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Summary We developed a user-friendly Internet-based tool for patients undergoing total hip replacement (THR) due to osteoarthritis to predict their pain and function after surgery. In the first step, the key questions were identified by statistical modelling in a data set of 375 patients undergoing THR. Based on multiple regression, we identified the two most predictive WOMAC questions for pain and the three most predictive WOMAC questions for functional outcome, while controlling for comorbidity, body mass index, age, gender and specific comorbidities relevant to the outcome. In the second step, a pilot study was performed to validate the resulting tool against the full WOMAC questionnaire among 108 patients undergoing THR. The mean difference between observed (WOMAC) and model-predicted value was −1.1 points (95% confidence interval, CI −3.8, 1.5) for pain and −2.5 points (95% CI −5.3, 0.3) for function. The model-predicted value was within 20% of the observed value in 48% of cases for pain and in 57% of cases for function. The tool demonstrated moderate validity, but performed weakly for patients with extreme levels of pain and extreme functional limitations at 3 months post surgery. This may have been partly due to early complications after surgery. However, the outcome-prediction tool may be useful in helping patients to become better informed about the realistic outcome of their THR.

Importance Milk consumption during adolescence is recommended to promote peak bone mass and thereby reduce fracture risk in later life. However, its role in hip fracture prevention is not established and high consumption may adversely influence risk by increasing height. Objectives To determine whether milk consumption during teenage years influences risk of hip fracture in older adults and to investigate the role of attained height in this association. Design, Setting, and Participants Prospective cohort study over 22 years of follow-up in more than 96 000 white postmenopausal women from the Nurses’ Health Study and men aged 50 years and older from the Health Professionals Follow-up Study in the United States. Exposures Frequency of consumption of milk and other foods during ages 13 to 18 years and attained height were reported at baseline. Current diet, weight, smoking, physical activity, medication use, and other risk factors for hip fractures were reported on biennial questionnaires. Main Outcomes and Measures Cox proportional hazards models were used to calculate relative risks (RRs) of first incidence of hip fracture from low-trauma events per glass (8 fl oz or 240 mL) of milk consumed per day during teenage years. Results During follow-up, 1226 hip fractures were identified in women and 490 in men. After controlling for known risk factors and current milk consumption, each additional glass of milk per day during teenage years was associated with a significant 9% higher risk of hip fracture in men (RR = 1.09; 95% CI, 1.01-1.17). The association was attenuated when height was added to the model (RR = 1.06; 95% CI, 0.98-1.14). Teenage milk consumption was not associated with hip fractures in women (RR = 1.00 per glass per day; 95% CI, 0.95-1.05). Conclusions and Relevance Greater milk consumption during teenage years was not associated with a lower risk of hip fracture in older adults. The positive association observed in men was partially mediated through attained height.

Aim Long-term pharmacokinetics after supplementation with vitamin D 3 or calcifediol (the 25-hydroxyvitamin D 3 metabolite) is not well studied. Additionally, it is unclear whether bolus doses of vitamin D 3 or calcifediol lead to 25(OH)D 3 plasma concentrations considered desirable for fracture prevention (30 ng/mL). We therefore investigated plasma pharmacokinetics of 25(OH)D 3 during different vitamin D 3 and calcifediol supplementation regimens. Methods In this seven-arm, randomized, double-blind, controlled parallel-group study, 35 healthy females aged 50–70 years (5 per group) received 20 μg calcifediol or vitaminD 3 daily, 140 μg calcifediol or vitaminD 3 weekly, for 15 weeks, or a single bolus of either 140 μg calcifediol, or vitaminD 3 , or both. 25(OH)D 3 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 (AUC 0–24h ), which is the measure for exposure, was 28% (67%) higher after the first dose of calcifediol than after the first dose of vitamin D 3 . After 15 weeks, this difference was 123% (178%). All women in the daily and weekly calcifediol groups achieved 25(OH)D 3 concentrations > 30 ng/mL (mean, 16.8 days), but only 70% in the vitamin D 3 daily or weekly groups reached this concentration (mean, 68.4 days). A single dose of 140 μg calcifediol led to 117% higher 25(OH)D 3 AUC 0–96h values than 140 μg vitamin D 3 , 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)D 3 concentrations than vitamin D 3 . Plasma 25(OH)D 3 concentrations of 30 ng/mL were reached more rapidly and reliably with calcifediol.

