Overreporting of vitamin D deficiency by the Roche Elecsys vitamin D3 (25-OH) method

Background: Vitamin D deficiency is common. Recently Roche Diagnostics removed their Elecsys Vitamin D3 (25OH) electrochemiluminescence immunoassay (ECLIA) from use, citing deteriorating traceability to the reference method (liquid chromatography tandem mass spectrometry; LCMSMS). We investigated the performance of the Roche assay (2 assay formulations) against an LCMSMS method and the widely used DiaSorin radioimmunoassay (RIA) method.

Methods: Two sets of samples from separate populations were assayed for vitamin D. The first set was assayed using three different methods: RIA (DiaSorin) in 2004, polyclonal ECLIA (Roche) in early 2009 and LCMSMS in early 2010. The second set was assayed using polyclonal and monoclonal ECLIA (Roche) and LCMSMS in mid-2010.

Results: The correlation of the polyclonal ECLIA with the RIA was poor (ECLIA = 0.45 x RIA + 19, r² = 0.59, n = 773). LCMSMS results correlated with RIA (RIA = 0.86 x LCMSMS + 4, r² = 0.69, n = 49) better than with polyclonal ECLIA (polyclonal ECLIA = 0.55 x LCMSMS + 6, r² = 0.62, n = 55) despite a storage interval of 6 years.

In recently collected samples monoclonal and polyclonal immunoassays gave similar results (monoclonal ECLIA = 0.93 polyclonal ECLIA -3, r² = 0.60, n = 153). The correlation between monoclonal Roche ECLIA and LCMSMS in these samples was very poor (monoclonal ECLIA = 0.31 x LCMSMS + 23, r² = 0.27).

Conclusions: At the time of its removal from the market, the Roche Elecsys Vitamin D3 (25OH) assay showed unacceptable performance, underestimating vitamin D levels. It seems that this bias preceded the introduction of the monoclonal assay. The worldwide distribution of the assay and the duration of this bias likely led to a significant number of patients starting supplementation unnecessarily.

Vitamin D and adult bone health in Australia and New Zealand : a position statement

• A significant number of Australians are deficient in vitamin D - it is a fallacy that Australians receive adequate vitamin D from casual exposure to sunlight.

• People at high risk of vitamin D deficiency include elderly people (particularly those in residential care), people with skin conditions where avoidance of sunlight is advised, those with dark skin (particularly if veiled), and those with malabsorption.

• Exposure of hands, face and arms to one-third of a minimal erythemal dose (MED) of sunlight (the amount that produces a faint redness of skin) most days is recommended for adequate endogenous vitamin D synthesis. However, deliberate sun exposure between 10:00 and 14:00 in summer (11:00-15:00 daylight saving time) is not advised.

• If this sun exposure is not possible, then a vitamin D supplement of at least 400IU (10 μg) per day is recommended.

• In vitamin D deficiency, supplementation with 3000-5000 IU ergocalciferol per day (Ostelin [Boots]; 3-5 capsules per day) for 6-12 weeks is recommended.

• Larger-dose preparations of ergocalciferol or cholecalciferol are available in New Zealand, Asia and the United States and would be useful in Australia to treat moderate to severe vitamin D deficiency states in the elderly and those with poor absorption; one or two annual intramuscular doses of 300 000 IU of cholecalciferol have been shown to reverse vitamin D deficiency states.

Prevention and treatment of infant and childhood vitamin D deficiency in Australia and New Zealand : a consensus statement

• Vitamin D deficiency has re-emerged as a significant paediatric health issue, with complications including hypocalcaemic seizures, rickets, limb pain and fracture.

• A major risk factor for infants is maternal vitamin D deficiency. For older infants and children, risk factors include dark skin colour, cultural practices, prolonged breastfeeding, restricted sun exposure and certain medical conditions.

• To prevent vitamin D deficiency in infants, pregnant women, especially those who are dark-skinned or veiled, should be screened and treated for vitamin D deficiency, and breastfed infants of dark-skinned or veiled women should be supplemented with vitamin D for the first 12 months of life.

• Regular sunlight exposure can prevent vitamin D deficiency, but the safe exposure time for children is unknown.

• To prevent vitamin D deficiency, at-risk children should receive 400 IU vitamin D daily; if compliance is poor, an annual dose of 150 000 IU may be considered.

• Treatment of vitamin D deficiency involves giving ergocalciferol or cholecalciferol for 3 months (1000 IU/day if < 1 month of age; 3000 IU/ day if 1-12 months of age; 5000 IU/day if > 12 months of age).

