Crosswalks between the Oxford hip and knee scores and the HOOS-12 and KOOS-12 instruments.

OBJECTIVE: To develop and validate bi-directional crosswalks between the Oxford Hip Score (OHS) and HOOS-12 summary impact score, and between the Oxford Knee Score (OKS) and KOOS-12 summary impact score. METHODS: Data were sourced from the Australian Orthopaedic Association National Joint Replacement Registry Patient-Reported Outcome Measures Program. Patients undergoing primary joint replacement for osteoarthritis who completed the OHS and HOOS-12 or OKS and KOOS-12 instruments were included in the analysis. An equipercentile method was used to create four crosswalks, with the distribution of scores smoothed using log-linear models prior to equating. Crosswalk validity was assessed through comparison of actual vs derived scores, Pearson correlation coefficients, root mean square errors (RMSE) and Bland-Altman plots. RESULTS: Paired OHS/HOOS-12 data and paired OKS/KOOS-12 data were available for 4,513 patients undergoing total hip replacement and 5,942 patients undergoing total knee replacement, respectively. Minimal differences were observed between actual and crosswalk-derived mean scores (actual OHS 27.55 vs derived OHS 27.56; actual HOOS-12 53.28 vs derived HOOS-12 53.31; actual OKS 27.34 vs derived OKS 27.34; actual KOOS-12 50.51 vs derived KOOS-12 50.58). High correlation was observed between actual and derived scores (Pearson's r for hip-specific instruments: 0.943-0.946; Pearson's r for knee-specific instruments: 0.925-0.931). Plotted actual vs mean derived scores also indicated robust concordance across the breadth of the instrument scales. CONCLUSION: These crosswalks provide close approximations of actual OHS, OKS, HOOS-12 and KOOS-12 scores, as indicated by multiple validation metrics. They offer a resource for clinicians, researchers and arthroplasty registries to support PROMs score conversion and data harmonisation efforts.

Implications for research and clinical use from a Rasch analysis of the HOOS-12 and KOOS-12 instruments.

OBJECTIVE: To evaluate the structural validity of the 12-item Hip disability and Osteoarthritis Outcome Score (HOOS-12) and 12-item Knee injury and Osteoarthritis Outcome Score (KOOS-12) using Rasch analysis and consider psychometric implications for research and clinical use. METHOD: Individual-level HOOS-12 and KOOS-12 data from the Australian Orthopaedic Association National Joint Replacement Registry, collected before and after primary total hip and knee replacement, were used for this analysis. Using the Rasch analytic approach, overall model fit and item fit were examined, together with potential reasons for misfit including response threshold ordering, differential item functioning, internal consistency, unidimensionality and item targeting. RESULTS: Overall misfit to the Rasch model was evident for both instruments. A degree of item misfit was also observed, although most items demonstrated logical sequencing of response options. Only two items (hip/knee pain frequency and awareness of hip/knee problems) displayed disordered response thresholds. The pain, function, and quality of life domains of the HOOS-12 and KOOS-12 demonstrated excellent internal consistency reliability (person separation index: 0.80-0.93) and unidimensionality. A mismatch between item difficulty and person ability scores at the highest end of the HOOS-12 and KOOS-12 scales contributed to post-operative ceiling effects (mean logit for HOOS-12: 3.57; KOOS-12: 2.58; ≈0 indicates well-targeted scale). CONCLUSION: We found evidence to support the structural validity of the three HOOS-12 and KOOS-12 domains for evaluating joint replacement outcomes. However, there may be missing content in both instruments particularly for high-functioning patients. Minor refinement of some response options may be warranted to improve item performance.

Performance of the HOOS-12 and KOOS-12 instruments for evaluating outcomes from joint replacement surgery.

