Cost-effectiveness of romosozumab for the treatment of postmenopausal women with osteoporosis at high risk of fracture in Belgium.

This study evaluated the cost-effectiveness of sequential treatment with romosozumab-to-alendronate compared to alendronate monotherapy and teriparatide-to-alendronate, in postmenopausal osteoporotic women from a Belgian healthcare perspective. Romosozumab-to-alendronate was found to be cost-effective compared to alendronate monotherapy and dominant compared to teriparatide-to-alendronate for osteoporotic women at high risk of fracture in Belgium. PURPOSE: This study aimed to evaluate the cost-effectiveness of sequential treatment with romosozumab followed by alendronate compared to alendronate monotherapy and teriparatide followed by alendronate, in postmenopausal osteoporotic women at high risk of fracture, from a Belgian healthcare perspective. Romosozumab is reimbursed in Belgium since December 2021. METHODS: A Markov microsimulation model was used to evaluate the cost-effectiveness of romosozumab-to-alendronate compared to alendronate monotherapy and to teriparatide-to-alendronate over a lifetime horizon. Patients transition between five different health states every 6 months based on fracture risks or death. The model was populated with Belgium-specific epidemiological and cost data, where available. The fracture risk reduction of romosozumab treatment was collated from the ARCH study, and from a published network meta-analysis. Costs were included from a healthcare perspective (NIHDI). Cost-effectiveness was reported in terms of costs per quality-adjusted life year (QALY), reported in Euro (€) 2022. Deterministic (DSA) and probabilistic sensitivity analyses (PSA) were performed. RESULTS: Romosozumab-to-alendronate was associated with 0.12 additional QALYs at an additional cost of €2314 compared to alendronate monotherapy, resulting in an ICER of €19,978. Compared to teriparatide-to-alendronate, romosozumab-to-alendronate was found to be dominant, with higher QALYs and lower costs. The base-case results were robust to uncertainty in the input parameters when conducting the sensitivity analysis. CONCLUSION: Sequential treatment with romosozumab followed by alendronate was found to be cost-effective compared to alendronate monotherapy and dominant compared to teriparatide followed by alendronate for postmenopausal women with osteoporosis at high risk of fracture in Belgium.

Local radiographic risk factors for MRONJ in osteoporotic patients undergoing tooth extraction.

OBJECTIVE: To identify local radiographic risk factors for Medication-Related Osteonecrosis of the Jaws (MRONJ) in osteoporotic patients treated with antiresorptive drugs (ARD) and undergoing tooth extraction. MATERIAL AND METHODS: Patients were included in this retrospective, longitudinal, case-control study, if having at least one administration of ARD, underwent tooth extraction(s), and had pre- and post-operative panoramic radiographs. Additionally, a matched control group was selected. Three calibrated, blinded, and independent observers assessed each tooth extraction site. Statistical analysis compared control against study group, and within the latter, sites MRONJ+ and MRONJ-. RESULTS: In total, 120 patients (99 females/21 males) with 354 tooth extractions were included, from which nine patients (7.5%) and eleven tooth extraction sites (3.1%) developed MRONJ. When comparing control with study group, the latter showed significantly more thickened lamina dura, persistence of the alveolar socket, heterogeneous bone patterns, and sequestrum formation. In the study group, MRONJ developed significantly more in males (19%, p = 0.049), smokers (25%, p = 0.008), in the mandible (82%, p = 0.027), when identifying a radiolucent or sclerotic trabecular pattern (p = 0.004) or when extracting teeth with furcation involvement (p < 0.001), root remnants (p = 0.017), or unrestored caries lesions (p = 0.005). CONCLUSIONS: Tooth extraction sites showing radiographic signs of chronic dental infection are prone to MRONJ.

Trial in Elderly with Musculoskeletal Problems due to Underlying Sarcopenia-Faeces to Unravel the Gut and Inflammation Translationally (TEMPUS-FUGIT): protocol of a cross-sequential study to explore the gut-muscle axis in the development and treatment of sarcopenia in community-dwelling older adults.

