FN) anatomy in a study of women aged 20-90years in relation to implications for FN fracture propensity in buckling. Five hundred and four participants were scanned by Quantitative Computed Tomography and analyzed using Quantitative Computed Tomography Pro BIT (Mindways). FN cross-section was split through geometric center into superior and inferior sectors. Bone mass, structural measurements, and bone mineral density were analyzed. Buckling ratio was calculated as ratio of buckling radius to cortical thickness. Between 2nd decade and 8th decade, age-related integral bone mass reduction in superior sector was substantially larger than in inferior sector (33% compared to 21%), especially in cortical bone superiorly compared to inferiorly (53% vs 21%; p < 0.001), principally due to reduction in cortical thickness, averaged cortical thickness (56%) with little difference in density. Superior and inferior sector trabecular bone mineral density reduction was similar at 41% and 43% respectively. Differential cortical bone loss in superior sector resulted in a 59% inferior displacement (δ) of center-of-mass from geometric center. Differences in δ and averaged cortical thickness with age accounted for a 151% increase in mean superior buckling ratio from 9 to 23. Analysis confirms significant progressive age-related superior cortical bone loss as the major age effect on FN structure with relative preservation of inferior cortex probably related to maintenance of inferior sector by regular loading as a result of standing and walking. Computation of buckling ratio may allow prediction of fracture propensity in a sideways fall., (Copyright © 2018 The International Society for Clinical Densitometry. All rights reserved.)

We undertook a systematic review and meta-analysis of published papers assessing dietary protein and bone health. We found little benefit of increasing protein intake for bone health in healthy adults but no indication of any detrimental effect, at least within the protein intakes of the populations studied. This systematic review and meta-analysis analysed the relationship between dietary protein and bone health across the life-course. The PubMed database was searched for all relevant human studies from the 1st January 1976 to 22nd January 2016, including all bone outcomes except calcium metabolism. The searches identified 127 papers for inclusion, including 74 correlational studies, 23 fracture or osteoporosis risk studies and 30 supplementation trials. Protein intake accounted for 0-4% of areal BMC and areal BMD variance in adults and 0-14% of areal BMC variance in children and adolescents. However, when confounder adjusted (5 studies) adult lumbar spine and femoral neck BMD associations were not statistically significant. There was no association between protein intake and relative risk (RR) of osteoporotic fractures for total (RR (random)  = 0.94; 0.72 to 1.23, I 2  = 32%), animal (RR (random)  = 0.98; 0.76 to 1.27, I 2  = 46%) or vegetable protein (RR (fixed)  = 0.97 (0.89 to 1.09, I 2  = 15%). In total protein supplementation studies, pooled effect sizes were not statistically significant for LSBMD (total n = 255, MD (fixed)  = 0.04 g/cm 2 (0.00 to 0.08, P = 0.07), I 2  = 0%) or FNBMD (total n = 435, MD (random)  = 0.01 g/cm 2 (-0.03 to 0.05, P = 0.59), I 2  = 68%). There appears to be little benefit of increasing protein intake for bone health in healthy adults but there is also clearly no indication of any detrimental effect, at least within the protein intakes of the populations studied (around 0.8-1.3 g/Kg/day). More studies are urgently required on the association between protein intake and bone health in children and adolescents.

Background: Lean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass., Objectives: To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci., Methods: We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms)., Results: Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts. Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R). In contrast, loci with an impact specifically on LM were termed "body builder" loci (VCAN and ADAMTSL3). Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection., Conclusions: In conclusion, we identified one novel LM locus (TNRC6B). Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.