Background: Recent studies have shown that vitamin D status may be relevant for physical and cognitive performance in the older population. This association may be of particular interest to older people at risk for cognitive impairment and functional decline. Objective: The aim of this study was to determine the association between serum 25-hydroxyvitamin D [25(OH)D] status and functional mobility in seniors assessed in a memory clinic. Methods: We conducted a cross-sectional study of outpatients (n = 404) in a memory clinic. Functional mobility was assessed with three endpoints: normal and fast walking speed and the Timed Up and Go (TUG) test. Adjusted multivariate analyses in all patients and two pre-planned subgroup analyses in vulnerable seniors (previous fall and MMSE score of ≥26 or no previous fall and MMSE score of Results: Overall, mean 25(OH)D serum levels were 63.2 ± 33.9 nmol/l, and 41.3% were vitamin D deficient (81 nmol/l); adjusted for all covariates, seniors in the highest quartile performed 9.4% better in normal (p = 0.02) and 9.2% better in fast (p = 0.004) walking speed, and 4.4% better in the TUG test (p = 0.24). The association between 25(OH)D status and functional mobility was most pronounced in less vulnerable seniors (p for trend significant for all three mobility tests). Seniors with a higher 25(OH)D status also had better cognitive function (MMSE score; p = 0.006). Conclusions: Lower serum 25(OH)D status is associated with poorer functional mobility and cognitive function, therefore supporting 25(OH)D assessment in this population at risk for both functional and cognitive decline.

In May 2012, a Sarcopenia Consensus Summit was convened by the Foundation of the National Institutes of Health (FNIH), National Institute of Aging (NIA), and the U.S. Food and Drug Administration (FDA); and co-sponsored by five pharmaceutical companies. At this summit, sarcopenia experts from around the world worked to develop agreement on a working definition of sarcopenia, building on the work of previous efforts to generate a consensus. With the ultimate goal of improving function and independence in individuals with sarcopenia, the Task Force focused its attention on people at greatly increased risk of muscle atrophy as a consequence of hip fracture. The rationale for looking at this population is that since hip fracture is a recognized condition, there is a clear regulatory path forward for developing interventions. Moreover, patients with hip fracture may provide an appropriate population to advance understanding of sarcopenia, for example helping to define diagnostic criteria, develop biomarkers, understand the mechanisms that underlie the age-related loss of muscle mass and strength, and identify endpoints for clinical trials that are reliable, objective, and clinically meaningful. Task Force members agreed that progress in treating sarcopenia will require strengthening of partnerships between academia, industry, and government agencies, and across continents to reach consensus on diagnostic criteria, optimization of clinical trials design, and identification of improved treatment and preventive strategies. In this report, the main results of the Task Force discussion are presented.

Chez les patients âges, les chutes sont frequentes, elles sont associees a un potentiel de blessure eleve et peuvent etre a l’origine d’une perte d’autonomie et donc d’une institutionnalisation. La detection des facteurs de risque de chute fait appel a des instruments de test valides, qui doivent etre adaptes au contexte actuel.

Sturze beim alteren Patienten sind haufig, haben ein erhebliches Verletzungspotential und sind Grund fur Verlust von Selbstandigkeit und damit verbundener Institutionalisierung. Das Erfassen von Sturz-Risikofaktoren geschieht mittels validierter Testinstrumente. Diese sollen dem aktuellen Setting (ambulant oder in der Institution) angepasst sein.

Background: Total Knee Replacement (TKR) is the standard treatment for patients with severe knee osteoarthritis (OA). Significant improvement in pain and function are seen after TKR and approximately 80% of patients are very satisfied with the outcome. Functional status prior to TKR is a major predictor of outcome after the intervention. Thus, improving functional status prior to surgery through exercise may improve after surgery outcome. However, results from several previous trials testing the concept have been inconclusive after surgery. Methods/design. In a randomized controlled trial (RCT) we will test the effect of a pre-operative neuromuscular trainingprogram versus an attention control program on lower extremity function - before and after surgery. We will enroll 80 participants, aged between 55-90 years, who are scheduled for TKR. In this single-blinded RCT, the intervention group will receive a minimum of 8 and a maximum of 24 training sessions plus 3 educational sessions of the knee school. The control group will receive the 3 educational sessions only. Assessments are performed immediately before and after the intervention (before surgery), at 6 weeks, 3 months and 12 months (after surgery).The primary outcome will include the Chair Stand Test as a measure of leg strength and reaction time. Secondary outcomes are knee function and pain assessed with the self-reported Knee Injury and Osteoarthritis Outcome Score (KOOS). All measurements will be carried out by a specially trained physical therapist, blinded to group allocation. Discussion. To our knowledge this is the first single-blinded RCT to test the effect of pre-operative neuromuscular training plus knee school against knee school alone - on knee function and pain, assessed immediately after the interventions prior to surgery and repeatedly after surgery. Trial registration. Clinical Trials NCT00913575.