BACKGROUND: Gut microbiota (GM) might play a role in muscle metabolism and physiological processes through a hypothesized gut-muscle axis, influencing muscle mass and function and thus, sarcopenia. The Trial in Elderly with Musculoskeletal Problems due to Underlying Sarcopenia-Faeces to Unravel the Gut and Inflammation Translationally (TEMPUS-FUGIT) aims to explore the gut-muscle axis in sarcopenia. METHODS: First, in a cross-sectional case-control phase, 100 community-dwelling adults without sarcopenia will be compared to 100 community-dwelling adults (≥ 65 years) with sarcopenia of similar age-, gender and BMI-ratio, participating in the ongoing 'Exercise and Nutrition for Healthy AgeiNg' (ENHANce; NCT03649698) study. Sarcopenia is diagnosed according to the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria. GM composition and intestinal inflammatory markers (fecal calprotectin, lactoferrin and S100A12) will be determined in fecal samples. Systemic inflammatory markers (hs-CRP, IL-4, IL-6, TNF-α, IL-13, IL-1ß and creatine kinase) will be determined in fasted blood samples. Both groups will be compared using appropriate statistical testing, whereas linear regression will be used for cross-sectional associations between gut, inflammatory and sarcopenia parameters. Second, in the longitudinal phase, sarcopenic older adults will be requested to deliver five fecal samples during the 12-week intervention to assess the effects of protein, omega-3 and a physical exercise program on the GM. DISCUSSION: TEMPUS-FUGIT aims to explore the gut-muscle axis by comparing GM composition between sarcopenic and non-sarcopenic older adults and to determine the association of GM with intestinal and systemic inflammatory markers and sarcopenia-defining parameters (muscle mass, muscle strength and physical performance). Furthermore, effects of single or combined, optimized and individualized anabolic interventions (exercise, protein and omega-3 supplementation), on GM will be explored in persons with sarcopenia. TEMPUS-FUGIT aims to impact clinical practice by clarifying the relationship between the gut-muscle axis and sarcopenia. TEMPUS-FUGIT is expected to contribute to the discovery of clinical and microbial biomarkers for sarcopenia and insights in its pathophysiology, opening possible future perspectives for novel sarcopenia treatment strategies targeting GM. TRIAL REGISTRATION: ClinicalTrails.gov NCT05008770, registered on August 17, 2021; first participant enrolled on September 21 2021.

Are dietary intake and nutritional status of specific polyunsaturated fatty acids correlated with sarcopenia outcomes in community-dwelling older adults with sarcopenia? - Exploratory results from ENHANce.

AIMS: To explore the relationship between dietary polyunsaturated fatty acids (PUFAs) intake, nutritional PUFAs status and sarcopenia outcomes in sarcopenic older adults. METHODS: The Exercise and Nutrition for Healthy AgeiNg (ENHANce) is an ongoing 5-armed triple blinded randomized controlled trial, in sarcopenic older adults (> 65y) aiming to assess the effect of combined anabolic interventions (protein, omega-3 supplement and exercise) on physical performance in these adults, compared to single/placebo interventions. Baseline data were used for a secondary, exploratory, cross-sectional analysis. Dietary PUFAs intake was assessed with 4-day food records, status with RBC membrane fatty acids profiles. Spearman's rho(ρ) correlation coefficients were calculated to explore associations of PUFAs intake and status with sarcopenia-defining parameters (muscle strength, mass and physical performance), physical activity (step count) and quality of life (SF-36, SarQoL). RESULTS: In total, 29 subjects (9♂/20♀, mean age 76.3 ± 5.4y) were included. Total omega-3 intake of participants (1.99 ± 0.99 g/d) was below the recommended intake (♂:2.8-5.6 g/d; ♀:2.2-4.4 g/d). Intake and status of PUFAs were not correlated. Regarding correlations with outcomes, α-linolenic acid status was inversely associated with appendicular lean mass (aLM) (ρ:-0.439; p = 0.017), whereas docosahexaenoic acid status was positively associated with aLM (ρ:0.388; p = 0.038). Some omega-3 PUFAs intake and status markers were positively associated with step count, SF-36 and SarQoL scores, whereas gamma-linolenic acid status was inversely associated with SF-36 physical component summary score (ρ = -0.426; p = 0.024). CONCLUSIONS: Although intake of omega-3 and omega-6 was low, the present exploratory study generated new hypotheses for potential correlations of PUFAs intake and status with sarcopenia outcomes in older adults with sarcopenia.

