The role of bone in energy metabolism: A focus on osteocalcin.

Understanding the mechanisms involved in whole body glucose regulation is key for the discovery of new treatments for type 2 diabetes (T2D). Historically, glucose regulation was largely focused on responses to insulin and glucagon. Impacts of incretin-based therapies, and importance of muscle mass, are also highly relevant. Recently, bone was recognized as an endocrine organ, with several bone proteins, known as osteokines, implicated in glucose metabolism through their effects on the liver, skeletal muscle, and adipose tissue. Research efforts mostly focused on osteocalcin (OC) as a leading example. This review will provide an overview on this role of bone by discussing bone turnover markers (BTMs), the receptor activator of nuclear factor kB ligand (RANKL), osteoprotegerin (OPG), sclerostin (SCL) and lipocalin 2 (LCN2), with a focus on OC. Since 2007, some, but not all, research using mostly OC genetically modified animal models suggested undercarboxylated (uc) OC acts as a hormone involved in energy metabolism. Most data generated from in vivo, ex vivo and in vitro models, indicate that exogenous ucOC administration improves whole-body and skeletal muscle glucose metabolism. Although data in humans are generally supportive, findings are often discordant likely due to methodological differences and observational nature of that research. Overall, evidence supports the concept that bone-derived factors are involved in energy metabolism, some having beneficial effects (ucOC, OPG) others negative (RANKL, SCL), with the role of some (LCN2, other BTMs) remaining unclear. Whether the effect of osteokines on glucose regulation is clinically significant and of therapeutic value for people with insulin resistance and T2D remains to be confirmed.

Best practice in dementia health care: Key clinical practice pointers from a national conference and innovative opportunities for pharmacy practice.

OBJECTIVE: Sub-optimal care of people living with dementia has serious consequences for older populations. The 2021 Australian Royal Commission noted that a large proportion of older adults in aged care live with dementia, yet there are limitations in the knowledge and understanding of staff who care for them. In the pursuit of educating pharmacists, physicians, allied health care professionals, researchers, academics, people living with dementia and their carers, and the public, who are facing the challenges of dementia management, the 'Best Practice in Dementia Health Care' conference was held on November 10, 2022 at Western Health (Sunshine Hospital, Melbourne, Australia). METHODS: Sixteen experts presented on the current practice and challenges associated with delivering best practice dementia health care to older Australians, often highlighting how medication-related challenges impacted on their area of practice. RESULTS: Presenters highlighted the importance of individualised medication management plans, considerations of culture and Indigenous communities, the role of technology, and the impact of exercise and the physical environment on care of people living with dementia. Key clinical practice messages from each expert presenter fit into four main topics: 'navigating complexities of medication management'; 'enhancing wellbeing'; 'supportive settings and environments'; and 'programs and services improving care'. CONCLUSIONS: Pharmacists are crucial members of allied health care teams. They have the necessary medication and comorbidity expertise to review medication regimens, liaise with all health care providers, and provide holistic, pharmacological and non-pharmacological patient education. Towards providing best practice dementia health care, pharmacists can contribute in several ways, such as providing health practitioner education to increase understanding about medications and how they can impact on allied health practice, to ensure that medications are prescribed appropriately and safely. Further, pharmacists can make available resources to ensure people living with dementia receive culturally safe and appropriate care, while advocating for greater understanding of the history and experiences of people living with dementia to ensure care aligns with their day-to-day routines. Finally, pharmacists can provide peer-support to other health care professionals and care staff to ensure optimal management of behavioural and psychological symptoms of dementia. The information and insights shared at the conference can serve as a valuable resource for pharmacists and other health care professionals and researchers working to improve the lives of those living with dementia.

Physical activity and depression symptoms in people with osteoarthritis-related pain: A cross-sectional study.