OBJECTIVE: To evaluate the psychometric properties of the 12-item Hip disability and Osteoarthritis Outcome Score (HOOS-12) and Knee injury and Osteoarthritis Outcome Score (KOOS-12) for use in evaluating outcomes after joint replacement for osteoarthritis. DESIGN: Patient-reported outcomes data collected by the Australian Orthopaedic Association National Joint Replacement Registry were used for this analysis. HOOS-12 and KOOS-12 domain (pain, function, quality of life) and summary impact data were available. The Oxford Hip Score (OHS), Oxford Knee Score (OKS) and EQ-5D-5L were used as comparators. Instruments were administered pre-operatively and at 6 months post-operatively. Internal consistency reliability, floor and ceiling effects, convergent validity, known groups validity, and responsiveness were evaluated using standard psychometric techniques. RESULTS: Baseline HOOS-12 and KOOS-12 data were available for 3,023 patients undergoing primary total hip replacement and 4,010 patients undergoing primary total knee replacement. At baseline, high internal consistency was demonstrated for all domains and summary scores (Cronbach's alpha: HOOS-12 = 0.81-0.93; KOOS-12 = 0.82-0.92). Post-operative ceiling effects (>15% of patients scoring the best possible score) were identified for the HOOS-12 pain (46%), function (39%) and quality of life domains (26%) and summary score (17%), and for the KOOS-12 pain (21%) and function domains (18%). The HOOS-12 and KOOS-12 could differentiate between two known groups (lowest/highest OHS or OKS quartiles post-operatively; p < 0.001) and were highly responsive to change (effect sizes for HOOS-12: 2.20-2.83; KOOS-12: 1.82-2.35). CONCLUSION: The HOOS-12 and KOOS-12 have good psychometric properties for capturing joint replacement outcomes including excellent responsiveness, although ceiling effects may limit monitoring of post-operative improvement.

Formation and dynamics of magma reservoirs.

The emerging concept of a magma reservoir is one in which regions containing melt extend from the source of magma generation to the surface. The reservoir may contain regions of very low fraction intergranular melt, partially molten rock (mush) and melt lenses (or magma chambers) containing high melt fraction eruptible magma, as well as pockets of exsolved magmatic fluids. The various parts of the system may be separated by a sub-solidus rock or be connected and continuous. Magma reservoirs and their wall rocks span a vast array of rheological properties, covering as much as 25 orders of magnitude from high viscosity, sub-solidus crustal rocks to magmatic fluids. Time scales of processes within magma reservoirs range from very slow melt and fluid segregation within mush and magma chambers and deformation of surrounding host rocks to very rapid development of magma and fluid instability, transport and eruption. Developing a comprehensive model of these systems is a grand challenge that will require close collaboration between modellers, geophysicists, geochemists, geologists, volcanologists and petrologists. This article is part of the Theo Murphy meeting issue 'Magma reservoir architecture and dynamics'.

Prevalence and changes in analgesic medication utilisation 1 year prior to total joint replacement in an older cohort of patients.

OBJECTIVES: To evaluate the prevalence and change in analgesic medications use prior to joint replacement in older patients between 2001 and 2012. METHODS: A population based epidemiological study was conducted. Opioids, non-steroidal anti-inflammatories (NSAIDs), paracetamol, corticosteroid injections, medications for neuropathic pain, hypnotics, and muscle relaxants supplied 1 year prior to total knee replacement (TKR, n = 15,517) and hip replacement (THR, n = 10,018) were assessed. Patient characteristics and surgical indication adjusted prevalence ratios (PRs) and 95% confidence intervals (CI) are provided. RESULTS: From 2001 to 2012, in the TKR cohort (median age 78.9) the prevalence of opioid use prior to surgery increased from 37% to 49% (PR = 1.01, 95% CI 1.00-1.01, P = 0.01), while in the THR cohort (median age 81.1) it increased from 44% to 54% (PR = 1.01, 95% CI 1.01-1.02, P < 0.001). Paracetamol use increased from 52% to 61% (PR = 1.0, 95% CI 1.0-1.0, P = 0.913) in the TKR cohort and from 55% to 67% (PR = 1.01, 95% CI 1.00-1.01, P = 0.005) in the THR cohort. Neuropathic pain medication use increased from 5% to 11% in the TKR cohort (PR = 1.04, 95% CI 1.02-1.06, P < 0.0001) and from 6% to 12% in the THR cohort (PR = 1.06, 95% CI 1.04-1.09, P < 0.0001). NSAID use decreased from 76% to 50% in the TKR cohort (PR = 0.96, 95% CI 0.95-0.96, P < 0.0001), and from 81% to 47% in THR cohort (PR = 0.95, 95% CI 0.94-0.95, P < 0.0001). Corticosteroid injections prevalence also decreased (TKR: 21-18%, PR = 0.97, 95% CI 0.96-0.97, P < 0.001, THR: 18-17%, PR = 0.97, 95% CI 0.96-0.98, P < 0.001). CONCLUSION: Pain medication utilization prior to joint replacement surgery changed significantly in this national older cohort of patients during the 2000s.