Does testosterone influence the association between sleep and frailty in men: results from the European Male Aging Study.

BACKGROUND: Previous studies have suggested an association between sleep disturbance and frailty. The mechanism is unknown, although it has been suggested that hormonal factors may play a role. METHODS: The aim was to determine the association between sleep duration, sleep quality and frailty, and to determine whether testosterone influenced this association. Males aged 40-79 years were recruited from eight European centres to the European Male Aging Study (EMAS). Subjects completed an interviewer-assisted questionnaire including questions regarding sleep quality and duration. Sleep quality was scored 0-20 and categorised as 0-4, 5-9, 10-14, and 15-20, with higher scores indicating poorer quality. A 39-component frailty index (FI) was constructed. Total testosterone levels were measured. The association between sleep duration, sleep quality and the FI was assessed using negative binomial regression, with adjustment for putative confounders including testosterone level. RESULTS: Two thousand three hundred ninety-three participants contributed data to the analysis. The mean age was 63.3 years and mean sleep duration was 7.01 h. The mean frailty index was 0.15. Mean testosterone levels declined with decreasing sleep quality. After adjustment, compared to those with a sleep score of 0-4, the FI was 57% (95% CI 38%, 78%) higher among those with a sleep score of 15-20. After adjustment compared to those with normal sleep duration (6-9 h), those with a short (< 6 h) and long (≥ 9 h) sleep duration had a 16% (95% CI 6%, 28%) and 11% (95% CI 0%, 23%) higher FI, respectively. Adjustment for testosterone did not influence the strength of either association. CONCLUSION: Frailty is associated with impaired sleep quality and sleep duration. The association cannot, however, be explained by variation in testosterone levels.

Romosozumab efficacy and safety in European patients enrolled in the FRAME trial.

In this post hoc analysis, we assessed romosozumab efficacy and safety in European patients enrolled in FRAME. Romosozumab treatment through 12 months, followed by denosumab for a further 24 months, resulted in early and sustained risk reduction for major fracture categories, associated with large gains in bone mineral density. INTRODUCTION: In the multinational FRAME phase 3 trial of romosozumab in postmenopausal women with osteoporosis, marked differences between clinical and non-vertebral fracture outcomes were observed among patients from Central and Southern America versus rest of world. This post hoc analysis assessed romosozumab efficacy and safety in European patients enrolled in the FRAME trial and extension study. METHODS: In FRAME (NCT01575834), patients were randomised 1:1 to romosozumab 210 mg or placebo monthly (QM) for 12 months, followed by open-label denosumab 60 mg Q6M to month 36, including a 12-month extension study. We report incidence of major fracture outcomes, bone mineral density (BMD) change from baseline and safety for European patients enrolled in FRAME. RESULTS: In FRAME, 3013/7180 (41.96%) patients were European; 1494 received romosozumab and 1519 received placebo. Through 12 months, romosozumab reduced fracture risk versus placebo for non-vertebral fracture (1.4% versus 3.0%; p = 0.004), clinical fracture (1.4% versus 3.6%; p < 0.001), new vertebral fracture (0.4% versus 2.1%; p < 0.001) and major osteoporotic fracture (0.9% versus 2.8%; p < 0.001), with results sustained through 36 months following transition to denosumab. Hip fractures were numerically reduced with romosozumab at month 12 (0.2% versus 0.6%; p = 0.092). Romosozumab increased BMD versus placebo at month 12; all patients in the romosozumab and placebo groups experienced further increases by month 36 after transition to denosumab. Adverse events were balanced between groups. CONCLUSIONS: Among European patients in FRAME, romosozumab resulted in early and sustained risk reduction for all major fracture categories, associated with large BMD gains that continued after transition to denosumab.

