Malachi J. McKenna

Differences in vitamin D status between countries in young adults and the elderly

PURPOSE To compare vitamin D status between countries in young adults and in the elderly. MATERIALS AND METHODS Reports on vitamin D status (as assessed by serum 25-hydroxyvitamin D) from 1971 to 1990 were reviewed. Studies were grouped according to geographic regions: North America (including Canada and the United States); Scandinavia (including Denmark, Finland, Norway, and Sweden); and Central and Western Europe (including Belgium, France, Germany, Ireland, The Netherlands, Switzerland, and the United Kingdom). RESULTS Vitamin D status varies with the season in young adults and in the elderly, and is lower during the winter in Europe than in both North America and Scandinavia. Oral vitamin D intake is lower in Europe than in both North America and Scandinavia. Hypovitaminosis D and related abnormalities in bone chemistry are most common in elderly residents in Europe but are reported in all elderly populations. CONCLUSIONS The vitamin D status in young adults and the elderly varies widely with the country of residence. Adequate exposure to summer sunlight is the essential means to ample supply, but oral intake augmented by both fortification and supplementation is necessary to maintain baseline stores. All countries should adopt a fortification policy. It seems likely that the elderly would benefit additionally from a daily supplement of 10 micrograms of vitamin D.

Multiple sclerosis prevalence in Ireland: relationship to vitamin D status and HLA genotype

Background The relationship between prevalence of multiple sclerosis (MS) and latitude may be due to both genetic and environmental factors. The hypothesis that, in Ireland, MS prevalence is increasing and that north–south differences relate to variation in serum 25-hydroxyvitamin D (25(OH)D) levels was tested in this study. Patients and methods Patients and matched control subjects were identified in counties Donegal, Wexford and South Dublin through multiple sources. Prevalence was determined. Blood samples were taken for serum 25(OH)D and serum intact parathyroid hormone measurement, and DNA was extracted. Results Prevalence in 2007 was significantly greater in Donegal (northwest) (290.3/105, 95% CI 262.3 to 321.7) compared with 2001 (184.6/105; 162 to 209.5). In Wexford (southeast), there was a non-significant increase in prevalence in 2007 compared with 2001. Prevalence was significantly higher in Donegal than in Wexford (144.8/105; 126.7 to 167.8, p<0.0001) and South Dublin (127.8/105; 111.3 to 148.2, p<0.0001). Overall, mean 25(OH)D levels were low and did not differ between patients (38.6 nmol/l) and controls (36.4 nmol/l) However, significantly more patients than controls had 25(OH)D levels <25 nmol/l (deficiency) (p=0.004). Levels of 25(OH)D (mean 50.74 nmol/l) were significantly higher in South Dublin (area with lowest prevalence) (p<0.0001) than in Donegal or Wexford. HLA DRB1*15 occurred most frequently in Donegal (greatest MS prevalence) and least frequently in South Dublin. Conclusion Vitamin D deficiency is common in Ireland. Latitudinal variation in MS probably relates to an interaction between genetic factors and environment (25(OH)D levels), and MS risk may be modified by vitamin D in genetically susceptible individuals.

Vitamin D nutritional status in preterm infants and response to supplementation.

Little is known about vitamin D status in preterm infants and their response to supplementation. To investigate this, we assessed serum 25-hydroxyvitamin D (25OHD) levels using RIA in a consecutive sample of stable preterm very low birth weight (VLBW) infants (born ≤ 32 weeks gestation or birth weight ≤ 1·5 kg), and we explored associated factors. Serum 25OHD level was first assessed once infants were tolerating feeds (n 274). If this first 25OHD level was below 50 nmol/l (20 ng/ml), which is the level associated with covering requirements in terms of skeletal health in the majority, then we recommended prolonged augmented vitamin D intake ( ≥ 10 μg (400 IU) daily) from a combination of fortified feeds and vitamin supplements and follow-up re-assessment at approximately 6 weeks corrected age (n 148). The first assessment, conducted at a median for chronological age of 18 (interquartile range (IQR) 11-28) d, found that 78 % had serum 25OHD levels below 50 nmol/l. Multivariable analysis demonstrated that the determinants of serum 25OHD levels were duration of vitamin D supplementation and gestational age at birth (r 2 0·215; P< 0·001). At follow-up, after a median of 104 (IQR 78-127) d, 87 % achieved levels ≥ 50 nmol/l and 8 % had levels >125 nmol/l, a level associated with potential risk of harm. We conclude that low 25OHD levels are an issue for preterm VLBW infants, warranting early nutritional intervention. In infants with serum 25OHD levels < 50 nmol/l, a vitamin D intake of ≥ 10 μg (400 IU) daily achieves target levels in the majority; however, further work is needed to determine the exact dose to safely meet target levels without overcorrection.

