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Background: Iron deficiency (ID) is associated with negative health outcomes in older adults. However, data on the impact of ID on the number of hospitalizations and length of hospital stay (LOS) is lacking. Objective: To explore the associations between baseline ID and the number of hospitalizations and between baseline ID and at least one LOS ≥5 days in community-dwelling older adults. Methods: This is a secondary observational analysis of a randomized controlled trial including 2157 community-dwelling adults aged ≥70 years without major diseases at baseline. The main exposure was defined as ID (soluble transferrin receptor [sTfR] concentrations >28.1 nmol/L) at baseline. The primary outcome was the number of hospitalizations over a 3-year follow-up. The secondary outcome was having at least one LOS ≥5 days over the study period among individuals with one or more hospitalizations. Interaction between ID and anemia (hemoglobin <130 g/L for men and <120 g/L for women) was also investigated. Results: Baseline sTfR concentration was determined in 2141 participants (median age 74.0 years). At 3 year, 1497 hospitalizations were reported with an incidence rate of hospitalization of 0.26 per person-year (95% CI: 0.24, 0.28). Overall, baseline ID was associated with a 24% increased incidence rate of hospitalization (incidence rate ratio: 1.24; 95% CI: 1.05, 1.45) over 3 years. This association was independent of anemia status at baseline since the interaction between ID and anemia at baseline was not significant. Moreover, ID was not significantly associated with having a LOS ≥5 days (OR: 1.40; 95% CI: 1.00, 1.97) among participants with at least one hospitalization over 3 years. Conclusions: ID is associated with increased hospitalization rate and not associated with LOS ≥5 days among generally healthy older adults. Efforts to minimize ID in older adults may improve overall health and optimize healthcare costs. [ABSTRACT FROM AUTHOR]

Background The roles of vitamin D, omega-3 fatty acids, and home exercise on fall prevention among generally healthy and active older adults are unclear. Objectives We tested the effects of daily supplemental vitamin D, daily supplemental marine omega-3s fatty acids, and a simple home exercise program (SHEP), alone or in combination, on the incidences of total and injurious falls among generally healthy older adults. Methods We performed a 2 × 2 × 2 factorial–design randomized controlled trial among 2157 community-dwelling adults aged 70 years and older, who had no major health events in the 5 years prior to enrolment, recruited from Switzerland, Germany, Austria, France, and Portugal between December 2012 and November 2014. Participants were randomly assigned to supplementation with 2000 international units/day of vitamin D3 and/or 1 g/day of marine omega-3s, and/or a SHEP compared with placebo and/or control exercise over 3 years. The primary endpoint for the present fall analysis was the incidence rate of total falls. Falls were recorded prospectively throughout the trial. Since there were no interactions between treatments, the main effects are reported based on a modified intent-to-treat analysis. Results Of 2157 randomized participants, 1900 (88%) completed the study. The mean age was 74.9 years, 61.7% were women, 40.7% had a serum 25-hydroxyvitamin D concentration < 20 ng/ml, and 83% were at least moderately physically active. In total, 3333 falls were recorded over a median follow-up of 2.99 years. Overall, vitamin D and the SHEP had no benefit on total falls, whilst supplementation with omega-3s compared to no omega-3 supplementation reduced total falls by 10% (incidence rate ratio = 0.90; 95% CI, 0.81–1.00; P  = 0.04). Conclusions Among generally healthy, active, and vitamin D–replete older adults, omega-3 supplementation may have a modest benefit on the incidence of total falls, whilst a daily high dose of vitamin D or a SHEP had no benefit. [ABSTRACT FROM AUTHOR]

Background and Aims: Animal and cell models indicated that vitamin D modulates inflammatory activity, which is considered relevant in the pathogenesis of arterial hypertension and cardiovascular diseases. We therefore aimed to investigate the effect of vitamin D supplementation on systemic markers of inflammation in a cohort of hypertensive patients.Methods and Results: The Styrian Vitamin D Hypertension Trial is a single-centre, double-blind, placebo-controlled study conducted from 2011 to 2014 in Austria. We enrolled 200 study participants with arterial hypertension and 25-hydroxy-vitamin-D (25(OH)D) concentration below 30 ng/mL. Study participants were randomized to receive either 2800 IU of vitamin D3 per day or placebo for 8 weeks. The present investigation is a post-hoc analysis using analysis of co-variance (ANCOVA). Outcome measures were biomarkers of inflammation including CRP, leukocytes including subtypes and leukocyte-to-lymphocyte ratio, leucine and kynurenic acid. A total of 187 participants (mean age 60.1 ± 11.3years; 47% women; mean baseline 25(OH)D 21.1 ± 5.6 ng/mL) completed the trial. ANCOVA revealed a mean treatment effect for none of the respective outcomes and no significant results were detected in various subgroup analyses.Conclusion: Vitamin D3 supplementation in hypertensive patients with insufficient 25(OH)D concentrations has no significant effect on lowering markers of systemic inflammation. Further studies investigating the effect of vitamin D on other inflammatory pathways and in populations with severe vitamin D deficiency and a significant inflammatory burden are required.Registration: ClinicalTrials.gov Identifier: NCT02136771; EudraCT No. 2009-018,125-70. Start Date: 2011-04-06. [ABSTRACT FROM AUTHOR]

