Vitamin D changes in an Arctic Inuit society in transition

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Abstracts

a

Medical sciences, Uppsala University, Uppsala, Sweden Department of Clinical Science, Intervention and Technology, Karolinska institutet, Stockholm, Sweden c Center for Bone and Arthritis Research at the Sahlgrenska Academy, Institute of Medicine, the Sahlgrenska Academy at Göteborg, Sweden d Wallenberg Laboratory for Cardiovascular Research, University of Göteborg, Göteborg, Sweden e Orthopaedic Surgery, Lund University, Skåne University Hospital, Lund, Sweden b

Abstract: Polymorphisms in the Klotho (Kl) gene, which is central for vitamin D regulation by fibroblast growth factor 23 (FGF23), have been associated with longevity, coronary disease and stroke. The CC genotype of the single nucleotide polymorphism (SNP) rs577912 in the Kl-gene is associated with decreased Kl expression, as well as increased mortality in end stage renal disease. We examined if SNP in the Kl-gene was associated with mortality in the community derived cohort of 70 to 80 year old males of MrOS Sweden (N = 3014). High throughput genotyping of the KLOTHO SNPs was achieved by use of SequenomR MassEXTEND/Mass/ARRAY technology. 2738 subjects had a valid result for rs577912: CC 73.1% and CA + AA 26.9%. There were no differences in the serum levels of FGF23, phosphate, parathyroid hormone or renal function between genotypes CC and CA + AA. During a follow-up of a median of 4.5 years there were 337 deaths, 253 (12.6%) in the CC group and 84 (11.4%) in the CA + AA group. With log rank analysis there were no differences in mortality between the genotypes for all cause mortality (P = 0.39) or cardiovascular mortality (P = 0.60). None of the other SNPs in the Kl gene was associated with mortality in this cohort either. Conclusion: There is no association between the SNP rs577912 in the Kl-gene and mortality among elderly men. This article is part of a Special Issue entitled ECTS 2012. Disclosure of interest: None declared.

doi:10.1016/j.bone.2012.02.314

PP126 Normocalcemic primary hyperparathyroidism in postmenopausal women: Relationship with bone metabolism R. Reyes-Garcia⁎, A. Garcia-Martin, M.D. Aviles-Perez, V. Avila-Rubio, A. Muñoz-Garach, M. Muñoz-Torres Bone Metabolic Unit. Endocrinology, Hospital Universitario San Cecilio, Granada, Spain Abstract: Introduction: Routine measurement of parathormone (PTH) has lead to the identification of high PTH levels without hypercalcemia, defined as normocalcemic primary hyperparathyroidism. There are conflicting data about its bone effects and clinical implications. Objectives: The aims of the study were to evaluate the frequency of normocalcemic primary hyperparathyroidism in postmenopausal women, and to analyse parameters related to bone metabolism after one-year follow-up. Patients and methods: Prospective study conducted in a cohort of 100 healthy postmenopausal women. Clinical and biochemical data and bone mass defined by QUS were determined at baseline and after one year. Results: 15/100 women had high PTH concentrations with normal calcium (PTH 78.4(12.7) pg/ml and serum calcium 9.3 (0.3) mg/dl). In this group six women had 25 OH vitamin D levels N 30 ng/ml and were classified as normocalcemic hyperparathyroidism after exclusion of other causes of secondary hyperparathyroidism. Baseline serum PTH concentrations were negatively related to QUS parameters QUI: r = − 0.621, p = 0.013; DMO r = − 0.554, p = 0.032; T-score r = − 0.571, p = 0.026). No episodes of hypercalcemia or other relevant clinical events were observed in the normocalcemic hyperparathyroidism group. In women with high PTH there were no significant changes in biochemical variables except for vitamin D levels, which raised from 21 (8.2) to 29.5 (12.7) ng/ml, p = 0.02 after a nutritional intervention. Conclusions: In summary, in our group of otherwise healthy postmenopausal women the frequency of normocalcemic hyperparathyroidism is 6% after excluding main causes of secondary hyperparathyroidism. There was no clinical or biochemical progression after one year of follow-up. However PTH and bone mass were inversely related. This article is part of a Special Issue entitled ECTS 2012. Disclosure of interest: None declared.

