Nutrient Intake and Its Association with Appendicular Total Lean Mass and Muscle Function and Strength in Older Adults: A Population-Based Study.

Treatment options for sarcopenia are currently limited, and primarily rely on two main therapeutic approaches: resistance-based physical activity and dietary interventions. However, details about specific nutrients in the diet or supplementation are unclear. We aim to investigate the relationship between nutrient intake and lean mass, function, and strength. Data were derived from the Gothenburg H70 birth cohort study in Sweden, including 719,70-year-olds born in 1944 (54.1% females). For independent variables, the diet history method (face-to-face interviews) was used to estimate habitual food intake during the preceding three months. Dependent variables were gait speed (muscle performance), hand grip strength (muscle strength), and the appendicular lean soft tissue index (ALSTI). Linear regression analyses were performed to analyze the relationship between the dependent variables and each of the covariates. Several nutrients were positively associated with ALSTI, such as polyunsaturated fatty acids (DHA, EPA), selenium, zinc, riboflavin, niacin equivalent, vitamin B12, vitamin D, iron, and protein. After correction for multiple comparisons, there were no remaining correlations with handgrip and gait speed. Findings of positive correlations for some nutrients with lean mass suggest a role for these nutrients in maintaining muscle volume. These results can be used to inform clinical trials to expand the preventive strategies and treatment options for individuals at risk of muscle loss and sarcopenia.

Exercise as a Therapeutic Tool in Age-Related Frailty and Cardiovascular Disease: Challenges and Strategies.

Understanding the link between heart disease and frailty in older adults is crucial. Although medical progress has extended life, it has not fully addressed the decline in function and quality of life in frail older people. Frailty is a state of vulnerability to health stressors that needs comprehensive solutions. Its assessment within health care, especially in cardiology, is important owing to its association with worse clinical outcomes. Recent evidence and guidelines suggest that the prescription of a comprehensive exercise regimen, tailored to progressively include strength, balance, mobility, and endurance training improves adherence, functionality, and health-related quality of life, in both acute and chronic cardiovascular diseases. In addition, exercise is a vital tool that improves function, targets frailty, and holistically affects the body's systems. Still, many frail people do not exercise enough, and when they do, they usually do not follow an appropriate plan tailored for better functional outcomes. Overcoming barriers and limitations in exercise enrollment and adherence through strategies such as automated cardiac rehabilitation referral, patient education, and eHealth tools can notably improve clinical outcomes.

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

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

Clinical Utility of Thigh and Mid-Thigh Dual-Energy x-Ray Absorptiometry to Identify Bone and Muscle Loss.

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 >0.95), 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.

Effects of 3 months of multi-nutrient supplementation on the immune system and muscle and respiratory function of older adults in aged care (The Pomerium Study): protocol for a randomised controlled trial.

INTRODUCTION: 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. METHODS AND ANALYSIS: 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 D3 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. ETHICS AND DISSEMINATION: 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. TRIAL REGISTRATION NUMBER: ACTRN12621000420842.

Leucine-enriched whey protein supplementation, resistance-based exercise, and cardiometabolic health in older adults: a randomized controlled trial.