Background Observational studies report higher blood pressure (BP) among individuals with lower 25-hydroxyvitamin D concentration. Whether dosage of vitamin D supplementation has a differential effect on BP control remains unclear. Objective The study aimed to determine if daily vitamin D supplementation with 2000 IU is more effective than 800 IU for BP control among older adults. Methods This randomized, double-blind, ancillary trial of the Zurich Multiple Endpoint Vitamin D Trial in Knee Osteoarthritis enrolled adults aged ≥60 y who underwent elective surgery due to severe knee osteoarthritis. Participants were randomly assigned to receive high dose (2000 IU) or standard dose (800 IU) daily vitamin D3 for 24 mo. Outcomes included daytime and 24-h mean systolic BP. BP variability and serum 25-hydroxyvitamin D concentration were examined in a post hoc and observational analysis. Results Of the 273 participants randomly assigned, 250 participants completed a follow-up 24-h ambulatory BP monitoring (mean age: 70.4 ± 6.4 y; 47.2% men). The difference in daytime mean systolic BP reduction between the 2000 IU (n  = 123) and 800 IU (n  = 127) groups was not statistically significant (−2.75 mm Hg vs. −3.94 mm Hg; difference: 1.18 mm Hg; 95% CI: −0.68, 3.05; P  = 0.21), consistent with 24-h mean systolic BP. However, systolic BP variability was significantly reduced with 2000 IU (average real variability: −0.37 mm Hg) compared to 800 IU vitamin D3 (0.11 mm Hg; difference: −0.48 mm Hg; 95% CI: −0.94, −0.01; P  = 0.045). Independent of group allocation, maximal reductions in mean BP were observed at 28.7 ng/mL of achieved serum 25-hydroxyvitamin D concentrations. Conclusions While daily 2000 IU and 800 IU vitamin D3 reduced mean systolic BP over 2 y to a small and similar extent, 2000 IU reduced mean systolic BP variability significantly more compared with 800 IU. However, without a placebo control group we cannot ascertain whether vitamin D supplementation effectively reduces BP. This trial was registered at www.clinicaltrials.gov as NCT00599807. [ABSTRACT FROM AUTHOR]

Background Findings on the effects of vitamin D on cognitive performance have been inconsistent and no clinical trials with detailed cognitive testing in healthy older adults have been reported. Objectives We tested whether 2000 IU is superior to 800 IU vitamin D3/d for cognitive performance among relatively healthy older adults. Design We analyzed data on cognitive performance as the secondary outcome of a 2-y double-blind randomized controlled trial that originally investigated the effect of vitamin D3 on knee function and pain in seniors with osteoarthritis. Participants were randomly assigned to either 2000 or 800 IU vitamin D3/d. Capsules had identical appearances and taste. A total of 273 community-dwelling older adults aged ≥60 y were enrolled 6–8 wk after unilateral joint replacement. Inclusion required a baseline Mini Mental State Examination (MMSE) score of 24. We implemented a detailed 2-h cognitive test battery. The primary cognitive endpoint was the score achieved in the MMSE. Secondary endpoints included a composite score of 7 executive function tests, auditory verbal and visual design learning tests, and reaction times. Results At baseline, mean age was 70.3 y, 31.4% were vitamin D–deficient [25(OH)D <20 ng/mL], and mean ± SD MMSE score was 28.0 ± 1.5. Although the mean ± SD 25(OH)D concentrations achieved differed significantly between treatment groups at 24-mo follow-up (2000 IU = 45.1 ± 10.2 ng/mL; 800 IU = 37.5 ± 8.8 ng/mL; P  < 0.0001), none of the primary or secondary endpoints of cognitive performance differed between treatment group. Results by treatment were similar for predefined subgroups of baseline 25(OH)D status (deficient compared with replete) and age (60–69 y compared with ≥70 y). Conclusions Our study does not support a superior cognitive benefit of 2000 IU compared with 800 IU vitamin D/d among relatively healthy older adults over a 24-mo treatment period. This trial was registered at clinicaltrials.gov as NCT00599807. [ABSTRACT FROM AUTHOR]

• There were some inconsistencies between studies, likely due to relatively small sample sizes, assessment of different outcomes using different tools, lack of clarification of exposures and nature of work, follow-up duration and disease duration. • Although a few studies suggested that physically demanding jobs and specific types of activities at work may be associated with increased radiographic progression in axSpA and PsA, many studies indicated that work is not likely to be detrimental and, in some cases, may be beneficial for disease-specific outcomes. • Given the importance of work participation for many people with RMDs to be part of the society and financial independence, finding the right balance between ability to work, beneficial effects of work and the association between work and physical and mental health is key and should receive attention within healthcare consultations. A EULAR taskforce was convened to develop recommendations for lifestyle behaviours amongst people with rheumatic and musculoskeletal diseases (RMDs). This paper reviews the literature on work-related factors and disease-specific outcomes for people with osteoarthritis, rheumatoid arthritis (RA), systemic lupus erythematosus, axial spondyloarthritis (axSpA), psoriatic arthritis, systemic sclerosis (SSc) and gout. Two separate systematic literature reviews (SLRs) were conducted. The first identified SLRs, published between 01/2013 and 09/2018. The second identified original observational and intervention studies published before 05/2019. Manuscripts were included if they assessed the effects of vocational interventions on disease-specific outcomes (i.e. clinical outcomes, patient-reported outcomes, and work outcomes) or if they assessed the association between work-related factors and these outcomes. Medline, Embase, Cochrane Library of systematic reviews and CENTRAL databases were searched. Two SLRs were identified including individuals with SSc and inflammatory arthritis. Subsequently, 23 original manuscripts were identified, with most of them (43.5%) including people with RA and no manuscripts on gout. Most observational studies evaluated the association between work-related factors and work outcomes while limited information was available on the impact of work on clinical outcomes. A few studies suggested that physically demanding jobs have a small detrimental effect on radiographic progression in axSpA and PsA. Intervention studies showed beneficial effects of vocational interventions for disease-specific outcomes, but with small effect sizes. Many studies indicated that work participation is not likely to be detrimental and, in some cases, may be beneficial for RMD-specific outcomes and should therefore receive attention within healthcare consultations. [ABSTRACT FROM AUTHOR]