The current diagnosis of osteoporosis is limited to a T-score ≤-2.5. However, asymptomatic vertebral fractures (VF) are known to predict a high risk of subsequent fractures and pharmaceutical intervention is known to reduce future fracture risk in these individuals. In a prospective, population-based cohort of ambulant older women, we sought to evaluate the role of VF detection by screening densitometric lateral spine imaging (LSI) for VF at time of bone density testing to the effect on the magnitude of fracture risk. A total of 1084 women (mean age 75 years ± SD 3 years) had baseline LSI that identified 100 (9%) women with VFs and 89 (8%) with femoral neck (FN) T-score osteoporosis ≤-2.5. Follow-up identified incident clinical spine fracture in 73 (7%), 305 (28%) with any fracture-related hospitalization, and 121 (11%) with a hip fracture-related hospitalization. Compared with those without baseline VF, in those with baseline VF, relative risk (RR) for incident clinical spine, hip, and any fracture were 3.46 (95% confidence interval [CI] 2.14-5.60, p < 0.001); 1.72 (95% CI 1.09-2.71, p = 0.02), and 1.4 (95% CI 1.07-1.84, p = 0.02), respectively. In 675 (62%) of women with femoral neck osteopenia (T-score <-1 to >-2.5), 61 (9%) also had a VF. Compared with those without baseline VF, RR for any incident fragility fractures and fractures at spine and hip in those with baseline VF were 1.6 (95% CI 1.2-2.1, p < 0.01), 3.9 (95% CI 2.2-6.9, p < 0.01), and 1.6 (95% CI 0.9-2.8, p = 0.10), respectively. On basis of the prognosis, older women with LSI VF with osteopenia should be diagnosed with osteoporosis and should be considered for pharmaceutical intervention. © 2018 American Society for Bone and Mineral Research., (© 2018 American Society for Bone and Mineral Research.)

Background Neutrophil gelatinase-associated lipocalin ( NGAL ) or lipocalin 2 may promote atherosclerosis and plaque instability leading to increased risk of cardiac events. We investigated the relationships between plasma NGAL , cardiovascular disease biomarkers, and long-term cardiac events. Methods and Results The study population consisted of 1131 ambulant older white women (mean age 75 years) without clinical coronary heart disease ( CHD ) and measures of plasma NGAL in the Perth Longitudinal Study of Ageing Women with 14.5-year CHD and heart failure hospitalizations or death (events) captured using linked records. Over 14.5 years, 256 women had CHD events, while 118 had heart failure events. Per SD increase in log-transformed NGAL there was a 35% to 37% increase in relative hazards for CHD and heart failure events in unadjusted analyses, which remained significant after adjustment for conventional risk factors for CHD events (hazard ratio 1.29, 95% CI 1.13-1.48, P<0.001) but not heart failure ( P>0.05). Women in the highest 2 quartiles of NGAL had higher relative hazards for CHD events compared with women in the lowest quartile hazard ratio 1.61, 95% CI 1.08-2.39, P=0.019 and hazard ratio 1.97, 95% CI 1.33-3.93, P=0.001, respectively. These associations were independent of high-sensitivity cardiac troponin I, homocysteine, and estimated renal function. NGAL correctly reclassified 1 in 4 women who sustained a CHD event up in risk and 1 in 10 women without CHD events down in risk. Conclusions NGAL was associated with increased risk of long-term CHD events, independent of conventional risk factors and biomarkers. These findings provide mechanistic insight into the role of NGAL with cardiac events.