• High-dose bolus therapy (300 000-500 000 IU) should be considered for children over 12 months of age if compliance or absorption issues are suspected.

Seasonal periodicity of serum vitamin D and parathyroid hormone, bone resorption, and fractures : the Geelong Osteoporosis Study

In this population-based study, seasonal periodicity was seen with reduced serum vitamin D, increased serum PTH, and increased bone resorption in winter. This was associated with an increased proportion of falls resulting in fracture and an increased risk of wrist and hip fractures.

Introduction: In a population of women who reside in a temperate climate and do not generally receive dietary vitamin D supplementation, we investigated whether seasonal vitamin D insufficiency is associated with increased risk of fracture.

Materials and Methods: An observational, cross-sectional, population-based study set in southeastern Australia (latitude 38–39° S). Participants were drawn from a well-defined community of 27,203 women ≥55 years old: 287 randomly selected from electoral rolls, 1635 with incident fractures, and 1358 presenting to a university hospital with falls. The main outcome measures were annual periodicities of ultraviolet radiation, serum 25-hydroxyvitamin D [25(OH)D], serum parathyroid hormone (PTH), serum C-telopeptide (CTx), BMD, falls, and fractures.

Results: Cyclic variations in serum 25(OH)D lagged 1 month behind ultraviolet radiation, peaking in summer and dipping in winter (p < 0.001). Periodicity of serum PTH was the inverse of serum 25(OH)D, with a phase shift delay of 1 month (p = 0.004). Peak serum CTx lagged peak serum PTH by 1–2 months. In late winter, a greater proportion of falls resulted in fracture (p < 0.001). Seasonal periodicity in 439 hip and 307 wrist fractures also followed a simple harmonic model (p = 0.078 and 0.002, respectively), peaking 1.5–3 months after the trough in 25(OH)D.

Conclusions: A fall in 25(OH)D in winter is accompanied by increases in (1) PTH levels, (2) bone resorption, (3) the proportion of falls resulting in fracture, and (4) the frequency of hip and wrist fracture. Whether vitamin D supplementation in winter can reduce the population burden of fractures requires further investigation.

Vitamin D status of women in the Geelong Osteoporosis Study : association with diet and casual exposure to sunlight

Objective: To assess vitamin D intake and casual exposure to sunshine in relation to serum 25-hydroxyvitamin D (25OHD) levels.

Design: Cross-sectional study of a population-based, random sample of women aged 20-92 years, assessed between 1994 and 1997.

Setting and participants: 861 women from the Barwon Statistical Division (population, 218 000), which includes the city of Geelong (latitude 38° south) in Victoria.

Main outcome measures: Vitamin D intake; serum 25OHD level; season of assessment; exposure to sunshine.

Results: Median intake of vitamin D was 1.2 μg/day (range, 0.0-11.4 μg/day). Vitamin D supplements, taken by 7.9% of participants, increased intake by 8.1% to 1.3 μg/day (range, 0.0-101.2 μg/day) (P < 0.001). A dose-response relationship in serum 25OHD levels was observed for sunbathing frequency before and after adjusting for age (P < 0.05). During winter (May-October), serum 25OHD levels were dependent on vitamin D intake (partial r2 = 0.01; P < 0.05) and were lower than during summer (November-April) (age-adjusted mean, 59 nmol/L [95% CI, 57-62] v 81 nmol/L [95% CI, 78-84]; P < 0.05). No association was detected between serum 25OHD and vitamin D intake during summer. The prevalences of low concentrations of serum 25OHD were, for <28 nmol/L, 7.2% and 11.3% overall and in winter, respectively; and, for <50 nmol/L, 30.0% and 43.2% overall and in winter, respectively.

Conclusions: At latitude 38° south, the contribution of vitamin D from dietary sources appears to be insignificant during summer. However, during winter vitamin D status is influenced by dietary intake. Australia has no recommended dietary intake (RDI) for vitamin D, in the belief that adequate vitamin D can be obtained from solar irradiation alone. Our results suggest that an RDI may be needed.

