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.

Vitamin K1 intake is associated with lower risk for all-cause and cardiovascular disease mortality in community-dwelling older Australian women.

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.

The Interconnection Between Muscle and Bone: A Common Clinical Management Pathway.

Often observed with aging, the loss of skeletal muscle (sarcopenia) and bone (osteoporosis) mass, strength, and quality, is associated with reduced physical function contributing to falls and fractures. Such events can lead to a loss of independence and poorer quality of life. Physical inactivity (mechanical unloading), especially in older adults, has detrimental effects on the mass and quality of bone as well as muscle, while increases in activity (mechanical loading) have positive effects. Emerging evidence suggests that the relationship between bone and muscle is driven, at least in part, by bone-muscle crosstalk. Bone and muscle are closely linked anatomically, mechanically, and biochemically, and both have the capacity to function with paracrine and endocrine-like action. However, the exact mechanisms involved in this crosstalk remain only partially explored. Given older adults with lower bone mass are more likely to present with impaired muscle function, and vice versa, strategies capable of targeting both bone and muscle are critical. Exercise is the primary evidence-based prevention strategy capable of simultaneously improving muscle and bone health. Unfortunately, holistic treatment plans including exercise in conjunction with other allied health services to prevent or treat musculoskeletal disease remain underutilized. With a focus on sarcopenia and osteoporosis, the aim of this review is to (i) briefly describe the mechanical and biochemical interactions between bone and muscle; (ii) provide a summary of therapeutic strategies, specifically exercise, nutrition and pharmacological approaches; and (iii) highlight a holistic clinical pathway for the assessment and management of sarcopenia and osteoporosis.

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).

Association between high-sensitivity cardiac troponin I and fall-related hospitalisation in women aged over 70 years.

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.

Protocol: Can coronary artery calcium score identified on thoracic planning CT scans be used and actioned to identify cancer survivors at high risk of cardiac events: A feasibility study in cancer survivors undergoing radiotherapy in Australia.

INTRODUCTION: A coronary artery calcium (CAC) CT scan can identify calcified plaque and predict risk of future cardiac events. Cancer survivors undergoing thoracic radiotherapy routinely undergo a planning CT scan, which presents a unique opportunity to use already obtained medical imaging to identify those at the highest risk of cardiac events. While radiation therapy is an important modality for many cancer treatments, radiation dose to the heart in thoracic radiotherapy leads to cardiotoxicity and may accelerate pre-existing atherosclerosis. The primary aims of this study are to investigate the feasibility of using CAC scores calculated on thoracic radiotherapy planning CT scans to identify a subset of cancer survivors at an increased risk of future cardiac events, and to establish and evaluate a referral pathway for assessment and management in a cardio-oncology clinic. An optional substudy aims to investigate using abdominal aortic calcification (AAC) as a practical, low-radiation alternative to CAC to evaluate and monitor vascular health. METHODS AND ANALYSIS: This is an observational, prospective study in a minimum of 100 cancer survivors commencing radiotherapy. Participants will have CAC scored from thoracic radiotherapy planning CT scans. Those identified as high risk (CAC score>0) will be referred to a cardio-oncology clinic. Feasibility, determined by adherence to the recommended pathway, and impact on quality of life and anxiety measured via questionnaire, will be assessed. Participants in Western Australia will be invited to participate in a 12-month observational pilot substudy, investigating lifestyle behaviours and the use of a dual-energy X-ray absorptiometry machine to measure musculoskeletal health and AAC. ETHICS AND DISSEMINATION: Ethics approval has been obtained from St Vincent's Hospital, Sydney (Project number 2021/ETH11847), GenesisCare and Edith Cowan University (2022-03326-DALLAVIA). Study results will be reported in peer-reviewed academic journals, at scientific conferences, and at clinical forums, irrespective of the results observed. TRIAL REGISTRATION NUMBER: ACTRN12621001343897.

Barriers and enablers associated with participation in a home-based pragmatic exercise snacking program in older adults delivered and monitored by Amazon Alexa: a qualitative study.