Background: Ensuring adequate vitamin D status in older adults may reduce the risk of osteoporosis. The serum 25-hydroxyvitamin D [25(OH)D] concentration is the recommended biomarker of vitamin D status, but the optimal serum 25(OH)D concentration for bone health in postmenopausal women remains unclear. Objective: The aim of this study was to apply the highly sensitive (41)Ca skeletal labeling technique and the measurement of urinary (41)Ca:(40)Ca ratios to determine the serum 25(OH)D concentration that has greatest benefit on bone calcium flux in postmenopausal women. Methods: We administered a mean intravenous (41)Ca dose of 870 pmol to healthy postmenopausal women [n = 24, age (mean ± SD): 64 ± 6.0 y] without osteoporosis. After 6 mo, at the nadir of their wintertime serum 25(OH)D status, each of the women sequentially consumed daily oral cholecalciferol supplements of 10, 25, and 50 μg/d (in this order), each for 3 mo. We assessed serum 25(OH)D concentrations monthly and urinary (41)Ca:(40)Ca ratios biweekly. (41)Ca:(40)Ca ratios were measured with low-energy accelerator mass spectrometry. With the use of pharmacokinetic analysis, we determined the effect of varying serum 25(OH)D concentrations on (41)Ca transfer rates. Results: At baseline, the mean (95% CI) serum 25(OH)D concentration was 16.2 (13.5, 18.8) μg/L. After the first, second, and third intervention periods, mean (95% CI) serum 25(OH)D increased to 29.8 (27.2, 32.4), 36.9 (34.2, 39.7), and 46.6 (41.2, 52.0) μg/L, respectively. Supplementation was associated with a downward shift in the urinary (41)Ca:(40)Ca ratio compared with the predicted (41)Ca:(40)Ca ratio without vitamin D supplementation. In the model, the most likely site of action of the increase in serum 25(OH)D was transfer from the central compartment to a fast exchanging compartment. At this transfer rate, predicted values were a concentration with half-maximal effect of 2.33 μg/L and an estimate of the maximal effect of 31.7%. After the first, second, and third intervention periods, the mean changes in this transfer rate were +18.0%, +25.7%, and +28.5%, respectively. Conclusion: In healthy postmenopausal women, increasing serum 25(OH)D primarily affects calcium transfer from the central compartment to a fast exchanging compartment; it is possible that this represents transfer from the extracellular space to the surface of bone. A serum 25(OH)D concentration of ~40 μg/L achieves ~90% of the expected maximal effect on this transfer rate. This trial was registered at clinicaltrials.gov as NCT01053481. [ABSTRACT FROM AUTHOR]

Abstract: Background: Since children have frequent contact with the health care system, while their young parents very often do not, screening children routinely might represent an important opportunity to target the young parents. We examined whether cardiovascular risk factors in children predicted the risk of their parents. Methods: Five silent (hypertension, high triglycerides, high LDL-, high non-HDL-, and low HDL-cholesterol) and two clinical apparent (general and central adiposity) risk factors were compared in 2720 child–parent pairs from a well-defined sample of German elementary school children and parents. Results: All clinical apparent and silent risk factors were significantly correlated between children and their parents, and most pronounced were those for three silent risk factors: HDL cholesterol, LDL cholesterol, and non-HDL cholesterol (correlation coefficient r =0.26–0.28). In multivariate models, adjusting for age and gender, child general and abdominal adiposity conferred a significant 2.9-fold and a 2.6-fold enhanced odds among parents of carrying the same risk factors. Similarly, abnormal LDL, HDL, or non-HDL among children conferred a significant 3.0-fold, 2.0-fold, or 2.9-fold increased odds among parents. The odds of parents appeared stronger if the child had the same sex only for clinical apparent risk factors, and most pronounced for general adiposity. Conclusions: Cardiovascular risk screening in children may serve as a case finding strategy for early prevention in high risk families. The inclusion of silent risk factors in a screening program of school children may be warranted for the high prevalence among children and enhanced case-finding potential among parents. [Copyright &y& Elsevier]

Abstract: Available data supporting a target serum level of at least 75nmol/l 25-hydroxyvitamin D (25-OHD) include studies on bone mineral density (bmd), fracture prevention, lower extremity function, and cancer prevention. Given the high cost and disability from falls, fractures, and cancer treatment a shared threshold for 25-OHD has significant public health implications, especially so, if a large part of the population is below this threshold. This article summarizes available evidence supporting the 75nmol/l threshold, reviews adherence to Vitamin D treatment in fracture trials in regard to achieved anti-fracture efficacy, and finally discusses current recommendations for Vitamin D intake. [Copyright &y& Elsevier]

Recent evidence suggests that vitamin D intakes above current recommendations may be associated with better health outcomes. However, optimal serum concentrations of 25-hydroxyvitamin D [25(OH)D] have not been defined. This review summarizes evidence from studies that evaluated thresholds for serum 25(OH)D concentrations in relation to bone mineral density (BMD), lowerextremity function, dental health, and risk of falls, fractures, and colorectal cancer. For all endpoints, the most advantageous serum concentrations of 25(OH)D begin at 75 nmol/L (30 ng/mL), and the best are between 90 and 100 nmol/L (36-40 ng/mL). In most persons, these concentrations could not be reached with the currently recommended intakes of 200 and 600 IU vitamin D/d for younger and older adults, respectively. A comparison of vitamin D intakes with achieved serum concentrations of 25(OH)D for the purpose of estimating optimal intakes led us to suggest that, for bone health in younger adults and all studied outcomes in older adults, an increase in the currently recommended intake of vitamin D is warranted. An intake for all adults of ⩾1000 IU (40 μg) vitamin D (cholecalciferol)/ d is needed to bring vitamin D concentrations in no less than 50% of the population up to 75 nmol/L. The implications of higher doses for the entire adult population should be addressed in future studies. [ABSTRACT FROM AUTHOR]

