Publications by authors named "Leifur Franzson"

25 Publications

  • Page 1 of 1

Neonatal Screening in Europe Revisited: An ISNS Perspective on the Current State and Developments Since 2010.

Int J Neonatal Screen 2021 Mar 5;7(1). Epub 2021 Mar 5.

Norwegian National Unit for Newborn Screening, 0424 Oslo, Norway.

Neonatal screening (NBS) was initiated in Europe during the 1960s with the screening for phenylketonuria. The panel of screened disorders ("conditions") then gradually expanded, with a boost in the late 1990s with the introduction of tandem mass spectrometry (MS/MS), making it possible to screen for 40-50 conditions using a single blood spot. The most recent additions to screening programmes (screening for cystic fibrosis, severe combined immunodeficiency and spinal muscular atrophy) were assisted by or realised through the introduction of molecular technologies. For this survey, we collected data from 51 European countries. We report the developments between 2010 and 2020 and highlight the achievements reached with the progress made in this period. We also identify areas where further progress can be made, mainly by exchanging knowledge and learning from experiences in neighbouring countries. Between 2010 and 2020, most NBS programmes in geographical Europe matured considerably, both in terms of methodology (modernised) and with regard to the panel of conditions screened (expanded). These developments indicate that more collaboration in Europe through European organisations is gaining momentum. We can only accomplish the timely detection of newborn infants potentially suffering from one of the many rare diseases and take appropriate action by working together.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijns7010015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006225PMC
March 2021

Mode of delivery was associated with transient changes in the metabolomic profile of neonates.

Acta Paediatr 2021 Jul 15;110(7):2110-2118. Epub 2021 Mar 15.

Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.

Aims: To estimate potential differences in neonatal metabolomic profiles at birth and at the time of newborn screening by delivery mode.

Methods: A prospective study at Women's Clinic at Landspitali-The National University Hospital of Iceland. Women having normal vaginal birth or elective caesarean section from November 2013 to April 2014 were offered participation. Blood samples from mothers before birth and umbilical cord at birth were collected and amino acids and acylcarnitines measured by tandem mass spectrometry. Results from the Newborn screening programme in Iceland were collected. Amino acids and acylcarnitines from different samples were compared by delivery mode.

Results: Eighty three normal vaginal births and 32 elective caesarean sections were included. Mean differences at birth were higher for numerous amino acids, and some acylcarnitines in neonates born vaginally compared to elective caesarean section. Maternal blood samples and newborn screening results showed small differences that lost significance after correction for multiple testing. Many amino acids and some acylcarnitines were numerically higher in cord blood compared to maternal. Many amino acids and most acylcarnitines were numerically higher in newborn screening results compared to cord blood.

Conclusion: We observed transient yet distinct differences in metabolomic profiles between neonates by delivery mode.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/apa.15822DOI Listing
July 2021

[Vitamin D status before and after metabolic and bariatric surgery at Landspitali].

Laeknabladid 2021 03;107(3):137-143

Department of Clinical Nutrition, Landspitali - The National University Hospital of Iceland, Faculty of food science and nutrition, University of Iceland.

Introduction: Long-term results from bariatric surgery amongst individuals with obesity is considered good in general, with regard to weight loss, complications of obesity or quality of life. However, risk of nutrient deficiency might be increased. The aim of the study was to assess vitamin D status of patients before and after metabolic and bariatric surgery at Landspitali.

Methods: Data on 25(OH)D concentration and parathyroid hormone (PTH) was retrieved from medical records for patients undergoing metabolic and bariatric surgery at Landspitali from 2001-2018 (n=539). Insufficient vitamin D status was defined as 25(OH)D concentration p<45 nmol/L in 2001-2012 but p<50 nnmol/L from 2013-2018, due to changes in analytical method during the study period. Vitamin D deficiency was defined as 25(OH)D p<30 nmol/L for both time periods. Guidelines on supplement use are provided before discharge from the hospital and up to 18 months after surgery, RESULTS: Mean concentration of 25(OH)D before surgery was 51 nmol/L (SD 30 nmol/L) and 278 (52%) had insufficient vitamin D status, of which quarter of subjects were defined as being vitamin D deficient. Concentration of 25(OH)D increased after surgery in majority of subjects (85%). However, about third of those defined as having insufficient vitamin D status before surgery still had insufficient status 18 months after surgery. When comparing time periods, 2001-2012 and 2013-2018 it can be seen that insufficient vitamin D status was less common in the second period, although still persistent in about 25% of cases before surgery and 8,5% 18 months after surgery.