BACKGROUND: 'Exercise snacking', which is characterised by shorter and more frequent exercise bouts compared with traditional exercise guidelines, may be an acceptable strategy for increasing physical activity and reducing sedentary behaviour in older adults. AIM: The aim of this study was to evaluate the enablers and barriers for older adults associated with participation in a home-based exercise snacking program delivered and monitored using an Amazon Echo Show 5 device (Alexa). METHODS: This study used an interpretive description qualitative design to conduct semi-structured interviews following a 12-week pilot study in 15 adults aged 60-89 years with at least one chronic condition. All participants were prescribed a home based, individualised, lower limb focussed 'exercise snacking' program (involving ≤ 10 min of bodyweight exercises 2-4 times per day) delivered and monitored by an Alexa. Qualitative interview data were analysed using thematic analysis. RESULTS: All 15 participants (mean age 70.3 years) attended the semi-structured interview. Themes including time efficiency, flexibility, perceived health benefits, and motivation were enablers for participation in the 'exercise snacking' program. A lack of upper body exercises and omission of exercise equipment in the program, as well as a lack of time and motivation for performing exercise snacks three or more times per day, were barriers to participation. CONCLUSION: While 'exercise snacking' is acceptable for older adults, future trials should provide equipment (e.g. adjustable dumbbells, exercise bands), prescribe whole-body exercise programs, and establish strategies to support participation in more than three exercise snacks per day.

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.

Effectiveness of combined nutrition and exercise interventions on body weight, lean mass, and fat mass in adults diagnosed with cancer: a systematic review and meta-analysis.

CONTEXT: Changes in body weight and composition (fat and lean mass) are prominent side effects of cancer treatment. Nutrition and exercise interventions are both key strategies to protect against these adverse effects, yet their impact when combined has not been comprehensively reviewed in adults with cancer. OBJECTIVE: This systematic review and meta-analysis aims to assess the effects of combined nutrition and exercise interventions on body weight and composition in adults with cancer. DATA SOURCES: Four databases were searched until January 2021. Combined nutrition and exercise randomized controlled trials that detailed the nutrition and exercise prescription and reported body weight and composition outcomes were eligible. DATA EXTRACTION: Risk of bias was assessed through the Cochrane Collaboration tool. The number of participants, mean values, and standard deviations of the outcome variables were extracted. Mean differences (MDs) were pooled using random-effects models. Predetermined subgroup analyses included cancer type, intervention intent, exercise modality, and use of behavior change strategies. DATA ANALYSIS: Twenty-three RCTs were included. Nutrition plus exercise interventions significantly reduced body weight (MD -  2.13 kg; 95%CI, - 3.07 to - 1.19), fat mass (MD - 2.06 kg; 95%CI, - 3.02 to - 1.09), and lean mass (MD - 0.43; 95%CI, - 0.82 to - 0.04). Subgroup analyses in women with breast cancer showed that weight loss interventions and interventions incorporating behavior change strategies significantly reduced body weight and fat mass but also reduced lean mass. Interventions aiming to maintain body weight showed no changes in body weight, as intended. CONCLUSION: Combined nutrition and exercise interventions successfully reduce body weight and fat mass in adults with cancer but also reduce lean mass. In contrast, weight loss-focused interventions are associated mostly with reduced lean mass. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42020161805.

Nutritional strategies to optimise musculoskeletal health for fall and fracture prevention: Looking beyond calcium, vitamin D and protein.

Falls and osteoporotic fractures are a major public health problem, particularly among older adults. A third of individuals aged 65 years and over fall at least once each year, with up to 20 % of these resulting in serious injury, including fracture. In conjunction with regular exercise, the importance of diet for musculoskeletal health has largely focused upon calcium, vitamin D, and protein, particularly in the context of preventing falls and fractures. Whilst there is evidence for the benefits of these nutrients for musculoskeletal health, other aspects of the diet remain largely underexplored. For example, vegetables are rich sources of macro- and micronutrients that are essential for muscle function and bone health, which are key factors in the prevention of falls and fractures. Recent work has highlighted the importance of nutrients such as vegetable-derived nitrate and vitamin K1 in optimising muscle strength, physical function, and bone quality. In the context of dietary patterns, vegan/plant-based diets have recently gained popularity due to perceived health benefits, animal welfare, or to tackle climate change. The elimination and/or substitution of animal-based products for plant foods (without careful planning and/or expert dietary guidance) could, however, have long-term negative musculoskeletal consequences; a trend uncovered by recent evidence. Within the overarching theme of nutrition for fall and fracture prevention in older populations, the aim of this review is to (i) summarise the current evidence for calcium, vitamin D and protein; (ii) describe the importance of vegetables and selected nutrients, such as nitrate and vitamin K1, for muscle function and bone structural integrity; and (iii) highlight current evidence around different dietary patterns (e.g., plant-based, diet quality, data driven approaches) and their impact on musculoskeletal health.