BACKGROUND: Increasing protein intake (above the Recommended Dietary Amount) alone or with resistance-based exercise is suggested to improve cardiometabolic health; however, randomized controlled trials (RCTs) are needed to confirm this. METHODS: The Liverpool Hope University-Sarcopenia Aging Trial (LHU-SAT) was a 16 week RCT (ClinicalTrials.gov Identifier: NCT02912130) of 100 community-dwelling older adults [mean age: 68.73 ± 5.80 years, body mass index: 27.06 ± 5.18 kg/m2 (52% women)] who were randomized to four independent groups [Control (C), Exercise (E), Exercise + Protein (EP), Protein (P)]. E and EP completed supervised and progressive resistance-based exercise (resistance exercise: two times per week, functional circuit exercise: once per week), while EP and P were supplemented with a leucine-enriched whey protein drink (three times per day) based on individual body weight (0.50 g/kg/meal, 1.50 g/kg/day). Outcome measures including arterial stiffness (pulse wave velocity), fasting plasma/serum biomarkers [glucose/glycated haemoglobin, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein, insulin, resistin, leptin, adiponectin, C-reactive protein, tumour necrosis factor-alpha, interleukin-6, cystatin-C, & ferritin], insulin resistance (HOMA-IR), and kidney function (eGFR) were measured before and after intervention. RESULTS: Total protein intake (habitual diet plus supplementation) increased to 1.55 ± 0.69 g/kg/day in EP and to 1.93 ± 0.72 g/kg/day in P, and remained significantly lower (P < 0.001) in unsupplemented groups (E: 1.08 ± 0.33 g/kg/day, C: 1.00 ± 0.26 g/kg/day). At 16 weeks, there was a group-by-time interaction whereby absolute changes in LDL-cholesterol were lower in EP [mean difference: -0.79 mmol/L, 95% confidence interval (CI): -1.29, -0.28, P = 0.002] and P (mean difference: -0.76 mmol/L, 95% CI: -1.26, -0.26, P = 0.003) vs. C. Serum insulin also showed group-by-time interactions at 16 weeks whereby fold changes were lower in EP (mean difference: -0.40, 95% CI: -0.65, -0.16, P = 0.001) and P (mean difference: -0.32, 95% CI: -0.56, -0.08, P = 0.009) vs. C, and fold changes in HOMA-IR improved in EP (mean difference: -0.37, 95% CI: -0.64, -0.10, P = 0.007) and P (mean difference: -0.27, 95% CI: -0.53, -0.00, P = 0.048) vs. C. Serum resistin declined in P only (group-by-time interaction at 16 weeks: P = 0.009). No other interactions were observed in outcome measures (P > 0.05), and kidney function (eGFR) remained unaltered. CONCLUSIONS: Sixteen weeks of leucine-enriched whey protein supplementation alone and combined with resistance-based exercise improved cardiometabolic health markers in older adults.

The effect of vitamin D supplementation on circulating osteoprogenitor cells: A pilot randomized controlled trial.

Circulating osteoprogenitor (COP) cells are a relatively newly discovered mesenchymal precursors population in the peripheral blood. While some aspects of their physiology have been documented in vitro, little is known about their behavior in vivo. To facilitate understanding regarding their potential role in the management of musculoskeletal disease, more research into how these cells respond to growth factors and hormones in vivo is still required. To this end, we performed a randomized controlled pilot study investigating the effect of vitamin D supplementation on COP cells in healthy older adults. Twenty-two individuals were recruited and stratified through their baseline vitamin D levels into deficient (<35 nmol/L), insufficient (35-49 nmol/L) and sufficient (>50 nmol/L) groups, and then randomized to receive either a 50,000 IU bolus dose of vitamin D, along with a 1000 IU daily supplement for six weeks, or the 1000 IU supplement alone. Participants were assessed at baseline, week three, and week six, with the primary outcome being a change in the number of COP cells. Secondary outcomes were vitamin D, markers of bone formation and resorption, parathyroid hormone, and calcium. The study showed that, independently of the dosing, increasing vitamin D levels led to a concomitant 52% increase in COP cell number (p < 0.001). There were no differences between strata, or any of the secondary outcomes in the trial. This suggests that COP cells are regulated in some way by vitamin D, similar to the bone marrow mesenchymal stem cell. Future studies are needed to evaluate the long-term effects of vitamin D supplementation, and how COP cells may be involved in chronic musculoskeletal disease.

Current Evidence and Possible Future Applications of Creatine Supplementation for Older Adults.

Sarcopenia, defined as age-related reduction in muscle mass, strength, and physical performance, is associated with other age-related health conditions such as osteoporosis, osteosarcopenia, sarcopenic obesity, physical frailty, and cachexia. From a healthy aging perspective, lifestyle interventions that may help overcome characteristics and associated comorbidities of sarcopenia are clinically important. One possible intervention is creatine supplementation (CR). Accumulating research over the past few decades shows that CR, primarily when combined with resistance training (RT), has favourable effects on aging muscle, bone and fat mass, muscle and bone strength, and tasks of physical performance in healthy older adults. However, research is very limited regarding the efficacy of CR in older adults with sarcopenia or osteoporosis and no research exists in older adults with osteosarcopenia, sarcopenic obesity, physical frailty, or cachexia. Therefore, the purpose of this narrative review is (1) to evaluate and summarize current research involving CR, with and without RT, on properties of muscle and bone in older adults and (2) to provide a rationale and justification for future research involving CR in older adults with osteosarcopenia, sarcopenic obesity, physical frailty, or cachexia.