doi:10.1016/j.bone.2012.02.315

PP127 High prevalence of vitamin d deficiency among pregnant women at term and their neonates in Thessaloniki, Northern Greece S. Karrasa,⁎, H. Bilia, D. Goulisa, F. Papadopouloub, V. Harizopouloua, E. Kintirakib, K. Gkastarisc, K. Badisd, B. Tarlatzisa a First Department of Obstetrics and Gynaecology, Aristotle University, Thessaloniki, Greece b Endocrinology-Diabetes Department, Panagia General Hospital, Thessaloniki, Greece c Department of Endocrinology and Diabetes, Bristol Royal Infirmary, Bristol, UK d Department of Endocrinology and Diabetes, Aristotle University, Thessaloniki, Greece, Thessaloniki, Greece Abstract: Introduction: Maternal vitamin D status is integral to fetal development. There are few data from Greece, a country with abundant sunshine, regarding the prevalence of vitamin D deficiency in pregnancy. Our aim was to assess vitamin D status of women at term and their neonates in a region of Northern Greece. Methods: Maternal serum and cord blood levels of calcium (Ca), 25-hydroxyvitamin D (25-0HD), alkaline phosphatase (ALP), phosphorus (P) and parathyroid hormone (PTH) were studied in 60 mother-newborn pairs at term. The study was conducted between February 2010 and March 2011. Dietary habits and skin phototype (Fitzpatrick's classification) were studied. Results: Mean level of maternal serum 25(OH) D was 10.11 ± 6.8 (6.2–21.2) ng/ml, significantly lower (P b 0.001-paired samples test) than that of cord blood 14.2 ± 9.5(10.2–23.8) ng/ml. Maternal serum 25-OH-D correlated positively with cord blood 25-OH-D(r = 0.79, P b 0.001) (Spearman's correlation). According criteria defining vitamin D deficiency, 82.3% of mothers and 62.5% of neonates were vitamin D deficient, respectively. Umbilical venous blood P was significantly (P b 0.001) higher than maternal blood levels [5.2 ± 1.2 (3.8–5.9) vs. 3.6 ± 1.2 (2.9–3.8) mg/dl], while umbilical PTH levels were significantly lower (P b 0.001) than maternal levels [4.5 ± 2.5(3.1–7.1) vs.22.1 ± 9.1 (6.5–36.2) pg/ml]. No differences were found between maternal and cord blood Ca and ALP levels (p = 0.710) .The intake of Ca and vitamin D was uniformly low [283 ± 103 mg/d and 48 ± 24 IU/d], respectively. Mothers who delivered during winter and spring had lower 25-OH-D levels (P b 0.001), than those who delivered in summer and autumn [8.9 ± 5.1 (4.2– 11.1) vs. 9.6 ± 6.8 (5.8–15.4)].Finally, women with fair phototype had higher 25-OH-D (P b 0.001) than women with darker phototypes. Conclusion: We observed a high prevalence of hypovitaminosis D among pregnant women and their newborns in Northern Greece. Further public health intervention and vitamin D supplementation are needed to improve maternal and neonatal vitamin D status. This article is part of a Special Issue entitled ECTS 2012. Disclosure of interest: None declared.

doi:10.1016/j.bone.2012.02.316

PP128 Vitamin D changes in an Arctic Inuit society in transition S. Andersena,b,⁎, P. Laurberga, K. Kleinschmidtb, B. Hvingelc, L. Heickendorfd, L. Mosekildee a Arctic Health Research Centre, Aalborg University Hospital, Aalborg, Denmark b Dept. Internal Medicine, Queen Ingrids Hospital, Nuuk, Greenland c Dept. of Surgery, Queen Ingrids Hospital, Nuuk, Greenland d Clinical Biochemistry, Århus University Hospital, Århus, Denmark e Endocrinology, Århus University Hospital, Århus, Denmark Abstract: Background: Circumpolar people rely on dietary sources of vitamin D (25-OHD). Transition of Arctic societies has profound dietary effects. Objective: To clarify vitamin D status and factors important to 25OHD in Arctic populations. Design: Inuit and non-Inuit in the capital city Nuuk in West Greenland and in the major town and in remote settlements in East Greenland were surveyed. Supplement use and life style factors were determined by questionnaires, dietary habits by a food frequency questionnaire, 25OHD in serum. Results: One percent of the population of Greenland was invited and 95% participated with 101 non-Inuit, 150 Inuit in the capital city, 141 in the coastal town, and 143 in settlements. Supplements were taken by 22, 15, 5 and 3 respectively. A diet of less than 60% traditional Iniut food item-scores was found in 92%, 41%, 13%, and 7% respectively. Diet associated with 25OHD (p b 0.001) and serum 25OHD was below 20/50 nM in 7.4/51.0% with an intake of traditional Inuit food items below 60% and 0.3/22.5% with a higher intake. Non-Inuit had the lowest median 25OHD, 25; 75 percentile of 41, 23; 53 nM, while the level was higher among Inuit (Nuuk 73, 58; 91; Tasiilaq 60, 50; 74; settlements 61, 50; 73). The major contributors were seal (p = 0.001) and fish (p = 0.028). Conclusions: Decreasing intake of