Background: Vitamin D has been shown to have immunomodulatory effects in in vitro and in animal studies. However, data from clinical studies of inflammatory diseases are scarce. Objective: The purpose of this study was to evaluate the association between serum concentrations of 25-hydroxyvitamin D [25(OH)D] and gingival inflammation. Design:Weanalyzed data from 77 503 gingival units (teeth) in 6700 never smokers aged 13 to >90 y from the third National Health and Nutrition Examination Survey. Multiple logistic regression models adjusted for subject- and site-specific covariates included age, sex, race-ethnicity, income, body mass index, diabetes, use of oral contraceptives and hormone replacement therapy among women, intake of vitamin C, missing teeth, full crown coverage, presence of calculus, frequency of dental visits, and dental examiner and survey phase. Generalized estimating equations were used to account for correlated observations within subjects. Results: Compared with sites in subjects in the lowest 25(OH)D quintile, sites in subjects in the highest 25(OH)D quintile were 20% (95% CI: 8%, 31%) less likely to bleed on gingival probing (P for trend<0.001). The association appeared to be linear over the entire 25(OH)D range, was consistent across racial or ethnic groups, and was similar among men and women as well as among users and nonusers of vitamin and mineral supplements. Conclusions: Vitamin D may reduce susceptibility to gingival inflammation through its antiinflammatory effects. Gingivitis may be a useful clinical model to evaluate the antiinflammatory effects of vitamin D. [ABSTRACT FROM AUTHOR]

Background: Vitamin D may improve muscle strength through a highly specific nuclear receptor in muscle tissue. Objectives: We investigated whether there is an association between 25-hydroxyvitamin D [25(OH)D] concentrations and lower-extremity function in ambulatory older persons, whether that association differs by activity level, and, if so, whether there is an identifiable threshold in the association. Design: The study was a population-based survey of the ambulatory US population aged 60 to ⩾90 y (n = 4100). Lower-extremity function according to serum 25(OH)D concentrations was assessed by linear regression analyses and regression plots after control for activity level (inactive or active) and several other potential confounders. Separate analyses were performed for the timed 8-foot (ie, 2.4 m) walk test and a repeated sit-to-stand test. Results: The 8-foot walk test compared subjects in the lowest and highest quintiles of 25(OH)D; the latter group had an average decrease of 0.27 s [95% CI: -0.44, -0.09 s (or 5.6%); P for trend < 0.001]. The sit-to-stand test compared subjects in the lowest and highest quintiles of 25(OH)D; the latter group had an average decrease of 0.67 s [95% CI: -1.11, -0.23 s (or 3.9%); P for trend = 0.017]. In the 25(OH)D reference range of 22.5-94 nmol/L, most of the improvement occurred in subjects with 25(OH)D concentrations between 22.5 and≈40 nmol/L, and further improvement was seen in the range of 40-94 nmol/L. Stratification by activity level showed no significant effect modification. Conclusion: In both active and inactive ambulatory persons aged⩾60 y, 25(OH)D concentrations between 40 and 94 nmol/L are associated with better musculoskeletal function in the lower extremities than are concentrations < 40 nmol/L. [ABSTRACT FROM AUTHOR]

Background: Periodontal disease (PD) is a common chronic inflammatory disease and an important risk factor for tooth loss. Vitamin D might affect periodontal disease risk via an effect on bone mineral density (BMD) or via immunomodulatory effects. Objective: The objective was to evaluate whether serum 25- hydroxyvitamin D3 [25(OH)D3] concentrations are associated with PD in the third National Health and Nutrition Examination Survey. Design: We analyzed data on periodontal attachment loss (AL) and serum 25(OH)D3 concentrations from 11 202 subjects aged ≥20 y. Mean AL was modeled in a multiple linear regression with quintile of serum 25(OH)D3 concentration as an independent variable. The model was stratified by age and sex and was adjusted for age within age groups, race or ethnicity, smoking, diabetes, poverty income ratio, body mass index, estrogen use, and gingival bleeding. Results: 25(OH)D3 concentrations were significantly and inversely associated with AL in men and women aged ≥50 y. Compared with men in the highest 25(OH)D33quintile, those in the lowest quintile had a mean AL that was 0.39 mm (95% CI: 0.17, 0.60 mm) higher; in women, the difference in AL between the lowest and highest quintiles was 0.26 mm (0.09, 0.43 mm). In men and women younger than 50 y, there was no significant association between 25(OH)D3 and AL. The BMD of the total femoral region was not associated with AL and did not mediate the association between 25(OH)D3 and AL. Conclusions: Low serum 25(OH)D3 concentrations may be associated with PD independently of BMD. Given the high prevalence of PD and vitamin D deficiency, these findings may have important public health implications. [ABSTRACT FROM AUTHOR]