The use of femoral stems with exchangeable necks in primary total hip arthroplasty increases the rate of revision.

AIMS: Femoral stems with exchangeable (modular) necks were introduced to offer surgeons an increased choice when determining the version, offset and length of the femoral neck during total hip arthroplasty (THA). It was hoped that this would improve outcomes and reduce complications, particularly dislocation. In 2010, the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) first reported an increased rate of revision after primary THA using femoral stems with an exchangeable neck. The aim of this study was to provide a more comprehensive up-to-date analysis of primary THA using femoral stems with exchangeable and fixed necks. MATERIALS AND METHODS: The data included all primary THA procedures performed for osteoarthritis (OA), reported to the AOANJRR between 01 September 1999 and 31 December 2014. There were 9289 femoral stems with an exchangeable neck and 253 165 femoral stems with a fixed neck. The characteristics of the patients and prostheses including the bearing surface and stem/neck metal combinations were examined using Cox proportional hazard ratios (HRs) and Kaplan-Meier estimates of survivorship. RESULTS: It was found that prostheses with an exchangeable neck had a higher rate of revision and this was evident regardless of the bearing surface or the size of the femoral head. Exchangeable neck prostheses with a titanium stem and a cobalt-chromium neck had a significantly higher rate of revision compared with titanium stem/titanium neck combinations (HR 1.83, 95% confidence interval 1.49 to 2.23, p < 0.001). Revisions were higher for these combinations compared with femoral stems with a fixed neck. CONCLUSION: There appears to be little evidence to support the continued use of prostheses with an exchangeable neck in primary THA undertaken for OA. Cite this article: Bone Joint J 2017;99-B:766-73.

Temporal Progression of Lesions in Guinea Pigs Infected With Lassa Virus.

Lassa virus (LASV) infection causes an acute, multisystemic viral hemorrhagic fever that annually infects an estimated 100 000 to 300 000 persons in West Africa. This pathogenesis study evaluated the temporal progression of disease in guinea pigs following aerosol and subcutaneous inoculation of the Josiah strain of LASV as well as the usefulness of Strain 13 guinea pigs as an animal model for Lassa fever. After experimental infection, guinea pigs ( Cavia porcellus; n = 67) were serially sampled to evaluate the temporal progression of infection, gross and histologic lesions, and serum chemistry and hematologic changes. Guinea pigs developed viremia on day 5 to 6 postexposure (PE), with clinical signs appearing by day 7 to 8 PE. Complete blood counts revealed lymphopenia and thrombocytopenia. Gross pathologic findings included skin lesions and congested lungs. Histologic lesions consisted of cortical lymphoid depletion by day 6 to 7 PE with lymphohistiocytic interstitial pneumonia at 7 to 8 days PE. Scattered hepatocellular degeneration and cell death were also noted in the liver and, to a lesser extent, in other tissues including the haired skin, lung, heart, adrenal gland, lymph nodes, thymus, and spleen. The first cell types to demonstrate staining for viral antigen were fibroblastic reticular cells and macrophages/dendritic cells in the lymph nodes on day 5 to 6 PE. This study demonstrates similarities between Lassa viral disease in human infections and experimental guinea pig infection. These shared pathologic characteristics support the utility of guinea pigs as an additional animal model for vaccine and therapeutic development under the Food and Drug Administration's Animal Rule.

The effect of high-dose vitamin D supplementation on muscular function and quality of life in postmenopausal women-A randomized controlled trial.