International audience; The prevalence of vitamin D insufficiency is very high in the nursing home (NH) population. Paradoxically, vitamin D insufficiency is rarely treated despite of strong clinical evidence and recommendations for supplementation. This review aims at reporting the current knowledge of vitamin D supplementation in NH and proposing recommendations adapted to the specificities of this institutional setting. Current literature on vitamin D supplementation for NH residents was narratively presented and discussed by the French Group of Geriatrics and Nutrition. Vitamin D supplementation is a safe and well-tolerated treatment. Most residents in NH have vitamin D insufficiency, and would benefit from vitamin D supplement. However, only few residents are actually treated. Current specific and personalized protocols for vitamin D supplementation may not be practical for use in NH settings (e.g., assessment of serum vitamin D concentrations before and after supplementation). Therefore, our group proposes a model of intervention based on the systematic supplementation of vitamin D (1,000 IU/day) since the patient's admission to the NH and throughout his/her stay without the need of a preliminary evaluation of the baseline levels. Calcium should be prescribed only in case of poor dietary calcium intake. A population-based rather than individual-based approach may probably improve the management of vitamin D insufficiency in the older population living in NH, without increasing the risks of adverse health problems. The clinical relevance and cost effectiveness of this proposal should be assessed under NH real-world conditions to establish its feasibility.

This chapter evaluates differences between oral supplementation with calcifediol (25-hydroxyvitamin D) and vitamin D3 (cholecalciferol). Oral supplementation with calcifediol results in an immediate and sustained increase in serum 25-hydroxyvitamin D concentrations. This may be relevant in clinical care as higher circulating level of 25-hydroxyvitamin D can be reached much faster than on the standard supplementation with vitamin D3. However, whether calcifediol has additional benefits superior to vitamin D3 will need further investigation in an equivalent dose comparison trial.

The reduced muscle mass and impaired muscle performance that define sarcopenia in older individuals are associated with increased risk of physical limitation and a variety of chronic diseases. They may also contribute to clinical frailty. A gradual erosion of quality of life (QoL) has been evidenced in these individuals, although much of this research has been done using generic QoL instruments, particularly the SF-36, which may not be ideal in older populations with significant comorbidities. This review and report of an expert meeting presents the current definitions of these geriatric syndromes (sarcopenia and frailty). It then briefly summarizes QoL concepts and specificities in older populations and examines the relevant domains of QoL and what is known concerning QoL decline with these conditions. It calls for a clearer definition of the construct of disability, argues that a disease-specific QoL instrument for sarcopenia/frailty would be an asset for future research, and discusses whether there are available and validated components that could be used to this end and whether the psychometric properties of these instruments are sufficiently tested. It calls also for an approach using utility weighting to provide some cost estimates and suggests that a time trade-off study could be appropriate. © 2013 Springer Science+Business Media New York.

On September 29, 2011, acknowledged experts in the field of vitamin D, mainly European, were brought together in order to discuss the recent scientific advances in relation to vitamin D: the current requirements and associations with various health outcomes. In this article, the discussions resulting from the meeting are summarized. INTRODUCTION: Several groups at risk for developing vitamin D insufficiency have been identified. Accordingly, reviews indicate that a significant percentage of the population worldwide have serum 25-hydroxyvitamin D levels below 50 nmol/l. In addition to the role of vitamin D in bone health, recent studies suggest that it may play a pivotal role in other systems, e.g., the cardiovascular system, pancreas, muscle, immune system and brain. Most evidence, however, is obtained from observational studies and yet inconclusive. METHODS: To exchange and broaden knowledge on the requirements for vitamin D and its effect on various health outcomes, a workshop entitled "Vitamin D Expert Meeting: Do we get enough?", was organized. RESULTS: Despite low vitamin D levels worldwide, consensus on the definition of deficiency is not yet reached. In order to define cut-off points for vitamin D whilst taking into account extraskeletal health effects, randomized controlled trials in these fields are warranted. The experts do emphasize that there is evidence to suggest an important role for vitamin D in the maintenance of optimal bone health at all ages and that vitamin D supplementation, in most studies co-administered with calcium, reduces fracture risk in the senior population. CONCLUSION: To reach a serum 25-hydroxyvitamin D level of 50 nmol/l older adults aged >/=65 years are therefore recommended to meet a mean daily vitamin D intake of 20 mug (800 IU), which is best achieved with a supplement.