Maternal vitamin D in pregnancy may influence not only offspring bone mass but other aspects of musculoskeletal health and adiposity

Osteoporotic fractures, falls and obesity are major health problems in developed nations. Evidence suggests that there are antenatal factors predisposing to these conditions. Data are emerging from Australia and elsewhere to suggest that maternal vitamin D status in pregnancy affects intrauterine skeletal mineralisation and skeletal growth together with muscle development and adiposity. Given that low levels of vitamin D have been documented in many urbanised populations, including those in countries with abundant sunlight, an important issue for public health is whether maternal vitamin D insufficiency during pregnancy has adverse effects on offspring health. The developing fetus may be exposed to low levels of vitamin D during critical phases of development as a result of maternal hypovitaminosis D. We hypothesise that this may have adverse effects on offspring musculoskeletal health and other aspects of body composition. Further research focused on the implications of poor gestational vitamin D nutrition is warranted as these developmental effects are likely to have a sustained influence on health during childhood and in adult life. We suggest that there is a clear rationale for randomised clinical trials to assess the potential benefits and harmful effects of vitamin D supplementation during pregnancy.

The high prevalence of vitamin D insufficiency across Australian populations is only partly explained by season and latitude

Background Inadequate sun exposure and dietary vitamin D intake can result in vitamin D insufficiency. However, limited data are available on actual vitamin D status and predictors in healthy individuals in different regions and by season.

Methods We compared vitamin D status [25-hydroxyvitamin D; 25(OH)D] in people < 60 years of age using data from cross-sectional studies of three regions across Australia: southeast Queensland (27°S; 167 females and 211 males), Geelong region (38°S; 561 females), and Tasmania (43°S; 432 females and 298 males).

Results The prevalence of vitamin D insufficiency (≤ 50 nmol/L) in women in winter/spring was 40.5% in southeast Queensland, 37.4% in the Geelong region, and 67.3% in Tasmania. Season, simulated maximum daily duration of vitamin D synthesis, and vitamin D effective daily dose each explained around 14% of the variation in 25(OH)D. Although latitude explained only 3.9% of the variation, a decrease in average 25(OH)D of 1.0 (95% confidence interval, 0.7–1.3) nmol/L for every degree increase in latitude may be clinically relevant. In some months, we found a high insufficiency or even deficiency when sun exposure protection would be recommended on the basis of the simulated ultraviolet index.

Conclusion Vitamin D insufficiency is common over a wide latitude range in Australia. Season appears to be more important than latitude, but both accounted for less than one-fifth of the variation in serum 25(OH)D levels, highlighting the importance of behavioral factors. Current sun exposure guidelines do not seem to fully prevent vitamin D insufficiency, and consideration should be given to their modification or to pursuing other means to achieve vitamin D adequacy.

Sex differences in achievement in year 12 mathematics and non-routine problem solving

In 1991 all Victorian year 12 students undertook the new Victorian Certificate of Education Mathematics Study designed by the Victorian Curriculum and Assessment Board. This paper presents the results of a study into sex difference in achievement in the new VCE Mathematics study in Victoria. An important goal of the study designers was to encourage more equal participation in senior secondary mathematics by females and males and to include assessment of mathematical skills previously not assessed in a year 12 course in Victoria. These new tasks could conceivably change the degree and direction of sex difference in achievement in senior secondary mathematics.

Blood mineral, trace-element and vitamin concentrations in Huacaya alpacas and Merino sheep grazing the same pasture

We aimed to determine whether the concentration of minerals and trace constituents in blood of Merino sheep and Huacaya alpacas grazing the same pasture differed with species and time of sampling. Blood samples and pasture samples were collected at frequent intervals over a period of 2 years for mineral and trace-nutrient assay. The concentration of the minerals and trace nutrients in the grazed pasture usually met the dietary needs of sheep at maintenance, apart from potassium, sulfur, cobalt and Vitamin E in occasional samples. Restricted maximum likelihood mixed model analysis indicated a significant (P < 0.001) species by month by year interaction for all blood constituents assayed, a significant (P < 0.05) species by coat shade interaction for plasma Vitamin D, E and B12 and a significant (P < 0.001) species by month by Vitamin D interaction for plasma phosphorus concentrations. In general, plasma calcium concentrations were greater in sheep than in alpacas but plasma magnesium concentrations were greater in alpacas than in sheep. There was no consistent difference between the two species in plasma phosphorus concentrations although low values were recorded in individual sheep and alpacas. Plasma Vitamin D concentrations were more responsive to increasing hours of sunlight in alpacas than they were in sheep. Sheep had consistently higher concentrations of plasma copper, zinc and Vitamin B12 and higher concentrations of blood selenium but lower concentrations of plasma selenium and Vitamin A, than did alpacas. No consistent difference was observed between the two species in plasma Vitamin E concentrations.

Rates of common communicable illnesses in non-anaemic 12-24 month old South Island, New Zealand children

Aims : To describe the incidence of parentally reported illness in otherwise healthy South Island toddlers; characterise the predictors of illness; and determine whether there was a relationship between teething and illness in this population.

