ORCID Profile
0000-0001-8126-0637
Current Organisations
Research Institute of the McGill University Health Centre
,
McGill University Health Centre
,
McGill University
,
Jewish General Hospital
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Publisher: Elsevier BV
Date: 10-2020
Publisher: BMJ
Date: 02-2018
DOI: 10.1136/BMJOPEN-2017-019381
Abstract: There is now substantial evidence of a social gradient in bone health. Social stressors, related to socioeconomic status, are suggested to produce an inflammatory response marked by increased levels of proinflammatory cytokines. Here we focus on the particular role in the years before the achievement of peak bone mass, encompassing childhood, adolescence and young adulthood. An examination of such associations will help explain how social factors such as occupation, level of education and income may affect later-life bone disorders. This paper presents the protocol for a systematic review of existing literature regarding associations between socioeconomic factors and proinflammatory cytokines in those aged 6–30 years. We will conduct a systematic search of PubMed, OVID and CINAHL databases to identify articles that examine associations between socioeconomic factors and levels of proinflammatory cytokines, known to influence bone health, during childhood, adolescence or young adulthood. The findings of this review have implications for the equitable development of peak bone mass regardless of socioeconomic factors. Two independent reviewers will determine the eligibility of studies according to predetermined criteria, and studies will be assessed for methodological quality using a published scoring system. Should statistical heterogeneity be non-significant, we will conduct a meta-analysis however, if heterogeneity prevent numerical syntheses, we will undertake a best-evidence analysis to determine whether socioeconomic differences exist in the levels of proinflammatory cytokines from childhood through to young adulthood. This study will be a systematic review of published data, and thus ethics approval is not required. In addition to peer-reviewed publication, these findings will be presented at professional conferences in national and international arenas.
Publisher: Wiley
Date: 03-2017
DOI: 10.1111/AJAG.12408
Abstract: Evidence regarding the efficacy and dosing of vitamin D on fall and fracture prevention, with or without calcium, is characterised by uncertainty. A panel of experts was organised at the First Australasian Conference on Sarcopenia and Frailty in Melbourne, Australia, in November 2016 to provide an interpretation of the current evidence and to give their opinions regarding the supplementation of vitamin D in three hypothetical cases. The authors conclude that (i) target serum 25(OH)D concentration should be 50 to 60 nmol/L year round, with a conservative upper limit <100 nmol/L (ii) change in serum concentrations at any given dose is highly variable among in iduals (iii) dosing interval may need to be <2 months to have a continuous benefit (iv) a loading dose can raise levels to target quickly, but there is no evidence yet that this has any positive effect on falls or fracture outcomes and (v) a maintenance dose of 1000 IU/day, or given as an equivalent dose weekly or monthly, is sufficient for most in iduals.
Publisher: Elsevier BV
Date: 03-2021
Publisher: Elsevier BV
Date: 09-2013
DOI: 10.1016/J.JAMDA.2013.05.015
Abstract: The overall effect of exercise on falls and fracture prevention in long term care facilities remains controversial. In this study, we aimed to analyze the impact and the characteristics of the most effective physical exercise regime to prevent falls and fractures in this particular setting. Our search looked for randomized controlled trials published in English language between January 1974 and June 2012 in electronic databases including MEDLINE, EMBASE, PubMed, Cochrane Central Register of Controlled Trials, Physiotherapy Evidence Database, Allied and Complementary Medicine, and Occupational Therapy Seeker that specifically tested the effect of exercise on falls and/or fractures in long term care residents. Two investigators independently extracted data and assessed study quality. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was applied throughout the systematic review and meta-analysis. Twelve studies were selected that included 1292 participants. Most of the participants were women (68%) with a mean age of 83.9 ± 9 years. The intervention period was between 3 and 24 months, and the most commonly performed intervention were balance and resistance training exercises. Meta-analysis showed that exercise has a preventive effect on falls (risk ratio [RR] = 0.77, 95% confidence interval [CI], 0.64-0.92 I(2) = 72.18, P < .001). This effect was stronger when mixing several types of exercises (RR = 0.71, 95% CI, 0.55-0.90 I(2) = 72.07, P < .001), for at least 1-3 months (RR = 0.65, 95% CI, 0.43-0.98 I(2) = 61.821 P < .001) or for more than 6 months (RR = 0.70, 95% CI, 0.56-0.87 I(2) = 68.407 P < .001), with a frequency of at least 2-3 times per week (RR = 0.74, 95% CI, 0.60-0.91 I(2) = 68.092 P < .001). Physical exercise did not show any effect on fracture prevention (RR = 0.57, 95% CI, 0.21-1.57 I(2) = 48.805). Combined, frequent and long-term exercise programs are effective to prevent falls in long term care facilities. No effect of exercise on fracture prevention was observed in this population.
Publisher: Elsevier BV
Date: 11-2023
Publisher: Wiley
Date: 03-2017
DOI: 10.1111/AJAG.12407
Publisher: The Endocrine Society
Date: 30-11-2021
Abstract: Osteoglycin (OGN) is a proteoglycan released from bone and muscle which has been associated with markers of metabolic health. However, it is not clear whether the levels of circulating OGN change throughout the adult lifespan or if they are associated with clinical metabolic markers or fitness. We aimed to identify the levels of circulating OGN across the lifespan and to further explore the relationship between OGN and aerobic capacity as well as OGN’s association with glucose and HOMA-IR. 107 in iduals (46 males and 61 females) aged 21-87 years were included in the study. Serum OGN levels, aerobic capacity (VO2peak), glucose, and homeostatic model assessment for insulin resistance (HOMA-IR) were assessed. T-tests were used to compare participant characteristics between sexes. Regression analyses were performed to assess the relationship between OGN and age, and OGN and fitness and metabolic markers. OGN displayed a nonlinear, weak “U-shaped” relationship with age across both sexes. Men had higher levels of OGN than women across the lifespan (β = 0.23, P = .03). Age and sex explained 16% of the variance in OGN (adjusted R2 = 0.16 P & .001). Higher OGN was associated with higher VO2peak (β = 0.02, P = .001) however, those aged & showed a stronger positive relationship than those aged & . A higher OGN level was associated with a higher circulating glucose level (β = 0.17, P & .01). No association was observed between OGN and HOMA-IR. OGN was characterized by a U-shaped curve across the lifespan which was similar between sexes. Those with a higher aerobic capacity or higher glucose concentration had higher OGN levels. Our data suggest an association between OGN and aerobic fitness and glucose regulation. Future studies should focus on exploring the potential of OGN as a biomarker for chronic disease.
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.BONE.2019.06.016
Abstract: Lipotoxicity is defined as cellular toxicity observed in the presence of an abnormal accumulation of fat and adipocyte-derived factors in non-fat tissues. Palmitic acid (PA), an abundant fatty acid in the bone marrow and particularly in osteoporotic bones, affects osteoblastogenesis and osteoblast function, decreasing their survival through induction of apoptosis and dysfunctional autophagy. In this study, we hypothesized that PA also has a lipotoxic effect on osteocytes in vitro. Initially, we tested the effect of PA on osteocyte-derived factors DKK1, sclerostin and RANKL. Then, we tested whether PA affects survival and causes apoptosis in osteocytes. Subsequently, we investigated the effect of PA on autophagy by detecting the membrane component LC3-II (Western blot) and staining it and lysosomes with Lysotracker Red dye. PA decreases RANKL, DKK1 and sclerostin expression in osteocytes. In addition, we found that PA induces apoptosis and reduces osteocyte survival. PA also caused autophagy failure identified by a significant increase in LC3-II and a reduced number of autophagosomes/lysosomes in the cytoplasm. In addition to the effects of PA on RANKL, DKK1 and sclerostin expression, which could have significant deleterious impact on bone cell coupling and bone turnover, PA also induced apoptosis and reduced autophagy in osteocytes. Considering that apoptosis and cell dysfunction are two common changes occurring in the osteocytes of osteoporotic bone, our findings suggest that PA could play a role in the pathogenesis of the disease. Suppression of these effects could bring new potential targets for therapeutic interventions in the future.
Publisher: Springer Science and Business Media LLC
Date: 03-07-2012
DOI: 10.1007/S12603-018-1113-6
Abstract: Globally there are several operational definitions for sarcopenia, complicating clinical and research applications. The objective of the Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR) Task Force on Diagnostic Criteria for Sarcopenia was to reach consensus on the operational definition of sarcopenia for regional use by clinicians and researchers. A four-Phase modified Delphi process was undertaken in which 24 in iduals with expertise or a recognised interest in sarcopenia from different fields across Australia and New Zealand were invited to be Task Force members. An initial face-to-face meeting was held in Adelaide, South Australia, in November 2017, followed by two subsequent online Phases conducted by electronic surveys. A final Phase was used to approve the final statements. Responses were analysed using a pre-specified strategy. The level of agreement required for consensus was 80%. In Phase 2, 94.1% of Task Force respondents voted in favour of adopting an existing operational definition of sarcopenia. In Phase 3, 94.4% of respondents voted in favour of adopting the European Working Group on Sarcopenia in Older People (EWGSOP) definition as the operational definition for sarcopenia in Australia and New Zealand. With consensus achieved, the ANZSSFR will adopt, promote and validate the EWGSOP operational definition of sarcopenia for use by clinicians and researchers in Australia and New Zealand.
Publisher: Springer Science and Business Media LLC
Date: 22-01-2016
Publisher: Elsevier BV
Date: 02-2021
Publisher: Springer Science and Business Media LLC
Date: 10-07-2019
DOI: 10.1007/S00223-019-00582-5
Abstract: Osteosarcopenia is defined as the concomitant occurrence of osteoporosis and sarcopenia. Current lack of consensus on sarcopenia definitions, combined with the low sensitivity and specificity of screening methodologies, has resulted in varying prevalences of sarcopenia, and consequently osteosarcopenia diagnosis. Previous research indicates that mid-thigh is a potential surrogate region for the assessment of bone, muscle, and fat mass in a single, efficient and low-radiation dual x-ray absorptiometry (DXA) scan. We hypothesized that muscle and bone mass measurements in the mid-thigh region can be used to evaluate bone and muscle health and function. A retrospective study was conducted on community-dwelling older subjects (> 65 y.o., n = 260) who were at risk of falls and fractures. Mid-thigh and mid-calf bone, lean muscle, and fat masses, as well as their association with muscle function, falls, and fractures were compared against conventional measures (hip/spine bone, appendicular lean, and gynoid/android fat masses). Mid-thigh bone, lean, and fat masses showed strong correlation with conventional measures. Mid-thigh lean mass showed similar associations with grip strength, gait speed, and timed up and go (TUG) test as appendicular lean mass. Appendicular, mid-thigh and mid-calf lean masses corrected for body mass index (BMI) showed stronger associations than when corrected for height
Publisher: Wiley
Date: 17-08-2020
DOI: 10.1002/JBMR.4125
Publisher: Springer Science and Business Media LLC
Date: 24-05-2022
Publisher: Springer Science and Business Media LLC
Date: 21-07-2022
DOI: 10.1007/S40520-022-02190-0
Abstract: Preclinical studies have shown a therapeutic role of the mechanistic/mammalian target of rapamycin complex 1 (mTORC1) inhibition with rapamycin and its analogues (rapalogues) on several age-related musculoskeletal disorders (MSKD). However, the applicability to humans of these findings is unknown. To assess the efficacy of rapalogues on age-related MSKD in humans. We conducted a systematic review according to the PRISMA guidelines. MEDLINE, EMBase, EMCare, and Cochrane Central Registry of Controlled Trials were searched for original studies examining the effects of rapalogues on outcomes linked to the age-related MSKD in humans. This review is registered in the PROSPERO database (University of New York registration number CRD42020208167). Fourteen studies met the inclusion criteria and were analyzed. The effect of rapamycin and other rapalogues, including everolimus and temsirolimus, on bone, muscle and joints have been evaluated in humans however, considerable variability concerning the subjects’ age, inclusion criteria, and drug administration protocols was identified. In bone, the use of rapamycin is associated with a decrease in bone resorption markers dependent on osteoclastic activity. In muscle, rapamycin and rapalogues are associated with a reduction in muscle protein synthesis in response to exercise. In the context of rheumatoid arthritis, rapamycin and rapalogues have been associated with clinical improvement and a decrease in inflammatory activity. Although there are studies that have evaluated the effect of rapamycin and rapalogues on MSKD in humans, the evidence supporting its use is still incipient, and the clinical implication of these results on the development of osteoporosis, sarcopenia, or osteosarcopenia has not been studied, opening an interesting field for future research.
Publisher: Springer Science and Business Media LLC
Date: 21-05-2020
Publisher: Oxford University Press (OUP)
Date: 18-06-2019
Abstract: Bone marrow fat infiltration is one of the hallmarks of aging and osteoporotic bones. Marrow adipocytes produce substantial amounts of palmitic acid (PA). PA is toxic to bone-forming osteoblasts in vitro, affecting their differentiation, function, and survival. Since rapamycin (RAP)-induced inhibition of target of rapamycin complex 1 (mTORC1) activates autophagy and prevents apoptosis, we hypothesized that RAP may preserve osteoblast viability and reduce PA-induced lipotoxicity. Normal human osteoblasts were incubated with RAP in the presence of a lipotoxic concentration of PA or vehicle for 24 and 48 hours. Expression of LC3 protein levels and the phosphorylation of the direct mTORC1 target p70S6K1-T389 were quantified by Western blot. Lysosomes and autophagosomes were studied using confocal fluorescence imaging, lysotracker, and live-cell imaging. RAP reduced PA-induced apoptosis. In addition, PA-induced autophagosome formation increased substantially over the time-course, an effect that was significantly regulated by the presence of RAP in the media. In addition, LC3I/II ratios were higher in PA-induced cells with RAP whereas p70S6K1-T389 were lower in PA and RAP together. In summary, this study highlights the role of the RAP-sensitive mTORC1 pathway in normal human osteoblasts under lipotoxic conditions. RAP-associated therapies could, potentially, be targeted for specific roles in osteoporosis and aging bone.
Publisher: Impact Journals, LLC
Date: 03-01-2020
Publisher: Wiley
Date: 17-10-2012
DOI: 10.1111/J.1741-6612.2012.00620.X
Abstract: Despite the increasingly ageing population, teaching geriatric medicine at medical schools is a challenge due to the particularities of this subspecialty and the lack of student interest in this subject. We assessed a blended system that combines e-learning and person-to-person interaction. Our program offered the students a hands-on learning experience based on self-reflection, access to technology, interactive learning, frequent interaction with the multidisciplinary team, more exposure to patients, and regular feedback. Our results indicate that the students appreciate this system as a rich and effective learning experience demonstrated by their positive feedback and by their significant improvement in knowledge assessed at the end of their rotation. Implementing an interactive blended system is a beneficial approach to teaching geriatric medicine in medical schools and to motivating medical students' interest in this important medical subspecialty.
Publisher: Oxford University Press (OUP)
Date: 15-12-2021
Abstract: 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 in idual 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). 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. 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. These findings support further investigation into the use of Cr:Cyc as a muscle biomarker to help clinicians identify in iduals at risk of falls for early inclusion into evidence-based primary prevention programs targeting improvements to diet and exercise.
Publisher: Research Square Platform LLC
Date: 17-10-2022
DOI: 10.21203/RS.3.RS-2160180/V1
Abstract: Circulating osteoprogenitors (COP) is a population of cells in the peripheral circulation that possess functional and phenotypical characteristics of multipotent stromal cells (MSCs). While there is functional overlap, it is not known how COP cells are related to bone marrow (BM)-derived MSCs (BM-MSCs) and other better characterized stromal progenitor populations such as adipose-derived stromal cells (ASCs). This study compares COP cells to BM-MSCs and ASCs through detailed transcriptomic and proteomic analyses. COP cells have a distinct gene and protein expression pattern to BM-MSCs and ASCs, with a significantly stronger immune footprint, likely owing to their hematopoietic lineage. However, they also have a similar pattern of expression BM-MSCs and ASCs, in genes and proteins in progenitor cell differentiation and proliferation pathways. This study shows COP cells to be a unique but functionally similar population to BM-MSCs and ASCs, sharing their proliferation and differentiation capacity, but with a strong immune phenotype, with potential for translational regenerative medicine strategies.