Osteoarthritis is a leading cause of chronic pain and is associated with high rates of depression. Physical activity reduces depression symptoms and pain levels. It remains unknown if physical activity is associated with lower symptoms of depression irrespective of pain levels in individuals with osteoarthritis. We explored whether pain mediated or moderated the relationship between levels of physical activity engagement and depression symptoms. Individuals with osteoarthritis who were waiting for an orthopaedic consultation at a public hospital in Melbourne, Australia, were recruited. Data collected on pain levels, physical activity engagement and depression symptoms. Descriptive statistics were used to summarise participant characteristics. Moderation and mediation analyses were used to establish the impact of pain on the relationship between physical activity and depression, after adjusting for demographic and joint specific characteristics. The results indicated that the inverse association between physical activity and depression depended on the level of pain, such that the association was stronger in people with greater pain. The mediation results confirm that participating in physical activity is indirectly, inversely associated with symptoms of depression through lower levels of pain. The highest levels of pain were associated with the most potential benefit in terms of reduction in symptoms of depression from engaging in physical activity. Physical activity may be particularly important to manage depression symptoms in people with greater osteoarthritis-related pain as patients with the highest pain may have the greatest benefits.

Resistance training and combined resistance and aerobic training as a treatment of depression and anxiety symptoms in young people: A systematic review and meta-analysis.

AIM: To determine the treatment effect of resistance training in reducing symptoms of anxiety and depression in young people. METHODS: We searched MEDLINE, PsychINFO, and PubMed for articles published in English from January 1980 to September 2023 for randomized controlled trials (RCT) that included at least 4 weeks of resistance training, with participants aged 26 years or younger with clinically elevated anxiety and depression symptoms. A random-effects meta-analysis was used to calculate a pooled effect size of resistance training pre-and post-intervention compared to control groups. The quality of evidence was assessed using the Cochrane risk-of-bias 2 (RoB 2) and Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) criteria. RESULTS: Ten RCTs involving 376 participants (209 females and 127 males) across educational, clinical, and community based setting were eligible for inclusion in the analysis. Resistance training was associated with a significant reduction in depressive (Hedge's g = -1.06, 95% CI -1.61 to -0.51, p < .001) and anxiety (Hedge's g = -1.02, 95% CI -1.50 to -0.54, p < .001) symptoms. Substantial heterogeneity was observed in the analysis of depression symptoms (I2 = 79%) and anxiety symptoms (I2 = 66%). Six trials had a low risk of bias, four trials showed some concerns. The GRADE analysis demonstrated a high level of certainty for depressive symptoms and a moderate level for anxiety symptoms. CONCLUSION: Resistance training is an effective intervention in reducing depression and anxiety symptoms in young people, delivered across a range of settings. Future trials exploring the effect resistance training interventions with long-term follow up are warranted to understand the outcomes.

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.

Development of a Digital Health Intervention to Support Patients on a Waitlist for Orthopedic Specialist Care: Co-Design Study.

BACKGROUND: The demand for orthopedic specialist consultations for patients with osteoarthritis in public hospitals is high and continues to grow. Lengthy waiting times are increasingly affecting patients from low socioeconomic and culturally and linguistically diverse backgrounds who are more likely to rely on public health care. OBJECTIVE: This study aimed to co-design a digital health intervention for patients with OA who are waiting for an orthopedic specialist consultation at a public health service, which is located in local government areas (LGAs) of identified social and economic disadvantage. METHODS: The stakeholders involved in the co-design process included the research team; end users (patients); clinicians; academic experts; senior hospital staff; and a research, design, and development agency. The iterative co-design process comprised several key phases, including the collation and refinement of evidence-based information by the research team, with assistance from academic experts. Structured interviews with 16 clinicians (female: n=10, 63%; male: n=6, 38%) and 11 end users (age: mean 64.3, SD 7.2 y; female: n=7, 64%; male: n=4, 36%) of 1-hour duration were completed to understand the requirements for the intervention. Weekly workshops were held with key stakeholders throughout development. A different cohort of 15 end users (age: mean 61.5, SD 9.7 y; female: n=12, 80%; male: n=3, 20%) examined the feasibility of the study during a 2-week testing period. The System Usability Scale was used as the primary measure of intervention feasibility. RESULTS: Overall, 7 content modules were developed and refined over several iterations. Key themes highlighted in the clinician and end user interviews were the diverse characteristics of patients, the hierarchical structure with which patients view health practitioners, the importance of delivering information in multiple formats (written, audio, and visual), and access to patient-centered information as early as possible in the health care journey. All content was translated into Vietnamese, the most widely spoken language following English in the local government areas included in this study. Patients with hip and knee osteoarthritis from culturally and linguistically diverse backgrounds tested the feasibility of the intervention. A mean System Usability Scale score of 82.7 (SD 16) was recorded for the intervention, placing its usability in the excellent category. CONCLUSIONS: Through the co-design process, we developed an evidence-based, holistic, and patient-centered digital health intervention. The intervention was specifically designed to be used by patients from diverse backgrounds, including those with low health, digital, and written literacy levels. The effectiveness of the intervention in improving the physical and mental health of patients will be determined by a high-quality randomized controlled trial.