Objectives: To investigate the relationship of 4 sarcopenia definitions with long-term all-cause mortality risk in older Australian women., Design: Data from the Perth Longitudinal Study in Aging Women from 2003 to 2013 was examined in this prospective cohort study. The 4 sarcopenia definitions were the United States Foundation for the National Institutes of Health (FNIH), the European Working Group on Sarcopenia in Older People (EWGSOP), and adapted FNIH (AUS-POP F ) and EWGSOP (AUS-POP E ) definitions using Australian population-specific cut-points [<2 standard deviation (SD)] below the mean of young healthy Australian women. All-cause mortality was captured via linked data systems., Setting and Participants: In total, 903 community-dwelling older Australian women (baseline mean age 79.9 ± 2.6 years) with concurrent measures of muscle strength (grip strength), physical function (timed-up-and-go; TUG) and appendicular lean mass (ALM) were included., Measures: Cox-proportional hazards modeling was used to examine the relationship between sarcopenia definitions and mortality over 5 and 9.5 years., Results: Baseline prevalence of sarcopenia by the 4 definitions differed substantially [FNIH (9.4%), EWGSOP (24.1%), AUS-POP F (12.0%), AUS-POP E (10.7%)]. EWGSOP and AUS-POP E had increased age-adjusted hazard ratios (aHRs) for mortality over 5 years [aHR 1.88 95% confidence interval (CI) (1.24‒2.85), P < .01; aHR 2.52 95% CI (1.55‒4.09), P < .01, respectively] and 9.5 years (aHR 1.39 95% CI (1.06‒1.81), P = .02; aHR 1.94 95% CI (1.40‒2.69), P < .01, respectively). No such associations were observed for FNIH or AUS-POP F . Sarcopenia components including weaker grip strength (per SD, 4.9 kg; 17%) and slower TUG (per SD, 3.1 seconds; 40%) but not ALM adjusted-variants (ALM/body mass index or ALM/height 2 ) were associated with greater relative hazards for mortality over 9.5 years., Conclusions/relevance: Unlike FNIH, the EWGSOP sarcopenia definition incorporating weak muscle strength and/or poor physical function was related to prognosis, as was the regionally adapted version of EWGSOP. Although sarcopenia definitions were not developed based on prognosis, this is an important consideration for globally standardizing the sarcopenia framework., (Copyright © 2018 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Numerous sarcopenia definitions are not associated with increased falls-related hospitalization risk over 5 years to 9.5 years in older community-dwelling Australian women. Measures of muscle strength and physical function, but not appendicular lean mass (measured by dual-energy X-ray absorptiometry) may help discriminate the risk of falls-related hospitalization., Introduction: The aim of this prospective, population-based cohort study of 903 Caucasian-Australian women (mean age 79.9 ± 2.6 years) was to compare the clinical utility of four sarcopenia definitions for the prediction of falls-related hospitalization over 9.5 years., Methods: The four definitions were the United States Foundation for the National Institutes of Health (FNIH), the European Working Group on Sarcopenia in Older People (EWGSOP), and modified FNIH (AUS-POP F ) and EWGSOP (AUS-POP E ) definitions using Australian population-specific cut points (< 2 SD below the mean of young healthy Australian women). Components of sarcopenia including muscle strength, physical function, and appendicular lean mass (ALM) were quantified using hand grip strength, timed-up-and-go (TUG), and dual-energy X-ray absorptiometry (DXA), respectively. Incident 9.5-year falls-related hospitalization were captured by linked data., Results: Baseline prevalence of sarcopenia according to FNIH (9.4%), EWGSOP (24.1%), AUS-POP F (12.0%), and AUS-POP E (10.7%) differed substantially. Sarcopenia did not increase the relative hazard ratio (HR) for falls-related hospitalization before or after adjustment for age (aHR): FNIH aHR 1.00 95%CI (0.69-1.47), EWGSOP aHR 1.20 95%CI (0.93-1.54), AUS-POP F aHR 0.96 95%CI (0.68-1.35), and AUS-POP E aHR 1.33 95%CI (0.94-1.88). When examining individual components of sarcopenia, only muscle strength and physical function but not ALM (adjusted for height 2 or BMI) were associated with falls-related hospitalization., Conclusion: Current definitions of sarcopenia were not associated with falls-related hospitalization risk in this cohort of community-dwelling older Australian women. Finally, measures of muscle strength and physical function, but not ALM (measured by DXA) may help discriminate the risk of falls-related hospitalization.