DO-HEALTH is a multi-center clinical trial among 2157 community-dwelling European men and women age 70 and older. The 2x2x2 randomized-control factorial design trial tested the individual and additive benefit, as well as the cost-effectiveness, of 3 interventions: vitamin D 2000 IU/day, omega-3 fatty acids 1000 mg/day (EPA + DHA, ratio 1:2), and a 30-minute 3 times/week home exercise (strength versus flexibility). Each treatment tested has shown considerable prior promise from mechanistic studies, small clinical trials, or large cohort studies, in the prevention of common age-related chronic diseases, but definitive data are missing. DO-HEALTH will test these interventions in relation to 6 primary endpoints (systolic and diastolic blood pressure, non-vertebral fractures, Short Physical Performance Battery score, the Montreal Cognitive Assessment, and risk of infections), plus several secondary endpoints explored in ancillary studies (i.e. rate of any falls and injurious falls, joint pain, oral health, quality of life, and incident frailty). As the 3 interventions have distinct mechanisms of action for each of the 6 primary endpoints, a maximum benefit is expected for their additive benefit as a "multi-modal" intervention. The trial duration is 3 years with in-person contacts with all participants at 4 clinical visits and by quarterly phone calls. Baseline and follow-up blood samples were collected in all participants to measure changes in 25-hydroxyvitamin D and poly-unsaturated fatty acid concentrations. Our objective was to test interventions that are expected to promote healthy aging and longer life expectancy and that can be easily and safely implemented by older community-dwelling adults. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: Recent large trials indicate that adherence associated with a daily regimen of vitamin D is low and limits anti-fracture efficacy with vitamin D supplementation. The aim of this report is to describe changes of 25-hydroxyvitamin D (25(OH)D) serum concentrations achieved with a single oral dose of 300000 IU vitamin D3. Methods: Over a course of 4 months, we identified 33 elderly with severe vitamin D deficiency (25(OH)D<25 nmol/l) on admission to acute care. Patients were admitted for musculoskeletal pain, bone disease, or gait abnormalities. The mean age was 80.5 years (SD±6.1). All patients were treated with a single oral dose of 300000 IU D3 in combination with 500–1000 mg calcium supplements per day depending on their dietary calcium intake. Results: Baseline mean 25(OH)D serum concentrations were 15 nmol/l (SD±5.5). Mean 25(OH)D serum concentrations increased to 81.4 nmol/l (SD±29.7) at 3 months (29 patients) and were still 69.0 nmol/l (SD±17.9) at 6 months (26 patients). Mean serum calcium levels were 2.24 mmol/l (SD±0.11) at baseline, 2.28 mmol/l (SD±0.18) at 3 months, and 2.28 mmol/l (SD±0.13) at 6 months. Two patients with mild hypercalcemia (2.69 mmol/l) at 3 months had normal values at 6 months. Conclusion: Based on our observations, a single oral dose of 300000 IU vitamin D3 raises mean 25(OH)D serum concentrations to the target mean of above 75 nmol/l at 3 months and a mean level of 69 nmol/l at 6 months. As calcium absorption is enhanced with higher 25(OH)D serum concentrations, calcium supplementation may need downward adjustment with this regimen to avoid mild hypercalcemia. [Copyright &y& Elsevier]

With the increasing number of elderly patients presenting with fragility fractures, their care has become a focus among trauma and orthopaedic surgeons. Protocols are ever evolving to improve the clinical pathways and treatment modalities targeting a more efficient and patient centred service. In this article, current approaches and their potential to reduce mortality and re-fracture in these patients are discussed. [ABSTRACT FROM AUTHOR]

Abstract: A meta-analysis of primary prevention high-quality trials published in 2005 found that oral cholecalciferol (D3) in a daily dose of 700–800 IU or intermittently 100,000 IU every 4 months with or without calcium, should reduce both hip and non-vertebral fracture risk significantly compared to placebo. Trials that administered 400 IU vitamin D did not achieve fracture efficacy. Notably, there was a significant association between higher achieved 25-hydroxyvitamin D levels (25(OH)D) in the treatment groups and fracture efficacy: The minimal mean level where fracture efficacy was observed was 74 nmol/l (25(OH)D). Epidemiological data for bone density and lower extremity strength support this threshold, and high-quality trials that used 700 to 800 IU D3 suggested fall risk reduction by 35 to 65% in institutionalized and community-dwelling older individuals. However, since the 2005 meta-analysis, benefits of vitamin D on fracture and fall reduction have been questioned by results from several recent trials. This review proposes that the interpretation of these recent trials is hindered by different doses of vitamin D, different types of supplemental vitamin D (D3 or ergocalciferol D2), low adherence, concurrent use of supplements outside the study protocol, open study design, short follow-up, and/or different patient risk profiles including primary and secondary fracture prevention. In most recent trials, low adherence, the use of the relatively less potent D2, or a too low dose of D3 (400 IU) may have prohibited a shift of (25(OH)D) levels in the treatment groups to the desirable range of at least 75 nmol/l. In summary, from recent trials, two lesson may be learned: (1) Adherence less than 60% is insufficient to achieve fracture efficacy with daily 800 IU D3 plus calcium, (2) D2 in any application or any previously studied dose may not reduce fractures in institutionalized or community-dwelling older individuals. [Copyright &y& Elsevier]

To evaluate the ability of 3 commonly used frailty measures to predict short-term clinical outcomes in older patients admitted for post-acute inpatient rehabilitation. Observational cohort study. Consecutive patients (n = 207) admitted to a geriatric inpatient rehabilitation facility. Frailty on admission was assessed using a frailty index, the physical frailty phenotype, and the Clinical Frailty Scale (CFS). Predictive capacity of the frailty instruments was analyzed for (1) nonhome discharge, (2) readmission to acute care, (3) functional decline, and (4) prolonged length of stay, using multivariate logistic regression models and receiver operating characteristic (ROC) curves. The number of patients classified as frail was 91 (44.0%) with the frailty index, 134 (64.7%) using the frailty phenotype, and 151 (73.0%) with the CFS. The 3 frailty measures revealed acceptable discriminatory accuracy for nonhome discharge (area under the curve ≥ 0.7) but differed in their predictive ability: the adjusted odds ratio (OR) for nonhome discharge was highest for the CFS [6.2, 95% confidence interval (CI) 1.8-21.1], compared to the frailty index (4.1, 95% CI 2.0-8.4) and the frailty phenotype (OR 2.9, 95% CI 1.2-6.6). For the other outcomes, discriminatory accuracy based on ROC tended to be lower and predictive ability varied according to frailty measure. Readmission to acute care from inpatient rehabilitation was predicted by all instruments, most pronounced by the frailty phenotype (OR 5.4, 95% CI 1.6-18.8) and the frailty index (OR 2.5, 95% CI 1.1-5.6), and less so by the CFS (OR 1.4, 95% CI 0.5-3.8). Frailty measures may contribute to improved prediction of outcomes in geriatric inpatient rehabilitation. The choice of the instrument may depend on the individual outcome of interest and the corresponding discriminatory ability of the frailty measure. [ABSTRACT FROM AUTHOR]