Publisher: Research Square Platform LLC
Date: 18-10-2022
DOI: 10.21203/RS.3.RS-2160180/V2
Abstract: Circulating osteoprogenitors (COP) are a population of cells in the peripheral circulation that possess functional and phenotypical characteristics of multipotent stromal cells (MSCs). These cells can differentiate into adipocyte, chondrocyte, myocyte, and osteoblast lineages. Considering that COP cells are isolated from peripheral blood, this population has a strong potential to become an abundant, accessible, and replenishable source of MSCs with multiple potential clinical applications for the repair and regeneration of acute and chronically damaged tissues. However, in order to fully test and develop their use in clinical settings, a comprehensive functional characterization of COP cells is still required. This study fully characterized COP cells by comparing them to bone marrow-derived MSCs (BM-MSCs) and adipose-derived MSCs (ASCs) through detailed transcriptomic and proteomic analyses. COP cells have a distinct gene and protein expression pattern to BM-MSCs and ASCs, with a significantly stronger immune footprint, likely owing to their hematopoietic lineage. In addition, regarding progenitor cell differentiation and proliferation pathways, COP cells have a similar pattern of expression to BM-MSCs and ASCs. In summary, this study shows COP cells to be a unique but functionally similar population to BM-MSCs and ASCs, sharing their proliferation and differentiation capacity, thus presenting an accessible source of MSCs with strong potential for translational regenerative medicine strategies.
Publisher: Oxford University Press (OUP)
Date: 20-07-2021
DOI: 10.1093/IBD/IZAB174
Abstract: Osteoporosis is a common extraintestinal manifestation of inflammatory bowel disease (IBD). However, studies have been scarce, mainly because of the lack of an appropriate animal model of colitis-associated bone loss. In this study, we aimed to decipher skeletal manifestations in the Winnie mouse model of spontaneous chronic colitis, which carries a MUC2 gene mutation and closely replicates ulcerative colitis. In our study, Winnie mice, prior to the colitis onset at 6 weeks old and progression at 14 and 24 weeks old, were compared with age-matched C57BL/6 controls. We studied several possible mechanisms involved in colitis-associated bone loss. We assessed for bone quality (eg, microcomputed tomography [micro-CT], static and dynamic histomorphometry, 3-point bending, and ex vivo bone marrow analysis) and associated mechanisms (eg, electrochemical recordings for gut-derived serotonin levels, real-time polymerase chain reaction [qRT-PCR], double immunofluorescence microscopy, intestinal inflammation levels by lipocalin-2 assay, serum levels of calcium, phosphorus, and vitamin D) from Winnie (6–24 weeks) and age-matched C57BL6 mice. Deterioration in trabecular and cortical bone microarchitecture, reductions in bone formation, mineral apposition rate, bone volume/total volume, osteoid volume/bone surface, and bone strength were observed in Winnie mice compared with controls. Decreased osteoblast and increased osteoclast numbers were prominent in Winnie mice compared with controls. Upregulation of 5-HTR1B gene and increased association of FOXO1 with ATF4 complex were identified as associated mechanisms concomitant to overt inflammation and high levels of gut-derived serotonin in 14-week and 24-week Winnie mice. Skeletal phenotype of the Winnie mouse model of spontaneous chronic colitis closely represents manifestations of IBD-associated osteoporosis/osteopenia. The onset and progression of intestinal inflammation are associated with increased gut-derived serotonin level, increased bone resorption, and decreased bone formation.
Publisher: Wiley
Date: 08-12-2023
DOI: 10.1111/AJAG.13164
Abstract: To develop guidelines, informed by health‐care consumer values and preferences, for sarcopenia prevention, assessment and management for use by clinicians and researchers in Australia and New Zealand. A three‐phase Consumer Expert Delphi process was undertaken between July 2020 and August 2021. Consumer experts included adults with lived experience of sarcopenia or health‐care utilisation. Phase 1 involved a structured meeting of the Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR) Sarcopenia Diagnosis and Management Task Force and consumer representatives from which the Phase 2 survey was developed. In Phase 2, consumers from Australia and New Zealand were surveyed online with opinions sought on sarcopenia outcome priorities, consultation preferences and interventions. Findings were confirmed and disseminated in Phase 3. Descriptive statistical analyses were performed. Twenty‐four consumers (mean ± standard deviation age 67.5 ± 12.8 years, 18 women) participated in Phase 2. Ten (42%) identified as being interested in sarcopenia, 7 (29%) were health‐care consumers and 6 (25%) self‐reported having/believing they have sarcopenia. Consumers identified physical performance, living circumstances, morale, quality of life and social connectedness as the most important outcomes related to sarcopenia. Consumers either had no preference (46%) or preferred their doctor (40%) to diagnose sarcopenia and preferred to undergo assessments at least yearly (54%). For prevention and treatment, 46% of consumers preferred resistance exercise, 2–3 times per week (54%). Consumer preferences reported in this study can inform the implementation of sarcopenia guidelines into clinical practice at local, state and national levels across Australia and New Zealand.
Publisher: Springer International Publishing
Date: 2019
Publisher: Elsevier BV
Date: 09-2016
Publisher: Wiley
Date: 14-10-2020
DOI: 10.1002/JBMR.4181
Publisher: Springer Science and Business Media LLC
Date: 14-04-2023
Publisher: Oxford University Press (OUP)
Date: 09-2022
Abstract: falls and fall-related injuries are common in older adults, have negative effects on functional independence and quality of life and are associated with increased morbidity, mortality and health related costs. Current guidelines are inconsistent, with no up-to-date, globally applicable ones present. to create a set of evidence- and expert consensus-based falls prevention and management recommendations applicable to older adults for use by healthcare and other professionals that consider: (i) a person-centred approach that includes the perspectives of older adults with lived experience, caregivers and other stakeholders (ii) gaps in previous guidelines (iii) recent developments in e-health and (iv) implementation across locations with limited access to resources such as low- and middle-income countries. a steering committee and a worldwide multidisciplinary group of experts and stakeholders, including older adults, were assembled. Geriatrics and gerontological societies were represented. Using a modified Delphi process, recommendations from 11 topic-specific working groups (WGs), 10 ad-hoc WGs and a WG dealing with the perspectives of older adults were reviewed and refined. The final recommendations were determined by voting. all older adults should be advised on falls prevention and physical activity. Opportunistic case finding for falls risk is recommended for community-dwelling older adults. Those considered at high risk should be offered a comprehensive multifactorial falls risk assessment with a view to co-design and implement personalised multidomain interventions. Other recommendations cover details of assessment and intervention components and combinations, and recommendations for specific settings and populations. the core set of recommendations provided will require flexible implementation strategies that consider both local context and resources.
Publisher: Wiley
Date: 30-08-2020
DOI: 10.1002/JCSM.12600
Publisher: Wiley
Date: 22-03-2020
DOI: 10.1002/JCSM.12567
Publisher: Springer Science and Business Media LLC
Date: 11-03-2020
Publisher: Springer Science and Business Media LLC
Date: 16-06-2021
Publisher: Impact Journals, LLC
Date: 23-06-2020
Publisher: Springer Science and Business Media LLC
Date: 21-08-2018
DOI: 10.1007/S00198-018-4671-X
Abstract: These data present associations between socioeconomic status (SES), different types of childhood maltreatment (CM) history and family dysfunction, and arthritis in men and women across a wide age range. Arthritis was less likely among those with higher SES, regardless of CM history. CM has been associated with increased risk of adult-onset arthritis however, little is known about whether socioeconomic status moderates arthritis risk in those with CM history. We investigated arthritis across education, income, and race/ethnicity and whether CM moderated associations between SES and arthritis. Data were drawn from Wave 2 (2004-2005) of the nationally representative (USA) National Epidemiological Survey on Alcohol and Related Conditions (NESARC, n = 34,563 aged ≥ 20 years). Self-reported CM history included physical abuse, sexual abuse, emotional abuse, emotional neglect, physical neglect, and exposure to intimate partner violence (IPV). We used descriptive statistics and logistic regression to determine relationships between SES, CM, and arthritis. Interaction terms were used to test if CM moderated relationships between SES and arthritis. Arthritis prevalence was 21.1% (n = 3093) among men and 30.1% (n = 6167) among women. In unadjusted analyses, women (p ≤ 0.001) and older age (both sexes, p ≤ 0.01) were associated with increased odds of arthritis. All CM types were associated with increased odds of arthritis, except exposure to IPV among women. In sex-stratified, age-adjusted analyses, lower education and income, family dysfunction, being Hispanic or Asian/Native Hawaiian/Pacific Islander, and ≥ 1 physical comorbidity were associated with increased odds of arthritis among those with and without CM: trends were similar for both sexes. In age-adjusted two-way interaction terms, CM did not moderate associations between SES and arthritis. Although CM was associated with arthritis, associations between SES and arthritis were not lified. Arthritis was less likely among those with higher SES, regardless of CM history.
Publisher: Oxford University Press (OUP)
Date: 10-07-2023
Abstract: Recent operational definitions of sarcopenia have not been replicated and compared in Australia and New Zealand (ANZ) populations. We aimed to identify sarcopenia measures that discriminate ANZ adults with slow walking speed (& .8 m/s) and determine the agreement between the Sarcopenia Definitions and Outcomes Consortium (SDOC) and revised European Working Group for Sarcopenia in Older People (EWGSOP2) operational definitions of sarcopenia. Eight studies comprising 8 100 ANZ community-dwelling adults (mean age ± standard deviation, 62.0 ± 14.4 years) with walking speed, grip strength (GR), and lean mass data were combined. Replicating the SDOC methodology, 15 candidate variables were included in sex-stratified classification and regression tree models and receiver operating characteristic curves on a pooled cohort with complete data to identify variables and cut points discriminating slow walking speed (& .8 m/s). Agreement and prevalence estimates were compared using Cohen’s Kappa (CK). Receiver operating characteristic curves identified GR as the strongest variable for discriminating slow from normal walking speed in women (GR & .50 kg, area under curve [AUC] = 0.68) and men (GR & .05 kg, AUC = 0.64). Near-perfect agreement was found between the derived ANZ cut points and SDOC cut points (CK 0.8–1.0). Sarcopenia prevalence ranged from 1.5% (EWGSOP2) to 37.2% (SDOC) in women and 1.0% (EWGSOP2) to 9.1% (SDOC) in men, with no agreement (CK & .2) between EWGSOP2 and SDOC. Grip strength is the primary discriminating characteristic for slow walking speed in ANZ women and men, consistent with findings from the SDOC. Sarcopenia Definitions and Outcomes Consortium and EWGSOP2 definitions showed no agreement suggesting these proposed definitions measure different characteristics and identify people with sarcopenia differently.
Publisher: MDPI AG
Date: 09-07-2019
DOI: 10.3390/NU11071551
Abstract: Understanding how changes in nutritional status influence musculoskeletal recovery after falling remains unclear. We explored associations between changes in nutritional status and musculoskeletal health in 106 community-dwelling older adults aged ≥65 years, who attended the Falls and Fractures Clinic at Sunshine Hospital in St Albans, Australia after falling. At baseline and after 6 months, in iduals were assessed for Mini Nutritional Assessment (MNA®), grip strength, gait speed, Timed Up and Go (TUG) test, Short Physical Performance Battery (SPPB), and bone turnover marker levels. Associations were examined using multiple linear regression, adjusted for baseline covariates and post-fall care plans. Over 6 months, the prevalence of malnutrition or risk thereof decreased from 29% to 15% using MNA /30. Specifically, 20 in iduals (19%) improved, 7 (7%) deteriorated, and 73 (69%) maintained nutritional status, including 65 (61%) who remained well-nourished and 8 (8%) who remained malnourished/at risk. A 1-point increase in MNA score over 6 months was associated with an increase of 0.20 points (95% confidence interval 0.10, 0.31, p 0.001) in SPPB score. Improvement in nutritional status was associated with improvement in physical performance, providing a basis for interventional studies to ascertain causality and evaluate nutritional models of care for post-fall functional recovery in older adults.
Publisher: SAGE Publications
Date: 2022
DOI: 10.1177/11786469211069951
Abstract: Frailty is defined as a syndrome of physiological decline in late life, characterized by marked vulnerability to adverse health outcomes. A robust biomarker for frailty is still lacking. Tryptophan (TRP) metabolism through the kynurenine pathway (KP) plays essential roles in aging, the musculoskeletal system, and physical performance. In this study, we quantified 7 KP metabolites, including kynurenine (KYN), kynurenine acid (KYNA), quinolinic acid (QUIN), picolinic acid (PIC), 3-hydroxykynurenine (3-HK), 3-hydroxyanthranilic acid (3-HAA), and anthranilic acid (AA) using ultra-high-performance liquid chromatography and gas chromatography-mass spectrometry in the serum of 85 participants (median age 75 65% female 28 non-frail, 29 pre-frail, and 28 frail) at the Nepean Osteoporosis and Frailty (NOF) Study. We looked at the association between TRP metabolites and physical performance, sarcopenia, and frailty. After adjusting for age and sex, our results showed that KYN and KYN/TRP were associated with higher interleukin (IL)-6 levels ( r = .324 and r = .390, respectively). KYNA and its ratios to other products (mainly KYNA/KYN, KYNA/QUIN, and KYNA/PIC) were associated with a lower likelihood of frailty by Fried’s criteria (OR 0.93 [0.88, 0.98], P = .009) and Rockwood index ( r = −.241, P = .028) as well as a lower likelihood of sarcopenia (OR 0.88 [0.78, 1.00], P = .049). QUIN and QUIN/KYN showed an association with increased IL-6 ( r = .293 and .204 respectively), higher likelihood of frailty (OR 1.02 [1.00, 1.04], P = .029 and OR 6.43 [2.23, 18.51], P = .001 respectively) and lower physical function ( r = −.205 and r = −.292). In conclusion, different TRP metabolites have various associations with physical performance, frailty, and sarcopenia. Defining the underlying mechanisms may permit the development and validation of new biomarkers and therapeutics for frailty and musculoskeletal conditions targeting specific metabolites of the TRP catabolic pathway.
Publisher: BMJ
Date: 05-2022
DOI: 10.1136/BMJOPEN-2021-059075
Abstract: Immunosenescence leads to increased morbidity and mortality associated with viral infections and weaker vaccine responses. This has been well documented for seasonal influenza and the current pandemic with SARS-CoV-2 (COVID-19), which disproportionately impact older adults, particularly those in residential aged care facilities. Inadequate nutrient intakes associated with impaired immunity, respiratory and muscle function are likely to augment the effects of immunosenescence. In this study, we test whether the impact of inadequate nutrition can be reversed using multi-nutrient supplementation, consequently enhancing vaccine responses, reducing the risk of viral infections and improving respiratory and muscle function. The Pomerium Study is a 3-month, single-blind, randomised, controlled trial testing the effects of two daily servings of an oral multi-nutrient supplement (330 kcal, 20 g protein, 1.5 g calcium 3-hydroxy-3-methylbutyrate monohydrate (CaHMB), 449 mg calcium, 500 IU vitamin D 3 and 25 vitamins and minerals) on the immune system and muscle and respiratory function of older adults in aged care in Melbourne, Australia. 160 older adults (≥75 years old) will be recruited from aged care facilities and randomised to treatment (multi-nutrient supplement) or control (usual care). The primary outcome is a change in T-cell subsets CD8 + and CD28null counts at months 1 and 3. Secondary outcomes measured at baseline and month 3 are multiple markers of immunosenescence (also at 1 month), body composition (bioimpedance), handgrip strength (dynamometer), physical function (short physical performance battery), respiratory function (spirometry) and quality of life (EQ-5D-5L). Incidence and complications of COVID-19 and/or viral infections (ie, hospitalisation, complications or death) will be recorded throughout the trial, including 3 months after supplementation is ceased. This study was approved by Melbourne Health Human Research Ethics Committee (Ref No. HREC/73985/MH-2021, ERM Ref No. RMH73985, Melbourne Health Site Ref No. 2021.115). Written informed consent will be obtained from participants. Results will be published in peer-reviewed journals and made available to key aged care stakeholders, including providers, residents, and government bodies. ACTRN12621000420842.
Publisher: SciELO Agencia Nacional de Investigacion y Desarrollo (ANID)
Date: 07-2017
DOI: 10.4067/S0034-98872017000700837
Abstract: Active commuting is associated with a lower risk for obesity in developed countries. To investigate the association between active commuting and obesity risk in Chile. Active commuting was measured using the Global Physical Activity Questionnaire (GPAQ v2) in 5,293 participants from the Chilean National Health Survey 2009-2010. Body mass index (BMI) and waist circumference (WC) were the study outcomes. The association between active commuting and obesity was investigated using linear and logistic regression analysis. Thirty four percent of responders [95% confidence intervals (CI): 32.6-35.1] were passive commuters. Active commuters had a lower BMI and WC than their passive counterparts. Thirty minutes increment in active commuting were associated with a -0.20 kg.m-2 lower BMI [95% CI: -0.33 to -0.07, p < 0.01] and a -076 cm lower WC [95% CI: -1.08 to -0.43, p 25 kg.m-2 was 0.93 [95% CI: 0.88 to 0.98, p = 0.01] per every 30 minutes' increment in active commuting, whereas the odds for central obesity was 0.87 [95% CI: 0.82 to 0.92, p < 0.01]. Active commuting is associated with a lower adiposity and lower risk for obesity in Chilean adults.