Abstracts traditional Inuit diet lowers 25OHD levels in Arctic populations. The risk of vitamin D deficiency rises with transition of societies in Greenland and 25OHD nutrition should be monitored in Arctic societies. This article is part of a Special Issue entitled ECTS 2012. Disclosure of interest: None declared. doi:10.1016/j.bone.2012.02.317

PP129 Effectiveness of a Mg-based phosphate binder on the development of vascular calcifications in uremic rats T. De Schuttera,⁎, E. Nevena, G. Behetsa, M. Peterb, S. Steppanb, J. Passlick-Deetjenc, P. D'Haesea a University of Antwerp, Antwerpen - Wilrijk, Belgium, Germany b Fresenius Medical Care, Bad Homburg, Germany c University of Dusseldorf, Dusseldorf, Germany Abstract: Calcium-based phosphate (P) binders are widely used to control hyperphosphatemia to however go along with hypercalcemia and accelerated progression of VC. We compared the effect of 2 doses of the magnesium-based phosphate binder CaMg (2/3 Ca-acetate and 1/3 Mg-carbonate, Osvaren) to that of sevelamer carbonate (sevelamer) on the development of vascular calcification (VC) in rats with chronic renal failure (CRF). 56 male rats were divided in 4 groups: vehicle, 375 mg/kg CaMg, 750 mg/kg CaMg, and 750 mg/kg sevelamer. CRF was induced by feeding 0.75% adenine-2.5% protein diet for 4 weeks. After 1 week of CRF, rats were gavaged with P-binders or vehicle (7 d/ week) until sacrifice at week 6. Renal function was significantly impaired after 4 weeks of adenine treatment and comparable in all groups. Vehicle treated CRF rats developed severe hyperphosphatemia which was well controlled in the groups receiving P-binders particularly those receiving CaMg even at the lowest dose (Cmax serum P: vehicle: 20.3-CaMg375: 11.5-CaMg750: 9.9-sev: 16.3 mg/dl). AUC0-6 wks of serum calcium did not differ significantly between groups. Serum Mg AUC0-6 wks dose-dependently increased in CaMg treated groups (vehicle: 15.0-CaMg375: 20.8-CaMg750: 27.16-sevelamer: 16.0 mg.wk/l). Induction of CRF went along with a significant increase in serum PTH. Treatment with CaMg dose-dependently prevented this increase whilst sevelamer did not. Based on tissue calcium measurements, aortas of CaMg treated rats were significantly less calcified compared to vehicle. Sevelamer had no significant effect on aortic calcifications although a clear reducing trend was seen. In contrast, calcifications in arteria femoralis and arteria carotis were significantly reduced by sevelamer and showed a clear trend for CaMg, indicating a possibly different mechanism of calcification in these arteries. Results were confirmed on Von Kossa stained sections, showing that both CaMg and sevelamer significantly reduced the area% calcification in the aorta. Treatment with the Mg-based phosphate binder CaMg effectively controlled serum P and PTH levels resulting in reduced VC in uremic rats. This article is part of a Special Issue entitled ECTS 2012. Disclosure of interest: None declared. doi:10.1016/j.bone.2012.02.318

PP130 Determination of vitamin D deficiency by urine measurement V. Schwetza,⁎, N. Hackera, C. Schnedla, K. Amreina, E. Lerchbauma, O. Trummera, N. Schweighofera, T. Piebera, H. Siggelkowb, B. Obermayer-Pietscha a Department of Internal Medicine, Medical University of Graz, Graz, Austria b Division of Gastroenterology and Endocrinology, Medical University of Göttingen, Göttingen, Germany Abstract: Background: Determination of 25-hydroxyvitamin D3 (25(OH)D) status can be of great importance in persons at risk for vitamin D deficiency, e.g. nursing home patients as well as children. In the first subset of individuals this is due to reduced vitamin D intake, diminished production of vitamin D in the aging skin, and little sun exposure. Especially in these patients, vitamin D deficiency enhances bone loss, falls, and fractures. Vitamin D sufficiency in neonates and infants has been acknowledged to have a long-lasting positive clinical outcome and therefore supplementation especially in the first year of life is recommended worldwide. However, in nursing home residents as well as in young children, drawing of blood samples for vitamin D status determination might be challenging or even problematic. Aim: Our aim was to