Although aging has a strong impact on visual acuity (VA) and falls, their interaction is understudied in generally healthy older adults. This study aimed to examine if and to what extent baseline VA is associated with an increased risk of all and injurious falls over 3 years in generally healthy community-dwelling older adults. Observational analysis of DO-HEALTH, a double-blind, randomized controlled trial. Multicenter trial with 7 European centers: Zurich, Basel, Geneva (Switzerland), Berlin (Germany), Innsbruck (Austria), Toulouse (France), and Coimbra (Portugal), including 2157 community-dwelling adults aged 70 years and older without any major health events in the 5 years prior to enrollment, sufficient mobility, and good cognitive status. The numbers of all and injurious falls were recorded prospectively by diary and in-person assessment every 3 months. Decreased VA at baseline was defined as better-eye VA lower than 1.0. We applied negative binomial regression models for all and injurious falls, adjusted for age, sex, prior falls, treatment allocation, study site, baseline body mass index, and use of walking aids. Among the 2131 participants included in this analysis (mean age: 74.9 years, 61.7% were women, 82.6% at least moderately physically active), 1464 (68.7%) had decreased VA. Overall, 3290 falls including 2116 injurious falls were recorded over 3 years. Decreased VA at baseline was associated with a 22% increased incidence rate of all falls [adjusted incidence rate ratio (aIRR) = 1.22, 95% CI 1.07, 1.38, P =.003] and 20% increased incidence rate of injurious falls (aIRR = 1.20, 95% CI 1.05, 1.37, P =.007). Our findings suggest that decreased VA is an independent predictor of an about 20% increased risk of all and injurious falls, highlighting the importance of regular eye examinations and VA measurements for fall prevention, even in generally healthy and active older adults. [ABSTRACT FROM AUTHOR]

To assess the validity of 4 functional tests in predicting falls within the first year after hip fracture. Prospective study of functional tests shortly after hip surgery and incident falls during 12 months' follow-up. The sample comprised 173 adults with acute hip fracture, aged 65 years and older (79% women, 77% community dwelling, mean age 84.2 years), who participated in a clinical trial of vitamin D or home exercise. We assessed 4 functional tests [Timed Up and Go test (TUG), grip strength, and knee flexor and extensor strength in the nonoperated leg] by trained study physiotherapists at baseline (1-12 days after hip fracture surgery). During 12 months' follow-up, we ascertained all fall events by monthly personal phone calls, a telephone hotline, and a patient diary. Then we compared TUG and strength test performance at baseline between future single fallers, recurrent fallers, and nonfallers over the 12-month follow-up. All analyses adjusted for age, body mass index, gender, 25-hydroxyvitamin D status at baseline, days of follow-up, and treatment allocation (the original trial tested vitamin D treatment and/or a home exercise program). Ninety-two of 173 (53%) participants fell and experienced 212 falls. Participants who became recurrent fallers (n = 54) had significantly longer TUG times at baseline than those who did not fall (n = 81) in the following 12 months (mean TUG for recurrent fallers = 71.6 seconds, SD = 8.2 seconds, vs mean TUG for nonfallers = 51.4 seconds, SD = 6.9 seconds; P =.02). There were no significant differences in TUG times between single fallers and nonfallers. For all 3 strength tests, there were no significant differences between single fallers, recurrent fallers, and nonfallers. In this population of frail older adults recruited shortly after hip fracture surgery, only the TUG test discriminated between future recurrent fallers and nonfallers over a 12-month follow-up. Because of the high incidence and serious consequences of falls in older adults after a hip fracture, it is very important to identify practical and clinically related tests to predict repeated falls in the first year after a hip fracture, which is of great public health importance. [ABSTRACT FROM AUTHOR]

Abstract Objective With advancing age, the prevalence of vitamin D deficiency and musculoskeletal pain increases. However, published data on the effectiveness of vitamin D supplementation in reducing chronic pain are inconclusive. The purpose of this study was to test the effect of 3 different monthly doses of vitamin D on chronic pain in seniors 70 years and older with a prior fall event. Design 1-year, double-blind randomized clinical trial. Setting The trial was conducted in Zurich, Switzerland. Participants were 200 community-dwelling men and women 70 years and older with a prior fall. Intervention Three study groups with monthly treatments were randomized to either a low-dose control group of vitamin D (24,000 IU vitamin D 3 /mo), a high dose of vitamin D 3 (60,000 IU vitamin D 3 /mo), or a combination of calcifediol and vitamin D 3 (24,000 IU vitamin D 3 plus 300 μg calcifediol/mo). Measurements The primary endpoint was the change in the mean number of painful areas using the McGill Pain map over 12 months of follow-up. All analyses were adjusted for age, sex, body mass index, 25-hydroxyvitamin (OH)D 3 levels, and pain scores at baseline. A predefined subgroup analysis was performed by baseline 25(OH)D status (<20 vs ≥ 20 ng/mL). Results The mean age of the participants was 78 years, 67.0% (134 of 200) were female, and 58.0% (116 of 200) were vitamin D deficient (<20 ng/mL) at baseline. Over 12 months of follow-up, the changes in the mean number of painful areas did not differ significantly among treatment groups (P =.46). However, there was a significant interaction effect between baseline vitamin levels (<20 vs ≥ 20 ng/mL) and treatment (P =.02). Among those who were vitamin D replete at baseline (n = 84), there was a significant difference between treatment groups over time (P =.04), and only seniors in the 24,000-IU vitamin D 3 group had a marginally significant decrease in their total mean pain score (−0.77; 95% CI, −1.56 to 0.01, P =.05), whereas there were no changes in the high-dose groups. Among seniors who were vitamin D deficient at baseline (n = 116), chronic pain did not differ by treatment groups over time (P =.33). Conclusion Our results suggest that both starting level of 25(OH)D 3 and monthly treatment dose of vitamin D may be important with respect to chronic pain reduction—with the only benefit seen among vitamin D–replete seniors treated with a monthly dose of 24,000 IU vitamin D 3. [ABSTRACT FROM AUTHOR]