OBJECTIVE: Observational studies have suggested positive associations between serum 25-hydroxyvitamin D (25(OH)D) levels and muscular strength, balance and quality of life. Our aim was to examine whether high-dose vitamin D supplementation would improve these measures as compared to standard-dose vitamin D, as well as the possible muscular effects of single nucleotide polymorphisms (SNPs) in genes encoding vitamin D-related enzymes. DESIGN: A 12-month randomized, double-blind, controlled trial where the participants received daily elemental calcium (1000 mg) plus vitamin D3 (800 IU). In addition, the participants were randomized to receive either capsules with vitamin D3 (20 000 IU) or matching placebos to be taken twice a week. PATIENTS: A total of 297 postmenopausal women with osteopenia or osteoporosis. MEASUREMENTS: Muscle strength (handgrip and knee extensor strength), balance (tandem test) and quality of life (EQ-5D) were measured at baseline and after 12 months. The subjects were genotyped for SNPs related to vitamin D metabolism. RESULTS: Of the 297 included women, 275 completed the study. Mean serum 25(OH)D levels dramatically increased in the high-dose group (from 64.7 to 164.1 nmol/L; P<.01), while a more moderate increased was observed in the standard-dose group (from 64.1 to 81.8 nmol/L; P<.01). There was no significant difference between the groups in change in muscular strength, balance or quality of life over the intervention period. Polymorphisms in rs3829251 (located in the 7-dehydrocholesterol reductase gene) were associated with muscle strength and treatment effects. CONCLUSION: One-year treatment with high-dose vitamin D had no effect on muscular strength, balance or quality of life in postmenopausal women with osteopenia or osteoporosis as compared to standard dose. The association between rs3829251 and muscle strength needs confirmation in other populations.

Magma storage in a strike-slip caldera.

Silicic calderas form during explosive volcanic eruptions when magma withdrawal triggers collapse along bounding faults. The nature of specific interactions between magmatism and tectonism in caldera-forming systems is, however, unclear. Regional stress patterns may control the location and geometry of magma reservoirs, which in turn may control the spatial and temporal development of faults. Here we provide new insight into strike-slip volcano-tectonic relations by analysing Bouguer gravity data from Ilopango caldera, El Salvador, which has a long history of catastrophic explosive eruptions. The observed low gravity beneath the caldera is aligned along the principal horizontal stress orientations of the El Salvador Fault Zone. Data inversion shows that the causative low-density structure extends to ca. 6 km depth, which we interpret as a shallow plumbing system comprising a fractured hydrothermal reservoir overlying a magmatic reservoir with vol% exsolved vapour. Fault-controlled localization of magma constrains potential vent locations for future eruptions.

Development, validation and implementation of a quantitative food frequency questionnaire to assess habitual vitamin D intake.

BACKGROUND: A well-designed, validated quantitative food frequency questionnaire (FFQ) could offer an efficient and cost-effective method for assessing habitual vitamin D intake. The present study aimed to describe the development, validation and implementation of a vitamin D FFQ. METHODS: National food consumption survey data obtained from Irish adults (18-64 years) were used to identify foods that contribute 95% of vitamin D intake. A winter-based validation study was carried out for the resulting FFQ in 120 females, including 98 women [mean (SD) 65.0 (7.3) years] and 22 girls [12.2 (0.8) years], using a 14-day diet history (DH) as a comparator. Serum 25(OH)D concentrations were analysed. Validity coefficients were calculated using the method of triads. Cross-classification and Bland-Altman analysis were also performed. RESULTS: Median (interquartile range) vitamin D intakes (including the contribution from nutritional supplements) were 5.4 (3.7) and 3.7 (5.9) µg day(-1) from the FFQ and DH, respectively and intakes of vitamin D from food sources were 3.6 (3.1) and 2.4 (2.2) µg day(-1) . The FFQ and DH classified 86% and 87% of individuals into the same and adjacent thirds of wintertime serum 25(OH)D status, respectively. There was a strong association (r = 0.71, P < 0.0001) and no significant systematic or proportional bias observed for the difference between estimates from the FFQ and DH. The validity coefficient for the FFQ was 0.92 (95% confidence interval = 0.80-0.97). Repeatability analysis (n = 56) performed 6-12 months later showed no significant difference in estimates of vitamin D between administrations. CONCLUSIONS: The data obtained in the present study indicate high validity and good reproducibility of a short, interviewer-administered FFQ for vitamin D.

Pathogenesis of Bolivian Hemorrhagic Fever in Guinea Pigs.