Fragility fractures contribute significantly to the morbidity and mortality of older individuals, and in a growing segment of the senior population a marked increase in these fractures is expected in the next 20 years [1, 2]. The most rapidly growing segment of the senior population consists of men and women aged 85 years and older [2]. This translates in a rising number of all fragility fractures, especially those of the hip. Hip fractures are the most serious and most frequent fractures occurring among seniors aged 75 years and older [3, 4], and an estimated 1 in 3 women, and 1 in 6 men will have sustained a hip fracture by their 90th decade [5]. Muscle weakness [6] and falling [7] are closely related to fragility fractures, and are critical in understanding them. Both muscle weakness and falling have been linked to the broad prevalence of vitamin D deficiency among the senior population. Severe vitamin D deficiency (serum concentrations < 10 ng/ml or < 25 nmol/l 25-hydroxyvitamin D) in the senior population causes secondary hyperparathyroidism, osteoporosis, and osteomalacia [8]. Histological osteomalacia, characterized by the accumulation of unmineralized matrix or osteoid in the skeleton, has been found to be common in several hip fracture case studies (12–44 %) [9–14]. At the same time it is well recognized that severe vitamin D deficiency is prevalent in about 60 % of hip fracture patients [15, 16] and that vitamin D supplementation reduces the risk of hip fracture by 30 % [17]. Thus, it is conceivable that a significant number of hip fractures occurring in seniors are explained by osteomalacic changes that soften the bone. Additionally, as a primary clinical sign of osteomalacia, muscle weakness may contribute to the risk of fracture [18], and vitamin D supplementation may not only mineralize bone, but has been shown to reduce the risk of falling by up to 34 % [19, 20]. Apart from hip fractures, the two other most common fragility fractures at non-vertebral sites are distal forearm and proximal humerus fractures, and, similar to hip fractures, distal forearm and proximal humerus fractures show a steep increase with age [3]. Notably, the circumstances of these fractures are strikingly different. Hip fractures tend to occur in less active individuals falling indoors from a standing height with little forward momentum, and they tend to fall sideways or straight down on their hip [21–23]. However, distal forearm or humerus fractures tend to occur among more active older individuals who are, correspondingly, more likely to be outdoors and have a greater forward momentum when they fall [24–26]. This may also explain why hip fracture incidence shows little to no seasonal change, while the winter/summer seasonal swing is pronounced in distal forearm and humerus fractures, and more so in men than in women [27]. Men aged 65 years and older are at a 51 % greater risk of sustaining a distal forearm fracture and a 23 % greater risk of sustaining a proximal humerus fracture in the winter compared with during the summer [27]. Women aged 65 years and older are at a 15 % greater risk of sustaining a distal forearm fracture and a 19 % greater risk of sustaining a proximal humerus fracture in the winter compared with during the summer [27]. In the same study, in winter, total snowfall was associated with a reduced risk of hip fracture (−5 % per 20 inch), but an increased risk of distal forearm and proximal humerus fractures (6–12 %; p

Die aktuelle Datenlage spricht dafur, dass ein 25(OH)D-Spiegel von mindestens 50 nmol/l notig ist, um die Knochengesundheit bei Erwachsenen und die Muskelgesundheit alterer Personen zu unterstutzen.

Les donnees actuelles parlent en faveur du fait qu’un taux de 25(OH)D d’au moins 50 nmol/l est necessaire pour soutenir la sante osseuse des adultes et la sante musculaire des personnes âgees.

Next to a healthy calcium and protein rich diet and exercise, vitamin D supplementation is a key pillar of osteoporosis prevention among postmenopausal women. This article reviews the recent recommendations on vitamin D by the IOF (2010), the Institute of Medicine (2010), and the US Endocrine Society (2011), including the evidence to support these recommendations for fracture and fall prevention. The recent recommendations agree that supplementation should be performed with vitamin D3 or vitamin D2, and that a minimal serum 25-hydroxyvitamin D threshold of 50 nmol/l (20 ng/ml)should be achieved to overcome vitamin D deficiency. In contrast to the Institute of Medicine, the IOF and the US Endocrine Society recommend vitamin D also for the prevention of falls, and state that for fracture prevention a higher serum 25-hydroxyvitamin D threshold of 75 nmol/l (30 ng/ml) should be targeted.

Vitamin D deficiency is prevalent in about 50 % of adults and limited data support a similar prevalence in children. This is of concern, as vitamin D deficiency is a risk factor for falls and fractures and several double-blind RCTs provide evidence that supplementation reduces the risk of fall and fractures among the senior population. Further, large epidemiologic studies consistently report that vitamin D deficiency confers an increased risk of mortality, cardiovascular disease and cancer, especially colo-rectal cancer. However, as large clinical trials for non-musculoskeletal endpoints are missing today, public health recommendations are based primarily on bone health to argue vitamin D repletion in the population.