Approximately 10-20% of inflammatory bowel disease (IBD) cases are diagnosed after 60 years of age. Due to the high prevalence of conditions mimicking IBD at older age - including bowel disease associated with non-steroidal anti-inflammatory drugs, diverticulitis, and microscopic colitis - differential diagnosis of IBD among older adults is frequently delayed. Late-onset IBD is characterized by a predominance of colonic disease and an overall milder disease course; disease progression and new intestinal manifestations are rare. However, older patients are less able to tolerate inflammation and their risk of mortality from severe disease is increased. Management of late-onset IBD has been insufficiently studied since older adults are underrepresented in clinical trials and specific problems of older patients such as incontinence have not been addressed. To date, treatment generally follows the same principles as in the younger. However, older patients are at higher risk of severe adverse effects of the disease and its treatments, including bone and muscle loss, infections and lymphoma. Therefore, the safety profile of a given drug is of paramount importance in older patients with IBD. Colectomy with ileo-anal pouch anastomosis for refractory ulcerative colitis can be performed safely, although functional results may be inferior to those in middle-aged patients. To decrease mortality among older patients, a timely surgical intervention is important. Patients with late-onset IBD frequently develop colorectal carcinoma within 8 years of diagnosis; therefore, colorectal cancer screening immediately after diagnosis should be considered. Further, the clinical care of older patients with IBD needs to extend to overall health, including nutrition, vaccination, bone, muscle and mental health. [ABSTRACT FROM AUTHOR]

Objectives After a hip fracture, 50% of senior patients are left with permanent functional decline and 30% lose their autonomy. The aim of this prospective study was to evaluate whether seniors who are in a caregiver role have better functional recovery after hip fracture compared with noncaregivers. Design Prospective observational study. Setting A total of 107 Swiss patients with acute hip fracture age 65 years and older (84% women; 83.0 ± 6.9 years; 87% community-dwelling). Measurements At baseline, participants were asked if they were caregivers for a person, a pet, or a plant. Lower-extremity mobility was measured using the Timed Up and Go (TUG) test at baseline during acute care (day 1–12 after hip fracture surgery) and at 6 and 12 months follow-up. Subjective physical functioning (SPF) was rated for prefracture values and at 6 and 12 months follow-up using the Short Form 36 Health Survey questionnaire. Differences in TUG performance or SPF between caregivers and noncaregivers at 6 and 12 months were assessed using multivariable repeated-measures analysis adjusted for age, sex, body mass index, Charlson comorbidity index, Mini-Mental State Examination, living condition, baseline TUG, and treatment (vitamin D, home exercise program as part of the original trial). Results At baseline, adjusted TUG performance was better in caregivers of any kind compared with noncaregivers (40.9 vs 84.4 seconds, P < .0001). At 6 months, and after adjustment for baseline TUG performance and other covariates, TUG was better in caregivers of any kind (−6.4 seconds, P = .007) and caregivers of plants (−6.6 seconds, P = .003) compared with noncaregivers. At 12 months, only caregivers of persons had better TUG performance compared with noncaregivers (−7.3 seconds, P = .009). Moreover, at 12 months, SPF was better in caregivers of persons (58.9 vs 45.6, P = .01) and caregivers of any kind (50.8 vs 39.3, P = .02) compared with noncaregivers. Conclusions Senior hip fracture patients who have a caregiver role of any kind, and especially of plants, had better short-term recovery after hip fracture assessed with the TUG. For long-term recovery, senior hip fracture patients who are caregivers for other persons appeared to have a significant benefit. These benefits were independent of baseline function and all other covariates. [ABSTRACT FROM AUTHOR]

To examine the association between the baseline number of chronic diseases and multimorbidity with regard to the incidence of all and injurious falls over 3 years among European community-dwelling older adults. Observational analysis of DO-HEALTH, a double-blind, randomized controlled trial. Multicenter trial with 7 European centers: Zurich, Basel, Geneva (Switzerland), Berlin (Germany), Innsbruck (Austria), Toulouse (France), and Coimbra (Portugal), including 2157 community-dwelling adults aged 70 years and older without any major health events in the 5 years prior to enrollment, sufficient mobility, and good cognitive status. The main outcomes were the number of all falls and injurious falls experienced over 3 years. The number of chronic diseases and multimorbidity, defined as the presence of 3 or more chronic diseases at baseline, were assessed with the Self-Administered Comorbidity Questionnaire by Sangha et al. Among the 2155 participants included in the analyses (mean age: 74.9 years, 62% were women, 52% were physically active more than 3 times a week), 569 (26.4%) had multimorbidity at baseline. Overall, each 1-unit increase in the baseline number of chronic diseases was linearly associated with a 7% increased incidence rate of all falls [adjusted incidence rate ratio (aIRR) 1.07, 95% CI 1.03-1.12, P <.001] and a 6% increased incidence rate of injurious falls (aIRR 1.06, 95% CI 1.02-1.11, P =.003). Baseline multimorbidity was associated with a 21% increased incidence rate of all falls (aIRR 1.21, 95% CI 1.07-1.37, P =.002) and a 17% increased incidence rate of injurious falls (aIRR 1.17, 95% CI 1.03-1.32, P =.02). Baseline number of prevalent chronic diseases and multimorbidity in generally healthy and active community-dwelling older adults were associated with increased incidence rates of all and injurious falls over 3 years. These findings support that multimorbidity may need consideration as a risk factor for falls, even in generally healthy and active older adults. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Long-term pharmacokinetics after supplementation with vitamin D3 or calcifediol (the 25-hydroxyvitamin D3 metabolite) is not well studied. Additionally, it is unclear whether bolus doses of vitamin D3 or calcifediol lead to 25(OH)D3 plasma concentrations considered desirable for fracture prevention (30ng/mL). We therefore investigated plasma pharmacokinetics of 25(OH)D3 during different vitamin D3 and calcifediol supplementation regimens. Methods: In this seven-arm, randomized, double-blind, controlled parallel-group study, 35 healthy females aged 50–70years (5 per group) received 20μg calcifediol or vitaminD3 daily, 140μg calcifediol or vitaminD3 weekly, for 15weeks, or a single bolus of either 140μg calcifediol, or vitaminD3, or both. 25(OH)D3 plasma concentrations were quantified using LC–MS/MS in 14 clinical visits among all participants. Results: For daily (weekly) dosing, the area under the concentration–time curve (AUC0–24h), which is the measure for exposure, was 28% (67%) higher after the first dose of calcifediol than after the first dose of vitamin D3. After 15weeks, this difference was 123% (178%). All women in the daily and weekly calcifediol groups achieved 25(OH)D3 concentrations >30ng/mL (mean, 16.8days), but only 70% in the vitamin D3 daily or weekly groups reached this concentration (mean, 68.4days). A single dose of 140μg calcifediol led to 117% higher 25(OH)D3 AUC0–96h values than 140μg vitamin D3, while the simultaneous intake of both did not further increase exposure. Conclusions: Calcifediol given daily, weekly, or as a single bolus is about 2–3 times more potent in increasing plasma 25(OH)D3 concentrations than vitamin D3. Plasma 25(OH)D3 concentrations of 30ng/mL were reached more rapidly and reliably with calcifediol. [Copyright &y& Elsevier]