Machupo virus, the cause of Bolivian hemorrhagic fever, is a highly lethal viral hemorrhagic fever with no Food and Drug Administration-approved vaccines or therapeutics. This study evaluated the guinea pig as a model using the Machupo virus-Chicava strain administered via aerosol challenge. Guinea pigs (Cavia porcellus) were serially sampled to evaluate the temporal progression of infection, gross and histologic lesions, and sequential changes in serum chemistry and hematology. The incubation period was 5 to 12 days, and complete blood counts revealed leukopenia with lymphopenia and thrombocytopenia. Gross pathologic findings included congestion and hemorrhage of the gastrointestinal mucosa and serosa, noncollapsing lungs with fluid exudation, enlarged lymph nodes, and progressive pallor and friability of the liver. Histologic lesions consisted of foci of degeneration and cell death in the haired skin, liver, pancreas, adrenal glands, lymph nodes, tongue, esophagus, salivary glands, renal pelvis, small intestine, and large intestine. Lymphohistiocytic interstitial pneumonia was also present. Inflammation within the central nervous system, interpreted as nonsuppurative encephalitis, was histologically apparent approximately 16 days postexposure and was generally progressive. Macrophages in the tracheobronchial lymph node, on day 5 postexposure, were the first cells to demonstrate visible viral antigen. Viral antigen was detected throughout the lymphoid system by day 9 postexposure, followed by prominent spread within epithelial tissues and then brain. This study provides insight into the course of Machupo virus infection and supports the utility of guinea pigs as an additional animal model for vaccine and therapeutic development.

Vitamin D, Muscle Function, and Cardiorespiratory Fitness in Adolescents From the Young Hearts Study.

CONTEXT: Vitamin D insufficiency is common among the adolescent population and may have implications for health outcomes in later life. Few studies have investigated the role of vitamin D status in muscle function and cardiorespiratory fitness (CRF) during adolescence. OBJECTIVE: The aim of this study was to investigate the association between vitamin D status and fat-free mass (FFM), muscle strength, muscle power, and CRF in a representative sample of adolescents from Northern Ireland. DESIGN, SETTING, AND PARTICIPANTS: This was a cross-sectional study involving 1015 adolescents (age 12 and 15 y), who had 25-hydroxyvitamin D [25(OH)D] data available as part of the Young Hearts Study 2000. MAIN OUTCOME MEASURES: The main outcome measures of this study were FFM (kg) and FFM corrected for height [fat-free mass index; FFM (kg)/height (m(2))], muscle strength (kg), peak muscle power (kW) and VO2 max (CRF; mL/kg/min). RESULTS: Multinomial regression analyses, controlling for environmental and lifestyle factors, demonstrated that boys age 15 years in the highest tertile of standardized serum 25(OH)D concentration (> 51 nmol/L) had significantly higher muscle strength (ß = 3.90; P ≤ .001) compared with those in the lowest tertile (< 32 nmol/L). These results were not evident in any other age-sex group and vitamin D status was not significantly associated with muscle power or CRF in any of the four age-sex groups. CONCLUSION: These results support a role for vitamin D in muscle function in adolescent males and suggest the need for more research in this vulnerable age group.

Pathology of experimental Machupo virus infection, Chicava strain, in cynomolgus macaques (Macaca fascicularis) by intramuscular and aerosol exposure.

Machupo virus, the causative agent of Bolivian hemorrhagic fever (BHF), is a highly lethal viral hemorrhagic fever of which little is known and for which no Food and Drug Administration-approved vaccines or therapeutics are available. This study evaluated the cynomolgus macaque as an animal model using the Machupo virus, Chicava strain, via intramuscular and aerosol challenge. The incubation period was 6 to 10 days with initial signs of depression, anorexia, diarrhea, mild fever, and a petechial skin rash. These were often followed by neurologic signs and death within an average of 18 days. Complete blood counts revealed leukopenia as well as marked thrombocytopenia. Serum chemistry values identified a decrease in total protein, marked increases in alanine aminotransferase and aspartate aminotransferase, and moderate increases in alkaline phosphatase. Gross pathology findings included a macular rash extending across the axillary and inguinal regions beginning at approximately 10 days postexposure as well as enlarged lymph nodes and spleen, enlarged and friable liver, and sporadic hemorrhages along the gastrointestinal mucosa and serosa. Histologic lesions consisted of foci of degeneration and necrosis/apoptosis in the haired skin, liver, pancreas, adrenal glands, lymph nodes, tongue, esophagus, salivary glands, stomach, small intestine, and large intestine. Lymphohistiocytic interstitial pneumonia was also present. Inflammation within the central nervous system (nonsuppurative encephalitis) was histologically apparent approximately 16 days postexposure and was generally progressive. This study provides insight into the course of Machupo virus infection in cynomolgus macaques and supports the usefulness of cynomolgus macaques as a viable model of human Machupo virus infection.