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.

Effects of a multicomponent resistance-based exercise program with protein, vitamin D and calcium supplementation on cognition in men with prostate cancer treated with ADT: secondary analysis of a 12-month randomised controlled trial.

OBJECTIVES: The aim of this preplanned secondary analysis of a 12-month randomised controlled trial was to investigate the effects of a multicomponent exercise programme combined with daily whey protein, calcium and vitamin D supplementation on cognition in men with prostate cancer treated with androgen deprivation therapy (ADT). DESIGN: 12-month, two-arm, randomised controlled trial. SETTING: University clinical exercise centre. PARTICIPANTS: 70 ADT-treated men were randomised to exercise-training plus supplementation (Ex+ Suppl, n=34) or usual care (control, n=36). INTERVENTION: Men allocated to Ex + Suppl undertook thrice weekly resistance training with weight-bearing exercise training plus daily whey protein (25 g), calcium (1200 mg) and vitamin D (2000 IU) supplementation. PRIMARY AND SECONDARY OUTCOME MEASURES: Cognition was assessed at baseline, 6 and 12 months via a computerised battery (CogState), Trail-making test, Rey auditory-verbal learning test and Digit span. Data were analysed with linear mixed models and an intention-to-treat and prespecified per-protocol approach (exercise-training: ≥66%, nutritional supplement: ≥80%). RESULTS: Sixty (86%) men completed the trial (Ex + Suppl, n=31; control, n=29). Five (7.1%) men were classified as having mild cognitive impairment at baseline. Median (IQR) adherence to the exercise and supplement was 56% (37%-82%) and 91% (66%-97%), respectively. Ex + Suppl had no effect on cognition at any time. CONCLUSIONS: A 12-month multicomponent exercise training and supplementation intervention had no significant effect on cognition in men treated with ADT for prostate cancer compared with usual care. Exercise training adherence below recommended guidelines does not support cognitive health in men treated with ADT for prostate cancer. TRIAL REGISTRATION NUMBER: Australian and New Zealand Clinical Trial Registry (ACTRN12614000317695, registered 25/03/2014) and acknowledged under the Therapeutic Goods Administration Clinical Trial Notification Scheme (CT-2015-CTN-03372-1 v1).

Feasibility and acceptability of a remotely delivered, home-based, pragmatic resistance 'exercise snacking' intervention in community-dwelling older adults: a pilot randomised controlled trial.

BACKGROUND: Very few older adults meet current muscle strengthening exercise guidelines, and several barriers exist to supervised, community-based resistance exercise programs. Older adults therefore require access to feasible resistance exercise modalities that may be performed remotely. This pilot study assessed the feasibility and acceptability of undertaking a four-week home-based resistance 'exercise snacking' intervention (performed either once, twice, or thrice daily) when delivered and monitored remotely in older adults. METHODS: Thirty-eight community-dwelling older adults [mean ± SD age 69.8 ± 3.8 y, 63% female] were randomised to complete resistance 'exercise snacks' (9-minute sessions) either once (n = 9), twice (n = 10), or thrice (n = 9) daily, or allocated to usual-activity control (n = 10). Exercise adherence and adverse events were assessed using an exercise diary, and acceptability of the intervention was explored using an online questionnaire. Physical function [balance, 5-times sit-to-stand (STS), and 30-second STS tests] was assessed remotely at baseline and follow-up using videoconferencing. RESULTS: The intervention was feasible and safe, with 100% participant retention, high adherence (97, 82, and 81% for once, twice, and thrice daily, respectively), and only two adverse events from a total of 1317 'exercise snacking' sessions. The exercise intervention was rated as enjoyable (75% reported their enjoyment as ≥4 on a 5-point Likert scale), easy to perform, and most (82%) planned to continue similar exercise at home. We also found it was feasible to assess measures of physical function via videoconferencing, although effect sizes for 4-week changes in both 5-STS (d range, 0.4-1.4) and 30-STS (d range, 0.7-0.9) following the exercise intervention were similar to controls (d = 1.1 and 1.0 for 5-STS and 30-STS, respectively). CONCLUSIONS: Resistance 'exercise snacking' may be a feasible strategy for engaging older adults in home-based resistance exercise when delivered and monitored remotely. The findings of this pilot feasibility trial support the need for longer-term studies in larger cohorts to determine the effectiveness of resistance 'exercise snacking' approaches for improving physical function in older adults. TRIAL REGISTRATION: The trial was retrospectively registered on 10/11/2021 with the Australian New Zealand Clinical Trials Registry (ANZCTR) ( ACTRN12621001538831 ).