Publisher: Wiley
Date: 20-12-2018
DOI: 10.1111/JGS.15716
Abstract: Osteoporosis is the most common bone disease in humans. Older persons are at higher risk of osteoporotic fractures that also result in poor quality of life, disability, loss of independence, institutionalization, and higher mortality. Osteoporosis shares a distinct pathophysiologic relationship with sarcopenia, an age-related disease comprising declines in muscle mass, strength, or function. The combination of these two diseases is known as osteosarcopenia. Understanding the pathophysiology of osteosarcopenia, in addition to its diagnostic and therapeutic approaches, is key in providing older adults with the best falls and fractures prevention strategies. This review provides updated information on new discoveries on the combined pathophysiology of osteoporosis and sarcopenia that have led to the development of novel therapeutic approaches. New recommendations for the use of risk calculators and densitometry are also presented in this review as well as evidence on current and upcoming pharmacologic treatments to prevent falls and fractures in older persons. J Am Geriatr Soc 67:831-840, 2019.
Publisher: Elsevier BV
Date: 02-2020
DOI: 10.1016/J.JAMDA.2019.09.005
Abstract: We sought to examine the associations of osteosarcopenia with physical performance, balance, and falls and fractures in community-dwelling older adults. Additionally, we aimed to determine which clinical outcomes are associated with specific components of osteosarcopenia. Cross-sectional study. 253 participants (77% women aged 77.9 ± 0.42 years) who presented for a falls and fractures risk assessment in Melbourne, Australia. Participants were mobile, community-dwelling older adults (≥65 years) free of cognitive impairment. Body composition (via dual-energy x-ray absorptiometry), physical performance [via Timed Up and Go (TUG) and Short Physical Performance Battery (SPPB)], and balance [via Four-Square Step test (FSS) and posturography] were examined. Falls in the past year and fractures in the past 5 years were self-reported. Osteosarcopenia was defined as (1) low bone mineral density (BMD) [T score <-1 standard deviation (SD)] combined with sarcopenia and (2) osteoporosis (BMD T score ≤-2.5 SD) combined with severe sarcopenia. For sarcopenia, we employed the criteria of the European Working Group on Sarcopenia in Older People (EWGSOP1), the revised criteria (EWGSOP2), and that of the Foundation for the National Institutes for Health (FNIH). Kruskal-Wallis and logistic regression tests were used for statistical analysis. Osteosarcopenia was associated with worse SPPB, TUG, FSS, limit of stability, and falls and fractures history. Additionally, osteosarcopenia (using the severe sarcopenia classification) conferred an increased rate of falls [odds ratios (ORs) from 2.83 to 3.63 P < .05 for all] and fractures (ORs from 3.86 to 4.38 P < .05 for all) when employing the EWGSOP2 and FNIH definitions, respectively. Compared with the nonosteosarcopenic group, those with osteosarcopenia had greater impairment of physical performance and balance. The EWGSOP2 and FNIH criteria resulted in the strongest associations with physical performance and self-reported falls and fractures.
Publisher: Springer Science and Business Media LLC
Date: 04-03-2020
Publisher: Wiley
Date: 23-09-2020
DOI: 10.1111/AJAG.12816
Abstract: To examine associations of education and occupation with handgrip strength (HGS), lower limb strength (LLS) and appendicular lean mass (ALM). Measures of HGS, LLS and ALM (dual‐energy X‐ray absorptiometry) were ascertained at baseline in 1090 adults (50‐80 years, 51% women), ~3 and 5 years. Education and occupation were self‐reported, the latter categorised as high‐skilled white collar (HSWC), low‐skilled white collar (LSWC) or blue collar. Separate general estimating equations were performed. The highest education group had greater HGS than the middle (0.33 psi) and lowest (0.48 psi) education groups, and 0.34 kg greater ALM than the lowest education group. HGS was 0.46 psi greater for HSWC than LSWC groups. Compared to LSWC groups, LLS was 5.38 and 7.08 kg greater in HSWC and blue‐collar groups. Blue‐collar and HSWC groups each had ~ 0.60‐0.80kg greater ALM than LSWC. Progressive muscle loss can be prevented by targeted intervention thus, we suggest clinical attention be directed towards specific social groups.
Publisher: Springer Science and Business Media LLC
Date: 13-09-2021
Publisher: Wiley
Date: 14-05-2021
DOI: 10.1002/JCSM.12712
Abstract: Reference ranges for lean mass (LM) and fat mass (FM) are essential in identifying soft tissue disorders however, no such reference ranges exist for the most commonly used Hologic dual‐energy X‐ray absorptiometry (DXA) machine in Australia. Cross‐sectional study of community‐dwelling adults (aged 18–88 years) who underwent a Hologic DXA scan at one of three commercialized densitometry centres in Australia. Age‐specific and sex‐specific percentile curves were generated for LM [LM, appendicular lean mass (ALM), ALM adjusted for height squared (ALM/h 2 ), and ALM adjusted for body mass index (ALM/BMI)] and FM [FM, FM adjusted for height squared (FM/h 2 ), appendicular fat mass, and android and gynoid fat] parameters using the LMS statistical method. Cutpoints equivalent to T ‐scores of −1, −2, and −2.5 standard deviations below the young mean reference group (20–29 years) were also generated for LM parameters. A total of 15 479 community‐dwelling adults (54% men) with a median age of 33 years (interquartile range: 28, 42) were included. LM, ALM, and ALM/h 2 remained stable until age 50, after which these parameters started to decline in both sexes. Compared with age 50, median percentiles of LM, ALM, and ALM/h 2 declined by −5.9 kg, −3.7 kg, and −0.86 kg/m 2 in men and by −2.5 kg, −1.8 kg, and −0.10 kg/m 2 in women at age 70, respectively. Adjusting ALM for BMI (rather than height squared) resulted in different trends, with ALM/BMI decreasing from as early as age 20. Compared with age 20, median percentiles of ALM/BMI at age 40 declined by −0.10 kg/kg/m 2 in men and by −0.06 kg/kg/m 2 in women and at age 70, ALM/BMI declined by −0.25 kg/kg/m 2 in men and by −0.20 kg/kg/m 2 in women. Cutpoints equivalent to T ‐scores of −1, −2, and −2.5 standard deviations for ALM/BMI were 1.01, 0.86, and 0.77 kg/kg/m 2 in men and 0.70, 0.59, and 0.53 kg/kg/m 2 in women, respectively. All FM parameters progressively increased from age 20 and continued up until age 70. We developed reference ranges for LM and FM parameters from Hologic DXA machines in a large cohort of Australian adults, which will assist researchers and clinicians in identifying soft tissue disorders such as obesity, sarcopenia, and cachexia.
Publisher: Wiley
Date: 11-2018
DOI: 10.1111/IMJ.13655
Publisher: JMIR Publications Inc.
Date: 09-04-2021
DOI: 10.2196/18777
Abstract: Bone and muscle are closely linked anatomically, biochemically, and metabolically. Acute exercise affects both bone and muscle, implying a crosstalk between the two systems. However, how these two systems communicate is still largely unknown. We will explore the role of undercarboxylated osteocalcin (ucOC) in this crosstalk. ucOC is involved in glucose metabolism and has a potential role in muscle maintenance and metabolism. The proposed trial will determine if circulating ucOC levels in older adults at baseline and following acute exercise are associated with parameters of muscle function and if the ucOC response to exercise varies between older adults with low muscle quality and those with normal or high muscle quality. A total of 54 men and women aged 60 years or older with no history of diabetes and warfarin and vitamin K use will be recruited. Screening tests will be performed, including those for functional, anthropometric, and clinical presentation. On the basis of muscle quality, a combined equation of lean mass (leg appendicular skeletal muscle mass in kg) and strength (leg press one-repetition maximum), participants will be stratified into a high or low muscle function group and randomized into the controlled crossover acute intervention. Three visits will be performed approximately 7 days apart, and acute aerobic exercise, acute resistance exercise, and a control session (rest) will be completed in any order. Our primary outcome for this study is the effect of acute exercise on ucOC in older adults with low muscle function and those with high muscle function. The trial is active and ongoing. Recruitment began in February 2018, and 38 participants have completed the study as of May 26, 2019. This study will provide novel insights into bone and muscle crosstalk in older adults, potentially identifying new clinical biomarkers and mechanistic targets for drug treatments for sarcopenia and other related musculoskeletal conditions. Australia New Zealand Clinical Trials Registry ACTRN12618001756213 www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375925. DERR1-10.2196/18777
Publisher: Springer Science and Business Media LLC
Date: 25-07-2017
DOI: 10.1038/S41467-017-00108-3
Abstract: Bone mineral density is known to be a heritable, polygenic trait whereas genetic variants contributing to lean mass variation remain largely unknown. We estimated the shared SNP heritability and performed a bivariate GWAS meta-analysis of total-body lean mass (TB-LM) and total-body less head bone mineral density (TBLH-BMD) regions in 10,414 children. The estimated SNP heritability is 43% (95% CI: 34–52%) for TBLH-BMD, and 39% (95% CI: 30–48%) for TB-LM, with a shared genetic component of 43% (95% CI: 29–56%). We identify variants with pleiotropic effects in eight loci, including seven established bone mineral density loci: WNT4 , GALNT3 , MEPE , CPED1/WNT16 , TNFSF11 , RIN3 , and PPP6R3/LRP5 . Variants in the TOM1L2/SREBF1 locus exert opposing effects TB-LM and TBLH-BMD, and have a stronger association with the former trait. We show that SREBF1 is expressed in murine and human osteoblasts, as well as in human muscle tissue. This is the first bivariate GWAS meta-analysis to demonstrate genetic factors with pleiotropic effects on bone mineral density and lean mass.
Publisher: Hindawi Limited
Date: 28-04-2023
DOI: 10.1155/2023/2519128
Abstract: Introduction. Growth differentiation factor 15 (GDF-15) has been shown to be a metabolic and appetite regulator in diabetes mellitus (DM) and obesity. We aimed to investigate (i) the association between GDF-15 and DM with and without poor physical function independent of inflammation and (ii) the prediction model for poor physical function in prefrail older adults. Methods. A cross-sectional study of 108-prefrail participants ≥60 years recruited for multidomain interventions. Data was collected for demographics, cognition, function, frailty, nutrition, handgrip strength (HGS), short physical performance battery (SPPB), and gait speed. Serum concentrations of GDF-15, IL-6, and TNF-α were measured. GDF-15 was classified into tertiles (T1, T2, and T3), and its association was studied with DM and physical function (DM poor physical function, DM no poor physical function, no DM poor physical function, and no DM no poor physical function). Results. Compared with T1, participants in T3 were significantly older, had a lower education level, had almost three times higher prevalence of DM, slower gait speed, longer chair-stand time, and lower SPPB scores. On multivariate analysis, the odds of having both DM and poor physical performance compared to having no DM and no poor physical performance were significantly higher in GDF-15 T3 vs. GDF-15 T1 (aOR 9.7, 95% CI 1.4-67.7 p = 0.021 ), and the odds of having DM no poor physical function compared to having no DM and no poor physical performance were significantly higher in GDF-15 T2 (aOR 12.7, 95% CI 1.1-143.7 p = 0.040 ) independent of BMI, IL-6, TNF-α, nutrition, physical function, education, age, and gender. Conclusion. The association of GDF-15 with DM-associated poor physical function is independent of inflammation in prefrail older adults. Its causal-association link needs to be determined in longitudinal studies.
Publisher: Wiley
Date: 23-02-2021
DOI: 10.1111/JGS.17043
Abstract: Osteoporosis and sarcopenia are common in older adults. Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. Bone fractures can result in changes in posture, pain, the need for surgical repair and functional impairment. Sarcopenia is the progressive and generalized loss of skeletal muscle mass, strength and/or physical performance. Older adults with sarcopenia experience increased risk of frailty, disability, hospitalizations, mortality, and a reduced quality of life. In this narrative review we provide guidance regarding the prevention of both osteoporosis and sarcopenia, including interventions that prevent both conditions from occurring, recommended screening and treatment to prevent progression.
Publisher: Springer International Publishing
Date: 2020
DOI: 10.1007/164_2020_358
Publisher: The Journal of Frailty and Aging (JFA)
Date: 2017
DOI: 10.14283/JFA.2017.7
Abstract: Physical exercise is one of the most effective non-pharmacological interventions aimed to improve mobility and independence in older persons. The effect of physical exercise and the most effective type of exercise in frail older persons remain undefined. This systematic review examines the effectiveness of physical exercise on frail older persons. Seven databases were search for randomized control trials which assessed the effect of exercise on participants who were identified as being frail using specific and validated criteria. Nine articles were reviewed from eight studies, from which seven used a validated definition of frailty. Based on the articles analyzed in our systematic review, the evidence suggests that exercise has a positive effect on various measures used to determine frailty including cognition, physical functioning, and psychological wellbeing. Some studies revealed that exercise may prevent or delay the onset of frailty which can enhance quality of life in older adults. Despite the evidence for exercise interventions in frail older adults, it appears that there is no clear guidance regarding the most effective program variables. The reviewed studies were generally long in duration (≥6 months) with sessions lasting around 60 minutes performed three or more times per week, including multicomponent exercises. In conclusion, although exercise interventions appear to be effective in managing the various components of frailty and preventing/delaying the onset of frailty, the most effective exercise program in this population remains unidentified.
Publisher: Wiley
Date: 07-01-2019
DOI: 10.1002/JBMR.3640
Abstract: Osteoporosis and osteopenia are increasingly prevalent conditions among older adults. Not only do the fractures associated with poor bone health have significant health consequences for the in idual, but also their economic impact is placing increasing financial burden on governments and society. This study aimed to determine the direct economic cost of osteoporosis, osteopenia, and fractures among Australians aged 50 years and older in 2017. This study uses previous Australian data on the incidence and prevalence of osteoporosis and osteopenia together with recent Australian data on health service utilization after fracture to provide an estimate of the economic burden of osteoporosis. A bottom-up costing approach was used to determine the average direct health care and non-health care total costs of a fracture, as well as the average community health service costs of managing in iduals with osteoporosis or osteopenia. The total direct cost of osteoporosis in Australia in 2017 was estimated to be $3.44 billion (AUD 2017, USD 2.77 billion). Treatment of fractures accounted for 68% of total direct costs, and non-fracture management of osteoporosis accounted for 32%. Hip fractures accounted for the highest proportion (43%) of the total direct cost of fractures, although fractures at "other" sites accounted for 38.5%. Fractures among in iduals aged 70 years and older accounted for 74% of the direct costs (55% and 19% in women and men, respectively). Fracture costs in those with osteopenia accounted for 50% of direct fracture treatment costs. This up-to-date cost analysis estimated that costs in 2017 were three times higher than in 2007. These estimates will aid clinicians, policy makers, researchers, and health care organizations to acknowledge the economic importance of reducing osteoporosis-related fractures and associated costs. This provides a strong public health case to promote bone health that will assist in reducing future fracture-related costs. © 2018 American Society for Bone and Mineral Research.
Publisher: Wiley
Date: 15-04-2018
DOI: 10.1002/HPJA.60
Abstract: Exercising outdoors provide beneficial effect on mental and physical health for all ages. However, few older people exercise outdoors other than walking. While outdoor gyms have become increasingly common in Australia, limited outdoor exercise equipment specifically designed for older people is available in public spaces. We have set up and evaluated a unique purpose-built outdoor exercise park for older people in the community setting and demonstrated positive physical and wellbeing outcomes associated with the provision of this unique exercise mode and social program. This study is a reflective narrative describing this innovative exercise approach and reports challenges associated with establishment of the exercise park, conducting the randomised trial, strategies adopted to address these challenges and recommendations for future implementation of this approach in the community. Many challenges were encountered, including securing appropriate land to locate the exercise park, control of environmental factors for safety (non-slippery ground and equipment) as well as logistics in running the exercise program itself. Several adjustments in the equipment were also required to ensure safe use by older people. The inclusion of outdoor equipment for older people in public spaces or urban parks is important and careful consideration needs to be taken by local ublic authorities to provide access, amenities and safety for all as well as activities to suit all ages. SO WHAT?: Seniors' exercise parks can be installed in public places and may provide an enjoyable and effective approach to engage older in iduals in a more active and healthier lifestyle.