Health service use pathways associated with recovery of quality of life at 12-months for individual fracture sites: Analyses of the International Costs and Utilities Related to Osteoporotic fractures Study (ICUROS).

PURPOSE: We aimed to identify combinations of health service use specific to each major osteoporotic fracture (MOF) site - hip, distal forearm, vertebrae and humerus - associated with recovery of health-related quality of life (HRQoL) 12-months post-MOF. METHODS: Patients were 4126 adults aged ≥50 years with a MOF (1657 hip, 1354 distal forearm, 681 vertebral, 434 humerus) from the International Costs and Utilities Related to Osteoporotic fractures Study (Australia, Austria, Estonia, France, Italy, Lithuania, Mexico, Russia, Spain and the UK). HRQoL (pre-fracture and 12-months post-fracture) was measured using the EQ-5D-3L. Health service use data were collected via interviews and medical record reviews and included in-hospital care, outpatient care, supported living, community health services, and medication use. Latent class analyses were undertaken to identify different combinations of health service use ("classes"); and logistic regression to assess associations between classes and HRQoL recovery. Fracture site-specific analyses were performed using pooled data from all 10 countries. RESULTS: The proportion of patients who recovered to their pre-fracture HRQoL at 12-month follow-up varied across fracture sites: 37.3%, 65.8%, 48.9% and 49.5% for hip, distal forearm, vertebrae, and humerus, respectively. We observed several site-specific classes associated with improved odds of HRQoL recovery. Generally, the combination of hospital presentations without admission; primary care center visits; use of osteoporosis-related medications; vitamin D/calcium supplementation; and non-opioid analgesic use was associated with greater likelihood of HRQoL recovery. CONCLUSION: The identified fracture site-specific health service use pathways associated with recovery of HRQoL could potentially improve the management and health outcomes of patients treated for a MOF.

Health Service Use and Quality of Life Recovery 12 Months Following Major Osteoporotic Fracture: Latent Class Analyses of the International Costs and Utilities Related to Osteoporotic Fractures Study (ICUROS).

Major osteoporotic fractures (MOFs) are associated with a rapid decline in health-related quality of life (HRQoL); however, there is limited knowledge about which healthcare services positively affect HRQoL postfracture. This study aimed to identify specific combinations of health service use associated with recovery of HRQoL 12 months post-MOF. The analyses included 4126 adults aged ≥50 years with an MOF (1657 hip, 1354 distal forearm, 681 vertebrae, 434 humerus) participating in the International Costs and Utilities Related to Osteoporotic fractures Study (ICUROS), a multinational observational study (Australia, Austria, Estonia, France, Italy, Lithuania, Mexico, Russia, Spain, United Kingdom, and United States). HRQoL at prefracture and 12 months postfracture was measured using the EuroQoL questionnaire (EQ-5D-3L). Health service use data were collected via participant interviews and medical record reviews including in-hospital care; outpatient care; community services; and medication use. Data analyses involved two stages: (i) latent class analyses to identify different combinations of health service use ("classes"); and (ii) logistic regression to assess effects of classes on HRQoL recovery. Analyses were repeated excluding hip fractures (non-hip MOFs). Overall, 2057 MOF participants (49.9%) recovered to their prefracture HRQoL at 12-month follow-up; this proportion was higher for non-hip MOFs (n = 1439; 58.3%). Several distinct classes were identified across countries (range, 2-5 classes). Classes that were associated with increased odds of HRQoL recovery were characterized by a combination of hospital presentations without admission; outpatient department visits; allied health visits; vitamin D/calcium supplementation; and/or non-opioid analgesic use. Similar classes were observed for non-hip MOFs. Understanding country-specific healthcare service pathways that influence greater recovery of HRQoL, particularly services that are uncommon in some countries and routine in others, could improve postfracture care on a global scale. © 2020 American Society for Bone and Mineral Research (ASBMR).

Nutrients to mitigate osteosarcopenia: the role of protein, vitamin D and calcium.