Increasing data suggest that higher 25-hydroxyvitamin D [25(OH)D] serum concentrations are advantageous for health. At present, strong evidence for causality is available for fracture and fall prevention, while promising epidemiologic and mechanistic studies suggest a key role of vitamin D in the preservation of cardiovascular health, and the prevention of cancer and other common chronic disease. For lower extremity function, fall prevention, hip bone density, and for fracture prevention optimal benefits are observed with 25(OH)D levels of at least 75 nmol/L to 100 nmol/L [1]. This threshold may be reached in 50 % of adults with 800 to 1000 IU vitamin D per day. This manuscript will discuss the evidence of vitamin D in fall and fracture prevention and how these data transfer to the most recent recommendations by the IOF (International Osteoporosis Foundation) and the IOM (Institute of Medicine).

BACKGROUND: The results of meta-analyses examining the relationship between vitamin D supplementation and fracture reduction have been inconsistent. METHODS: We pooled participant-level data from 11 double-blind, randomized, controlled trials of oral vitamin D supplementation (daily, weekly, or every 4 months), with or without calcium, as compared with placebo or calcium alone in persons 65 years of age or older. Primary end points were the incidence of hip and any nonvertebral fractures according to Cox regression analyses, with adjustment for age group, sex, type of dwelling, and study. Our primary aim was to compare data from quartiles of actual intake of vitamin D (including each individual participant's adherence to the treatment and supplement use outside the study protocol) in the treatment groups of all trials with data from the control groups. RESULTS: We included 31,022 persons (mean age, 76 years; 91% women) with 1111 incident hip fractures and 3770 nonvertebral fractures. Participants who were randomly assigned to receive vitamin D, as compared with those assigned to control groups, had a nonsignificant 10% reduction in the risk of hip fracture (hazard ratio, 0.90; 95% confidence interval [CI], 0.80 to 1.01) and a 7% reduction in the risk of nonvertebral fracture (hazard ratio, 0.93; 95% CI, 0.87 to 0.99). By quartiles of actual intake, reduction in the risk of fracture was shown only at the highest intake level (median, 800 IU daily; range, 792 to 2000), with a 30% reduction in the risk of hip fracture (hazard ratio, 0.70; 95% CI, 0.58 to 0.86) and a 14% reduction in the risk of any nonvertebral fracture (hazard ratio, 0.86; 95% CI, 0.76 to 0.96). Benefits at the highest level of vitamin D intake were fairly consistent across subgroups defined by age group, type of dwelling, baseline 25-hydroxyvitamin D level, and additional calcium intake. CONCLUSIONS: High-dose vitamin D supplementation (≥800 IU daily) was somewhat favorable in the prevention of hip fracture and any nonvertebral fracture in persons 65 years of age or older. (Funded by the Swiss National Foundations and others.) Copyright © 2012 Massachusetts Medical Society.

Several studies in pregnant women and early childhood suggest that vitamin D deficiency (serum 25-hydroxyvitamin D levels

This review will summarize the impact of vitamin D deficiency on muscle health. Mechanistic evidence regarding the presence of the specific vitamin D receptor in muscle tissue and muscle biopsy abnormalities observed with deficiency will be reviewed, as well as molecular and non-molecular effects of vitamin D in muscle tissue. At the clinical level, the evidence from randomized controlled trials of vitamin D supplementation on functional improvement and fall reduction will be summarized. Further, the manuscript will discuss whether vitamin D effects on fall prevention modulate in part its benefit on fracture prevention and why fall prevention is essential in fracture prevention at higher age. Finally, trial and epidemiological data will be reviewed to assess desirable serum 25-hydroxyvitamin D levels for optimal muscle health.

Decreased vitamin D levels have been described in various forms of chronic liver disease and associated with advanced fibrosis. Whether this association is a cause or consequence of advanced fibrosis remains unclear to date.To analyse combined effects of 25-OH vitamin D plasma levels and vitamin D receptor gene (VDR; NR1I1) polymorphisms on fibrosis progression rate in HCV patients.251 HCV patients underwent VDR genotyping (bat-haplotype: BsmI rs1544410 C, ApaI rs7975232 A and TaqI rs731236 A). Plasma 25-OH vitamin D levels were quantified in a subgroup of 97 patients without advanced fibrosis. The VDR haplotype and genotypes as well as plasma 25-OH vitamin D levels were associated with fibrosis progression.The bAt[CCA]-haplotype was significantly associated with fibrosis progression0.101 U/year (P = 0.007; OR = 2.02) and with cirrhosis (P = 0.022; OR = 1.84). Forty-five percent of bAt[CCA]-haplotype patients were rapid fibrosers, 21.1% were cirrhotic. Likewise, ApaI rs7975232 CC genotype was significantly associated with fibrosis progression and cirrhosis. Lower plasma 25-OH vitamin D levels were significantly associated with fibrosis progression0.101 U/year in F0-2 patients (P = 0.013). Combined analysis of both variables revealed a highly significant additive effect on fibrosis progression with 45.5% rapid fibrosers for bAt[CCA]-haplotype and 25-OH vitamin D20 μg/L compared with only 9.1% for the most favourable combination (P = 0.006). In multivariate analysis, the bAt-haplotype was an independent risk factor for fibrosis progression (P = 0.001; OR = 2.83).Low 25-OH vitamin D plasma levels and the unfavourable VDR bAt[CCA]-haplotype are associated with rapid fibrosis progression in chronic HCV patients. In combination, both variables exert significant additive effects on fibrosis progression.