Effects of Orthogeriatric Care Models on Outcomes of Hip Fracture Patients: A Systematic Review and Meta-Analysis.

Orthogeriatrics is increasingly recommended in the care of hip fracture patients, although evidence for this model is conflicting or at least limited. Furthermore, there is no conclusive evidence on which model [geriatric medicine consultant service (GCS), geriatric medical ward with orthopedic surgeon consultant service (GW), integrated care model (ICM)] is superior. The review summarizes the effect of orthogeriatric care for hip fracture patients on length of stay (LOS), time to surgery (TTS), in-hospital mortality, 1-year mortality, 30-day readmission rate, functional outcome, complication rate, and cost. Two independent reviewers retrieved randomized controlled trials, controlled observational studies, and pre/post analyses. Random-effects meta-analysis was performed. Thirty-seven studies were included, totaling 37.294 patients. Orthogeriatric care significantly reduced LOS [mean difference (MD) - 1.55 days, 95% confidence interval (CI) (- 2.53; - 0.57)], but heterogeneity warrants caution in interpreting this finding. Orthogeriatrics also resulted in a 28% lower risk of in-hospital mortality [95%CI (0.56; 0.92)], a 14% lower risk of 1-year mortality [95%CI (0.76; 0.97)], and a 19% lower risk of delirium [95%CI (0.71; 0.92)]. No significant effect was observed on TTS and 30-day readmission rate. No consistent effect was found on functional outcome. Numerically lower numbers of complications were observed in orthogeriatric care, yet some complications occurred more frequently in GW and ICM. Limited data suggest orthogeriatrics is cost-effective. There is moderate quality evidence that orthogeriatrics reduces LOS, in-hospital mortality, 1-year mortality, and delirium of hip fracture patients and may reduce complications and cost, while the effect on functional outcome is inconsistent. There is currently insufficient evidence to recommend one or the other type of orthogeriatric care model.

Patient-related risk factors for in-hospital functional decline in older adults: A systematic review and meta-analysis.

BACKGROUND: Functional decline (FD) is a common and serious problem among hospitalised older adults. OBJECTIVE: This systematic review and meta-analysis aims to identify patient-related risk factors for in-hospital FD in older adults. METHODS: Previous reviews on this topic (1970-2007) and the databases PubMed, Embase, and CINAHL (January 2007-December 2020) were searched. Reference lists of included articles were screened. Studies investigating patient-related risk factors for FD from (pre)admission to discharge in older adults admitted to an acute geriatric or internal medical unit were included. Study quality was assessed using the modified Newcastle-Ottawa Scale. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using random-effects models. The quality of evidence was assessed using GRADE. RESULTS: Twenty-nine studies met the inclusion criteria. Statistically significant risk factors were living in a nursing home (OR, 2.42; 95% CI, 1.29-4.52), impairment in instrumental activities of daily living (OR, 2.08; 95% CI, 1.51-2.86), history of falls (OR, 1.71; 95% CI, 1.00-2.92), cognitive impairment (OR, 1.83; 95% CI, 1.56-2.14), dementia (OR, 1.71; 95% CI, 1.23-2.38), delirium (OR, 2.34; 95% CI, 1.88-2.93), (risk of) malnutrition (OR, 1.76; 95% CI, 1.03-3.03), hypoalbuminemia (OR, 1.79; 95% CI, 1.36-2.36), comorbidity (OR, 1.09; 95% CI, 1.03-1.16), and the presence of pressure ulcers (OR, 3.33; 95% CI, 1.82-6.09). The narrative synthesis suggested prehospital FD, needing assistance with walking, and low body mass index as additional risk factors. CONCLUSIONS: Several patient-related risk factors for in-hospital FD were identified that can be used at hospital admission to identify older patients at risk of FD.

SARC-F Is Inaccurate to Identify Geriatric Rehabilitation Inpatients at Risk for Sarcopenia: RESORT.