Abstract: Background: There is increasing evidence that, in addition to the well-known effects on musculoskeletal health, vitamin D status may be related to a number of non-skeletal diseases. An international expert panel formulated recommendations on vitamin D for clinical practice, taking into consideration the best evidence available based on published literature today. In addition, where data were limited to smaller clinical trials or epidemiologic studies, the panel made expert-opinion based recommendations. Methods: Twenty-five experts from various disciplines (classical clinical applications, cardiology, autoimmunity, and cancer) established draft recommendations during a 2-day meeting. Thereafter, representatives of all disciplines refined the recommendations and related texts, subsequently reviewed by all panelists. For all recommendations, panelists expressed the extent of agreement using a 5-point scale. Results and conclusion: Recommendations were restricted to clinical practice and concern adult patients with or at risk for fractures, falls, cardiovascular or autoimmune diseases, and cancer. The panel reached substantial agreement about the need for vitamin D supplementation in specific groups of patients in these clinical areas and the need for assessing their 25-hydroxyvitamin D (25(OH)D) serum levels for optimal clinical care. A target range of at least 30 to 40ng/mL was recommended. As response to treatment varies by environmental factors and starting levels of 25(OH)D, testing may be warranted after at least 3months of supplementation. An assay measuring both 25(OH)D2 and 25(OH)D3 is recommended. Dark-skinned or veiled individuals not exposed much to the sun, elderly and institutionalized individuals may be supplemented (800IU/day) without baseline testing. [Copyright &y& Elsevier]

Information on the impact of polypharmacy on kidney function in older adults is limited. We prospectively investigated the association between intake of total number of drugs or nonsteroidal anti-inflammatory drugs (NSAIDs) and kidney function. Our study is a prospective observational analysis of the 2-year Zurich Multiple Endpoint Vitamin D Trial in Knee Osteoarthritis Patients. Of the 273 participants of the original trial, 270 participants (mean age 70.3 ± 6.4 years, 53% women) were included in this observational analysis. The associations between (1) total number of drugs (or NSAIDs) at baseline or (2) cumulative number of drugs (or NASAIDs) repeatedly measured over 24 months and kidney function repeatedly measured over 24 months as estimated glomerular filtration rate (eGFR) were investigated using multivariable-adjusted repeated-measures analysis. Per drug at baseline, kidney function decreased by 0.64 mL/min/1.73 m2 eGFR (Beta = −0.64; 95% CI −1.19 to −0.08; P =.024) over 24 months. With every additional drug taken cumulatively over 24 months, kidney function decreased by 0.39 mL/min/1.73 m2 eGFR (Beta = −0.39; 95% CI −0.63 to −0.15; P =.002). In a high-risk subgroup, per NSAID taken cumulatively over 24 months, kidney function declined by 1.21 mL/min/1.73 m2 eGFR (Beta = −1.21; 95% CI −2.35 to −0.07; P =.021). For every additional drug prescribed among older adults, our study supports an independent and immediate harmful impact on kidney function. This negative impact seems to be about 3 times greater for NSAIDs compared with an additional average drug. [ABSTRACT FROM AUTHOR]

To evaluate 2 simple strategies, vitamin D 3 and a home exercise program, in functional recovery during the first year after hip fracture. Secondary analysis of a factorial clinical trial. Patients were randomly allocated to 800 IU (standard of care) or 2000 IU vitamin D 3 and a daily instruction of a simple home exercise program (SHEP) or standard physiotherapy alone during acute care. Acute hip fracture patients aged ≥65 years, after hip fracture surgery, admitted to a large hospital in Zurich, Switzerland. Three objective measures of lower extremity function were assessed at baseline and 6 and 12 months, with the Timed Up and Go test (TUG) as the primary endpoint, and knee flexor and extensor strength, and a self-reported physical function score (PF-10) as secondary endpoints. Linear mixed model regression analyses were based on intention to treat, adjusting for baseline function, time, age, sex, and baseline 25-hydroxyvitamin D level. We enrolled 173 patients (79.2% women; mean age 84 years; 77.5% living at home). A significant interaction was found between vitamin D 3 dose and SHEP for TUG (P =.045). Thus, findings compared the standard of care reference arm with 800 IU vitamin D 3 without SHEP to 3 interventions arms (800 IU vitamin D 3 +SHEP; 2000 IU vitamin D 3 without SHEP; 2000 IU vitamin D 3 +SHEP). For TUG, over 12 months the 800 IU vitamin D 3 +SHEP group performed significantly better than the standard-of-care group (13.8 vs 19.5 seconds; P =.01). Findings for knee flexor strength were in line with TUG results and approached significance (P =.07), whereas knee extensor strength and PF-10 did not differ by treatments. For functional recovery after hip fracture, combining home exercise with 800 IU vitamin D 3 is superior to no home exercise or 2000 IU vitamin D 3. None of the interventions improved subjective physical functioning. [ABSTRACT FROM AUTHOR]