Close to 75% of hip and non-hip fractures occur among seniors age 65 years and older. Notably, the primary risk factor for a hip fracture is a fall, and over 90% of all fractures occur after a fall. Thus, critical for the understanding and prevention of fractures at later age is their close relationship with muscle weakness and falling. In fact, antiresorptive treatment alone may not reduce fractures among individuals 80 years and older in the presence of nonskeletal risk factors for fractures despite an improvement in bone metabolism. This article will review the epidemiology of falls, and their importance in regard to fracture risk. Finally, fall prevention strategies and how these translate into fracture reduction are evaluated based on data from randomized controlled trials.

Milk contains calcium, phosphorus, and protein and is fortified with vitamin D in the United States. All these ingredients may improve bone health. However, the potential benefit of milk on hip fracture prevention is not well established. The objective of this study was to assess the association of milk intake with risk of hip fracture based on a meta-analysis of cohort studies in middle-aged or older men and women. Data sources for this study were English and non-English publications via Medline (Ovid, PubMed) and EMBASE search up to June 2010, experts in the field, and reference lists. The idea was to compare prospective cohort studies on the same scale so that we could calculate the relative risk (RR) of hip fracture per glass of milk intake daily (approximately 300 mg calcium per glass of milk). Pooled analyses were based on random effects models. The data were extracted by two independent observers. The results show that in women (6 studies, 195,102 women, 3574 hip fractures), there was no overall association between total milk intake and hip fracture risk (pooled RR per glass of milk per day = 0.99; 95% confidence interval [CI] 0.96–1.02; Q-test p = .37). In men (3 studies, 75,149 men, 195 hip fractures), the pooled RR per daily glass of milk was 0.91 (95% CI 0.81–1.01). Our conclusion is that in our meta-analysis of cohort studies, there was no overall association between milk intake and hip fracture risk in women but that more data are needed in men. © 2011 American Society for Bone and Mineral Research.

Publisher Summary Vitamin D deficiency may cause muscular impairment even before adverse effects on bone occur. Vitamin D is essential for bone growth and preservation, and higher 25(OH)D levels are associated with higher bone density in younger and older adults. Vitamin D deficiency may cause muscular impairment even before adverse effects on bone occur. Mechanistically, fractures at later age are closely linked to muscle weakness and falling. Several recent meta-analyses of randomized, controlled trials have addressed the benefit of vitamin D on fracture risk reduction with conflicting findings. Different findings and conclusions may be explained by differences in the selection of trials included in the meta-analysis, with respect to design. Also, in double-blind RCTs, vitamin D supplementation increase bone density and reduce bone loss. Based on evidence from RCTs, oral vitamin D supplementation reduces both falls and non-vertebral fractures, including those at the hip. However, this benefit is dose-dependent and a dose of 700–1000 IU vitamin D per day is required to assure both fall and fracture prevention. For optimal fall and fracture reduction a serum 25(OH)D concentration of at least 75 nmol/l is required. This threshold may be reached with 800 to 1000 IU vitamin D in 50% of adults, whereas higher doses of vitamin D would be required to shift all adults to this threshold.

Die hier kommentierte Veroffentlichung von Bolland und Kollegen hat mehrere Studien mit insgesamt sehr grosen Teilnehmerzahlen zusammengefasst (Metaanalyse), in denen es um die Effekte einer Vitamin-D-Supplementierung auf verschiedene Endpunkte wie Herzinfarkt, Krebs, Huftfrakturen und Mortalitat ging. Die Autoren schlussfolgern, dass eine zusatzliche Vitamin-D-Gabe, mit oder ohne Kalzium, nicht in der Lage ist, das Auftreten der genannten Krankheiten/Frakturen um mehr als 15 % zu verringern. Originalarbeit: Bolland MJ, Grey A, Gamble GD, Reid IR. The effect of vitamin D supplementation on skeletal, vascular, or cancer outcomes: a trial sequential meta-analysis. Lancet Diabetes Endocrinol 2014; 2: 307–320

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, auto-immunity, 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 40 ng/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 3 months of supplementation. An assay measuring both 25(OH)D-2 and 25(OH)D-3 is recommended. Dark-skinned or veiled individuals not exposed much to the sun, elderly and institutionalized individuals may be supplemented (800 IU/day) without baseline testing. (C) 2010 Elsevier B.V. All rights reserved.