Methods : A 20-week randomised controlled trial was conducted on 1-year-old children (n=225) from Otago and Southland between February 2004 and December 2005. Information on symptoms of morbidity, occurrence of teething, and childcare attendance were recorded daily throughout the intervention period. Morbidity symptoms were categorised into respiratory illness (RI), gastrointestinal illness (GII), ear infection, and total illness, and the number and duration of events were determined.

Results : The mean (SD) number of total illnesses was 3.4 (2.3) per 20 weeks, with an average duration of 4.5 days. Episodes of RI were most common (50% of total illness events), and tended to be the longest in duration (mean of 3.7 days). Having siblings aged less than 5 years (23% increase, 95%CI 6%–42%, p=0.007) and attending childcare (72% increase, 95%CI 38%–113%, p<0.001)), were positively associated with the number of total illness events but not duration. In addition, teething was positively associated with total events (OR 1.94, 95%CI 1.45–2.60, p<0.001), RI events (OR 2.03, 95%CI 1.41–2.93, p<0.001) and GII events (OR 1.90, 95%CI 1.36–2.67, p<0.001).

Conclusion : This study has shown that illness (particularly RI) is common in the second year of life. It has also confirmed that attending childcare and having siblings aged under 5 years increases the number of illness events. An association between teething and the occurrence of illness was also seen but the exact nature of this relationship requires verification.

Vitamin D-fortified milk achieves the targeted serum 25-hydroxyvitamin D concentration without affecting that of parathyroid hormone in New Zealand toddlers

For young children, the level of vitamin D required to ensure that most achieve targeted serum 25-hydroxyvitamin D [25(OH)D] ≥50 nmol/L has not been studied. We aimed to investigate the effect of vitamin D-fortified milk on serum 25(OH)D and parathyroid hormone (PTH) concentrations and to examine the dose–response relationship between vitamin D intake from study milks and serum 25(OH)D concentrations in healthy toddlers aged 12–20 mo living in Dunedin, New Zealand (latitude 46°S). Data from a 20-wk, partially blinded, randomized trial that investigated the effect of providing red meat or fortified toddler milk on the iron, zinc, iodine, and vitamin D status in young New Zealand children (n = 181; mean age 17 mo) were used. Adherence to the intervention was assessed by 7-d weighed diaries at wk 2, 7, 11, 15, and 19. Serum 25(OH)D concentration was measured at baseline and wk 20. Mean vitamin D intake provided by fortified milk was 3.7 μg/d (range, 0–10.4 μg/d). After 20 wk, serum 25(OH)D concentrations but not PTH were significantly different in the milk groups. The prevalence of having a serum 25(OH)D <50 nmol/L remained relatively unchanged at 43% in the meat group, whereas it significantly decreased to between 11 and 15% in those consuming fortified study milk. In New Zealand, vitamin D intake in young children is minimal. Our findings indicate that habitual consumption of vitamin D-fortified milk providing a mean intake of nearly 4 μg/d was effective in achieving adequate year-round serum 25(OH)D for most children.

Quantities of foods consumed by 12- to 24-month-old New Zealand children

Aim:  The present study aimed to estimate small, median and large daily quantities of frequently consumed foods and identify which food groups are important sources of key micronutrients for 12- to 24-month-old New Zealand children.

Methods:  A community-based cross-sectional survey was conducted in three cities in the South Island of New Zealand. Healthy toddlers (n = 188) were randomly selected using multistage sampling. Three non-consecutive 1-day weighed food records were collected from each child and the frequencies and daily quantities of foods and beverages, and important sources of iron and zinc, were determined.

Results:  Fifty percent or more of the children consumed the following foods at least once over 3 days (median gram intake among toddlers who consumed the food): milk (366 g), white bread (29 g), banana (70 g), potato (34 g), cheese (12 g), apple (39 g), ‘Weetbix’ whole-wheat breakfast cereal (16 g), yeast extract spread (‘Marmite’, ‘Vegemite’) (2 g), carrot (17 g) and margarine (4 g). Dairy, cereals and the meat/fish/poultry/eggs/nuts food group were the most important sources of iron and zinc in the toddlers' diets, providing 69.1% of iron and 86.3% of zinc.

Conclusion:  This research provides dietitians, other health professionals, researchers and policy-makers with detailed information on daily quantities of foods and beverages frequently consumed by toddlers that can be used for dietetic counselling, dietary assessment, and to develop food-based dietary guidelines specifically for toddlers.