PURPOSE OF REVIEW: Osteosarcopenia (the joint loss of bone density and muscle mass and function) is an emerging geriatric syndrome, which associates with poor health outcomes. Several nutrients including protein, vitamin D and calcium interact (directly or through absorption properties) to regulate muscle and bone metabolism. We provided an update on the efficacy of these nutrients on musculoskeletal outcomes in older adults with, or at risk of, osteosarcopenia. RECENT FINDINGS: Randomized trials show that correcting vitamin D and calcium deficiencies to meet the recommended dietary allowance (RDA) increases bone density and reduces fracture (but not falls) risk. Supplementing above the RDA with protein supports gains in lean mass and lumbar-spine bone density; however, there is inconclusive evidence for muscle strength, physical function or other bone density sites. A likely explanation for this relates to the significant heterogeneity between trials regarding protein dose, type and timing, as well as baseline protein intake. Further high-quality trials are needed in older osteosarcopenic adults to investigate the effects of protein (while correcting vitamin D and calcium deficiencies) on clinically meaningful outcomes such as activities of daily living, falls and fractures. SUMMARY: An adequate intake of protein (1.2-1.5 g/kg/day), vitamin D (800 IU/day) and calcium (1000-1200 mg/day), is well tolerated and effective at mitigating some aspects of osteosarcopenia such as lean mass, bone density and fracture risk.

Effects of protein supplementation on muscle wasting disorders: A brief update of the evidence.

OBJECTIVE: To examine the effects of protein supplementation on muscle mass, strength and function in individuals at risk of muscle wasting disorders. METHODS: A narrative overview of the literature based on a PubMed search. RESULTS: Increasing protein intake beyond the recommended dietary intake may prevent or attenuate muscle loss in people at risk of muscle wasting disorders; however, there is inconsistent evidence for any benefits on muscle strength or physical function. This is likely due to the significant heterogeneity and bias regarding baseline demographics, basal protein/energy intakes and protein supplement type, dose, timing and compliance. CONCLUSION: Protein supplementation attenuates muscle loss in some populations at increased risk of muscle wasting, but there is no consistent evidence to support benefits on muscle strength or physical function. Further randomised controlled trials are needed that focus on whether there is an optimal type, dose and timing of protein intake, and potential interaction with other nutrients.

Osteosarcopenia: the Path Beyond Controversy.

PURPOSE OF REVIEW: Osteosarcopenia is commonly accepted as the presence of low muscle mass and function (sarcopenia) and low bone mineral density (osteopenia and osteoporosis). Osteosarcopenia remains a topic of controversy as researchers worldwide seek to elucidate whether osteosarcopenia is associated with greater risk of negative outcomes than its component parts. This review examines the latest research and controversies, and charts a path forward. RECENT FINDINGS: Osteosarcopenia may occur in 5-37% of community-dwelling adults over the age of 65. This wide range is driven by variation in population, setting, and definitions applied. These differences in study design have resulted in mixed findings in associations with adverse outcomes for older adults living with osteosarcopenia. Research into interventions to prevent or treat osteosarcopenia, such as exercise, protein supplementation, and pharmacotherapy, is in its infancy but examined herein. The absence of a consensus operational definition of sarcopenia, and inaccurate measures of muscle mass, has hampered global progress in the field. We present a case for the path forward by reflecting on our recent history.

The effect of protein supplements on functional frailty in older persons: A systematic review and meta-analysis.

BACKGROUND: 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. OBJECTIVE: 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). DESIGN: 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 individuals 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. RESULTS: 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). CONCLUSION: Protein supplementation alone does not significantly improve muscle mass, strength or function in pre-frail or frail older people.

The effects of dietary fatty acids on bone, hematopoietic marrow and marrow adipose tissue in a murine model of senile osteoporosis.

Purpose: Marrow adipose tissue (MAT) expansion and associated lipotoxicity are important drivers of age-related bone loss and hematopoietic bone marrow (HBM) atrophy. Fish oil and borage oil (rich in ω3 fatty acids) can partially prevent aged-related bone loss in SAMP8 mice. However, whether preservation of bone mass in this progeria model is associated with MAT volumes remains unknown.Results: MAT volume fraction (MAT%) showed a negative association with hematopoietic bone marrow (HBM%;r=-0.836, p<0.001) and bone (bone%;r=-0.344, p=0.013) volume fractions.Adjusting for multiple comparisons, bone% was higher and MAT% was lower in Fish oil (FO)-supplemented groups vs. controls (p<0.001). HBM% did not differ significantly between the four groups. However, in the group supplemented with FO, HBM comprised higher fractions and MAT constituted lower fractions of total marrow vs. controls (p<0.001).Conclusion: Feeding FO-enriched diet prevented age-related bone and HBM loss, by reducing MAT expansion. Our results further emphasize on the role(s) of MAT expansion in bone and HBM atrophy.Methods: SAMP8 mice (n>9 /group) were allocated into 4 categories and fed a control ration, FO-, sunflower oil (SFO)- and borage oil-enriched diets for lifetime. Femurs were scanned using microcomputed tomography (µCT) and bone, MAT, and HBM volumes were determined using an image analysis software.