The Effect of Narrowband UV-B Treatment for Psoriasis on Vitamin D Status During Wintertime in Ireland

OBJECTIVES To determine whether narrowband UV-B (NB-UV-B) may mediate its beneficial effect on psoriasis by increasing vitamin D levels, and to assess the effect of NB-UV-B on vitamin D status in patients with psoriasis in wintertime. DESIGN A prospective controlled study from October 2008 to February 2009. SETTING A dermatology outpatient department at a university teaching hospital. PATIENTS Thirty consecutive patients with psoriasis treated with NB-UV-B and 30 control patients with psoriasis were recruited. Control patients were recruited within 1 week of treated patients to control for seasonal variation of serum 25-hydroxyvitamin D [25(OH)D] levels. One patient with photo aggravated psoriasis was withdrawn from the study. INTERVENTION Narrowband UV-B was administered 3 times per week. MAIN OUTCOME MEASURE Serum 25(OH)D was measured at baseline, after 4 weeks and at completion of treatment. RESULTS Levels of serum 25(OH)D increased significantly(P< .001) from a median (range) of 23 (9-46)ng/mL at baseline to 51 [rather than 59, as given in the originally published article] (32-112) ng/mL at the end of NB–UV-B treatment compared with no change in the control group [corrected]. The change in serum 25(OH)D level correlated with the number of exposures of NB-UV-B (r = 0.61; P < .001) and cumulative UV-B dose (r = 0.47; P = .01) but not with treatment response. At the end of the study, all patients in the treatment group were vitamin D sufficient, but 75% of the control group had vitamin D insufficiency [serum 25(OH)D level <20 ng/mL]. In a multiple regression model, prior phototherapy was the sole predictor of baseline serum 25(OH)D level (r(2) = 0.13; P = .006), whereas the number of exposures of NB-UV-B predicted change in serum 25(OH)D level (r(2) = 0.38; P = .001). CONCLUSIONS Narrowband UV-B effectively increases serum 25(OH)D level while clearing psoriasis. Up to 75% of Irish patients with psoriasis were shown to be vitamin D insufficient during wintertime.

Effect of Chronic Hepatitis C Virus Infection on Bone Disease in Postmenopausal Women

BACKGROUND & AIMS Limited data are available on the contribution of chronic HCV infection to the development of bone disease in postmenopausal women. We studied whether women who acquired HCV infection through administration of HCV genotype 1b-contaminated anti-D immunoglobulin from a single source had decreased bone mineral density (BMD) or altered levels of bone turnover markers (BTMs), compared with women who spontaneously resolved infection or age-matched healthy controls. METHODS From a cohort of postmenopausal Irish women, we compared BMD, determined by dual-energy x-ray absorptiometry, and a panel of BTMs in 20 women chronically infected with HCV (PCR(+)), 21 women who had spontaneously resolved infection (PCR(-)), and 23 age-matched healthy controls. RESULTS Levels of BTMs and BMD were similar in PCR(+) and PCR(-) women and healthy age-matched controls. However, there was an increased frequency of fractures in PCR(+) (n = 6) compared with PCR(-) women (n = 0, P = .007). PCR(+) women with fractures were postmenopausal for a longer time (median, 15.5, range, 5-20 years vs 4.5, range, 1-20 years in PCR(+) women without fractures; P = .033), had lower BMD at the hip (0.79, range, 0.77-0.9 g/cm(2) vs 0.96, range, 0.81-1.10 g/cm(2); P = .007), and had a lower body mass index (23.7, range 21.2-28.5 kg/m(2) vs 25.6, range 22.1-36.6 kg/m(2); P = .035). There was no difference in liver disease severity or BTMs in PCR(+) women with or without fractures. CONCLUSIONS Chronic HCV infection did not lead to discernable metabolic bone disease in postmenopausal women, but it might be a risk factor for bone fractures, so preventive measures should be introduced. To view this articles video abstract, go to the AGAs YouTube Channel.

Prevention of hypovitaminosis D in the elderly

SummaryConflicting opinions are held on the efficacy and safety of low-dose oral vitamin D supplementation. In this study, the value of short-term and long-term low-dose vitamin D supplementation (20 μg D3 daily) is demonstrated in elderly subjects. Short-term therapy readily restored serum 25-hydroxy-vitamin D (25OHD) values to normal, and ameliorated biochemical abnormalities of calcium, phosphate, and alkaline phosphatase, consistent with healing of mild osteomalacia. Prolonged therapy (16 months) maintained serum 25OHD levels within the young adult range, and was not associated with hypercalcemia. Withdrawal of therapy was associated with a steady decline in serum 25OHD levels. Low-dose vitamin D supplementation is recommended for elderly subjects to prevent the development of hypovitaminosis D osteopathy.