Recommended dietary intakes for vitamin D: Where do they come from, what do they achieve and how can we meet them?

There is substantial evidence that the prevalence of vitamin D deficiency is high across Europe, particularly, but not exclusively, among those resident at Northerly latitudes. This has significant implications for human health throughout the lifecycle and impacts upon healthy growth and development and successful ageing for current and possibly future generations. In recent years, there have been several important reports from North America and Europe in relation to dietary reference values (DRVs) for vitamin D. These may be of enormous value from a public health perspective in terms of preventing vitamin D deficiency and promoting adequate vitamin D status in the population. In this concise review, we provide a brief summary of current DRVs for vitamin D, their background and their application to vitamin D deficiency prevention. The review also provides some brief guidance with respect to applying the DRVs in a clinical nutrition setting. In addition, the review illustrates how current dietary intakes of most populations, young and adult, are well short of the newly established DRVs. Accordingly, the review highlights potential food-based or dietary strategies for increasing the distribution of vitamin D intake in the population with the aim of preventing vitamin D deficiency. Finally, despite the explosion in scientific research in vitamin D and health, there are many fundamental gaps in the field of vitamin D from the public health perspective. The impact of these knowledge gaps on current DRVs for vitamin D is highlighted, as are some future developments that may help address these gaps.

Pathology of experimental aerosol Zaire ebolavirus infection in rhesus macaques.

There is limited knowledge of the pathogenesis of human ebolavirus infections and no reported human cases acquired by the aerosol route. There is a threat of ebolavirus as an aerosolized biological weapon, and this study evaluated the pathogenesis of aerosol infection in 18 rhesus macaques. Important and unique findings include early infection of the respiratory lymphoid tissues, early fibrin deposition in the splenic white pulp, and perivasculitis and vasculitis in superficial dermal blood vessels of haired skin with rash. Initial infection occurred in the respiratory lymphoid tissues, fibroblastic reticular cells, dendritic cells, alveolar macrophages, and blood monocytes. Virus spread to regional lymph nodes, where significant viral replication occurred. Virus secondarily infected many additional blood monocytes and spread from the respiratory tissues to multiple organs, including the liver and spleen. Viremia, increased temperature, lymphocytopenia, neutrophilia, thrombocytopenia, and increased alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, total bilirubin, serum urea nitrogen, creatinine, and hypoalbuminemia were measurable mid to late infection. Infection progressed rapidly with whole-body destruction of lymphoid tissues, hepatic necrosis, vasculitis, hemorrhage, and extravascular fibrin accumulation. Hypothermia and thrombocytopenia were noted in late stages with the development of disseminated intravascular coagulation and shock. This study provides unprecedented insight into pathogenesis of human aerosol Zaire ebolavirus infection and suggests development of a medical countermeasure to aerosol infection will be a great challenge due to massive early infection of respiratory lymphoid tissues. Rhesus macaques may be used as a model of aerosol infection that will allow the development of lifesaving medical countermeasures under the Food and Drug Administration's animal rule.

Relationships between vitamin D status and cardio-metabolic risk factors in young European adults.

BACKGROUND/AIMS: To explore associations between vitamin D and cardiovascular disease risk factors in young European adults. METHODS: This was a cross-sectional analysis of serum 25-hydroxyvitamin D [s25(OH)D], intact parathyroid hormone (iPTH) and biomarkers of cardiovascular disease risk in 195 healthy 20- to 40-year-olds (109 women) with a BMI between 27.5 and 32.5 from Iceland (64° N; n = 82), Ireland (51° N; n = 37) and Spain (42° N; n = 76) during mid-late winter. RESULTS: The median s25(OH)D was 52.8 nmol/l (IQR 38.1-69.9) or 21.1 ng/ml (IQR 15.2-28.0) with a latitude-dependent gradient (p ≤ 0.0001): Iceland, 41.7 nmol/l (IQR 32.7-54.2) or 16.7 ng/ml (IQR 13.1-21.7); Ireland, 52.9 nmol/l (IQR 35.3-68.6) or 21.2 ng/ml (IQR 14.1-27.4), and Spain, 67.1 nmol/l (IQR 47.1-87.1) or 26.8 ng/ml (IQR 18.8-34.8). Eleven percent of Icelandic participants had s25(OH)D concentrations <25 nmol/l (10 ng/ml) and 66% of Icelandic, 43% of Irish, and 30% of Spanish volunteers had concentrations <50 nmol/l (20 ng/ml), respectively. Overall, 17% met 3 or more of the NCEP/ATP III criteria for cardio-metabolic syndrome (MetS). Participants in the lowest third of s25(OH)D [≤ 42.5 nmol/l (17 ng/ml)] were more likely to have MetS (OR 2.49, p = 0.045) and elevated TAG (OR 3.46, p = 0.019). Individuals with iPTH concentrations in the lowest third [2.34 pmol/l (22.2 pg/ml)] were more likely to have elevated fasting TAG (OR 4.17, p = 0.039), insulin (OR 3.15, p = 0.029) and HOMA-IR (OR 2.15, p = 0.031), and they were less likely to have elevated IL-6 (OR 0.24, p = 0.003). CONCLUSION: There were interactions between s25(OH)D, iPTH and cardio-metabolic risk factors which, given the increasing prevalence of overweight and obesity and a low vitamin D status among adults, require randomised controlled vitamin D intervention studies in overweight persons.