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elucidate whether urinary measurement of 25(OH)D could serve as an alternative to serum 25(OH)D measurement. Material and methods: 25(OH)D was measured both in serum and spot urine samples using an adapted enzyme immunoassay (IDS, Boldon, UK) in 229 patients during acute hospitalization. Additionally, 25(OH)D levels were compared in 24-h urine samples obtained from 305 in-patients on three consecutive days in order to determine the reproducibility of the results. Results: A correlation (Spearman) of r = 0.62 (p b 0.001) was observed between serum and spot urinary 25(OH)D levels. A receiver operating characteristic (ROC) curve analysis revealed that an equivalent cutoff urinary 25(OH)D value to determine vitamin D deficiency (serum 25(OH)D ≤ 20 ng/ml) was 21.2 ng/ml (sensitivity 0.89, specificity 0.58). The area under the curve was 0.80. The correlations (Spearman) of the three consecutively obtained 24 h-urine samples were r = 0.697, r = 0.728, r = 0.765 (p b 0.001, respectively). Discussion: 25(OH)D can be measured by EIA in a probably water-soluble form in urine samples. This might be a cheap and stable alternative to determine overall vitamin D status. This could be especially useful in nursing home residents and young children and in any other patients at risk of vitamin D deficiency for whom the drawing of blood samples might be difficult. This article is part of a Special Issue entitled ECTS 2012. Disclosure of interest: None declared. doi:10.1016/j.bone.2012.02.319

PP131 Lactational changes in bone metabolism in calcitonin receptordeleted mice Y. Maa,⁎, B.J. Kirbya, D.L. Galsonb, C.S. Kovacsa a Memorial University of Newfoundland, St. John's, NL, Canada b University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Abstract: Calcitonin (CT) prevents excessive bone resorption during lactation. Previous work showed that CT null mice lost twice as much bone mineral content (BMC) as wild type (WT) littermates during lactation. The calcitonin receptor (CTR) is expressed in osteoclasts, lactating mammary tissue, and prolactin-producing pituitary cells, and so CT may modulate bone metabolism during lactation by acting at all 3 sites. In this study we examined whether loss of CTR causes the same lactational phenotype as in CT null mice. Unfortunately most CTR null mice die prior to birth, and so we studied WT and CTR+/− sister mice at baseline, late pregnancy, early and late lactation, and weekly during post-weaning recovery. BMC at total body, lumbar spine and hind limb was measured by DXA (PIXImus, Lunar). Serum and urine were collected at every time point. Milk was collected during mid-lactation and bone was collected at the end of lactation. Expressed relative to baseline values, total body BMC in CTR+/− mice reached 108 ± 4% during pregnancy, declined to 89 ± 2% during lactation, and recovered to 103 ± 2% (lactational loss p b 0.01 vs. baseline, but not different from WT). Lumbar spine declined even more during lactation and also recovered fully with no significant differences between genotypes. Serum calcium, phosphorus, and magnesium showed no differences at any time point. Urine calcium was unchanged, but urine phosphorus and magnesium rose significantly during lactation in both genotypes, with no significant difference between WT and CTR+/− mice. The bone resorption marker deoxypyridinoline (DPD) and bone formation marker P1NP each rose significantly during lactation and postweaning recovery. Parathyroid hormone (PTH) also increased from baseline during pregnancy and post-weaning recovery. All DPD, P1NP and PTH values were not significantly different between WT and CTR+/− mice. Additional analyses examining milk calcium, bone histomorphometry, and bone strength will be reported. In summary, WT and CTR+/− mice had the same magnitude of bone loss during lactation with full recovery post-weaning, and identical changes in serum and urine chemistries, bone turnover markers, and serum PTH. In conclusion, loss of one allele of the CTR does not cause the same phenotype that complete loss of the ligand (CT) caused in mice. Loss of one allele is not sufficient to impair calcitonin's role in regulating bone metabolism during lactation. This article is part of a Special Issue entitled ECTS 2012. Disclosure of interest: None declared. doi:10.1016/j.bone.2012.02.320

PP132 Impact of combined estrogen deficiency and resistance on bone mass and body fat O.K. Oza,⁎, J. Fordb a Radiology, UT Southwestern Medical Center, Dallas, USA b UT Health Sciences Center San Antonio, San Antonio, USA