Detecting the vitamin D receptor (VDR) protein in mouse and human skeletal muscle: Strain-specific, species-specific and inter-individual variation.

Vitamin D, and its receptor (VDR), play roles in muscle development/function, however, VDR detection in muscle has been controversial. Using different sample preparation methods and antibodies, we examined differences in muscle VDR protein abundance between two mouse strains and between mice and humans. The mouse D-6 VDR antibody was not reliable for detecting VDR in mouse muscle, but was suitable for human muscle, while the rabbit D2K6W antibody was valid for mouse and human muscle. VDR protein was generally lower in muscles from C57 B l/6 than FVB/N mice and was higher in human than mouse muscle. Two putative VDR bands were detected in human muscle, possibly representing VDR isoforms/splice variants, with marked inter-individual differences. This study provides new information on detecting VDR in muscle and on inter-mouse strain and inter-human individual differences in VDR expression. These findings may have implications for future pre-clinical and clinical studies and prompt further investigation to confirm possible VDR isoforms in human muscle.

Relationship between VO2peak, VO2 Recovery Kinetics, and Muscle Function in Older Adults.

INTRODUCTION: The efficiency of the cardiovascular system to recover following an exercise bout is measured by oxygen (VO2) recovery kinetics. In older adults with a chronic disease, a higher aerobic capacity (VO2peak) and faster VO2 recovery kinetics are associated with higher muscle strength and physical capacity. Yet, this relationship in healthy older adults remains unclear. The aim of this cross-sectional study was to determine whether a higher VO2peak and faster VO2 recovery kinetics are associated with higher muscle strength and physical performance in healthy community-dwelling older adults. METHODS: Thirty-five healthy older adults (female 25/male 10, mean age 73 ± 6 years) performed a graded exercise test on a cycle ergometer. VO2peak and VO2 recovery kinetics were assessed through gas exchange analysis. Muscle strength was determined by maximal leg (one-repetition maximum on leg press; 1RM) and grip strength, and physical performance was determined by the physical performance test (PPT) which assessed gait speed, stair ascent and descent, and timed up-and-go. RESULTS: Higher VO2peak was associated with stronger leg (r = 0.59, p < 0.001) and grip strength (r = 0.39, p < 0.03), but no relationship to PPT (p > 0.05). There was also no relationship between VO2 recovery kinetics and leg and grip strength or PPT (p > 0.05). CONCLUSION: In healthy community-dwelling older adults, VO2peak, but not VO2 recovery kinetics, is associated with muscle strength. This suggests that muscle strength may be an important factor related to aerobic capacity that could assist in identifying older adults who should be prioritized for resistance training.

Prevalence of diagnosable depression in patients awaiting orthopaedic specialist consultation: a cross-sectional analysis.