Proceedings of the Rank Forum on Vitamin D.

The Rank Forum on Vitamin D was held on 2nd and 3rd July 2009 at the University of Surrey, Guildford, UK. The workshop consisted of a series of scene-setting presentations to address the current issues and challenges concerning vitamin D and health, and included an open discussion focusing on the identification of the concentrations of serum 25-hydroxyvitamin D (25(OH)D) (a marker of vitamin D status) that may be regarded as optimal, and the implications this process may have in the setting of future dietary reference values for vitamin D in the UK. The Forum was in agreement with the fact that it is desirable for all of the population to have a serum 25(OH)D concentration above 25 nmol/l, but it discussed some uncertainty about the strength of evidence for the need to aim for substantially higher concentrations (25(OH)D concentrations>75 nmol/l). Any discussion of 'optimal' concentration of serum 25(OH)D needs to define 'optimal' with care since it is important to consider the normal distribution of requirements and the vitamin D needs for a wide range of outcomes. Current UK reference values concentrate on the requirements of particular subgroups of the population; this differs from the approaches used in other European countries where a wider range of age groups tend to be covered. With the re-emergence of rickets and the public health burden of low vitamin D status being already apparent, there is a need for urgent action from policy makers and risk managers. The Forum highlighted concerns regarding the failure of implementation of existing strategies in the UK for achieving current vitamin D recommendations.

Vitamin D status and measures of cognitive function in healthy older European adults.

BACKGROUND/OBJECTIVES: Data from human studies that have investigated the association between vitamin D status and cognitive function in elderly adults are conflicting. The objective of this study was to assess vitamin D status (reflected by serum 25-hydroxyvitamin D (25(OH)D)) in older European subjects (n=387; aged 55-87 years) and examine its association with measures of cognitive function. SUBJECTS/METHODS: Serum 25(OH)D was assessed using enzyme-linked immunosorbent assay, whereas measures of cognitive function were assessed using a comprehensive Cambridge Neuropsychological Testing Automated Battery (CANTAB). RESULTS: In all, 12, 36 and 64% of subjects had serum 25(OH)D concentrations <30, <50 and <80 nmol/l, respectively, throughout the year. Serum 25(OH)D was significantly and inversely correlated with four assessments within the spatial working memory (SWM) test parameter (SWM between errors (r=-0.166; P=0.003); SWM between errors 8 boxes (r=-0.134; P=0.038); SWM strategy (r=-0.246; P<0.0001); and SWM total errors (r=-0.174; P<0.003)). When subjects were stratified on the basis of tertiles (T) of serum 25(OH)D (<47.6 (T(1)); 47.6-85.8 (T(2)); and >85.8 (T(3)) nmol/l), fewer errors in SWM test scores occurred in subjects in the third T when compared with the first T (P<0.05-0.084). Stratification by sex showed that these differences between tertiles strengthened (P<0.001-0.043) in the females, but the differences were not significant (P>0.6) in males. CONCLUSIONS: Vitamin D insufficiency, but not deficiency, is widespread in the older population of several European countries. Low vitamin D status was associated with a reduced capacity for SWM, particularly in women.

Does vitamin D supplementation of healthy Danish Caucasian girls affect bone turnover and bone mineralization?