Publisher: Elsevier BV
Date: 06-2017
Publisher: Elsevier BV
Date: 2019
Publisher: BMJ
Date: 2018
DOI: 10.1136/BMJOPEN-2017-019088
Abstract: Sarcopenia (or loss of muscle mass and function) is a relatively new area within the field of musculoskeletal research and medicine. Investigating whether there is a social gradient, including occupation type and income level, of sarcopenia, as observed for other diseases, will contribute significantly to the limited evidence base for this disease. This new information may inform the prevention and management of sarcopenia and widen the evidence base to support existing and future health c aigns. We will conduct a systematic search of the databases PubMed, Ovid, CINAHL, Scopus and EMBASE to identify articles that investigate associations between social determinants of health and sarcopenia in adults aged 50 years and older. Eligibility of the selected studies will be determined by two independent reviewers. The methodological quality of eligible studies will be assessed according to predetermined criteria. Established statistical methods to identify and control for heterogeneity will be used, and where appropriate, we will conduct a meta-analysis. In the event that heterogeneity prevents numerical synthesis, a best evidence analysis will be employed. This systematic review protocol adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols reporting guidelines and will be registered with the International Prospective Register of Systematic Reviews (PROSPERO). This systematic review will use published data, thus ethical permissions will not be required. In addition to peer-reviewed publication, our results will be presented at (inter)national conferences relevant to the field of sarcopenia, ageing and/or musculoskeletal health and disseminated both electronically and in print. CRD42017072253.
Publisher: BMJ
Date: 12-2018
DOI: 10.1136/BMJOPEN-2018-023962
Abstract: Describe research methods used in priority-setting exercises for musculoskeletal conditions and synthesise the priorities identified. Scoping review. Studies that elicited the research priorities of patients/consumers, clinicians, researchers, policy-makers and/or funders for any musculoskeletal condition were included. We searched MEDLINE and EMBASE from inception to November 2017 and the James Lind Alliance top 10 priorities, Cochrane Priority Setting Methods Group, and Cochrane Musculoskeletal and Back Groups review priority lists. The reported methods and research topics/questions identified were extracted, and a descriptive synthesis conducted. Forty-nine articles fulfilled our inclusion criteria. Methodologies and stakeholders varied widely (26 included a mix of clinicians, consumers and others, 16 included only clinicians, 6 included only consumers or patients and in 1 participants were unclear). Only two (4%) reported any explicit inclusion criteria for priorities. We identified 294 broad research priorities from 37 articles and 246 specific research questions from 17 articles, although only four (24%) of the latter listed questions in an actionable format. Research priorities for osteoarthritis were identified most often (n=7), followed by rheumatoid arthritis (n=4), osteoporosis (n=4) and back pain (n=4). Nearly half of both broad and specific research priorities were focused on treatment interventions (n=116 and 111, respectively), while few were economic (n=8, 2.7% broad and n=1, 0.4% specific), implementation (n=6, 2% broad and n=4, 1.6% specific) or health services and systems research (n=15, 5.1% broad and n=9, 3.7% specific) priorities. While many research priority-setting studies in the musculoskeletal field have been performed, methodological limitations and lack of actionable research questions limit their usefulness. Future studies should ensure they conform to good priority-setting practice to ensure that the generated priorities are of maximum value. CRD42017059250.
Publisher: Springer Science and Business Media LLC
Date: 11-07-2019
Publisher: Informa UK Limited
Date: 02-2019
DOI: 10.2147/CIA.S168687
Publisher: Wiley
Date: 09-11-2023
DOI: 10.1002/JCSM.13115
Abstract: Sarcopenia is an age‐associated skeletal muscle condition characterized by low muscle mass, strength, and physical performance. There is no international consensus on a sarcopenia definition and no contemporaneous clinical and research guidelines specific to Australia and New Zealand. The Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR) Sarcopenia Diagnosis and Management Task Force aimed to develop consensus guidelines for sarcopenia prevention, assessment, management and research, informed by evidence, consumer opinion, and expert consensus, for use by health professionals and researchers in Australia and New Zealand. A four‐phase modified Delphi process involving topic experts and informed by consumers, was undertaken between July 2020 and August 2021. Phase 1 involved a structured meeting of 29 Task Force members and a systematic literature search from which the Phase 2 online survey was developed (Qualtrics). Topic experts responded to 18 statements, using 11‐point Likert scales with agreement threshold set a priori at %, and five multiple‐choice questions. Statements with moderate agreement (70%–80%) were revised and re‐introduced in Phase 3, and statements with low agreement ( %) were rejected. In Phase 3, topic experts responded to six revised statements and three additional questions, incorporating results from a parallel Consumer Expert Delphi study. Phase 4 involved finalization of consensus statements. Topic experts from Australia ( n = 62, 92.5%) and New Zealand ( n = 5, 7.5%) with a mean ± SD age of 45.7 ± 11.8 years participated in Phase 2 38 (56.7%) were women, 38 (56.7%) were health professionals and 27 (40.3%) were researchers/academics. In Phase 2, 15 of 18 (83.3%) statements on sarcopenia prevention, screening, assessment, management and future research were accepted with strong agreement. The strongest agreement related to encouraging a healthy lifestyle (100%) and offering tailored resistance training to people with sarcopenia (92.5%). Forty‐seven experts participated in Phase 3 5/6 (83.3%) revised statements on prevention, assessment and management were accepted with strong agreement. A majority of experts (87.9%) preferred the revised European Working Group for Sarcopenia in Older Persons (EWGSOP2) definition. Seventeen statements with strong agreement ( %) were confirmed by the Task Force in Phase 4. The ANZSSFR Task Force present 17 sarcopenia management and research recommendations for use by health professionals and researchers which includes the recommendation to adopt the EWGSOP2 sarcopenia definition in Australia and New Zealand. This rigorous Delphi process that combined evidence, consumer expert opinion and topic expert consensus can inform similar initiatives in countries/regions lacking consensus on sarcopenia.
Publisher: Springer Science and Business Media LLC
Date: 26-03-2018
DOI: 10.1007/S00223-018-0412-6
Abstract: Marrow (MAT) and subcutaneous (SAT) adipose tissues display different metabolic profiles and varying associations with aging, bone density, and fracture risk. Using a non-invasive imaging methodology, we aimed to investigate the associations between MAT, SAT, and visceral fat (VAT) with bone volume, bone remodeling markers, insulin resistance, and circulating inflammatory mediators in a population of older men. In this cross-sectional study, 96 healthy men (mean age 67 ± 5.5) were assessed for anthropometric parameters, body composition, serum biochemistry, and inflammatory panel. Using single-energy computed tomography images, MAT (in L2 and L3 and both hips), VAT, and SAT (at the level of L2-L3 and L4-L5) were measured employing Slice-O-Matic software (Tomovision), which enables specific tissue demarcation applying previously reported Hounsfield unit thresholds. MAT volume was similar in all anatomical sites and independent of BMI. In all femoral regions of interest (ROIs) there was a strong negative association between bone and MAT volumes (r = - 0.840 to - 0.972, p < 0.001), with location-dependent variations in the lumbar spine. Unlike VAT and SAT, no associations between MAT and serum glucose, inflammatory markers or insulin resistance indicators were found. Bone decline occurred without red marrow expansion thus lost bone was mainly (if not exclusively) replaced by MAT. In conclusion, strong inverse correlations between MAT and bone mass, which have been previously observed in women, were also confirmed in older men. However, MAT volume in all ROIs was interrelated and unlike women, mainly independent of VAT or SAT. The lack of strong association between MAT vs VAT/SAT, and its discordant associations with metabolic and inflammatory mediators provide further evidence on MAT's distinct attributes in older men.
Publisher: Elsevier BV
Date: 10-2021
DOI: 10.1016/J.TOX.2021.152960
Abstract: Picolinic acid (PIC) is a byproduct of tryptophan catabolism through the kynurenine pathway, with anabolic effects on bone in vivo and in vitro. Hence, PIC has been nominated as a possible candidate to treat and/or prevent osteoporosis. However, the effective dose and toxicity of PIC are not known yet. To test the effect of escalating and very high doses of oral PIC, male Sprague-Dawley rats were gavaged PIC: Group 1 (n = 3) received incremental doses of 125, 250 and 500 mg/kg/day PIC on days 1, 3 and 5. Group 2 (n = 3) received 500 mg/kg BID (8 h apart i.e. 1000 mg/kg/day) PIC on Day 1. Group 3 (n = 3) received 125 mg/kg/day PIC for seven consecutive days. Group 4 (n = 3) received 250 mg/kg/day PIC for seven consecutive days. Groups 1, 3 and 4 rats were euthanized on Day 8. Group 5 (n = 6) received 500 mg/kg/day PIC for two consecutive days and then once a week dose (Days 9, 16 and 23) of 500 mg/kg/dose PIC, until euthanasia (Day 30). Blood and cerebrospinal fluid (CSF) were s led at euthanasia, and tissues showing abnormalities at necropsy underwent histopathology evaluation. All rats displayed some degree of mild hypercalcemia and hyperkalemia. Rats receiving high doses (500 or 1000 mg/kg/day) of PIC died or were euthanized on humane grounds within the first week after showing clinical neurological signs, with animals later revealed to have brain necrosis and hemorrhage at histopathology. Rats receiving lower doses (125 or 250 mg/kg/day) of PIC completed treatment course without apparent clinical adverse events. In summary, very high doses of PIC (≥500 mg/kg/day) were vascular-neurotoxic. Possible future experiments must consider significantly lower doses.
Publisher: Springer Science and Business Media LLC
Date: 27-12-2018
DOI: 10.1007/S12603-018-1153-Y
Abstract: Beta-hydroxy-beta-methylbutyrate (HMB) has been shown to be effective and superior to other types of protein supplements to attenuate loss of muscle mass, strength and function, however, its benefits in sarcopenic and frail older people remain unclear. We seek to determine the effect of HMB on muscle mass, strength and function in older people with sarcopenia or frailty by reviewing results from available randomized controlled trials (RCTs). This review was registered at PROSPERO (University of York) with registration number CRD42018088462 and conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Using a pre-determined e-search strategy, we searched PubMed, Medline, EMBASE, CINAHL, LILACS, Web of Science, Cochrane and Scopus databases. Our inclusion criteria were RCTs that assessed the effect of HMB on muscle mass, strength and function in older people with sarcopenia and frailty aged ≥60 years. The main outcomes were lean body mass, handgrip, leg press strength, and Short Physical Performance Battery (SPPB) score. Three studies matched our eligibility criteria which enrolled 203 subjects through a variety of definitions of sarcopenia or frailty. Lean body mass increased and muscle strength and function were preserved following HMB supplementation. HMB improves lean muscle mass and preserves muscle strength and function in older people with sarcopenia or frailty.
Publisher: Human Kinetics
Date: 06-2023
Abstract: Background : The Exercise interveNtion outdoor proJect in the cOmmunitY (ENJOY) Seniors Exercise Park program uses specialized outdoor equipment and a physical activity program to engage older people in physical activity, with multiple health benefits. We determined the cost-effectiveness of the ENJOY program. Methods : The economic evaluation compared health care utilization costs 6 months prior to and 6 months post ENJOY program participation. Incremental cost-utility analysis for the primary aim (quality of life) and incremental cost-effectiveness analysis for the secondary aim (falls) were used. Analyses took a societal perspective inclusive of Australian government-funded health care and pharmaceuticals in addition to hospitalizations, community-based nursing and allied health, and community services. Productivity costs were also calculated. Results : Fifty participants (average age 72.8 y [SD 7.4] and 78.0% [n = 39/50] women) were included. Participation in the ENJOY program reduced health care costs in the 6 months following the program: preintervention, $9764.49 (SD $26,033.35) postintervention, $5179.30 (SD $3826.64) observed postintervention reduction −$4.585.20 (95% confidence interval, −$12,113.99 to $2943.59 P = .227) without compromising quality of life (mean difference [MD] 0.011 95% confidence interval, −0.034 to 0.056 P = .631) or increasing the likelihood of a fall (−0.5 95% confidence interval, 0.00 to −0.50 P = .160). The ENJOY intervention is likely cost-effective. Conclusions : Planning for shared community spaces should consider the benefits of a Seniors Exercise Park as part of the built environment.
Publisher: Wiley
Date: 03-12-2021
DOI: 10.1002/JBMR.4208
Abstract: Evidence from animal models suggests that undercarboxylated osteocalcin (ucOC) is involved in muscle mass maintenance and strength. In humans, the ucOC to total (t)OC ratio may be related to muscle strength and perhaps physical function and falls risk, but data are limited. We tested the hypothesis that ucOC and ucOC/tOC ratio are associated with muscle function (muscle strength and physical function) in older women and 15‐year falls‐related hospitalizations. Serum tOC and ucOC were assessed in 1261 older women (mean age 75.2 ± 2.7 years) forming the Perth Longitudinal Study of Aging Women (1998 to 2013). Timed‐up‐and‐go (TUG) and grip strength were assessed at baseline and at 5 years. Falls‐related hospitalizations (14.5‐year follow‐up) were captured by the Hospital Morbidity Data Collection, via the Western Australian Data Linkage System. At baseline, women with higher ucOC/tOC ratio (quartile 4) had slower TUG performance compared with quartile 1 (~0.68 seconds, p .01). Grip strength and 5‐year change of TUG and grip were not different ( p .05) between quartiles. Fear of falling limiting house, outdoor, and combined activities was significantly different across quartiles ( p .05). Higher ucOC/tOC was significantly associated with poorer TUG performance at baseline and 5‐year change in performance, increased walking aid use, and fear of falling (all p .05). Higher ucOC was related to lower grip strength at baseline ( p .05) but not 5‐year change in strength. Those with the highest ucOC/tOC had greater falls‐related hospitalizations (unadjusted log rank, p = .004) remaining significant after adjusting for key variables (hazard ratio [HR] = 1.31, 95% confidence interval [CI] 1.09–1.57, p = .004). We identified a large proportion of older women with high ucOC/tOC ratio who had reduced physical function, including its long‐term decline and increased risk of falls‐related hospitalizations. Early identification of women at higher risk can enable prevention and intervention strategies to occur, reducing risk for injurious falls. © 2020 American Society for Bone and Mineral Research (ASBMR)..
Publisher: Springer Science and Business Media LLC
Date: 15-07-2021
DOI: 10.1007/S11657-021-00981-Y
Abstract: Little is known about factors that lead to excess mortality post-fracture. This study demonstrated that 5-year mortality is lower in older adults who recovered to their pre-fracture health-related quality of life (HRQoL) at 12-months compared to those who did not recover. Our results highlight the importance of post-fracture interventions known to improve HRQoL. Fragility fractures lead to increased mortality and decreased health-related quality of life (HRQoL) in older adults, although whether an association exists between these outcomes remains uncertain. The aim of this study was to determine whether recovery of HRQoL 12-month post-fracture is associated with lower 5-year mortality. This data linkage study included 524 adults (mean age: 70.2 years 79.2% women) with fragility fracture (150 hip, 261 distal forearm, 61 vertebral, 52 humerus) from the Australian arm of the International Costs and Utilities Related to Osteoporotic fractures Study (AusICUROS). HRQoL was measured using the EQ-5D-3L and all-cause mortality post-fracture was ascertained from the Australian National Death Index (NDI). Cox proportional hazards models were used to assess the association between HRQoL recovery (vs. non-recovery) and all-cause mortality within 5 years. Overall, 279 participants (53.2%) recovered to their pre-fracture HRQoL at 12-month follow-up. There were 70 deaths (13.4%) during the 5-year post-fracture. Mortality rate was the highest in hip fracture participants (24.7%), followed by vertebral (16.4%), humeral (13.5%), and distal forearm fracture participants (6.1%). After adjustment for age, pre-fracture HRQoL, and fracture site, mortality risk was lower in participants who recovered to their pre-fracture HRQoL at 12-months compared to those who did not recover (HR = 0.56, 95% CI: 0.33-0.96, p = 0.034). This study provides evidence that HRQoL recovery post-fracture is associated with improved 5-year survival in older adults. The extent to whether current interventions known to improve HRQoL post-fracture could prevent some of these deaths is unknown.