Vitamin D modulates fracture risk in two ways: by decreasing falls and increasing bone density. Two 2009 metaanalyses of double-blind randomized controlled trials came to the conclusion that vitamin D reduces the risk of falls by 19%, the risk of hip fracture by 18%, and the risk of any nonvertebral fracture by 20%; however, this benefit was dose-dependent. Fall prevention was only observed in trial of at least 700 IU vitamin D per day, and fracture prevention required a received dose (treatment dose*adherence) of more than 400 IU vitamin D per day. Antifall efficacy started with achieved 25-hydroxyvitamin D levels of at least 60 nmol/L (24 ng/mL) and antifracture efficacy started with achieved 25-hydroxyvitamin D levels of at least 75 nmol/L (30 ng/mL) and both end points improved further with higher achieved 25-hydroxyvitamin D levels. Based on these evidence-based data derived from the general older population, vitamin D supplementation should be at least 700–1,000 IU/day and taken with good adherence to cover the needs for both fall and fracture prevention. Ideally, the target range for 25-hydroxyvitamin D should be at least 75 nmol/L, which may need more than 700–1,000 IU vitamin D in individuals with severe vitamin D deficiency or those overweight.

Increasing data suggest that many or most adults in the United States and Europe would benefit from vitamin D supplements. This review summarizes the benefits of vitamin D with the strongest evidence today from randomized controlled trials for fall and fracture prevention. Beyond fall and fracture prevention, vitamin D may also reduce overall morbidity by multiple mechanisms. Prospective epidemiological studies supported by strong mechanistic evidence suggest a reduction of cardiovascular disease (incident hypertension and cardiovascular mortality) and colorectal cancer, extending to weaker evidence on immune-modulatory and anti-inflammatory benefits of vitamin D.

OBJECTIVES: To evaluate the prevalence of 25-hydroxyvitamin D [25(OH)D] deficiency in HIV-positive patients, a population at risk for osteoporosis. DESIGN: Retrospective assessment of vitamin D levels by season and initiation of combined antiretroviral therapy (cART). METHODS: 25(OH)D was measured in 211 HIV-positive patients: samples were taken before initiation of cART from February to April or from August to October as well as 12 (same season) and 18 months (alternate season) after starting cART. 1,25-Dihydroxyvitamin D [1,25(OH)2D] was measured in a subset of 74 patients. Multivariable analyses included season, sex, age, ethnicity, BMI, intravenous drug use (IDU), renal function, time since HIV diagnosis, previous AIDS, CD4 cell count and cART, in particular nonnucleoside reverse transcriptase inhibitor (NNRTI) and tenofovir (TDF) use. RESULTS: At baseline, median 25(OH)D levels were 37 (interquartile range 20-49) nmol/l in spring and 57 (39-74) nmol/l in the fall; 25(OH)D deficiency less than 30 nmol/l was more prevalent in spring (42%) than in fall (14%), but remained unchanged regardless of cART exposure. In multivariable analysis, 25(OH)D levels were higher in white patients and those with a longer time since HIV diagnosis and lower in springtime measurements and in those with active IDU and NNRTI use. 1-Hydroxylation rates were significantly higher in patients with low 25(OH)D. Hepatitis C seropositivity, previous AIDS and higher CD4 cell counts correlated with lower 1,25(OH)2D levels, whereas BMI and TDF use were associated with higher levels. In TDF-treated patients, higher 1,25(OH)2D correlated with increases in serum alkaline phosphatase. CONCLUSION: Based on the high rate of vitamin D deficiency in HIV-positive patients, systematic screening with consideration of seasonality is warranted. The impact of NNRTIs on 25(OH)D and TDF on 1,25(OH)2D needs further attention.