INTRODUCTION: A high peak bone mass may be essential for reducing the risk of osteoporosis later in life and a sufficient vitamin D level during puberty may be necessary for optimal bone accretion and obtaining a high peak bone mass. Dietary intake and synthesis during winter of vitamin D might be limited but the effect of vitamin D supplementation in adolescence on bone mass is not well established. OBJECTIVE: To investigate the effect of supplementation with 5 and 10 microg/day vitamin D(3) for 12 months in 11- to 12-year-old girls on bone mass and bone turnover as well as the possible influence of VDR and ER genotype on the effect of the supplementation. METHODS: The girls (n=221) were randomized to receive either 5 microg or 10 microg vitamin D(3) supplementation per day or placebo for 12 months. Whole body and lumbar spine bone mass measured by DXA and pubertal status were determined at baseline and after 12 months whereas physical activity and dietary intake of calcium and vitamin D were assessed at baseline. Serum (S) 25-hydroxyvitamin D (25OHD), S-osteocalcin, S-parathyroid hormone, S-calcium, S-inorganic phosphate, urinary (U) pyridinoline (Pyr) and deoxpyridinoline (Dpyr) were measured at baseline and after 6 and 12 months. RESULTS: The S-25OHD concentration increased (p<0.001) relative to the baseline values in the groups receiving either 5 microg/day (mean+/-SD; 11.0+/-10.3 nmol/l, baseline 41.9+/-17.6 nmol/l) or 10 microg/day (13.3+/-11.8 nmol/l, baseline 44.4+/-16.6 nmol/l) vitamin D(3) for 12 months compared to placebo (-3.1+/-9.8 nmol/l, baseline 43.4+/-17.1 nmol/l). There was no effect of vitamin D-supplementation on biomarkers for bone turnover or on whole body or spine bone mineral augmentation. However, vitamin D supplementation increased whole body bone mineral density (BMD) (p=0.007) and bone mineral content (BMC) (p=0.048) in the FF VDR genotype but not in the Ff or ff VDR genotypes. CONCLUSION: Supplementation with vitamin D (5 or 10 microg/day) over 12 months increased the S-25OHD concentration but there was no effect on indices of bone health in the entire group of girls. However, there was an effect on BMD for a subgroup with the FF VDR genotype indicating an influence of genotype.

Vitamin D status and parathyroid hormone relationship in adolescents and its association with bone health parameters: analysis of the Northern Ireland Young Heart's Project.

UNLABELLED: In girls, a plateau in parathyroid hormone (PTH) was observed at a 25-hydroxyvitamin D (25(OH)D) concentration of approximately 60 nmol/l. In boys, there was no plateau in PTH concentrations as 25(OH)D concentration increased. A 25(OH)D threshold of 60 nmol/l appears to have implications for bone health outcomes in both girls and boys. INTRODUCTION: Our objective was to investigate if there is a threshold 25(OH)D concentration where a plateau in PTH concentration is evident and to examine the impact of this relationship on bone mineral density (BMD) and bone turnover in a representative sample of adolescents. METHODS: We conducted a cross-sectional analysis among 1,015 Northern Irish adolescents aged 12 and 15 years. Serum 25(OH)D, PTH, osteocalcin, type 1 collagen cross-linked C-telopeptide (CTx), and BMD of the nondominant forearm and heel were measured. Nonlinear regression analysis was used to model the association between 25(OH)D and PTH. RESULTS: In girls, a plateau in PTH was observed at a 25(OH)D concentration of approximately 60 nmol/l (PTH = 47.146 + 370.314 x exp((-0.092 x 25(OH)D))) while no plateau in PTH was observed in boys (PTH = 42.144 + 56.366 x exp((-0.022 x 25(OH)D))). Subjects with 25(OH)D levels <60 nmol/l had significantly higher osteocalcin concentrations (P < 0.05) compared with those who had >or=60 nmol/l, while no significant (P > 0.05) differences were noted for CTx concentrations. In girls only, nondominant forearm BMD but not heel BMD was significantly higher (P = 0.046) in those with 25(OH)D concentrations >or= 60 nmol/l. CONCLUSIONS: Serum 25(OH)D levels above 60 nmol/l in Northern Irish adolescent girls prevent an increase in serum PTH levels and maintaining 25(OH)D >60 nmol/l in both girls and boys may lead to improved bone health outcomes.