BACKGROUND: Musculoskeletal conditions, including osteoarthritis (OA), are a leading cause of disability and chronic pain, and are associated with high rates of comorbid depression. However, signs of depression are often masked by pain. The aim of this study was to determine the prevalence and severity of depression and pain in individuals awaiting specialist orthopaedic consultation. A secondary objective was to determine the relationship between pain and depression, irrespective of demographic factors and clinical diagnosis. METHODS: Cross-sectional analysis of individuals awaiting orthopaedic consultation at a public hospital in Melbourne, Australia. Relevant data were extracted from medical records and questionnaires. Descriptive statistics were used to summarise participant characteristics. The patient health questionnaire (PHQ-9) was used to assess depression and a numerical rating scale (NRS) was used to assess pain severity. Multiple linear regression analyses were used to establish the relationship between pain and depression. RESULTS: Nine hundred and eighty-six adults (mean ± standard deviation, age = 54.1 ± 15.7 years, 53.2% women) participated in the study. OA was present in 56% of the population and 34% of the entire population had moderate depression or greater, 19% of which met the criteria for major depressive disorder. Moderate-to-severe pain was present in 79% of individuals with OA and 55% of individuals with other musculoskeletal complaints. Pain was significantly associated with depression scores (ß = 0.84, adjusted R2 = 0.13, P < 0.001), and this relationship remained significant after accounting for gender, age, education and employment status, OA status, number of joints affected and waiting time (ß = 0.91, adjusted R2 = 0.19, P < 0.001). CONCLUSIONS: Depression affects one-third of individuals on an orthopaedic waitlist. A strong link between pain and depression in patients awaiting specialist orthopaedic consultation exists, indicating a need for an integrated approach in addressing pain management and depression to manage this complex and comorbid presentation.

Circulating lipocalin-2 and features of metabolic syndrome in community-dwelling older women: A cross-sectional study.

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.

Train Smart Study: protocol for a randomised trial investigating the role of exercise training dose on markers of brain health in sedentary middle-aged adults.

INTRODUCTION: Regular aerobic exercise is associated with improved cognitive function, implicating it as a strategy to reduce dementia risk. This is reinforced by the association between greater cardiorespiratory fitness and larger brain volume, superior cognitive performance and lower dementia risk. However, the optimal aerobic exercise dose, namely the intensity and mode of delivery, to improve brain health and lower dementia risk has received less attention. We aim to determine the effect of different doses of aerobic exercise training on markers of brain health in sedentary middle-aged adults, hypothesising that high-intensity interval training (HIIT) will be more beneficial than moderate-intensity continuous training (MICT). METHODS AND ANALYSIS: In this two-group parallel, open-label blinded endpoint randomised trial, 70 sedentary middle-aged (45-65 years) adults will be randomly allocated to one of two 12-week aerobic exercise training interventions matched for total exercise training volume: (1) MICT (n=35) or HIIT (n=35). Participants will perform ~50 min exercise training sessions, 3 days per week, for 12 weeks. The primary outcome will be measured as between-group difference in cardiorespiratory fitness (peak oxygen uptake) change from baseline to the end of training. Secondary outcomes include between-group differences in cognitive function and ultra-high field MRI (7T) measured markers of brain health (brain blood flow, cerebrovascular function, brain volume, white matter microstructural integrity and resting state functional brain activity) changes from baseline to the end of training. ETHICS AND DISSEMINATION: The Victoria University Human Research Ethics Committee (VUHREC) has approved this study (HRE20178), and all protocol modifications will be communicated to the relevant parties (eg, VUHREC, trial registry). Findings from this study will be disseminated via peer-review publications, conference presentations, clinical communications and both mainstream and social media. TRIAL REGISTRATION NUMBER: ANZCTR12621000144819.

Undercarboxylated osteocalcin and ibandronate combination ameliorates hindlimb immobilization-induced muscle wasting.

