Frailty increases the long-term risk for fall and fracture-related hospitalizations and all-cause mortality in community-dwelling older women.

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.

Frailty is often linked to decline in the sensory, neurological, and musculoskeletal systems. Frailty can be identified and graded using a frailty index (FI). In a cohort of 1261 community-dwelling older women with an average age of 75 yr, this study found that increasing grades of frailty fit, (mildly, moderately and severely frail) were associated with higher long-term risk for a fall and/or fracture (including hip fractures) that required hospitalization. Increasing grades of frailty were also linked with greater risk of death, especially due to cardiovascular causes. In conclusion, the FI may be used to identify community-dwelling older women with a high long-term risk for the most serious falls and fractures, as well as individuals with a poorer prognosis.

Extent of Abdominal Aortic Calcification Is Associated With Incident Rapid Weight Loss Over 5 Years: The Perth Longitudinal Study of Ageing Women.

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.

Machine-Learning Assessed Abdominal Aortic Calcification is Associated with Long-Term Fall and Fracture Risk in Community-Dwelling Older Australian Women.

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).

Cardiovascular disease, muscle function, and long-term falls risk: The Perth Longitudinal Study of Ageing Women.

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.

Abdominal Aortic Calcification, Bone Mineral Density, and Fractures: A Systematic Review and Meta-analysis of Observational Studies.

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.

Evidence for the cardiovascular effects of osteoporosis treatments in randomized trials of post-menopausal women: A systematic review and Bayesian network meta-analysis.

Osteoporosis medications have been reported to have beneficial and harmful cardiovascular effects. Much of this evidence stems from single reports and as such, a comprehensive examination of the evidence is needed. We conducted a network meta-analysis (NMA) of cardiovascular adverse event (CAE) data from randomized trials of osteoporosis medications in postmenopausal women. Trials were identified from recent NMAs of osteoporosis treatment for fracture reduction with an updated literature search (December 2020). Included studies were randomized, included over 100 participants, and reported skeletal primary outcomes. We investigated three-point major adverse cardiovascular events (MACE3), four- (MACE4) and five-point MACE (MACE5), as well as myocardial infarction (MI) and stroke. Data were synthesized in a random-effects network meta-analysis using Bayesian modelling. Probabilistic ranking of treatment safety was performed. Relative to placebo, point estimates for the odds ratios (OR) with 95 % credible intervals (CrI) were also generated. We identified 75 trials (n = 136,940 women), of which 27 (68,699 women, nine arms) reported CAEs. In women randomized to placebo, the overall event rate for the MACE3 outcome was 2.58 % compared with 1.99 % in those randomized to all other active comparators. Probabilistic ranking found abaloparatide, oral bisphosphonates, teriparatide, and menopausal hormone therapy were less likely to have increased risk of CAEs than placebo, while romosozumab ranked more likely to have increased risk of CAEs than placebo for all outcomes. Compared with placebo, abaloparatide (one trial, n = 1642) was associated with a reduced odds for MACE3 (OR = 0·31; 95%CrI: 0·06 to 0·99), MACE4 (0·28; 0·06 to 0·88) and MACE5 (0·25; 0·06 to 0·79). When all PTH analogues were grouped together, magnitude and direction of effects were consistent but no longer statistically significant. We did not find pooled direct and indirect evidence that osteoporosis treatments significantly increased the risk of adverse cardiovascular events relative to placebo. (PROSPERO: CRD42020178702).

Measures of carotid atherosclerosis and fall-related hospitalization risk: The Perth Longitudinal Study of Ageing Women.

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.

Provision of non-invasive coronary and carotid vascular imaging results on changes in diet and physical activity in asymptomatic adults: A scoping review.

Background: Although a healthy diet and physical activity have been shown to prevent or delay cardiovascular disease (CVD) hospitalizations and deaths, most adults do not meet current guidelines. Provision of coronary artery calcification (CAC) and carotid ultrasound (CUS) imaging results may motivate beneficial lifestyle changes. We scoped the existing literature for studies providing non-invasive vascular imaging results and reporting diet, physical activity, and/or anthropometric measures to identify knowledge gaps and opportunities for further research. Methods: A systematic search was performed across three electronic databases, in line with PRISMA ScR guidelines and Arksey and O'Malley's scoping review framework. Results: Twenty studies (thirteen observational and seven randomized controlled trials) examining the impact of provision of CAC/CUS imaging results on diet and/or physical activity behaviors were included. Nearly half the studies did not clearly state whether participants received dietary and physical activity advice along with vascular imaging results, and these were secondary outcomes in most studies, with data assessment and reporting being inconsistent. Conclusion: Well-designed clinical trials with consistent and clear messaging based on detailed subjective and objective measures of diet and physical activity are needed to determine whether this approach may stimulate long-term dietary and physical activity change.

Association of Abdominal Aortic Calcification with Peripheral Quantitative Computed Tomography Bone Measures in Older Women: The Perth Longitudinal Study of Ageing Women.

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 (rs = - 0.088, p = 0.044), 4% tibia (rs = - 0.085, p = 0.052) and 15% radius (rs = - 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.

Abdominal aortic calcification is associated with a higher risk of injurious fall-related hospitalizations in older Australian women.

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.