INTRODUCTION: Sarcopenia is highly prevalent in geriatric rehabilitation inpatients; screening using the Strength, Assistance in walking, Rise from a chair, Climb stairs, Falls history questionnaire (SARC-F) has been recommended. This study assessed the diagnostic accuracy of the SARC-F in identifying sarcopenia according to the European Working Group on Sarcopenia in Older People (EWGSOP), EWGSOP2, and Asian Working Group for Sarcopenia (AWGS) definitions in geriatric rehabilitation inpatients. METHODS: REStOring health of acutely unwell adulTs (RESORT) is an observational, longitudinal cohort of geriatric rehabilitation inpatients. The SARC-F was completed for 2 time-points, status at preadmission (1 month before admission) and at admission; a score ≥4 was considered at risk for sarcopenia. Muscle mass (bioelectrical impedance analysis), handgrip strength (handheld dynamometry), and gait speed (4-m walk test) were measured at admission. Diagnostic accuracy was determined by sensitivity, specificity, and area under the curve (AUC). RESULTS: The sarcopenia prevalence (n = 290, median age 84.0 years [IQR 79.0-89.0], 56.9% female) was 40.3% (EWGSOP1), 25.4% (EWGSOP2), and 38.8% (AWGS). For preadmission and admission status, respectively, the SARC-F identified 67.9 and 82.1% (EWGSOP), 66.0 and 81.0% (EWGSOP2), and 67.5 and 81.6% (AWGS) inpatients at risk for sarcopenia. The SARC-F showed fair sensitivity (67-74%), poor specificity (32-37%), and poor AUC (0.411-0.474) to identify inpatients at risk for sarcopenia at preadmission status, and fair-good sensitivity (79-84%), poor specificity (17-20%), and poor AUC (0.401-0.432) to identify inpatients at risk for sarcopenia at admission, according to EWGSOP, EWGSOP2, and AWGS definitions. CONCLUSION: The SARC-F showed poor diagnostic accuracy in identifying sarcopenia in geriatric rehabilitation inpatients. Assessment of sarcopenia is recommended without screening.

Update on the ESCEO recommendation for the conduct of clinical trials for drugs aiming at the treatment of sarcopenia in older adults.

BACKGROUND: In 2016, an expert working group was convened under the auspices of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and formulated consensus recommendations for the conduct of clinical trials for drugs to prevent or treat sarcopenia. AIMS: The objective of the current paper is to provide a 2020 update of the previous recommendations in accordance with the evidence that has become available since our original recommendations. METHODS: This paper is based on literature reviews performed by members of the ESCEO working group and followed up with face to face meetings organized for the whole group to make amendments and discuss further recommendations. RESULTS: The randomized placebo-controlled double-blind parallel-arm drug clinical trials should be the design of choice for both phase II and III trials. Treatment and follow-up should run at least 6 months for phase II and 12 months for phase III trials. Overall physical activity, nutrition, co-prescriptions and comorbidity should be recorded. Participants in these trials should be at least 70-years-old and present with a combination of low muscle strength and low physical performance. Severely malnourished individuals, as well as bedridden patients, patients with extremely limited mobility or individuals with physical limitations clearly attributable to the direct effect of a specific disease, should be excluded. Multiple outcomes are proposed for phase II trials, including, as example, physical performance, muscle strength and mass, muscle metabolism and muscle-bone interaction. For phase III trials, we recommend a co-primary endpoint of a measure of functional performance and a Patient Reported Outcome Measure. CONCLUSION: The working group has formulated consensus recommendations on specific aspects of trial design, and in doing so hopes to contribute to an improvement of the methodological robustness and comparability of clinical trials. Standardization of designs and outcomes would advance the field by allowing better comparison across studies, including performing individual patient-data meta-analyses, and different pro-myogenic therapies.

Hypophosphatasia in Adults: Clinical Spectrum and Its Association With Genetics and Metabolic Substrates.