Creatinine to Cystatin C Ratio, a Biomarker of Sarcopenia Measures and Falls Risk in Community-Dwelling Older Women.

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 Effect of Exercise Training on Lean Body Mass in Breast Cancer Patients: A Systematic Review and Meta-analysis.

PURPOSE: Reduced lean body mass (LBM) is common during and after treatment for breast cancer, and it is associated with increased treatment-induced toxicity, shorter time to tumor progression, and decreased survival. Exercise training is a potential intervention for maintaining or increasing LBM. We conducted a systematic review and a meta-analysis to investigate the effects of exercise training on LBM in breast cancer. METHODS: A comprehensive search was performed to November 2020 for randomized controlled trials reporting the effects of structured exercise training on LBM compared with control in women with breast cancer during or after cancer treatment. A random-effects meta-analysis was completed using the absolute net difference in the change in LBM between intervention and control groups as the outcome measure. Sensitivity and subgroup analyses were also performed. RESULTS: Data from 17 studies involving 1743 breast cancer survivors were included in the meta-analysis. Overall, there was a significant benefit of exercise training compared with control on LBM (0.58 kg, 95% confidence interval = 0.27 to 0.88, P < 0.001). Subgroup analysis showed positive effects for resistance training (0.59 kg) and aerobic training (0.29 kg), and for exercise training conducted during (0.47 kg) or after (0.66 kg) cancer treatment. Exercise training was beneficial in studies enrolling postmenopausal women (0.58 kg) as well as in those with participants of mixed menopausal status (1.46 kg). CONCLUSIONS: Compared with usual care, exercise training has a beneficial effect on LBM in women with breast cancer, both during and after cancer treatment. Given the physiological and functional importance of LBM in women with breast cancer, oncologists should encourage their patients to engage in regular exercise training, with particular emphasis on resistance training.

Musculoskeletal Responses to Exercise Plus Nutrition in Men with Prostate Cancer on Androgen Deprivation: A 12-Month RCT.

PURPOSE: Androgen deprivation therapy (ADT) for prostate cancer has multiple adverse effects on musculoskeletal health. This 12-month randomized controlled trial aimed to assess the effects of multicomponent exercise training combined with whey protein, calcium and vitamin D supplementation on bone mineral density (BMD), structure and strength, body composition, muscle strength, and physical function in ADT-treated men. METHODS: Seventy ADT-treated men were randomized to exercise plus supplementation (Ex + Suppl; n = 34) or usual care (control; n = 36). Ex + Suppl involved thrice weekly progressive resistance training plus weight-bearing impact exercise with daily multinutrient supplementation. Primary outcomes were DXA hip and spine areal BMD. Secondary outcomes included the following: tibia and radius pQCT volumetric BMD, bone structure and strength, DXA body composition, pQCT muscle and fat cross-sectional area and muscle density, and muscle strength and physical function. RESULTS: Sixty men (86%) completed the study. Mean exercise and supplement adherence were 56% and 77%, respectively. There were no effects of the intervention on bone or body composition outcomes. Ex + Suppl improved leg muscle strength (net difference, (95% confidence interval, or CI), 14.5% (-0.2 to 29.2); P = 0.007) and dynamic mobility (four-square-step test time, -9.3% (-17.3 to -1.3), P = 0.014) relative to controls. Per-protocol analysis of adherent participants (≥66% exercise, ≥80% supplement) showed Ex + Suppl preserved femoral neck aBMD (1.9% (0.1 to 3.8), P = 0.026) and improved total body lean mass (1.0 kg (-0.23 to 2.22), P = 0.044) relative to controls. CONCLUSIONS: Exercise training combined with multinutrient supplementation had a limited effect on ameliorating the adverse musculoskeletal consequences of ADT, likely related to the modest intervention adherence.