Effects of the falls and fractures clinic as an integrated multidisciplinary model of care in Australia: a pre-post study.

OBJECTIVES: 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. SETTING: Falls and Fractures Clinic (FFC) at Nepean Hospital (Penrith, NSW, Australia). PARTICIPANTS: Pre-effects and posteffects assessment of 106 community-dwelling older patients referred from the community. PRIMARY AND SECONDARY OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSIONS: 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.

The Effect of Antidepressants on Mesenchymal Stem Cell Differentiation.

BACKGROUND: Use of antidepressant medications has been linked to detrimental impacts on bone mineral density and osteoporosis; however, the cellular basis behind these observations remains poorly understood. The effect does not appear to be homogeneous across the whole class of drugs and may be linked to affinity for the serotonin transporter system. In this study, we hypothesized that antidepressants have a class- and dose-dependent effect on mesenchymal stem cell (MSC) differentiation, which may affect bone metabolism. METHODS: Human MSCs (hMSCs) were committed to differentiate when either adipogenic or osteogenic media was added, supplemented with five increasing concentrations of amitriptyline (0.001-10 µM), venlafaxine (0.01-25 µM), or fluoxetine (0.001-10 µM). Alizarin red staining (mineralization), alkaline phosphatase (osteoblastogenesis), and oil red O (adipogenesis) assays were performed at timed intervals. In addition, cell viability was assessed using a MTT. RESULTS: We found that fluoxetine had a significant inhibitory effect on mineralization. Furthermore, adipogenic differentiation of hMSC was affected by the addition of amitriptyline, venlafaxine, and fluoxetine to the media. Finally, none of the tested medications significantly affected cell survival. CONCLUSIONS: This study showed a divergent effect of three antidepressants on hMSC differentiation, which appears to be independent of class and dose. As fluoxetine and amitriptyline, but not venlafaxine, affected both osteoblastogenesis and adipogenesis, this inhibitory effect could be associated to the high affinity of fluoxetine to the serotonin transporter system.

Vitamin D, bones and muscle: myth versus reality.

OBJECTIVES: Evidence regarding the efficacy and dosing of vitamin D on fall and fracture prevention, with or without calcium, is characterised by uncertainty. METHODS: 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. RESULTS AND CONCLUSION: 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 individuals; (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 individuals.

Undercarboxylated osteocalcin, muscle strength and indices of bone health in older women.

We investigated the association between undercarboxylated osteocalcin (ucOC) and lower-limb muscle strength in women over the age of 70years. The study also aims to confirm the association between bone turnover markers and heel ultrasound measures. A post-hoc analysis using data collected as part of a randomized placebo-controlled trial of vitamin D supplementation. An immunoassay was used to quantify total OC (tOC), with hydroxyapatite pre-treatment for ucOC. We determined associations of absolute and relative (ucOC/tOC; ucOC%) measures of ucOC with lower-limb muscle strength, heel ultrasound measures of speed of sound (SOS) and broadband ultrasound attenuation (BUA), bone turnover markers (BTMs; P1NP and CTx) and the acute phase protein alpha-1-antichymotrypsin (α-ACT). ucOC%, but not absolute ucOC concentration, was positively associated with hip flexor, hip abductor and quadriceps muscle strength (all p<0.05). ucOC% was negatively associated with α-ACT (ß-coefficient=-0.24, p=0.02). tOC was positively associated with both P1NP and CTx (p<0.001). For each per unit increase in tOC (µg/L) there was a corresponding lower BUA, SOS and SI (ß-coefficient = -0.28; -0.23 and -0.23, respectively; all p<0.04). In conclusion, ucOC% is positively associated with muscle strength and negatively associated with α-ACT. These data support a role for ucOC in musculoskeletal interactions in humans. Whilst tOC is associated with bone health, ucOC% and ucOC may also be linked to falls and fracture risk by influencing muscle function.