BACKGROUND: Hypophosphatasia (HPP) is a rare metabolic bone disorder caused by mutations in the alkaline phosphatase (ALPL) gene, and characterized by low circulating alkaline phosphatase (ALP) levels and bone, muscle, dental and systemic manifestations. In this case series we investigate the clinical spectrum, genetic and biochemical profile of adult HPP patients from the University Hospitals Leuven, Belgium. METHODOLOGY: Adults with HPP were identified through medical record review. Inclusion criteria were: (1) age ≥ 16 yr; (2) consecutively low ALP levels not explained by secondary causes; (3) one or more of the following supporting criteria: biochemical evidence of elevated enzyme substrates; subtrochanteric fractures, metatarsal fractures or other typical clinical features; family history of HPP; a known or likely pathogenic ALPL mutation. RESULTS: Nineteen patients met our inclusion criteria (n = 2 infantile, n = 6 childhood, n = 10 adult-onset HPP and one asymptomatic carrier). Fractures and dental abnormalities were the most reported symptoms. Fatigue was reported in n = 7/19 patients (37%), three of which had previously been misdiagnosed as having chronic fatigue syndrome and/or fibromyalgia. Empirical pyridoxine therapy in four patients (without seizures) did not provide symptomatic relief. N = 7/19 patients (37%) were inappropriately treated or planned to be treated with antiresorptive treatment. Two patients developed atypical femoral fractures following exposure to bisphosphonates and/or denosumab. Patients detected by screening were less severely affected, while patients with homozygous or compound heterozygous mutations had the most severe symptoms, significantly lower circulating ALP levels (p = 0.013) and significantly higher pyridoxal-5'-phosphate (p = 0.0018) and urinary phosphoethanolamine (p = 0.0001) concentrations. CONCLUSIONS: Screening may detect mainly less severely affected individuals, which may nevertheless avoid misdiagnosis and inappropriate antiresorptive drug exposure. Patients with biallelic mutations had more severe symptoms, significantly lower ALP and higher substrate levels. Whether the latter finding has implications for the classification and treatment of HPP should be investigated further in larger cohorts.

Exercise and Nutrition for Healthy AgeiNg (ENHANce) project - effects and mechanisms of action of combined anabolic interventions to improve physical functioning in sarcopenic older adults: study protocol of a triple blinded, randomized controlled trial.

BACKGROUND: The Exercise and Nutrition for Healthy AgeiNg (ENHANce) project aims to assess the combined effects of exercise and nutritional interventions to prevent loss of skeletal muscle mass and function with ageing, and to determine the underlying mechanisms of action. METHODS: One hundred eightycommunity-dwelling sarcopenic individuals (≥ 65 years) are allocated in a randomized controlled trial (RCT) in a 1:1 ratio into five groups for a 12-week intervention period, followed by a 12-week follow-up period: 1) exercise intervention +protein placebo +omega-3 fatty acids placebo; 2) protein +omega-3 fatty acids placebo; 3) exercise intervention +protein +omega-3 fatty acids placebo; 4) exercise intervention +protein +omega-3 fatty acids; 5) protein placebo +omega-3 fatty acids placebo. All interventions are in line with recommendations of expert groups such as the American College of Sports Medicine and the PROT-AGE study group and individualized to the physical capabilities and nutritional intake of each participant. Sarcopenia is diagnosed by the assessment of gait speed, handgrip strength (Jamar handheld dynamometer), chair stand test and muscle mass (DXA) according to the European Working Group on Sarcopenia in Older People (EWGSOP2) criteria. Participants, researchers and statisticians are blinded to omega-3 fatty acids and protein treatment. Compliance to the exercise program, protein and omega-3 fatty acids interventions is objectively measured, by monitoring movement by an activity monitor, determining nitrogen content in urine and analyzing the fatty acid composition of the red blood cell membrane. The primary outcome of the RCT is the change in Short Physical Performance Battery (SPPB) score. Secondary endpoints are, among others, changes in muscle mass, strength and function, objective compliance to interventions, changes in muscle and blood biomarkers related to sarcopenia, cognition, quality of life and falls. DISCUSSION: This RCT in well-defined sarcopenic older adults assesses the effects of combined anabolic interventions, including the additive effects of omega-3 fatty acids supplements, compared to single or placebo interventions. Compliance with the exercise intervention and with the intake of nutritional supplements is measured objectively. Also, blood and muscle samples will be used to explore the underlying determinants that contribute to the mechanism of action of anabolic interventions. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03649698 , retrospectively registered at 28 August 2018, first participant was randomized 16 February 2018.