Immobilization leads to muscle wasting and insulin resistance, particularly during ageing. It has been suggested that undercarboxylated osteocalcin (ucOC) improves muscle mass and glucose metabolism. Bisphosphonates, an anti-osteoporosis treatment, might protect muscle wasting independent of ucOC. We hypothesize that the combination of ucOC and ibandronate (IBN) treatments has superior protective effects against immobilization-induced muscle wasting and insulin resistance than either treatment alone. C57BL/6J mice were hindlimb-immobilized for two weeks, with injections of vehicle, ucOC (90 ng/g daily) and/or IBN (2 µg/g weekly). Insulin/oral glucose tolerance tests (ITT/OGTT) were performed. Immediately after immobilization, muscles (extensor digitorum longus (EDL), soleus, tibialis anterior, gastrocnemius and quadriceps) were isolated and measured for muscle mass. Insulin-stimulated glucose uptake (EDL and soleus) was examined. Phosphorylation/expression of proteins in anabolic/catabolic pathways were examined in quadriceps. Primary human myotubes derived from older adult muscle biopsies were treated with ucOC and/or IBN, then signalling proteins were analysed. Combined treatment, but not individual treatments, significantly increased the muscle weight/body weight ratio in immobilized soleus (31.7%; P = 0.013) and quadriceps (20.0%; P = 0.0008) muscles, concomitant with elevated p-Akt (S473)/Akt ratio (P = 0.0047). Combined treatment also enhanced whole-body glucose tolerance (16.6%; P = 0.0011). In human myotubes, combined treatment stimulated greater activation of ERK1/2 (P = 0.0067 and 0.0072) and mTOR (P = 0.036), and led to a lesser expression of Fbx32 (P = 0.049) and MuRF1 (P = 0.048) than individual treatments. These findings suggest a potential therapeutic role for the ucOC and bisphosphonates combination in protecting against muscle wasting induced by immobilization and ageing. KEY POINTS: It has been suggested that undercarboxylated osteocalcin (ucOC) improves muscle mass and glucose metabolism. Bisphosphonates, an anti-osteoporosis treatment, might protect against muscle wasting independent of ucOC. The combination treatment of ucOC and ibandronate was shown to exert a greater therapeutic effect against immobilization-induced muscle wasting, and led to greater activation of anabolic pathway and less expression of catabolic signalling proteins in myotubes derived from older adults, compared with individual treatments. The combination treatment was found to improve whole-body glucose tolerance. Our findings suggest a potential therapeutic role for the ucOC and bisphosphonates combination in protecting against muscle wasting induced by immobilization and ageing.

The Effects of Acute High-Intensity Interval Exercise and Hyperinsulinemic-Euglycemic Clamp on Osteoglycin Levels in Young and Middle-Aged Men.

Osteoglycin (OGN) is a leucine-rich proteoglycan that has been implicated in the regulation of glucose in animal models. However, its relationship with glucose control in humans is unclear. We examined the effect of high-intensity interval exercise (HIIE) and hyperinsulinemic-euglycemic clamp on circulating levels of OGN as well as whether circulating OGN levels are associated with markers of glycemic control and cardio-metabolic health. Serum was analyzed for OGN (ELISA) levels from 9 middle-aged obese men (58.1 ± 2.2 years, body mass index [BMI] = 33.1 ± 1.4 kg∙m-2, mean ± SEM) and 9 young men (27.8 ± 1.6 years, BMI = 24.4 ± 0.08 kg∙m-2) who previously completed a study involving a euglycemic-hyperinsulinemic clamp at rest and after HIIE (4x4 minutes cycling at approximately 95% peak heart rate (HRpeak), interspersed with 2 minutes of active recovery). Blood pressure, body composition (dual-energy X-ray absorptiometry), and insulin sensitivity (hyperinsulinemic-euglycemic clamp) were assessed. Serum OGN was higher in the young cohort compared with the middle-aged cohort (65.2 ± 10.1 ng/mL versus 36.5 ± 4. 5 ng/mL, p ≤ 0.05). Serum OGN was unaffected by acute HIIE but decreased after the insulin clamp compared with baseline (~-27%, p = 0.01), post-exercise (~-35%, p = 0.01), and pre-clamp (~-32%, p = 0.02) time points, irrespective of age. At baseline, lower circulating OGN levels were associated with increased age, BMI, and fat mass, whereas higher OGN levels were related to lower fasting glucose. Higher OGN levels were associated with a higher glucose infusion rate. Exercise had a limited effect on circulating OGN. The mechanisms by which OGN affects glucose regulation should be explored in the future. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Higher bone remodeling biomarkers are related to a higher muscle function in older adults: Effects of acute exercise.

