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Effectiveness of a Mg-based phosphate binder on the development of vascular calcifications in uremic rats
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
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
S105
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