The role of omega-3 in the prevention and treatment of sarcopenia.

Sarcopenia is a geriatric syndrome with increasing importance due to the aging of the population. It is known to impose a major burden in terms of morbidity, mortality and socio-economic costs. Therefore, adequate preventive and treatment strategies are required. Progressive resistance training and protein supplementation are currently recommended for the prevention and treatment of sarcopenia. Omega-3 polyunsaturated fatty acids (PUFAs) might be an alternative therapeutic agent for sarcopenia due to their anti-inflammatory properties, which target the 'inflammaging', the age-related chronic low-grade inflammation which is assumed to contribute to the development of sarcopenia. In addition, omega-3 PUFAs may also have an anabolic effect on muscle through activation of the mTOR signaling and reduction of insulin resistance. This narrative review provides an overview of the current knowledge about omega-3 PUFAs and their role in the prevention and treatment of sarcopenia. We conclude that there is growing evidence for a beneficial effect of omega-3 PUFAs supplementation in sarcopenic older persons, which may add to the effect of exercise and/or protein supplementation. However, the exact dosage, frequency and use (alone or combined) in the treatment and prevention of sarcopenia still need further exploration.

Glycemia but not the Metabolic Syndrome is Associated with Cognitive Decline: Findings from the European Male Ageing Study.

OBJECTIVE: Previous research has indicated that components of the metabolic syndrome (MetS), such as hyperglycemia and hypertension, are negatively associated with cognition. However, evidence that MetS itself is related to cognitive performance has been inconsistent. This longitudinal study investigates whether MetS or its components affect cognitive decline in aging men and whether any interaction with inflammation exists. METHODS: Over a mean of 4.4 years (SD ± 0.3), men aged 40-79 years from the multicenter European Male Ageing Study were recruited. Cognitive functioning was assessed using the Rey-Osterrieth Complex Figure (ROCF), the Camden Topographical Recognition Memory (CTRM) task, and the Digit Symbol Substitution Test (DSST). High-sensitivity C-reactive protein (hs-CRP) levels were measured using a chemiluminescent immunometric assay. RESULTS: Overall, 1,913 participants contributed data to the ROCF analyses and 1,965 subjects contributed to the CTRM and DSST analyses. In multiple regression models the presence of baseline MetS was not associated with cognitive decline over time (p > 0.05). However, logistic ordinal regressions indicated that high glucose levels were related to a greater risk of decline on the ROCF Copy (ß = -0.42, p < 0.05) and the DSST (ß = -0.39, p < 0.001). There was neither a main effect of hs-CRP levels nor an interaction effect of hs-CRP and MetS at baseline on cognitive decline. CONCLUSION: No evidence was found for a relationship between MetS or inflammation and cognitive decline in this sample of aging men. However, glycemia was negatively associated with visuoconstructional abilities and processing speed.

Evaluation of cognitive subdomains, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D in the European Male Ageing Study.