Current intake recommendations of 200 to 600 IU vitamin D per day may be insufficient for important disease outcomes reduced by vitamin D.This study assessed the benefit of higher-dose and higher achieved 25-hydroxyvitamin D levels [25(OH)D] versus any associated risk.Based on double-blind randomized control trials (RCTs), eight for falls (n = 2426) and 12 for non-vertebral fractures (n = 42,279), there was a significant dose-response relationship between higher-dose and higher achieved 25(OH)D and greater fall and fracture prevention. Optimal benefits were observed at the highest dose tested to date for 700 to 1000 IU vitamin D per day or mean 25(OH)D between 75 and 110 nmol/l (30-44 ng/ml). Prospective cohort data on cardiovascular health and colorectal cancer prevention suggested increased benefits with the highest categories of 25(OH)D evaluated (median between 75 and 110 nmol/l). In 25 RCTs, mean serum calcium levels were not related to oral vitamin D up to 100,000 IU per day or achieved 25(OH)D up to 643 nmol/l. Mean levels of 75 to 110 nmol/l were reached in most RCTs with 1,800 to 4,000 IU vitamin D per day without risk.Our analysis suggests that mean serum 25(OH)D levels of about 75 to 110 nmol/l provide optimal benefits for all investigated endpoints without increasing health risks. These levels can be best obtained with oral doses in the range of 1,800 to 4,000 IU vitamin D per day; further work is needed, including subject and environment factors, to better define the doses that will achieve optimal blood levels in the large majority of the population.

Antifracture efficacy with supplemental vitamin D has been questioned by recent trials.We performed a meta-analysis on the efficacy of oral supplemental vitamin D in preventing nonvertebral and hip fractures among older individuals (or =65 years). We included 12 double-blind randomized controlled trials (RCTs) for nonvertebral fractures (n = 42 279) and 8 RCTs for hip fractures (n = 40 886) comparing oral vitamin D, with or without calcium, with calcium or placebo. To incorporate adherence to treatment, we multiplied the dose by the percentage of adherence to estimate the mean received dose (dose x adherence) for each trial.The pooled relative risk (RR) was 0.86 (95% confidence interval [CI], 0.77-0.96) for prevention of nonvertebral fractures and 0.91 (95% CI, 0.78-1.05) for the prevention of hip fractures, but with significant heterogeneity for both end points. Including all trials, antifracture efficacy increased significantly with a higher dose and higher achieved blood 25-hydroxyvitamin D levels for both end points. Consistently, pooling trials with a higher received dose of more than 400 IU/d resolved heterogeneity. For the higher dose, the pooled RR was 0.80 (95% CI, 0.72-0.89; n = 33 265 subjects from 9 trials) for nonvertebral fractures and 0.82 (95% CI, 0.69-0.97; n = 31 872 subjects from 5 trials) for hip fractures. The higher dose reduced nonvertebral fractures in community-dwelling individuals (-29%) and institutionalized older individuals (-15%), and its effect was independent of additional calcium supplementation.Nonvertebral fracture prevention with vitamin D is dose dependent, and a higher dose should reduce fractures by at least 20% for individuals aged 65 years or older.

Fractures contribute significantly to morbidity and mortality of older individuals. Approximately 75 % of all osteoporotic fractures occur among seniors age 65 and older [1], and 1 in 2 women and 1 in 5 men age 50 are expected to sustain a fracture in their remaining life time [2].

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.Over a course of 4 months, we identified 33 elderly with severe vitamin D deficiency (25(OH)D25 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.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.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.

In the presence of an aging population, public health priorities need to evolve. As the populations gets older, the already existing pathologies have become commonplace with specific geriatric clinical syndromes like frailty, mobility disability, or cognitive impairment, among others. Sarcopenia is a good example for which geriatricians, neurologists, physiologists, nutritionists and epidemiologists need to find a consensual definition and diagnostic tool as well as guidelines for the management of clinical trials and possible treatments. The Carla Sarcopenia Task Force, which met in the south of France (Toulouse) for an expert consensus meeting called "Les Entretiens du Carla", have addressed a series of existing issues to place Sarcopenia into a nosological context: a definition which should be a composite of a change in muscle mass and a change in strength/function depending on either a progressive and chronic wasting process or an acute onset of loss of muscle mass; a recommendation for DXA and the Short Physical Performance Battery as a clinical pragmatic approach of Sarcopenia; a differentiated approach for clinical studies according to prevention or treatment objectives and depending on the sub-groups and target populations; and finally, a summary of therapeutic strategies currently recommended. The aim of "Les Entretiens du Carla", based on an expert meeting panel, was to address a series of unsolved issues in the field of Sarcopenia by combining the expert opinion with a revision of the existing literature on the topic. Through this report, the reader will appreciate the determination to find conclusions on the various issues and further studies to be developed to determine the best multidisciplinary approach needed. The Journal of Nutrition, Health & Aging©.

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.

BACKGROUND: The effect of supplementation with calcium alone on risk fractures in a healthy population is not clear. OBJECTIVE: The objective was to determine whether 4 y of calcium supplementation would reduce the fracture risk during treatment and subsequent follow-up in a randomized placebo-controlled trial. DESIGN: The participants were aged