Bone and muscle are closely linked mechanically and biochemically. Bone hormones secreted during bone remodeling might be linked to muscle mass and strength maintenance. Exercise elicits high mechanical strain and is essential for bone health. However, the relationship between commonly used bone turnover markers (BTMs) and muscle function in community dwelling older adults remains unclear. It is also unknown how acute exercise with differing mechanical strain may affect BTMs, and whether baseline muscle function alters BTM responses differently. We tested the hypothesis that BTMs are associated with muscle function, and that acute exercise could change the circulating levels of BTMs. Thirty-five older adults (25 females/10 males, 72.8 ± 6.0 years) participated. Baseline assessments included body composition (DXA), handgrip strength and a physical performance test (PPT) (gait speed, timed-up-and-go [TUG], stair ascent/descent). Leg muscle quality (LMQ) and stair climb power (SCP) were calculated. Participants performed (randomized) 30 min aerobic (AE) (cycling 70%HRPeak) and resistance (RE) (leg press 70%RM, jumping) exercise. Serum ß-isomerized C-terminal telopeptides (ß-CTX), procollagen of type I propeptide (P1NP), total osteocalcin (t)OC and ucOC were assessed at baseline and post-exercise. Data were analyzed using linear mixed models and simple regressions, adjusted for sex. At baseline, higher muscle strength (LMQ, handgrip) was related to higher P1NP, higher SCP was related to higher P1NP and ß-CTX, and better physical performance (lower PPT) related to higher P1NP and ß-CTX (p < 0.05). Exercise, regardless of mode, decreased ß-CTX and tOC (all p < 0.05), while P1NP and ucOC remained unaltered. Higher baseline handgrip strength, SCP and LMQ was associated with lower post-exercise ß-CTX responses, and poorer baseline mobility (increased TUG time) was associated with higher post-exercise ß-CTX. Independently of exercise mode, acute exercise decreased ß-CTX and tOC. Our data suggest that in older adults at baseline, increased BTM levels were linked to better muscle function. Altogether, our data strengthens the evidence for bone-muscle interaction, however, mechanisms behind this specific component of bone-muscle crostalk remain unclear.

Prior aerobic exercise mitigates the decrease in serum osteoglycin and lipocalin-2 following high-glucose mixed-nutrient meal ingestion in young men.

Osteoglycin (OGN) and lipocalin-2 (LCN2) are hormones that can be secreted by bone and have been linked to glucose homeostasis in rodents. However, the endocrine role of these hormones in humans is contradictory and unclear. We examined the effects of exercise and meal ingestion on circulating serum OGN and LCN2 levels in eight healthy males {age: 28 [25, 30] years [median ± interquartile range (IQR)] and body mass index [BMI]: 24.3 [23.6, 25.5] kg/m2}. In a randomized crossover design, participants ingested a high-glucose (1.1 g glucose/kg body wt) mixed-nutrient meal (45% carbohydrate, 20% protein, and 35% fat) on a rest-control day and 3 and 24 h after aerobic cycling exercise (1 h at 70%-75% V̇o2peak). Acute aerobic exercise increased serum LCN2 levels immediately after exercise (∼61%), which remained elevated 3-h postexercise (∼55%). In contrast, serum OGN remained similar to baseline levels throughout the 3-h postexercise recovery period. The ingestion of a high-glucose mixed-nutrient meal led to a decrease in serum OGN at 90-min (approximately -17%) and 120-min postprandial (approximately -44%), and a decrease in LCN2 at 120-min postprandial (approximately -26%). Compared with the control meal, prior exercise elevated serum OGN and LCN2 levels at 120-min postprandial when the meal was ingested 3-h (OGN: ∼74% and LCN2: ∼68%) and 24-h postexercise (OGN: ∼56% and LCN2: ∼16%). Acute exercise increases serum LCN2 and attenuates the postprandial decrease in OGN and LCN2 following high-glucose mixed-nutrient meal ingestion. The potential endocrine role of circulating OGN and LCN2 in humans warrants further investigation.NEW & NOTEWORTHY We provide novel evidence that OGN and LCN2 decrease 120 min after ingesting a high-glucose mixed-nutrient meal in healthy adults. Acute aerobic exercise increases circulating LCN2 for up to 3-h postexercise, whereas circulating OGN remains similar to baseline. Despite differing postexercise responses, postprandial LCN2 and OGN are elevated when the high-glucose meal is ingested 3-h and 24-h postexercise. Findings support that OGN and LCN2 are dynamically linked to energy homeostasis in humans.