PURPOSE: Although lower levels of vitamin D have been related to poor cognitive functioning and dementia in older adults, evidence from longitudinal investigations is inconsistent. The objective of this study was to determine whether 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] levels are associated with specified measures of cognitive decline in ageing men. METHODS: The European Male Ageing Study (EMAS) followed 3369 men aged 40-79 over 4.4 years. 25(OH)D levels at baseline were measured by radioimmunoassay, and 1,25(OH)2D levels were obtained with liquid chromatography-tandem mass spectrometry. Visuoconstructional abilities, visual memory, and processing speed at baseline and follow-up were assessed using the Rey-Osterrieth Complex Figure Test (ROCF), Camden Topographical Recognition Memory (CTRM), and the Digit Symbol Substitution Test (DSST). RESULTS: Following attritions, a total of 2430 men with a mean (SD) age of 59.0 (10.6) were included in the analyses. At baseline, the mean 25(OH)D concentration was 64.6 (31.5) nmol/l, and mean 1,25(OH)2D level was 59.6 (16.6) pmol/l. In age-adjusted linear regression models, high 25(OH)D concentrations were associated with a smaller decline in the DSST (ß = 0.007, p = 0.020). Men with low 25(OH)D levels (<50 nmol/l) showed a greater decline in the CTRM compared to men with higher (≥75 nmol/l) levels (ß = -0.41, p = 0.035). However, these associations disappeared after adjusting for confounders such as depressive symptoms, BMI, and comorbidities. There was no indication of a relationship between 1,25(OH)2D and decline in cognitive subdomains. CONCLUSION: We found no evidence for an independent association between 25(OH)D or 1,25(OH)2D levels and visuoconstructional abilities, visual memory, or processing speed over on average 4.4 years in this sample of middle-aged and elderly European men.

Frailty and bone health in European men.

Background: frailty is associated with an increased risk of fragility fractures. Less is known, however, about the association between frailty and bone health. Methods: men aged 40-79 years were recruited from population registers in eight European centres for participation in the European Male Aging Study. Subjects completed a comprehensive assessment which included quantitative ultrasound (QUS) scan of the heel (Hologic-SAHARA) and in two centres, dual-energy bone densitometry (dual-energy x-ray absorptiometry, DXA). Frailty was defined based on an adaptation of Fried's phenotype criteria and a frailty index (FI) was constructed. The association between frailty and the QUS and DXA parameters was determined using linear regression, with adjustments for age, body mass index and centre. Results: in total, 3,231 subjects contributed data to the analysis. Using the Fried categorisation of frailty, pre-frail and frail men had significantly lower speed of sound (SOS), broadband ultrasound attenuation (BUA) and quantitative ultrasound index (QUI) compared to robust men (P< 0.05). Similar results were seen using the FI after categorisation into 'high', 'medium' and 'low' levels of frailty. Using the Fried categorisation, frail men had lower femoral neck bone mineral density (BMD) compared to robust men (P < 0.05), but not lower lumbar spine BMD. Using the FI categorisation, a 'high' level of frailty (FI > 0.35) was associated with lower lumbar spine BMD (P < 0.05) when compared to those with low (FI < 0.2), but not lower femoral neck BMD. When analysed as a continuous variable, higher FI was linked with lower SOS, BUA and QUI (P < 0.05). Conclusions: optimisation of bone health as well as prevention of falls should be considered as strategies to reduce fractures in frail older people.

[The use of fall prevention strategies in home care: a survey in Flanders]. / Het toepassen van valpreventiemaatregelen bij thuiswonende ouderen: een survey onderzoek in Vlaanderen.

OBJECTIVES: Falls in community-dwelling older persons occur frequently. The consequences emphasize the need to screen systematically for an increased fall risk and a targeted multifactorial and multidisciplinary approach. This study describes the extent to which fall prevention strategies are applied by primary healthcare workers in Flanders. Insight in barriers is provided. METHOD: An online survey was collected by the Centre of Expertise for Falls and fracture Prevention Flanders. RESULTS: 1483 respondents are included. 93% are confronted monthly with falls. 96% believe they can make a positive contribution to fall prevention. At least once a year, respondents inquire about falls (62%) and screen for gait/balance problems (84%). A multifactorial assessment is performed in case of a recent fall (95%) or an increased fall risk (76%). Most frequently respondents give advice on safe environment/behaviour (93%), walking aid (91%), personal alarm system (89%) and footwear (85%). Unmotivated older persons (75%) who ignore their fall risk (85%), insufficient time (60%), financial compensation (54%), staff (50%), communication (31%) and knowledge (23%) are important barriers. CONCLUSIONS: Although respondents are aware of the importance of fall prevention, these results reveal a necessity of sufficient knowledge, structured multidisciplinary cooperation and a clear policy. Raising awareness of older persons remains crucial.