Publisher: Wiley
Date: 04-09-2019
DOI: 10.1111/JGS.16165
Publisher: Elsevier BV
Date: 04-2021
Publisher: Springer Science and Business Media LLC
Date: 22-06-2021
DOI: 10.1186/S12889-021-11224-7
Abstract: The physical environment has been shown to have a positive effect on the promotion of physical activity of older people. Outdoor environments that incorporate specialised exercise equipment suitable for older people are uniquely placed to promote physical activity and social connectedness amongst older people. The ENJOY project included the installation of specialised outdoor exercise equipment (the Seniors Exercise Park) and the delivery of a physical and social activity program for older people as part of a prospective pre-post research design. The installation of the specialised equipment in public sites and an aged care facility was also aimed at increasing usage of the equipment by older people from the wider community and to increase physical and social activities. A conceptual framework for implementation and several engagement methods were utilised to guide the research and to support the participating partners throughout the project. This paper is a reflective narrative describing the collaborative process and approach utilised to engage local governments and community, and reports the challenges and the lessons learnt to inform future strategies for implementation. The conceptual framework for the implementation process that guided the conduct and delivery of the ENJOY project included the core elements of the Interactive Systems Framework and the ecologic framework. These models incorporate elements of research-to-practice and community-centred implementation to accommodate the unique perspectives of a range of stakeholders. Partner characteristics such as local governments’ structure and policy as well as community factors can impact on implementation. Partnership with local governments with effective communication, strategic planning and community and seniors engagement approaches are recommended for successful implementation. The lessons learnt can further assist public health research design around changes to the built environment to positively impact on older people’s physical activity levels. Trial registration number ACTRN12618001727235. Date of registration 19th October 2018, www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375979
Publisher: Wiley
Date: 17-10-2021
DOI: 10.1002/JBM4.10561
Abstract: Circulating osteo progenitor (COP) cells are a heterogeneous population of cells that circulate within the peripheral blood with characteristics of the bone marrow mesenchymal stem and progenitor pool. Little is known about the behavior of this cell population in humans. The aim of this study was to identify whether a relationship exists between COP cells (as a percentage of the peripheral blood monocytic cells) and musculoskeletal morphometry and to identify if COP have potential clinical utility as a biomarker for osteoporosis. We recruited 57 older adults (median age: 69 years IQR: 65, 75 years) living independently in the community and performed cross‐sectional analysis to identify associations between the percentage of COP cells and body composition parameters, and through receiver operating characteristic analysis, we evaluated their ability to act as a biomarker of osteoporosis. COP cells were moderately associated with whole‐body bone mineral density (BMD) ( r = 0.323, p = 0.014) and bone mineral content (BMC) ( r = 0.387, p = 0.003), neck of femur BMD ( r = 0.473, p 0.001), and BMC ( r = 0.461, p 0.001) as well as appendicular lean mass (ALM) ( p = 0.038) and male sex ( p = 0.044) in univariable analysis. In multivariable analysis controlling for age, gender, height, and weight, COP cells remained strongly associated with neck of femur BMD ( p = 0.001) and content ( p = 0.003). COP cells were also a good predictor of osteoporosis (dual‐energy X‐ray absorptiometry [DXA] T ‐score −2.5) at the neck of femur (cutoff: 0.4% sensitivity: 100% specificity 79%) and total body (cutoff: 0.35% sensitivity: 80% specificity: 81%). This study shows strong relationships between bone parameters and COP cell number and male sex. They also have potential as a biomarker of osteoporosis, which may provide a new tool for advanced detection and screening in clinical settings. Future larger evaluation studies should verify the cutoffs for biomarker use, and further explore the relationship between COP cells and muscle. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Publisher: Oxford University Press (OUP)
Date: 09-2022
Abstract: our aim was to assess the effectiveness of medication review and deprescribing interventions as a single intervention in falls prevention. systematic review and meta-analysis. Medline, Embase, Cochrane CENTRAL, PsycINFO until 28 March 2022. randomised controlled trials of older participants comparing any medication review or deprescribing intervention with usual care and reporting falls as an outcome. title/abstract and full-text screening by two reviewers. Cochrane Collaboration revised tool. results reported separately for different settings and sufficiently comparable studies meta-analysed. forty-nine heterogeneous studies were included. meta-analyses of medication reviews resulted in a risk ratio (RR) of 1.05 (95% confidence interval, 0.85–1.29, I2 = 0%, 3 studies(s)) for number of fallers, in an RR = 0.95 (0.70–1.27, I2 = 37%, 3 s) for number of injurious fallers and in a rate ratio (RaR) of 0.89 (0.69–1.14, I2 = 0%, 2 s) for injurious falls. meta-analyses assessing medication reviews resulted in an RR = 0.97 (0.74–1.28, I2 = 15%, 2 s) and in an RR = 0.50 (0.07–3.50, I2 = 72% %, 2 s) for number of fallers after and during admission, respectively. meta-analyses investigating medication reviews or deprescribing plans resulted in an RR = 0.86 (0.72–1.02, I2 = 0%, 5 s) for number of fallers and in an RaR = 0.93 (0.64–1.35, I2 = 92%, 7 s) for number of falls. the heterogeneity of the interventions precluded us to estimate the exact effect of medication review and deprescribing as a single intervention. For future studies, more comparability is warranted. These interventions should not be implemented as a stand-alone strategy in falls prevention but included in multimodal strategies due to the multifactorial nature of falls. PROSPERO registration number: CRD42020218231
Publisher: Oxford University Press (OUP)
Date: 23-08-2023
Abstract: Circulating osteoprogenitors (COP) are a population of cells in the peripheral circulation that possess functional and phenotypical characteristics of multipotent stromal cells (MSCs). This population has a solid potential to become an abundant, accessible, and replenishable source of MSCs with multiple potential clinical applications. However, a comprehensive functional characterization of COP cells is still required to test and fully develop their use in clinical settings. This study characterized COP cells by comparing them to bone marrow-derived MSCs (BM-MSCs) and adipose-derived MSCs (ASCs) through detailed transcriptomic and proteomic analyses. We demonstrate that COP cells have a distinct gene and protein expression pattern with a significantly stronger immune footprint, likely owing to their hematopoietic lineage. In addition, regarding progenitor cell differentiation and proliferation pathways, COP cells have a similar expression pattern to BM-MSCs and ASCs. COP cells are a unique but functionally similar population to BM-MSCs and ASCs, sharing their proliferation and differentiation capacity, thus presenting an accessible source of MSCs with strong potential for translational regenerative medicine strategies.
Publisher: Wiley
Date: 12-11-2020
DOI: 10.1002/JBMR.4204
Publisher: Springer Science and Business Media LLC
Date: 30-04-2020
Publisher: Springer Science and Business Media LLC
Date: 12-06-2020
Publisher: Elsevier BV
Date: 06-2018
DOI: 10.1016/J.MATURITAS.2018.04.003
Abstract: Sarcopenia is an age-related decline in skeletal muscle mass and function that results in disability and loss of independence. It affects up to 30% of older adults. Exercise (particularly progressive resistance training) and nutrition are key strategies in preventing and reversing declines in muscle mass, strength and power during ageing, but many sarcopenic older adults fail to meet recommended levels of both physical activity and dietary nutrient intake. Assistive technology (AT) describes devices or systems used to maintain or improve physical functioning. These may help sarcopenic older adults to maintain independence, and also to achieve adequate physical activity and nutrition. There is a paucity of research exploring the use of AT in sarcopenic patients, but there is evidence that AT, including walking aids, may reduce functional decline in other populations with disability. Newer technologies, such as interactive and virtual reality games, as well as wearable devices and smartphone applications, smart homes, 3D printed foods, exoskeletons and robotics, and neuromuscular electrical stimulation also hold promise for improving engagement in physical activity and nutrition behaviours to prevent further functional declines. While AT may be beneficial for sarcopenic patients, clinicians should be aware of its potential limitations. In particular, there are high rates of patient abandonment of AT, which may be minimised by appropriate training and monitoring of use. Clinicians should preferentially prescribe AT devices which promote physical activity. Further research is required in sarcopenic populations to identify strategies for effective use of current and emerging AT devices.
Publisher: Elsevier BV
Date: 2019
DOI: 10.1016/J.JAMDA.2018.10.016
Abstract: To investigate the relationship of 4 sarcopenia definitions with long-term all-cause mortality risk in older Australian women. Data from the Perth Longitudinal Study in Aging Women from 2003 to 2013 was examined in this prospective cohort study. The 4 sarcopenia definitions were the United States Foundation for the National Institutes of Health (FNIH), the European Working Group on Sarcopenia in Older People (EWGSOP), and adapted FNIH (AUS-POP In total, 903 community-dwelling older Australian women (baseline mean age 79.9 ± 2.6 years) with concurrent measures of muscle strength (grip strength), physical function (timed-up-and-go TUG) and appendicular lean mass (ALM) were included. Cox-proportional hazards modeling was used to examine the relationship between sarcopenia definitions and mortality over 5 and 9.5 years. Baseline prevalence of sarcopenia by the 4 definitions differed substantially [FNIH (9.4%), EWGSOP (24.1%), AUS-POP Unlike FNIH, the EWGSOP sarcopenia definition incorporating weak muscle strength and/or poor physical function was related to prognosis, as was the regionally adapted version of EWGSOP. Although sarcopenia definitions were not developed based on prognosis, this is an important consideration for globally standardizing the sarcopenia framework.
Publisher: Elsevier BV
Date: 03-2017
DOI: 10.1016/J.ARCHGER.2017.12.006
Abstract: To determine characteristics of sarcopenic obesity that are independently associated with bone health and balance in older adults. Cross-sectional study of 168 community-dwelling older adults (mean age 67.7 ± 8.4 years 55% women). Appendicular lean mass (ALM), whole-body areal BMD (aBMD) and body fat percentage were assessed by dual-energy X-ray absorptiometry. Peripheral quantitative computed tomography assessed muscle density and cortical volumetric BMD (vBMD), area, thickness, and strength-strain index (SSI) at 66% tibial length. Hand grip strength (dynamometry) and balance path length (computerised posturography) were assessed. Obesity was defined as high body fat percentage. Greater lower-leg muscle density was associated with lower balance path length in men (r = -0.36 P < .01) and women (r = -0.40 P = < .01). Obese participants by body fat percentage did not differ to non-obese on bone indices, although a trend towards lower cortical vBMD was observed in obese compared with non-obese men (1041.4 ± 39.8 vs 1058.8 ± 36.1 mg/cm Amongst components of sarcopenic obesity, higher ALM is a consistent independent predictor of better bone health. Low muscle density may also compromise bone health and balance. Interventions which improve muscle mass and composition may lower fracture risk in sarcopenic obesity.
Publisher: Springer Science and Business Media LLC
Date: 08-07-2021
DOI: 10.1007/S00198-021-06058-3
Abstract: In this study of 695 Australian older adults (aged ≥50 years), we found that men and women had a similar trajectory of health-related quality of life (HRQoL) recovery following fragility fracture at any skeletal site. These results provide us with critical knowledge that improves our understanding of health outcomes post-fracture. Mortality is higher in men than that in women following a fragility fracture, but it is unclear whether recovery of patient-reported outcomes such as health-related quality of life (HRQoL) differs between sexes. This study aimed to identify sex differences in HRQoL recovery 12 months post-fracture. Data were from the Australian arm of the International Costs and Utilities Related to Osteoporotic Fractures Study (AusICUROS). Participants recruited to AusICUROS were adults aged ≥50 years who sustained a fragility fracture. HRQoL was measured using the EQ-5D-3L at three time-points post-fracture: within 2 weeks (including pre-fracture recall) and at 4 and 12 months. Multivariate logistic regression analyses were undertaken, adjusting for confounders including age, education, income, and healthcare utilization post-fracture. Overall, 695 AusICUROS participants (536 women, 77.1%) were eligible for analysis with fractures at the hip (n = 150), distal forearm (n = 261), vertebrae (n = 61), humerus (n = 52), and other skeletal sites (n = 171). At the time of fracture, men were younger, reported a higher income, and were more likely to be employed, compared with women. For all fracture sites combined, there were no differences between men and women in recovery to pre-fracture HRQoL at 12-month follow-up (adjusted OR = 1.09 95% CI: 0.75-1.61). When stratified by fracture site, no significant sex differences were seen for hip (OR = 1.02 95% CI: 0.42-2.52), distal forearm (OR = 1.60 95% CI: 0.68-3.78), vertebral (OR = 2.28 95% CI: 0.61-8.48), humeral (OR = 1.62 95% CI: 0.16-9.99), and other fractures (OR = 1.00 95% CI: 0.44-2.26). Community-dwelling men and women who survived the 12 months following fragility fracture had a similar trajectory of HRQoL recovery at any skeletal site.
Publisher: Elsevier BV
Date: 03-2022
Publisher: Informa UK Limited
Date: 02-12-2019
Publisher: BMJ
Date: 07-2019
DOI: 10.1136/BMJOPEN-2018-027013
Abstract: Traditionally, the approach to fracture prevention has focused on increasing bone mineral density while typically lacking a combined clinical approach to falls prevention and vice versa. To resolve this gap, we implemented and evaluated a novel combined model of care to the assessment and prevention of osteoporosis and falls in the outpatients setting. Falls and Fractures Clinic (FFC) at Nepean Hospital (Penrith, NSW, Australia). Pre-effects and posteffects assessment of 106 community-dwelling older patients referred from the community. Previous falls and fractures were recorded. Clinical, functional and paraclinical evaluations were performed. A comprehensive multidisciplinary care plan was then tailored based on the presence of risk factors. Six-month follow-ups were performed assessing the incidence of falls and fractures, change in risk factors for falls and level of risk, with the recommended plan. We report that 97% of patients had a fall in the preceding 6 months, 47.6% of whom experienced a fracture from the fall. Furthermore, 64% of patients had a marked risk for falling by Physiological Profile Assessment (PPA), 90% had intermediate–high 10-year probability of fracture according to FRAX and 78% had sarcopenia. At 6-month follow-up, we observed more than an 80% reduction in falls and recurrent falls, and 50% reduction in fractures. In addition, 65% of patients had reduced PPA and a 57% reduction in 10-year fracture probability. In conclusion, we suggest that a multidisciplinary FFC can provide substantial reductions in falls and fractures for high-risk older people, even over a relatively short 6-month time period. The current model of service provision via traditional falls clinics could be significantly improved by encompassing fracture prevention within the multifactorial approach to interventions.
Publisher: Elsevier BV
Date: 12-2022
DOI: 10.1016/J.BONE.2022.116545
Abstract: 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%HR
Publisher: Elsevier BV
Date: 12-2021
Publisher: Cold Spring Harbor Laboratory
Date: 25-01-2022
DOI: 10.1101/2022.01.23.22269669
Abstract: Immunosenescence leads to increased morbidity and mortality associated with viral infections and weaker vaccine responses. This has been well documented for seasonal influenza and the current pandemic with Sars-Cov2, which disproportionately impact older adults, particularly those in residential aged care facilities. Inadequate nutrient intake associated with impaired immunity, respiratory and muscle function are likely to augment the effects of immunosenescence. In this study, we test whether the effects of inadequate nutrition can be reversed by multi-nutrient supplementation, consequently enhancing vaccine responses, reducing the risk of viral infections, and improving respiratory and muscle function. The Pomerium Study is a 12-week, single-blinded, randomised, placebo-controlled trial testing the effects of two daily servings of an oral multi-nutrient supplement (330 kcal, 20g protein, 1.2g CaHMB, 449mg calcium, 520IU vitamin D 3 , and 25 vitamins and minerals) on the immune system and muscle and respiratory function of older adults in aged-care in Melbourne, Australia. 160 older adults (≥75 years old) will be recruited from aged-care facilities and randomised to treatment (multi-nutrient supplement) or control (usual care). Primary outcome is the change in T-cell subsets CD8+ and CD28null counts at 4 and 12 weeks post-intervention. Secondary outcomes measured at baseline and after 12 weeks post-intervention are multiple markers of immunosenescence, body composition (bioimpedance), handgrip strength (dynamometer), physical function (short physical performance battery), respiratory function (spirometry), and quality of life (EQ-5D-3L). Incidence and complications of COVID-19 and/or viral infections (i.e., hospitalisation, complications, or death) will be recorded throughout the trial. If the Pomerium Study demonstrates efficacy and safety of a multi-nutrient supplement on immune, muscle and respiratory function, it may be suitable as a strategy to reduce the adverse outcomes from seasonal influenza and viral infections such as COVID-19 in older adults in aged-care. The study is funded by the Australian Medical Research Future Fund. It is approved by Melbourne Health Human Research Ethics Committee (Ref No. HREC/73985/MH-2021, ERM Ref No. RMH73985, Melbourne Health Site Ref No. 2021.115), and registered at ANZCTR (12621000420842). Results will be published in peer-reviewed journals and made available to aged-care stakeholders, including providers, residents, and government bodies. This is the first study performing a comprehensive immune, respiratory and functional assessment in aged care residents after receiving a multi-nutrient solution that is commercially available. Our design and tested intervention assure that the results of the study will be rapidly translated into practice. The main limitation is that any biological effect observed cannot be attributed to one component of the multi-nutrient supplement. Another limitation is that the potential effect of group differences in energy intake on outcomes can only be monitored by assessing regular dietary intake and weight changes during the study period.