Bone Turnover Markers Including Undercarboxylated Osteocalcin Are Associated With Mortality Risk in Older Men.

Osteocalcin in its undercarboxylated form (ucOC) may influence diabetes risk; however, its relationship with all-cause and cause-specific mortality is unclear. Whether other bone turnover markers (BTMs) are associated with mortality risk differently from ucOC also remains uncertain. Our aim was to determine associations of serum ucOC with all-cause and cause-specific mortality and compare these with the corresponding associations of serum total osteocalcin (TOC), procollagen type I N-propeptide (PINP), and collagen type 1 C-terminal cross-linked telopeptide (CTX) in older men. We conducted a prospective cohort study of 3871 community-dwelling men, aged 77.0 ± 3.6 years at baseline, followed for a median of 12.3 years. Exposure variables were ucOC, TOC, PINP, and CTX concentrations assayed in serum. Outcomes were incidence of all deaths and deaths due to cardiovascular disease (CVD) or cancer, ascertained using death registry data. Cox regression analyses adjusted for cardiovascular risk factors and prevalent CVD and for prevalent cancer in analyses of cancer-related mortality. Higher concentrations of ucOC, PINP, and CTX were associated with all-cause mortality (hazard ratio [HR] per 1 standard deviation increase: ucOC 1.12, 95% confidence interval [CI] 1.06-1.18, p < 0.001; PINP HR = 1.06, 95% CI 1.01-1.11, p = 0.009; CTX HR = 1.13, 95% CI 1.08-1.19, p < 0.001), but TOC was not associated. Similar results were found after excluding men with an incident fracture during follow-up. Higher ucOC and CTX were associated with CVD mortality (ucOC HR per 1 SD increase 1.13, 95% CI 1.05-1.22, p = 0.001; CTX HR = 1.12, 95% CI 1.04-1.20, p = 0.003), but this result was not significant in competing risks analysis. Higher CTX was also associated with cancer mortality (HR = 1.12, 95% CI 1.01-1.23, p = 0.024). In conclusion, in older men, higher bone turnover, assessed by BTMs including ucOC, is a biomarker for all-cause mortality risk. Undercarboxylated osteocalcin was a more informative biomarker for this outcome than TOC. Higher CTX was associated with all-cause and cancer-related mortality. Further evaluation of causality and potential underlying mechanisms is warranted. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Progressive Resistance Training for Concomitant Increases in Muscle Strength and Bone Mineral Density in Older Adults: A Systematic Review and Meta-Analysis.