Effects of exercise frequency and training volume on bone changes following a multi-component exercise intervention in middle aged and older men: Secondary analysis of an 18-month randomized controlled trial.

Progressive resistance training (PRT) combined with weight-bearing impact exercise are recommended to optimize bone health, but the optimal frequency and dose of training remains uncertain. This study, which is a secondary analysis of an 18-month intervention in men aged 50-79 years, examined the association between exercise frequency and the volume of training with changes in DXA and QCT-derived femoral neck (FN) and lumbar spine (LS) bone outcomes, respectively. Men were allocated to either thrice-weekly PRT plus impact exercise training (n = 87) or a non-exercising (n = 85) group. Average weekly exercise frequency (ExFreq) and training volume per session [PRT volume (weight lifted, kg), number of weight-bearing impacts (jumps completed) and total training volume] over the 18-months were calculated from the participants' exercise cards. Regression analysis showed that average weekly ExFreq and training volume per session were positively associated with the 18-month changes in FN BMD and LS trabecular volumetric BMD. Men completing on average 1 to <2 and ≥2 sessions/week had a 1.6 to 2.2% greater net gain in FN BMD relative to non-exercising men, while those completing ≥2 sessions/week had 3.9 to 5.2% net gain in LS trabecular vBMD compared to non-exercising men and those completing <1 session/week. Further analysis showed that the average number of impact loads per session, but not the average PRT weight-lifted, was positively associated with changes in BMD. Every 10 impact loads per session over 18 months was associated with a 0.3% and 1.3% increase in FN BMD and LS trabecular vBMD, respectively. In conclusion, this study indicates that exercise frequency and training volume were predictors of the changes in hip and spine BMD following a multi-component exercise program, and that the number of impact loads rather than PRT weight lifted per session was more important for eliciting positive skeletal responses in middle-aged and older men.

Does androgen deprivation impact associations between cognition and strength, fitness and function in community-dwelling men with prostate cancer? A cross-sectional study.

OBJECTIVES: We investigated whether there were differences in associations between cognition with muscle strength, fitness and function in men with prostate cancer (PCa) treated with, and without androgen deprivation therapy (ADT) and non-PCa controls. A secondary aim was to compare differences in the prevalence of cognitive impairment. DESIGN: This cross-sectional study compared 70 ADT-treated men with PCa aged 50-85 years to non-ADT-treated men (n=52) and non-PCa controls (n=70). SETTING: University clinical exercise laboratory. INTERVENTIONS: Nil. PRIMARY AND SECONDARY OUTCOME MEASURES: Standardised assessments were conducted for cognition (learning, memory, attention, processing speed and executive function), muscle strength (grip strength and leg press), fitness (400 m walk), gait speed (4 m walk) and dual-tasking mobility (timed-up-and-go with a cognitive task). RESULTS: ADT-treated men showed stronger associations between fitness and executive function and task switching relative to controls (both: p≤0.03). For both PCa groups (independent of ADT use), poorer dual-task mobility was more strongly associated with decreased psychomotor attention (both: p≤0.027) and global cognitive function (both: p≤0.031) compared with non-PCa controls. The overall prevalence of cognitive impairment was low (4%-13%) and did not differ between the groups. CONCLUSIONS: The presence of PCa, with or without ADT treatment, did not increase the risk of cognitive impairment relative to non-PCa controls, yet did alter the associations between physical fitness and some measures of functional performance with certain cognitive domains. This highlights the importance of men with PCa maintaining fitness and functional capacity to optimise cognitive health. TRIAL REGISTRATION NUMBER: This study was registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12614000317695).

Exercise and Nutritional Approaches to Combat Cancer-Related Bone and Muscle Loss.

PURPOSE OF REVIEW: The aim of this narrative review is to summarise recent literature on the effects of exercise and nutrition interventions alone or in combination on muscle and bone loss in people with cancer. RECENT FINDINGS: There is emerging evidence to support the inclusion of targeted exercise and nutrition strategies to counter loss of muscle and bone associated with cancer treatments. Although research in this field is advancing, the optimal exercise and nutrition prescription to combat cancer-related bone and muscle loss remain unknown. This review identifies specific components of nutrition and exercise interventions that are promising although require further exploration through studies designed to determine the effect on muscle and bone. A focused research effort is required to elucidate the full potential of exercise and nutrition intervention for people with cancer at risk of bone and muscle loss.