Publisher: Research Square Platform LLC
Date: 26-03-2020
DOI: 10.21203/RS.3.RS-16033/V2
Abstract: BACKGROUND: Sarcopenia is defined as the age-related loss of muscle mass, strength and physical performance. The original European Working Group on Sarcopenia in Older Persons (EWGSOP1) definition, and its revision (EWGSOP2), provide new cut-points and alternate measures for sarcopenia diagnosis. However, sarcopenia is rarely diagnosed in clinical settings owing to its labour-intensive screening process. Given the Short Physical Performance Battery (SPPB) is a quick, easily administrable and objective measure of muscle strength and physical performance, both of which are key components of sarcopenia, this study examined the diagnostic value of the SPPB for this muscle disease. METHODS: A cross-sectional analysis of 294 community-dwelling older persons (≥65 years) was conducted. Appendicular lean body mass [(ALM) ided by height squared (ALM/h 2 )], muscle strength (handgrip/sit to stand), and physical performance [gait speed, timed up and go (TUG) and SPPB] were assessed using validated procedures, while participants were diagnosed with sarcopenia following the EWGSOP1 and EWGSOP2 criteria. Diagnostic ability of the SPPB independently and combined with ALM/h 2 for sarcopenia was determined using area under the curve (AUC). Potential cut-points were identified, and sensitivity and specificity calculated. RESULTS: Prevalence of sarcopenia ranged from 4 to 16% depending on the definition. The SPPB demonstrated moderate (AUC = 0.644-0.770) value in diagnosing sarcopenia, and a cut-point of ≤8points in SPPB performance resulted in high sensitivity (82-100%) but low specificity (36-41%) for diagnosing those with severe sarcopenia. CONCLUSIONS: The SPPB displayed acceptable value in diagnosing older adults with severe sarcopenia. Moreover, the high sensitivity of the SPPB when using the cut-point of ≤8 suggests it may be a favourable screening tool for sarcopenia in clinical settings where ALM measurements are not available.
Publisher: Informa UK Limited
Date: 08-2019
DOI: 10.2147/CIA.S220890
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.EXGER.2019.110778
Abstract: Osteoporosis is highly prevalent in older persons. While many advances have been made in the field of osteoporosis, current treatments have been affected by unexpected side effects and limited efficacy therefore, new approaches to identify disease mechanisms and pathways are required. This review focuses on the influence of tryptophan metabolites, particularly kynurenines and serotonin on bone. The kynurenine (KYN) pathway is associated with osteoblastogenesis and can be linked to the pathophysiology of osteoporosis. The activity of osteoblasts is reduced by 3-hydroxykynurenine (3-HKYN), a product of KYN. In addition, decreasing concentrations of 3-hydroxyanthranilic acid with aging can be one of the causes of bone loss. In contrast, picolinic acid, an end-product of the KYN pathway, acts as a bone anabolic. On the other hand, gut-derived serotonin (GDS) inhibits bone formation, whereas brain-derived serotonin enhances bone formation and decreases bone resorption. Overall, understanding the exact mechanisms of action of tryptophan metabolites on bone could have great potential to develop effective treatments for osteoporosis and other bone diseases.
Publisher: Elsevier BV
Date: 05-2022
DOI: 10.1016/J.JAMDA.2021.12.041
Abstract: Osteoporosis is underdiagnosed and undertreated in people living in Residential Aged Care Facilities (RACFs), even though aged-care residents are at greater risk of experiencing fractures than their community-dwelling counterparts. The first (2009) and second (2016) Consensus Conferences on the Treatment of Osteoporosis in RACFs in Australia addressed the prevention of falls and fractures in RACFs. A third Consensus Conference was held to review advances in the field of osteoporosis for people living in RACFs and to update current guidelines. The Conference was held virtually in October 2020 due to the COVID-19 pandemic. Attendance at the meeting was open to health practitioners (n = 116) (eg, general practitioners, geriatricians, rehabilitation specialists, endocrinologists, pharmacists, and physiotherapists) working in RACFs. Participants chose and/or were assigned to breakout groups to review the evidence and reach a consensus on the topic area assigned to the group, which was then presented to the entire group by a nominated spokesperson. Recommendations developed by breakout groups were discussed and voted on by all attending participants. This article updates the evidence for preventing falls and fractures and managing osteoporosis in older adults living in RACFs based on agreed outcomes from the group. We anticipate these updated recommendations will provide health practitioners with valuable guidance when practicing in RACFs.
Publisher: Springer Science and Business Media LLC
Date: 23-02-2018
DOI: 10.1007/S11914-018-0427-Y
Abstract: Bone marrow fat expresses mixed characteristics, which could correspond to white, brown, and beige types of fat. Marrow fat could act as either energy storing and adipokine secreting white fat or as a source of energy for hematopoiesis and bone metabolism, thus acting as brown fat. However, there is also a negative interaction between marrow fat and other elements of the bone marrow milieu, which is known as lipotoxicity. In this review, we will describe the good and bad roles of marrow fat in the bone, while focusing on the specific components of the negative effect of marrow fat on bone metabolism. Lipotoxicity in the bone is exerted by bone marrow fat through the secretion of adipokines and free fatty acids (FFA) (predominantly palmitate). High levels of FFA found in the bone marrow of aged and osteoporotic bone are associated with decreased osteoblastogenesis and bone formation, decreased hematopoiesis, and increased osteoclastogenesis. In addition, FFA such as palmitate and stearate induce apoptosis and dysfunctional autophagy in the osteoblasts, thus affecting their differentiation and function. Regulation of marrow fat could become a therapeutic target for osteoporosis. Inhibition of the synthesis of FFA by marrow fat could facilitate osteoblastogenesis and bone formation while affecting osteoclastogenesis. However, further studies testing this hypothesis are still required.
Publisher: American Medical Association (AMA)
Date: 15-12-2021
DOI: 10.1001/JAMANETWORKOPEN.2021.38911
Abstract: With the global population aging, falls and fall-related injuries are ubiquitous, and several clinical practice guidelines for falls prevention and management for in iduals 60 years or older have been developed. A systematic evaluation of the recommendations and agreement level is lacking. To perform a systematic review of clinical practice guidelines for falls prevention and management for adults 60 years or older in all settings (eg, community, acute care, and nursing homes), evaluate agreement in recommendations, and identify potential gaps. A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-analyses statement methods for clinical practice guidelines on fall prevention and management for older adults was conducted (updated July 1, 2021) using MEDLINE, PubMed, PsycINFO, Embase, CINAHL, the Cochrane Library, PEDro, and Epistemonikos databases. Medical Subject Headings search terms were related to falls, clinical practice guidelines, management and prevention, and older adults, with no restrictions on date, language, or setting for inclusion. Three independent reviewers selected records for full-text examination if they followed evidence- and consensus-based processes and assessed the quality of the guidelines using Appraisal of Guidelines for Research & Evaluation II (AGREE-II) criteria. The strength of the recommendations was evaluated using Grades of Recommendation, Assessment, Development, and Evaluation scores, and agreement across topic areas was assessed using the Fleiss κ statistic. Of 11 414 records identified, 159 were fully reviewed and assessed for eligibility, and 15 were included. All 15 selected guidelines had high-quality AGREE-II total scores (mean [SD], 80.1% [5.6%]), although in idual quality domain scores for clinical applicability (mean [SD], 63.4% [11.4%]) and stakeholder (clinicians, patients, or caregivers) involvement (mean [SD], 76.3% [9.0%]) were lower. A total of 198 recommendations covering 16 topic areas in 15 guidelines were identified after screening 4767 abstracts that proceeded to 159 full texts. Most (≥11) guidelines strongly recommended performing risk stratification, assessment tests for gait and balance, fracture and osteoporosis management, multifactorial interventions, medication review, exercise promotion, environment modification, vision and footwear correction, referral to physiotherapy, and cardiovascular interventions. The strengths of the recommendations were inconsistent for vitamin D supplementation, addressing cognitive factors, and falls prevention education. Recommendations on use of hip protectors and digital technology or wearables were often missing. None of the examined guidelines included a patient or caregiver panel in their deliberations. This systematic review found that current clinical practice guidelines on fall prevention and management for older adults showed a high degree of agreement in several areas in which strong recommendations were made, whereas other topic areas did not achieve this level of consensus or coverage. Future guidelines should address clinical applicability of their recommendations and include perspectives of patients and other stakeholders.
Publisher: SAGE Publications
Date: 2019
Abstract: Osteopenia/osteoporosis and sarcopenia are both age-related conditions. Given the well-defined bone and muscle interaction, when osteopenia and sarcopenia occur simultaneously, this geriatric syndrome is defined as ‘osteosarcopenia’. Evidence exists about therapeutic interventions common to both bone and muscle, which could thereby be effective in treating osteosarcopenia. In addition, there are roles for common nonpharmacological strategies such as nutritional intervention and physical exercise prescription in the management of this condition. In this review we summarize the evidence on current and upcoming therapeutic approaches to osteosarcopenia.
Publisher: Elsevier BV
Date: 10-2015
DOI: 10.1016/J.JOCD.2015.04.011
Abstract: Sarcopenia is a major component of the frailty syndrome and is also a strong predictor of disability, morbidity, and mortality in older persons. Without any available pharmacological intervention to sarcopenia, non-pharmacological interventions are the only option to prevent these poor outcomes in sarcopenic patients. Among those interventions, physical activity with or without protein supplementation has demonstrated to be effective in improving muscle mass and function and in preventing disability and frailty in older persons. Additionally, to the beneficial effect of physical activity on metabolic and cardiovascular diseases, a regular exercise program (3 times/wk) that includes resistance and endurance exercise training would have a major positive effect on sarcopenic muscle through improving muscle mass, strength, and function. In this review, we looked at the effect of exercise on sarcopenic frail older persons from the biological aspects of the response of the muscle to exercise to some practical aspects of exercise prescription in this high-risk population. We conclude that, although challenging, older persons should be encouraged to participate in this type of programs, which would improve not only their function and independence but also their quality of life.
Publisher: Public Library of Science (PLoS)
Date: 25-11-2020
DOI: 10.1371/JOURNAL.PONE.0242774
Abstract: There are conflicting reports on the association of undercarboxylated osteocalcin (ucOC) in cardiovascular disease development, including endothelial function and hypertension. We tested whether ucOC is related to blood pressure and endothelial function in older adults, and if ucOC directly affects endothelial-mediated vasodilation in the carotid artery of rabbits. In older adults, ucOC, blood pressure, pulse wave velocity (PWV) and brachial artery flow-mediated dilation (BAFMD) were measured (n = 38, 26 post-menopausal women and 12 men, mean age 73 ± 0.96). The vasoactivity of the carotid artery was assessed in male New Zealand White rabbits following a four-week normal or atherogenic diet using perfusion myography. An ucOC dose response curve (0.3–45 ng/ml) was generated following incubation of the arteries for 2-hours in either normal or high glucose conditions. ucOC levels were higher in normotensive older adults compared to those with stage 2 hypertension (p 0.05), particularly in women (p 0.01). In all participants, higher ucOC was associated with lower PWV (p 0.05), but not BAFMD (p 0.05). In rabbits, ucOC at any dose did not alter vasoactivity of the carotid artery, either following a normal or an atherogenic diet (p 0.05). Increased ucOC is associated with lower blood pressure and increased arterial stiffness, particularly in post-menopausal women. However, ucOC administration has no direct short-term effect on endothelial function in rabbit arteries. Future studies should explore whether treatment with ucOC, in vivo , has direct or indirect effects on blood vessel function.
Publisher: Springer Science and Business Media LLC
Date: 13-07-2020
DOI: 10.1186/S12877-020-01642-4
Abstract: Sarcopenia is defined as the age-related loss of muscle mass, strength, and physical performance. The original European Working Group on Sarcopenia in Older Persons (EWGSOP1) definition, and its revision (EWGSOP2), provide new cut-points and alternate measures for sarcopenia diagnosis. However, sarcopenia is rarely diagnosed in clinical settings owing to its labor-intensive diagnostic process. Given the Short Physical Performance Battery (SPPB) is a quick, easily administrable, and objective measure of muscle strength and physical performance, both of which are key components of sarcopenia, this study examined the diagnostic value of the SPPB for this muscle disease. A cross-sectional analysis of 294 community-dwelling older persons (≥65 years) was conducted. Appendicular lean body mass [(ALM) ided by height squared (ALM/h 2 )], muscle strength (handgrip/sit to stand), and physical performance [gait speed, timed up and go (TUG) and SPPB] were assessed using validated procedures, while participants were diagnosed with sarcopenia following the EWGSOP1 and EWGSOP2 criteria. Diagnostic ability of the SPPB independently and combined with ALM/h 2 for sarcopenia was determined using area under the curve (AUC). Potential cut-points were identified, and sensitivity and specificity calculated. Prevalence of sarcopenia ranged from 4 to 16% depending on the definition. The SPPB demonstrated moderate (AUC = 0.644–0.770) value in diagnosing sarcopenia, and a cut-point of ≤8points in SPPB performance resulted in high sensitivity (82–100%) but low specificity (36–41%) for diagnosing those with severe sarcopenia. The SPPB displayed acceptable value in diagnosing older adults with severe sarcopenia. Moreover, the high sensitivity of the SPPB when using the cut-point of ≤8 suggests it may be a favorable screening tool for sarcopenia in clinical settings where ALM measurements are not available.
Publisher: BMJ
Date: 08-2023
DOI: 10.1136/BMJOPEN-2023-072050
Abstract: Minimal trauma fractures (MTFs) often occur in older patients with osteoporosis and may be precipitated by falls risk-increasing drugs. One category of falls risk-increasing drugs of concern are those with sedative/anticholinergic properties. Collaborative medication management services such as Australia’s Home Medicine Review (HMR) can reduce patients’ intake of sedative/anticholinergics and improve continuity of care. This paper describes a protocol for an randomised controlled trial to determine the efficacy of an HMR service for patients who have sustained MTF. Eligible participants are as follows: ≥65 years of age, using ≥5 medicines including at least one falls risk-increasing drug, who have sustained an MTF and under treatment in one of eight Osteoporosis Refracture Prevention clinics in Australia. Consenting participants will be randomised to control (standard care) or intervention groups. For the intervention group, medical specialists will refer to a pharmacist for HMR focused on reducing falls risk predominately through making recommendations to reduce falls risk medicines, and adherence to antiosteoporosis medicines. Twelve months from treatment allocation, comparisons between groups will be made. The main outcome measure is participants’ cumulative exposure to sedative and anticholinergics, using the Drug Burden Index. Secondary outcomes include medication adherence, emergency department visits, hospitalisations, falls and mortality. Economic evaluation will compare the intervention strategy with standard care. Approval was obtained via the New South Wales Research Ethics and Governance Information System (approval number: 2021/ETH12003) with site-specific approvals granted through Human Research Ethics Committees for each research site. Study outcomes will be published in peer-reviewed journals. It will provide robust insight into effectiveness of a pharmacist-based intervention on medicine-related falls risk for patients with osteoporosis. We anticipate that this study will take 2 years to fully accrue including follow-up. ACTRN12622000261718.
Publisher: Informa UK Limited
Date: 23-08-2021
DOI: 10.1080/13697137.2021.1965118
Abstract: Osteoporosis and sarcopenia are two conditions associated with aging and characterized by a simultaneous decline in bone and muscle mass, respectively. These conditions share common risk factors (genetic, endocrine, nutritional and lifestyle factors) and biological pathways that often co-exist in a syndrome known as osteosarcopenia. Among the endocrine causes, estrogens play a critical role, especially in women. Estrogens have been demonstrated to exert a positive effect on bone and muscle development and maintenance. For this reason, menopause is characterized by a loss in bone mineral density and skeletal muscle quality and quantity. To date, studies indicate a positive effect of hormonal therapy on the prevention and management of osteoporosis, to the point that estrogen is prescribed as a first-line treatment for osteoporosis by the major international authorities. While results on sarcopenia are still disputable, such that estrogens are not recommended to prevent muscle loss in postmenopausal women, increased response to anabolic stimuli with estrogen therapy suggests similar beneficial effects on muscle as seen with bone, particularly when combined with resistance exercise.