Adaptor protein-2 sigma subunit mutations causing familial hypocalciuric hypercalcaemia type 3 (FHH3) demonstrate genotype–phenotype correlations, codon bias and dominant-negative effects

The adaptor protein-2 sigma subunit (AP2σ2) is pivotal for clathrin-mediated endocytosis of plasma membrane constituents such as the calcium-sensing receptor (CaSR). Mutations of the AP2σ2 Arg15 residue result in familial hypocalciuric hypercalcaemia type 3 (FHH3), a disorder of extracellular calcium (Ca2+o) homeostasis. To elucidate the role of AP2σ2 in Ca2+o regulation, we investigated 65 FHH probands, without other FHH-associated mutations, for AP2σ2 mutations, characterized their functional consequences and investigated the genetic mechanisms leading to FHH3. AP2σ2 mutations were identified in 17 probands, comprising 5 Arg15Cys, 4 Arg15His and 8 Arg15Leu mutations. A genotype–phenotype correlation was observed with the Arg15Leu mutation leading to marked hypercalcaemia. FHH3 probands harboured additional phenotypes such as cognitive dysfunction. All three FHH3-causing AP2σ2 mutations impaired CaSR signal transduction in a dominant-negative manner. Mutational bias was observed at the AP2σ2 Arg15 residue as other predicted missense substitutions (Arg15Gly, Arg15Pro and Arg15Ser), which also caused CaSR loss-of-function, were not detected in FHH probands, and these mutations were found to reduce the numbers of CaSR-expressing cells. FHH3 probands had significantly greater serum calcium (sCa) and magnesium (sMg) concentrations with reduced urinary calcium to creatinine clearance ratios (CCCR) in comparison with FHH1 probands with CaSR mutations, and a calculated index of sCa × sMg/100 × CCCR, which was ≥ 5.0, had a diagnostic sensitivity and specificity of 83 and 86%, respectively, for FHH3. Thus, our studies demonstrate AP2σ2 mutations to result in a more severe FHH phenotype with genotype–phenotype correlations, and a dominant-negative mechanism of action with mutational bias at the Arg15 residue.

Incomplete Atypical Femoral Fractures: Assessing the Diagnostic Utility of DXA by Extending Femur Length

Atypical femoral fractures (AFFs) are associated with prolonged bisphosphonate therapy. A feature of incomplete AFF is a localized periosteal reaction. It has been suggested that extending the length of the femur image at the time of dual-energy X-ray absorptiometry (DXA) may diagnose an incomplete AFF. In patients older than 50 yr on bisphosphonate therapy for more than 5 yr, we extended femur length at the time of routine DXA. Abnormal DXA images were suggested in 19 of 257 patients (7.4%). On X-ray, 7 patients (2.7%) showed no abnormality, 7 patients (2.7%) showed evidence of AFF, and 5 patients (2.0%) showed an unrelated radiographic abnormality. Of the 7 cases with X-ray evidence of AFF, 5 had a periosteal flare and 2 had a visible fracture line, both of whom needed insertion of an intramedullary nail. We demonstrated that it is feasible to detect incomplete AFF early using extended femur length imaging with a prevalence in our sample of 2.7% (95% confidence interval: 1.7%-3.7%).

In vitro optimisation of a microdialysis system with potential for on-line monitoring of lactate and glucose in biological samples.

The optimisation and evaluation of the microdialysis component of a prototype miniaturised total analysis system for application in the continuous monitoring of lactate and glucose is reported. The complete unit comprises a high efficiency microdialysis sampling system, a miniaturised microflow manifold with an integrated biosensor array, together with the hardware and software necessary for controlling the flow parameters and monitoring the sensor signals. Sampling occurs via a microdialysis shunt probe which is perfused continuously with a physiological buffered saline solution. The continuous dialysate outflow is presented to the biosensor array, resulting in the appropriate amperometric signals. Aspects of technological significance addressed here include probe membrane size, perfusate flow rate, sample flow rate, temperature change, probe sterilisation procedures, and heparin content of the physiological saline solution employed.

Relationship between vitamin D knowledge and 25‐hydroxyvitamin D levels amongst pregnant women

BACKGROUND Pregnant women living at northerly latitudes are at risk of suboptimal vitamin D status. There is a paucity of studies correlating knowledge, attitudes and practices of vitamin D with serum levels amongst pregnant women. We aimed to determine the prevalence of suboptimal vitamin D status in pregnant women of various ethnicities attending two Dublin maternity hospitals and to assess levels of knowledge, attitudes and practices concerning vitamin D. METHODS We conducted a cross-sectional study of 116 pregnant women of Irish, Asian, Sub-Saharan African and Middle Eastern and North African (MENA) origin. Vitamin D status was determined by measurement of serum 25-hydroxyvitamin D (25OHD). We examined knowledge, attitudes and practices concerning vitamin D using an interview-assisted questionnaire. RESULTS The median (interquartile range) 25OHD level was 25.9 (16.5-44.7) nmol L(-1). Using a cut-off point of <30 nmol L(-1) , the proportion at risk of deficiency was significantly higher among MENA (88%; P < 0.001) and Sub-Saharan African women (68%; P = 0.019) than Irish women (36%). Eighty-two women (71%) reported they had insufficient knowledge about vitamin D and its sources. Vitamin D containing supplement usage was the strongest predictor of 25OHD levels ≥30 nmol L(-1) (odds ratio = 18.03, 95% confidence interval = 5.7256.8, P < 0.001). CONCLUSIONS Suboptimal vitamin D status is common in this cohort of pregnant women, especially among those of Sub-Saharan African and MENA origin. Awareness of vitamin D dietary sources is poor among all subgroups. Recommending vitamin D containing supplements may be the best strategy at present for improving vitamin D status with a need for increased vitamin D education.