The objective of the study was to determine the association between AAC and neuromuscular function over 5 years. Participants in this study were ambulant women over 70 years old residing in Perth, Western Australia who participated in the Calcium Intake Fracture Outcomes Study, a randomised controlled trial of calcium supplementation. 1046 women (mean age = 74.9 ± 2.6 years; BMI = 27.1 ± 4.4 kg/m 2 ) were included. Lateral spine images captured during bone density testing were scored for AAC (AAC24; 0-24) at baseline. Severe AAC (AAC sev ) was defined using established cut points (AAC24 ≥ 6). At baseline and follow-up, isometric grip strength was assessed using a dynamometer. Mobility was assessed by the Timed-Up-and-Go (TUG) test. Using pre-defined criteria, muscle weakness was considered as grip strength < 22 kg and poor mobility defined as TUG > 10.2 s. A subset of women had appendicular lean mass (ALM) determined by dual-energy X-ray absorptiometry at baseline and follow-up (n = 261). AAC sev was evident in 193 (18.5%) women. Average decline in grip strength after 5 years was greater in those with AAC sev than those without (3.6 ± 3.7 vs. 2.9 ± 4.2 kg; p = 0.034). This remained significant after adjustment for age, treatment allocation, diabetes, smoking history, renal function, medical record-derived prevalent vascular disease, BMI and physical activity (β = - 0.184; 95% confidence interval: - 0.361, - 0.008; p = 0.040). AAC sev was not associated with 5-year changes in TUG or ALM in univariable or multivariable analyses (all p > 0.05). In older women, severe aortic calcification was associated with greater 5-year decline in muscle strength, but not TUG or ALM. These findings support the concept that vascular disease may have an effect on the loss of muscular strength.

The role of vegetable and fruit intake in reducing falls risk in elderly populations is uncertain. This study examined the associations of vegetable and fruit intake with falls-related hospitalisations in a prospective cohort study of elderly women (n 1429, ≥70 years), including effects on muscular function, which represented a potential causal pathway. Muscular function, measured using grip strength and timed-up-and-go (TUG), and vegetable and fruit intake, quantified using a validated FFQ, were assessed at baseline (1998). Incident falls-related hospitalisation over 14·5-year follow-up was captured by the Hospital Morbidity Data Collection, linked via the Western Australian Data Linkage System. Falls-related hospitalisation occurred in 568 (39·7 %) of women. In multivariable-adjusted models, falls-related hospitalisations were lower in participants consuming more vegetables (hazard ratio (HR) per 75 g serve: 0·90 (95 % CI 0·82, 0·99)), but not fruit intake (per 150 g serve: 1·03 (95 % CI 0·93, 1·14)). Only total cruciferous vegetable intake was inversely associated with falls-related hospitalisation (HR: per 20 g serve: 0·90 (95 % CI 0·83, 0·97)). Higher total vegetable intake was associated with lower odds for poor grip strength (OR: 0·87 (95 % CI 0·77, 0·97)) and slow TUG (OR: 0·88 (95 % CI 0·78, 0·99)). Including grip strength and TUG in the multivariable-adjusted model attenuated the association between total vegetable intake and falls-related hospitalisations. In conclusion, elderly women with higher total and cruciferous vegetable intake had lower injurious falls risk, which may be explained in a large part by better physical function. Falls reduction may be considered an additional benefit of higher vegetable intake in older women.

Context: In a previous community-based, cross-sectional study, males with type 1 diabetes (T1D) had lower bone mineral density (BMD) than did matched people without diabetes but females with T1D had normal BMD., Objective: To determine whether BMD in the males continued to decline, the neutral effect of T1D on BMD in females persisted, and whether temporal BMD changes reflected changes in bone turnover markers., Design: Longitudinal observational study., Setting: Urban community., Patients: Forty-eight of the original 102 original cross-sectional study participants (20 males, 28 females) of mean age 42.0 years and median diabetes duration 14.6 years at baseline who were restudied a mean of 10.3 years later., Main Outcome Measures: BMD at total hip, femoral neck, lumbar spine (L1 to L4), and distal forearm. Biochemical bone turnover markers., Results: After adjustment for age, body mass index (BMI), and renal function, there was no temporal change in BMD at the hip or forearm in the males (P ≥ 0.12), but lumbar spine BMD increased (P = 0.009). Females exhibited no statistically significant change in BMD in similar multivariable models that also included postmenopausal status, except a mild increase at the forearm (P = 0.046). Age- and sex-related changes in bone turnover markers paralleled those in general population studies., Conclusions: There is a reduction in BMD in males with T1D that occurs early in the course of the disease but then stabilizes. BMD in females with T1D remains similar to that expected for age, BMI, and postmenopausal status.