Publisher: Elsevier BV
Date: 02-2024
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.JAMDA.2019.02.022
Abstract: To evaluate the effect of clinical care pathways (CCPs) on health-related quality of life (HRQoL) and physical function following fragility fracture and identify the specific characteristics of CCPs that are associated with improved outcomes. Systematic review and meta-analysis. Randomized controlled studies and nonrandomized studies that involved participants aged ≥50 years who sustained a fragility fracture, evaluated the effects of a CCP compared to usual care, and reported outcomes of HRQoL or physical function. We systematically searched Ovid Medline, CINAHL, Embase, and the Cochrane Central Register of Controlled Trials from the earliest records to July 25, 2018. Two reviewers independently extracted study data and assessed methodologic quality. Overall, 22 studies (17 randomized controlled trials, 5 nonrandomized studies) were included, comprising 5842 participants. Twenty-one studies included hip fracture patients, and 1 included wrist fracture patients. Majority of studies (82%) were assessed as high quality. Meta-analyses showed moderate improvements in the CCP group for HRQoL [standardized mean difference (SMD) = 0.24, 95% confidence interval (CI) 0.12, 0.35] and physical function (SMD 0.21, 95% CI 0.10, 0.33) compared with usual care post hip fracture. Inpatient CCPs that extended to the outpatient setting showed greater improvements in HRQoL and physical function compared to CCPs that were only inpatient or outpatient. CCPs that included a care coordinator, geriatric assessment, rehabilitation, prevention of inpatient complications, nutritional advice, or discharge planning also showed greater improvements in outcomes. Treatment with CCPs following fragility fracture showed greater improvements in HRQoL and physical function compared with usual care. Further research is warranted to assess the combination of CCP components that provide the most beneficial results, evaluate the effect of CCPs in patients with nonhip fractures, and determine which patient groups are more likely to benefit from CCPs.
Publisher: AMPCo
Date: 28-11-2019
DOI: 10.5694/MJA2.50432
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.MATURITAS.2018.12.013
Abstract: A high level of parathyroid hormone (PTH) was recently identified as a risk factor for falling. As balance instability is one of the major risk factors for falls, we aimed to investigate whether high PTH concentrations are associated with poor balance in older persons. Cross-sectional study with 127 community-dwelling older adults (75% female), aged 65-96 years, at the Falls and Fracture Clinic, Western Health-Sunshine Hospital, Melbourne, Australia. Patients with clinical conditions that could affect balance (e.g. Meniere's disease), denosumab users, and those with advanced kidney failure were excluded. We assessed dynamic balance by timed "up and go" (TUG)and four-square step tests, and by gait parameters and static balance by posturography on a force platform. Blood tests provided values of PTH, vitamin D, calcium, albumin, and creatinine. Standard questionnaires were applied to assess clinical condition, medications and nutritional status, and to screen for depression. For dynamic balance, elevated PTH concentrations resulted in increased time to complete the TUG test (β = 0.13 95%CI: 0.01-0.26), indicating worse performance. For static balance, increased PTH was associated with increased instability in the center of pressure while standing with eyes closed on a hard surface (β = 0.38 95%CI: 0.03-0.73). Both models were controlled for vitamin D, renal function, nutritional and depressive status, age, sex, and number of medications. Increasing concentrations of PTH in this population of older persons had an independent negative association with both static and dynamic balance, which could place them at risk of falls. However, longitudinal studies are still required.
Publisher: Springer Science and Business Media LLC
Date: 15-06-2022
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.ARCHGER.2019.103938
Abstract: The effect of protein supplementation in attenuating loss of muscle mass, strength and function in community-dwelling older people has been promising, however, its benefits in pre-frail and frail older people remains unclear. To determine the effect of protein supplementation on muscle mass, strength and function in frail older people by reviewing and conducting meta-analysis of relevant randomized controlled trials (RCTs). This review was registered at PROSPERO (CRD42017079276) and conducted according to Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Using a pre-determined e-search strategy, we searched PubMed, Medline, EMBASE, CINAHL, LILACS, Web of Science, Cochrane and Scopus databases. Inclusion criteria were RCTs that assessed the effect of protein supplementation on muscle mass, strength and function in frail in iduals aged ≥65 years. The main outcomes were lean body mass (LBM), handgrip, leg extension, leg press strength, short physical performance battery (SPPB) score, and gait velocity. Of the eight studies included in this review, 503 subjects were enrolled and four different protein supplements were assessed. Despite the variation in methodology, studies were homogenous with I-squared <10.0%. The meta-analysis showed no significant effect of protein supplementation on LBM (mean difference 1.17 kg, 95% CI: -1.97-4.3), handgrip (mean difference 0.15, 95% CI: -0.95-1.24), leg extension (mean difference -3.68 kg, 95% CI: -12.72-5.36), leg press (mean standardized difference 0.26 kg, 95% CI: -0.30-0.82), SPPB (mean difference 0.61, 95% CI: -0.02-1.23), or gait velocity (mean difference -0.20 m/s, 95% CI: -0.95-0.55). Protein supplementation alone does not significantly improve muscle mass, strength or function in pre-frail or frail older people.
Publisher: Elsevier BV
Date: 07-2021
Publisher: Springer Science and Business Media LLC
Date: 19-11-2019
DOI: 10.1007/S00198-018-4755-7
Abstract: Numerous sarcopenia definitions are not associated with increased falls-related hospitalization risk over 5 years to 9.5 years in older community-dwelling Australian women. Measures of muscle strength and physical function, but not appendicular lean mass (measured by dual-energy X-ray absorptiometry) may help discriminate the risk of falls-related hospitalization. The aim of this prospective, population-based cohort study of 903 Caucasian-Australian women (mean age 79.9 ± 2.6 years) was to compare the clinical utility of four sarcopenia definitions for the prediction of falls-related hospitalization over 9.5 years. The four definitions were the United States Foundation for the National Institutes of Health (FNIH), the European Working Group on Sarcopenia in Older People (EWGSOP), and modified FNIH (AUS-POP Baseline prevalence of sarcopenia according to FNIH (9.4%), EWGSOP (24.1%), AUS-POP Current definitions of sarcopenia were not associated with falls-related hospitalization risk in this cohort of community-dwelling older Australian women. Finally, measures of muscle strength and physical function, but not ALM (measured by DXA) may help discriminate the risk of falls-related hospitalization.
Publisher: Wiley
Date: 11-04-2023
DOI: 10.1113/JP283990
Abstract: 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 in idual 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 in idual treatments. These findings suggest a potential therapeutic role for the ucOC and bisphosphonates combination in protecting against muscle wasting induced by immobilization and ageing. image 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 in idual 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.
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.CGER.2017.03.003
Abstract: A comprehensive geriatric assessment, combined with a battery of imaging and blood tests, should be able to identify those hip fracture patients who are at higher risk of short- and long-term complications. This comprehensive assessment should be followed by the implementation of a comprehensive multidimensional care plan aimed to prevent negative outcomes in the postoperative period (short and long term), thus assuring a safe and prompt functional recovery while also preventing future falls and fractures.
Publisher: Elsevier BV
Date: 05-2022
Publisher: Wiley
Date: 16-02-2023
DOI: 10.1002/JBM4.10704
Abstract: Sarcopenia and osteoporosis are highly prevalent syndromes in older people, characterized by loss of muscle and bone tissue, and related to adverse outcomes. Previous reports indicate mid‐thigh dual‐energy X‐ray absorptiometry (DXA) is well suited for the simultaneous assessment of bone, muscle, and fat mass in a single scan. Using cross‐sectional clinical data and whole‐body DXA images of 1322 community‐dwelling adults from the Geelong Osteoporosis Study (57% women, median age 59 years), bone and lean mass were quantified in three unconventional regions of interest (ROIs): (i) a 2.6‐cm‐thick slice of mid‐thigh, (ii) a 13‐cm‐thick slice of mid‐thigh, and (iii) the whole thigh. Conventional indices of tissue mass were also calculated (appendicular lean mass [ALM] and bone mineral density [BMD] of lumbar spine, hip, and femoral neck). The performance of thigh ROIs in identifying osteoporosis, osteopenia, low lean mass and strength, past falls, and fractures was evaluated. All thigh regions (especially whole thigh) performed well in identifying osteoporosis (area under the receiver‐operating characteristic [ROC] curve [AUC] 0.8) and low lean mass (AUC .95), but they performed worse in the diagnosis of osteopenia (AUC 0.7–0.8). All thigh regions were equivalent to ALM in discrimination of poor handgrip strength, gait speed, past falls, and fractures. BMD in conventional regions was more strongly associated with past fractures than thigh ROIs. In addition to being faster and easier to quantify, mid‐thigh tissue masses can be used for identifying osteoporosis and low lean mass. They are also equivalent to conventional ROIs in their associations with muscle performance, past falls, and fractures however, further validation is required for the prediction of fractures. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Publisher: MDPI AG
Date: 20-09-2021
DOI: 10.3390/NU13093284
Abstract: Background: Sarcopenia is associated with significant morbidity and mortality in patients with chronic kidney disease. The prevalence of sarcopenia in the dialysis population varies from 4% to 63%. However, the prevalence and risk factors of sarcopenia in the Australian dialysis population remain uncertain. Aim: To study the prevalence of sarcopenia in patients on maintenance dialysis by using the European Working Group on Sarcopenia in Older People (EWGSOP) diagnostic criteria of sarcopenia and to identify associated risk factors. Methods: We evaluated adult patients on maintenance haemodialysis and peritoneal dialysis in this single-centre cross-sectional study in Australia. Patient’s clinical (age, gender, dialysis modality and diabetic status) and laboratory parameters (serum albumin, calcium, phosphate, 25-hydroxy-vitamin D and parathyroid hormone levels) were investigated. We employed bioimpedance spectroscopy, hand grip dynamometer and the timed up and go test (TUG) to evaluate muscle mass, strength and function, respectively. Results: We evaluated 39 dialysis patients with a median age of 69 years old. The prevalence of sarcopenia was 18%. Sarcopenia was associated with low serum albumin (p = 0.02) and low serum phosphate level (p = 0.04). Increasing age and female sex were potential risk factors for sarcopenia (p = 0.05 and 0.08, respectively). Low lean muscle mass, reduced hand grip strength and prolonged TUG were present in 23.1%, 41% and 40.5%, respectively, of the cohort. The hand grip test had good correlation with lean muscle evaluation and the TUG. Conclusions: Sarcopenia was prevalent in 18% of maintenance haemodialysis patients from an Australian single-centre cohort, with low serum albumin and phosphate as significant risk factors.
Publisher: Cold Spring Harbor Laboratory
Date: 28-09-2020
DOI: 10.1101/2020.09.28.317495
Abstract: We aimed to investigate the skeletal phenotype of Winnie mouse model of spontaneous chronic colitis, which carries a mutation in the Muc2 gene and closely replicates IBD symptoms and pathophysiology. These mice have a high level of gut-derived serotonin (GDS), a potent osteoblastogenesis inhibitor. We explored the underlying mechanisms of bone loss associated with chronic intestinal inflammation. Winnie male and female mice prior to colitis onset (6 weeks old) and progression (14 and 24 weeks) were compared to age- and sex-matched C57BL/6 controls. We assessed bone quality (static and dynamic histomorphometry, micro-CT, 3-point bending), intestinal inflammation (lipocalin-2), GDS levels, serum levels of calcium, phosphorus and vitamin D, ex vivo bone marrow analysis and molecular mechanisms inhibiting osteoblastogenesis. Significant deterioration in trabecular and cortical microarchitecture, reductions in bone formation, mineral apposition rate, bone volume, osteoid volume and bone strength were observed in Winnie mice compared to C57BL/6 controls. Decreased osteoblast and increased osteoclast numbers were prominent in Winnie mice. We report for the first time that elevated GDS cross-talks with molecular pathways to inhibit bone formation in Winnie mice. Increased expression of 5-HTR1B and FOXO1 mRNAs, dissociation of FOXO1/CREB1 complex and association of FOXO1 with ATF4, promoting the transcriptional activity of FOXO1, results in suppression of osteoblast proliferation in Winnie mice compared to controls. These findings open avenues for the development of targeted therapies for IBD-related bone loss. - Osteoporosis is a common extraintestinal manifestation of inflammatory bowel disease (IBD). - Currently available treatments are not effective for IBD-associated bone loss. - The mechanisms of bone loss are poorly understood. A major limitation has been the lack of an appropriate animal model for IBD-associated bone loss. - We report for the first-time the skeletal phenotype in Winnie mouse model of IBD - This study presents a novel mechanism of IBD-associated bone loss, involving elevated gut-derived serotonin crosstalk with molecular pathways inhibiting bone formation. - These findings open avenues for the development of targeted therapies for IBD-related bone loss.
Publisher: Elsevier BV
Date: 09-2022
DOI: 10.1016/J.MAD.2022.111690
Abstract: Osteosarcopenia is an age-related condition characterized by fragile bone and low muscle mass and function. Fat infiltration concomitantly contributes to age-related bone and muscle decline. Fat-secreted factors could be locally secreted in the muscle and bone marrow milieu affecting cell function and survival. However, the specific fat-related secretory factors that may simultaneously affect those tissues remain unknown. Using targeted-lipidomics approach, we comprehensively quantified fat composition (lipid mediators [LMs]) in bone marrow flush, gastrocnemius and serum obtained from 6-, 24- and 42-week-old C57BL6 mice. Compared to young mice (6wks), all tissues in older mice showed significantly higher levels of arachidonic acid (AA) and AA-derived eicosanoids, PGA 2, TXB 2, and 11,12-EET, which are known to affect muscle and bone function. Moreover, Lipoxin B4, another AA product and an enhancer of bone turnover and negative regulator for muscle, showed significantly lower values in older mice compared to young mice in both genders. Furthermore, eicosapentaenoic acid and docosahexaenoic acid autoxidation products (20-HDoHE, 11-HDoHE, 7-HDoHE and 4-HDoHE), and omega-3 fatty acids that negatively regulate bone and muscle health, were significantly higher in older mice. In conclusion, these results suggest that LMs could play a role in modulating musculoskeletal function during aging.
Publisher: Elsevier BV
Date: 10-2017
DOI: 10.1016/J.JSBMB.2017.01.022
Abstract: Muscle function is often impaired in patients with knee osteoarthritis (OA), with reduced strength and increased pain. The role of vitamin D and the vitamin D-endocrine pathway in muscle health has recently been placed in the spotlight, with various groups reporting positive effects on muscle development, function and health. Recently, it has been shown that uptake into muscle of the specialized vitamin D binding protein (DBP) is dependent on the endocytic receptor, megalin. Here we analyse circulating vitamin D, and muscle DBP, megalin and the cognate vitamin D receptor (VDR) in patients with knee OA and compare them to asymptomatic controls. Muscle and blood s les were collected from 19 patients with end-stage OA of the knee and 10 age-matched controls. Muscle biopsies from the OA group were performed during knee replacement surgery and a needle biopsy was used on control volunteers. Immunoblots performed with specific antibodies were used to detect the presence of DBP, megalin, VDR (using the specific D-6 antibody) and albumin in the muscle biopsies. Results were correlated with FoxO1, a key regulator of the ubiquitin-proteasome degradation pathway in muscle. There were no differences in circulating levels of 25 (OH) vitamin D3 between the groups, and no subjects were vitamin D deficient. We found increased VDR, DBP and albumin protein in the muscle from patients with OA compared to controls, with no change in muscle megalin expression. Furthermore, DBP levels in the muscle correlated with FoxO1, suggesting an association between muscle protein breakdown and the activation of the vitamin D-endocrine pathway in muscle surrounding an OA affected joint. We show, for the first time, that the factors involved in the vitamin D-endocrine-pathway are present at higher levels in muscles from OA patients compared to asymptomatic controls. This is despite no differences in circulating 25 (OH) vitamin D levels between the groups. These findings indicate the activation of vitamin D pathway in these muscles that may provide a beneficial compensatory stimulation of the repair process in muscles that are subject to inflammatory and proteolytic processes.