BACKGROUND: Older adults experience considerable muscle and bone loss that are closely interconnected. The efficacy of progressive resistance training programs to concurrently reverse/slow the age-related decline in muscle strength and bone mineral density (BMD) in older adults remains unclear. OBJECTIVES: We aimed to quantify concomitant changes in lower-body muscle strength and BMD in older adults following a progressive resistance training program and to determine how these changes are influenced by mode (resistance only vs. combined resistance and weight-bearing exercises), frequency, volume, load, and program length. METHODS: MEDLINE/PubMed and Embase databases were searched for articles published in English before 1 June, 2021. Randomized controlled trials reporting changes in leg press or knee extension one repetition maximum and femur/hip or lumbar spine BMD following progressive resistance training in men and/or women ≥ 65 years of age were included. A random-effects meta-analysis and meta-regression determined the effects of resistance training and the individual training characteristics on the percent change (∆%) in muscle strength (standardized mean difference) and BMD (mean difference). The quality of the evidence was assessed using the Cochrane risk-of-bias tool (version 2.0) and Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) criteria. RESULTS: Seven hundred and eighty studies were identified and 14 were included. Progressive resistance training increased muscle strength (∆ standardized mean difference = 1.1%; 95% confidence interval 0.73, 1.47; p ≤ 0.001) and femur/hip BMD (∆ mean difference = 2.77%; 95% confidence interval 0.44, 5.10; p = 0.02), but not BMD of the lumbar spine (∆ mean difference = 1.60%; 95% confidence interval - 1.44, 4.63; p = 0.30). The certainty for improvement was greater for muscle strength compared with BMD, evidenced by less heterogeneity (I2 = 78.1% vs 98.6%) and a higher overall quality of evidence. No training characteristic significantly affected both outcomes (p > 0.05), although concomitant increases in strength and BMD were favored by higher training frequencies, increases in strength were favored by resistance only and higher volumes, and increases in BMD were favored by combined resistance plus weight-bearing exercises, lower volumes, and higher loads. CONCLUSIONS: Progressive resistance training programs concomitantly increase lower-limb muscle strength and femur/hip bone mineral density in older adults, with greater certainty for strength improvement. Thus, to maximize the efficacy of progressive resistance training programs to concurrently prevent muscle and bone loss in older adults, it is recommended to incorporate training characteristics more likely to improve BMD.

Digital self-management interventions for osteoarthritis: a systematic scoping review of intervention characteristics, adherence and attrition.

BACKGROUND: Osteoarthritis (OA) is a chronic, progressive condition that can be effectively managed via conservative treatments including exercise, weight management and education. Offering these treatments contemporaneously and digitally may increase adherence and engagement due to the flexibility and cost-effectiveness of digital program delivery. The objective of this review was to summarise the characteristics of current digital self-management interventions for individuals with OA and synthesise adherence and attrition outcomes. METHODS: Electronic databases were searched for randomised controlled trials utilising digital self-management interventions in individuals with OA. Two reviewers independently screened the search results and extracted data relating to study characteristics, intervention characteristics, and adherence and dropout rates. RESULTS: Eleven studies were included in this review. Intervention length ranged from 6 weeks to 9 months. All interventions were designed for individuals with OA and mostwere multi-component and were constructed around physical activity. The reporting of intervention adherence varied greatly between studies and limited the ability to form conclusions regarding the impact of intervention characteristics. However, of the seven studies that quantified adherence, six reported adherence > 70%. Seven of the included studies reported attrition rates < 20%, with contact and support from researchers not appearing to influence adherence or attrition. CONCLUSIONS: Holistic digital interventions designed for a targeted condition are a promising approach for promoting high adherence and reducing attrition. Future studies should explore how adherence of digital interventions compares to face-to-face interventions and determine potential influencers of adherence.

Sarcopenia definition: Does it really matter? Implications for resistance training.

The loss of muscle mass, strength and function, known as sarcopenia, is common in older adults, and is associated with falls, fractures, cardiometabolic diseases, and lower quality of life. Sarcopenia can also occur secondarily to chronic diseases. Recently, sarcopenia was recognized as a disease with an International Classification of Disease (ICD) code, yet, at least five definitions for its clinical identification exist. Most definitions include three themes: low muscle mass, strength and physical performance. However, the definitions vary by the number of themes needed to diagnose sarcopenia and, within each theme various parameters and cut-off levels exist. The lack of consensus on what constitutes a diagnosis can create confusion and hesitation in sarcopenia diagnosis. Currently, no pharmacological treatment exists for sarcopenia. Resistance training (RT) is safe and effective to improve muscle mass, strength and physical performance in older adults and clinical populations. Based on current guidelines, whether an individual is defined as "sarcopenic", or not, does not change the way RT is prescribed. Here, we present evidence and the inconsistencies in sarcopenia definitions and recommend that focus should be on optimizing ways to prescribe RT and increase long-term adherence, rather than on slight modifications to sarcopenia definitions.