Publisher: Elsevier BV
Date: 12-2020
Publisher: Springer Science and Business Media LLC
Date: 04-11-2020
DOI: 10.1186/S12877-020-01824-0
Abstract: Many research studies evaluate physical activity interventions for older people in the community, however relatively few successfully promote maintenance of physical activity beyond the completion of the intervention. This study aimed to implement and evaluate the effects of sustained engagement in physical activity on mental, social and physical health outcomes through the use of the Seniors Exercise Park physical activity program for older people (the ENJOY project). People aged ≥60 years underwent a 12-week structured supervised physical activity program using outdoor exercise park equipment followed by 6 months unstructured independent use of the exercise park. Participants were assessed at baseline, 3 months and 9 months and completed a test battery evaluating physical activity, physical function and health related quality of life measures. Repeated measures ANOVA was used to compare differences between baseline, 3 and 9 months. Of the 95 participants, 80 (84.2%) completed the 3 months supervised program, and 58 (61%) completed the 9 month assessment (the latter impacted by COVID-19 restrictions). A significant increase in physical activity level was demonstrated following the 12 weeks intervention ( p 0.01). Significant improvements were also demonstrated in all physical function measures ( p 0.01), self-rated quality of life ( p 0.05), wellbeing ( p 0.01), fear of falls ( p 0.01), falls risk ( p 0.01), depressive symptoms ( p = 0.01) and loneliness ( p = 0.03) at 3 months. At the 9 months follow up, significant improvements from baseline were demonstrated in the frequency, duration and total of physical activity level ( p 0.05), and all physical function measures ( p 0.05), with no decline in these measures from 3 to 9 months. At 9 months, significant changes were observed in the health related quality of life mobility and self care domains with reductions in both fear of falls and falls risk ( p 0.05). The Seniors Exercise Park may be an effective modality for improving and sustaining older people’s physical function and wellbeing and can be an important public health infrastructure investment in promoting physical activity for older people. Future work should focus on wider implementation of the program and on scaling up this initiative to achieve public health benefit for the community. Trial registration number ACTRN12618001727235, Date of registration 19th October 2018, www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375979
Publisher: Elsevier BV
Date: 12-2019
Publisher: Wiley
Date: 10-2020
DOI: 10.1111/AJAG.12853
Publisher: Springer Science and Business Media LLC
Date: 06-11-2017
DOI: 10.1007/S11657-017-0396-2
Abstract: Compared to urban residents, those in rural/regional areas often experience inequitable healthcare from specialist service providers. Independent of small between-area differences in utilisation, socially advantaged groups had the greatest uptake of joint replacement. These data suggest low correlation between 'need' vs. 'uptake' of surgery in rural/regional areas. Compared to urban residents, those in rural and regional areas often experience inequitable healthcare from specialist service providers, often due to geographical issues. We investigated associations between socioeconomic position (SEP), region of residence and utilisation of primary total knee replacement (TKR) and/or total hip replacement (THR) for osteoarthritis. As part of the Ageing, Chronic Disease and Injury study, we extracted data from the Australian Orthopaedic Association National Joint Replacement Registry (2011-2013) for adults that utilised primary TKR (n = 4179 56% female) and/or THR (n = 3120 54% female). Residential addresses were matched with the Australian Bureau of Statistics (ABS) 2011 census data: region of residence was defined according to local government areas (LGAs), and area-level SEP (quintiles) defined using an ABS-derived composite index. The ABS-determined control population (n = 591,265 51% female) excluded in iduals identified as cases. We performed multilevel logistic regression modelling using a stratified two-stage cluster design. TKR was higher for those aged 70-79 years (AOR 1.4 95%CI 1.3-1.5 referent = 60-69 years) and in the most advantaged SEP quintile (AOR 2.1, 95%CI 1.8-2.3 referent = SEP quintile 3) results were similar for THR (70-79 years = AOR 1.7, 95%CI 1.5-1.8 SEP quintile 5 = AOR 2.5, 95%CI 2.2-2.8). Total variances contributed by the variance in LGAs were 2% (SD random effects ± 0.28) and 3% (SD ± 0.32), respectively. Independent of small between-LGA differences in utilisation, and in contrast to the expected greater prevalence of osteoarthritis in disadvantaged populations, we report greater TKR and THR in more advantaged groups. Further research should investigate whether more advantaged populations may be over-serviced.
Publisher: JMIR Publications Inc.
Date: 18-03-2020
Abstract: one and muscle are closely linked anatomically, biochemically, and metabolically. Acute exercise affects both bone and muscle, implying a crosstalk between the two systems. However, how these two systems communicate is still largely unknown. We will explore the role of undercarboxylated osteocalcin (ucOC) in this crosstalk. ucOC is involved in glucose metabolism and has a potential role in muscle maintenance and metabolism. he proposed trial will determine if circulating ucOC levels in older adults at baseline and following acute exercise are associated with parameters of muscle function and if the ucOC response to exercise varies between older adults with low muscle quality and those with normal or high muscle quality. total of 54 men and women aged 60 years or older with no history of diabetes and warfarin and vitamin K use will be recruited. Screening tests will be performed, including those for functional, anthropometric, and clinical presentation. On the basis of muscle quality, a combined equation of lean mass (leg appendicular skeletal muscle mass in kg) and strength (leg press one-repetition maximum), participants will be stratified into a high or low muscle function group and randomized into the controlled crossover acute intervention. Three visits will be performed approximately 7 days apart, and acute aerobic exercise, acute resistance exercise, and a control session (rest) will be completed in any order. Our primary outcome for this study is the effect of acute exercise on ucOC in older adults with low muscle function and those with high muscle function. he trial is active and ongoing. Recruitment began in February 2018, and 38 participants have completed the study as of May 26, 2019. his study will provide novel insights into bone and muscle crosstalk in older adults, potentially identifying new clinical biomarkers and mechanistic targets for drug treatments for sarcopenia and other related musculoskeletal conditions. ustralia New Zealand Clinical Trials Registry ACTRN12618001756213 www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375925. ERR1-10.2196/18777
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.BONE.2019.115085
Abstract: Osteocalcin (OC), an osteoblast-specific secreted protein expressed by mature osteoblasts, is used in clinical practice and in research as a marker of bone turnover. The carboxylated (cOC) and undercarboxylated (ucOC) forms may have a different biological function but age-specific reference ranges for these components are not established. Given the different physiological roles, development of reference ranges may help to identify people at risk for bone disease. Blood was collected in the morning after an overnight fast from 236 adult men (18 to 92 years old) free of diabetes, antiresorptive, warfarin or glucocorticoid use. Serum was analyzed for total osteocalcin (tOC) and the ucOC fraction using the hydroxyapatite binding method. cOC, ucOC/tOC and cOC/tOC ratios were calculated. Reference intervals were established by polynomial quantile regression analysis. The normal ranges for young men (≤30 years) were: tOC 17.9-56.8 ng/mL, ucOC 7.1-22.0 ng/mL, cOC 8.51-40.3 ng/mL (2.5th to 97.5th quantiles). Aging was associated with a "U" shaped pattern for tOC, cOC and ucOC levels. ucOC/tOC ratio was higher, while cOC/tOC ratio was lower in men of advanced age. Age explained ∼31%, while body mass index explained ∼4%, of the variance in the ratios. We have defined normal reference ranges for the OC forms in Australian men and demonstrated that the OC ratios may be better measures, than the absolute values, to identify the age-related changes on OC in men. These ratios may be incorporated into future research and clinical trials, and their associations with prediction of events, such as fracture or diabetes risk, should be determined.
Publisher: Wiley
Date: 09-2019
DOI: 10.1002/AGM2.12080
Publisher: Springer Science and Business Media LLC
Date: 11-11-2019
DOI: 10.1007/S11914-019-00539-5
Abstract: The significance and roles of marrow adipose tissue (MAT) are increasingly known, and it is no more considered a passive fat storage but a tissue with significant paracrine and endocrine activities that can cause lipotoxicity and inflammation. Changes in the MAT volume and fatty acid composition appear to drive bone and hematopoietic marrow deterioration, and studying it may open new horizons to predict bone fragility and anemia development. MAT has the potential to negatively impact bone volume and strength through several mechanisms that are partially described by inflammaging and lipotoxicity terminology. Evidence indicates paramount importance of MAT in age-associated decline of bone and red marrow structure and function. Currently, MAT measurement is being tested and validated by several techniques. However, purpose-specific adaptation of existing imaging technologies and, more importantly, development of new modalities to quantitatively measure MAT are yet to be done.
Publisher: The Company of Biologists
Date: 06-11-2013
DOI: 10.1242/BIO.20136700
Abstract: Lipotoxicity is an overload of lipids in non-adipose tissues that affects function and induces cell death. Lipotoxicity has been demonstrated in bone cells in vitro using osteoblasts and adipocytes in coculture. In this condition, lipotoxicity was induced by high levels of saturated fatty acids (mostly palmitate) secreted by cultured adipocytes acting in a paracrine manner. In the present study, we aimed to identify the underlying mechanisms of lipotoxicity in human osteoblasts. Palmitate induced autophagy in cultured osteoblasts, which was preceded by the activation of autophagosomes that surround palmitate droplets. Palmitate also induced apoptosis though the activation of the Fas/Jun kinase (JNK) apoptotic pathway. In addition, osteoblasts could be protected from lipotoxicity by inhibiting autophagy with the phosphoinositide kinase inhibitor 3-methyladenine or by inhibiting apoptosis with the JNK inhibitor SP600125. In summary, we have identified two major molecular mechanisms of lipotoxicity in osteoblasts and in doing so we have identified a new potential therapeutic approach to prevent osteoblast dysfunction and death, which are common features of age-related bone loss and osteoporosis.
Publisher: Oxford University Press (OUP)
Date: 16-04-2020
Abstract: Long-term caloric restriction (CR) has been shown to be beneficial to various tissues and organs. In contrast, CR exerts differential effects on bone, which could be due in part to the nature of the protein regime utilized. Male Sprague Dawley rats (8-month-old) were subjected for 12 months to 40% CR in macronutrients and compared with rats fed ad libitum for the same period. Casein- and soy-fed groups were compared. There was a significant decrease in bone quality in both CR groups, which was independent of the source of protein in the diet. In contrast, the group fed soy protein ad libitum showed better bone quality and higher levels of bone formation compared with casein-fed animals. Notably, bone marrow adipocytes were not mobilized upon CR as demonstrated by an absence of change in adipocyte number and tissue expression of leptin. This study demonstrates that the negative effect of CR on bone quality could not be prevented by the most common protein regimes.
Publisher: Elsevier BV
Date: 03-2019
Publisher: S. Karger AG
Date: 02-12-2021
DOI: 10.1159/000520488
Abstract: b i Background: /i /b Circulating osteoprogenitor (COP) cells are a surrogate of the bone marrow mesenchymal stem cells with high levels observed in osteoporosis and the initial stages of fracture healing. Conversely, a low percentage of COP cells (%COP) is strongly associated with frailty and disability. However, it is unknown whether %COP is associated with sarcopenia, a musculoskeletal disease closely related to frailty. b i Objectives: /i /b This study sought to determine the associations between %COP and sarcopenia defined using the Sarcopenia Definitions and Outcomes Consortium (SDOC) criteria. b i Methods: /i /b Data from a random s le of 73 community-dwelling older persons enrolled in the Nepean Osteoporosis and Frailty study (median age 74 years 60% female) were analyzed. %COP was quantified by flow cytometry using selective gating of CD45/osteocalcin (OCN) + cells. Sarcopenia was defined using handgrip strength and gait speed with cut points as per the SDOC criteria. Linear regression was used for analysis. b i Results: /i /b Sarcopenia was identified in 19% of participants, all of whom were frail. After adjusting for age, sex, and interleukin 6, sarcopenic participants had 36% lower %COP (95% confidence interval [CI] −56%, −6%, i = /i 0.024). Both grip strength and gait speed showed associations with %COP ( i = /i 0.065 and 0.002, respectively) however, after adjusting for age and frailty, only gait speed remained associated with %COP (0.1 m/s increase in gait velocity was associated with a 5% increase in %COP cells (95% CI 0%, 10%, i = /i 0.052). b i Conclusions: /i /b High levels of %COP are associated with better muscle function. Future longitudinal studies are required to elucidate the clinical utility of %COP as a potential biomarker or disease stratifier for sarcopenia.
Publisher: Springer Science and Business Media LLC
Date: 08-06-2018
Publisher: Elsevier BV
Date: 12-2020
Publisher: Elsevier BV
Date: 04-2021
Publisher: Elsevier BV
Date: 03-2022
DOI: 10.1016/J.GAITPOST.2022.01.022
Abstract: Falls in older persons are associated with muscle mass and strength alterations, which may also affect balance parameters. However, the most appropriate combined approach to assess muscle and balance components that predict falls in older persons is still lacking. We hypothesized that appendicular lean and/or mid-thigh mass and muscle strength and performance are positively associated with balance indices and fall risk in older persons. Cross-sectional analyses of retrospective data from 260 participants with risk and/or history of falls examined at a Falls and Fracture Clinic. Assessments included a comprehensive clinical exam, bone densitometry and body composition by DXA, grip strength, gait speed, posturography, timed up and go (TUG) and four-square step (FSST) tests. Retrospective falls and fracture history was collected. Associations between appendicular and mid-thigh lean mass and muscle strength erformance vs balance indicators were determined before and after adjusting for age and gender. Mean age of participants was 78 ± 6.7 (65-96) years. Both appendicular and mid-thigh lean masses corrected for BMI (but not for height Combined with strength and performance parameters, ALM and mid-thigh estimates adjusted by BMI strongly correlate with dynamic balance parameters and could become practical elements of falls risk assessment as well as markers of therapeutic response to falls prevention interventions.
Publisher: The Endocrine Society
Date: 31-12-2019
Abstract: Androgen deprivation therapy (ADT) for prostate cancer (PCa) leads to a selective loss of leg muscle function during walking. Rodent models of ADT have demonstrated that the levator ani is exquisitely androgen sensitive. To determine whether the high androgen responsiveness of the levator ani muscle documented in rodents is evolutionarily conserved and ADT is associated with a selective loss in leg muscle volume. Prospective longitudinal case-control study. Tertiary referral hospital. Thirty-four men newly beginning ADT and 29 age-matched controls with PCa. The muscle volumes in liters of the levator ani and primary muscles involved in walking (iliopsoas, quadriceps, gluteus maximus, gluteus medius, calf). Compared with controls, during a 12-month period, men receiving ADT experienced a mean reduction in total testosterone from 14.1 to 0.4 nmol/L and demonstrated greater decreases in levator ani [mean adjusted difference (MAD), -0.005 L 95% CI, -0.007 to -0.002 P = 0.002 -16% of initial median value], gluteus maximus (MAD, -0.032 L 95% CI, -0.063 to -0.002 P = 0.017 -5% of initial median value), iliopsoas (MAD, -0.005 L 95% CI, -0.001 to 0.000 P = 0.013 -5% of initial median value), and quadriceps (MAD, -0.050 L 95% CI, -0.088 to -0.012 P = 0.031 -3% of initial median value). No substantial differences were observed in the gluteus medius and calf muscles. The androgen responsiveness of the levator ani appears to be evolutionarily conserved in humans. ADT selectively decreases the volume of muscles that support body weight. Interventional strategies to reduce ADT-related sarcopenia and sexual dysfunction should assess whether targeting these muscle groups, including the pelvic floor, will improve clinical outcomes.
Publisher: SAGE Publications
Date: 2021
Abstract: The kynurenine (KYN) pathway has been implicated in many diseases associated with inflammation and aging (“inflammaging”). Targeting the kynurenine pathway to modify disease outcomes has been trialled pharmacologically, but the evidence of non-pharmacological means (ie, exercise) remains unclear. We aim to assess the evidence of the effects of exercise on the kynurenine pathway and psychological outcomes. Under Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, a systematic literature search was performed in MEDLINE, EMBASE, EMCARE, and the Cochrane Central Registry of Controlled Trials. The main outcomes were changes in kynurenine pathway metabolite levels and psychological outcomes. Six studies were analyzed (total n = 379) with exercise demonstrating significant concomitant effects on kynurenine pathway metabolite levels and associated psychological outcomes in domains of somatization, anxiety, and depression. Exercise has significant concomitant effect on kynurenine pathway metabolite levels and psychological outcomes. However, clear limitations exist in determining if the changes in the kynurenine pathway can fully explain the changes in psychological outcomes, or whether different diseases and exercise interventions act as confounding factors.
Publisher: Elsevier BV
Date: 06-2021
Location: Canada
Start Date: 2010
End Date: 2012
Funder: National Health and Medical Research Council
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