Conclusion: Insufficient vitamin D status is relatively common before metabolic and bariatric surgery at Landspitali. In large majority of subjects, 25(OH)D concentration increased after surgery, following recomendations on supplement intake. The results highlight the need for greater emphasis on correcting possible nutrient deficiencies before surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.17992/lbl.2021.03.627DOI Listing
March 2021

Does metabolomic profile differ with regard to birth weight?

Pediatr Res 2021 Apr 29;89(5):1144-1151. Epub 2020 Jun 29.

Faculty of Pharmaceutical Sciences, School of Health Science, Univeristy of Iceland, Reykjavik, Iceland.

Background: Macrosomia and child obesity are growing health-care issues worldwide. The purpose of the study was to evaluate how extremely high or low birth weight affects metabolic markers evaluated in newborn screening.

Methods: The study was register-based and included full-term singletons born in Iceland from 2009 to 2012 with newborn screening samples taken 72-96 h after birth. Three groups based on birth weight were compared: low birth weight (<2500 g), appropriate-for-gestational age, and extreme macrosomia (≥5000 g). The comparison was adjusted for possible confounding factors.

Results: Compared to appropriate-for-gestational age neonates, both low birth weight and extreme macrosomia were associated with higher levels of glutamic acid. The amino acids alanine and threonine were increased in low birth weight neonates. Free carnitine and some medium- and long-chain acylcarnitines were higher in low birth weight infants. Hydroxybutyrylcarnitine was lower in low birth weight infants, but higher in extremely macrosomic neonates. Acetylcarnitine was higher in low birth weight and extremely macrosomic neonates. Succinylcarnitine was lower and hexadecenoylcarnitine higher in macrosomic newborns.

Conclusion: Low birth weight and extremely macrosomic neonates show distinctive differences in their metabolomic profile compared to appropriate-for-gestational age newborns. The differences are not explained by gestational age.

Impact: The key message of this article is that both low birth weight and extremely macrosomic newborns show dissimilar metabolomic profiles compared to appropriate-for-gestational age neonates. The article contributes to knowledge on what affects evaluation of results in newborn screening. The impact of this article is to provide information on metabolism at both ends of the birth weight range after accounting for confounding factors including gestational age.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41390-020-1033-0DOI Listing
April 2021

Raising Awareness of False Positive Newborn Screening Results Arising from Pivalate-Containing Creams and Antibiotics in Europe When Screening for Isovaleric Acidaemia.

Int J Neonatal Screen 2018 Mar 10;4(1). Epub 2018 Feb 10.

Reference Laboratory for Neonatal Screening, Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), 3720 BA Bilthoven, The Netherlands.

While the early and asymptomatic recognition of treatable conditions offered by newborn screening confers clear health benefits for the affected child, the clinical referral of patients with screen positive results can cause significant harm for some families. The use of pivalate-containing antibiotics and more recently the inclusion of neopentanoate as a component within moisturising creams used as nipple balms by nursing mothers can result in a significant number of false positive results when screening for isovaleric acidaemia (IVA) by measuring C5 acylcarnitine. A recent survey conducted within centres from nine countries indicated that this form of contamination had been or was a significant confounding factor in the detection of IVA in seven of the nine who responded. In three of these seven the prominent cause was believed to derive from the use of moisturising creams and in another three from antibiotics containing pivalate; one country reported that the cause was mixed. As a result, four of these seven centres routinely perform second tier testing to resolve C5 isobars when an initial C5 result is elevated, and a fifth is considering making this change within their national programme. The use of creams containing neopentanoate by nursing mothers and evolving patterns in the prescription of pivalate-containing antibiotics during pregnancy require those involved in the design and operation of newborn screening programmes used to detect IVA and the doctors who receive clinical referrals from these programmes to maintain an awareness of the potential impact of this form of interference on patient results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijns4010008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510208PMC
March 2018

Gender comparison of factors associated with age-related differences in bone mineral density.

Arch Osteoporos 2015 4;10:214. Epub 2015 Aug 4.

School of Medicine, University of Iceland, Reykjavik, Iceland.

Unlabelled: We found that age-related decline in bone mineral density (BMD) is more pronounced in women than in men, that lean mass was the most important determinant of BMD in all age groups in both sexes, and that different factors may be important for bone health of men and women and at different ages.

Introduction: Multiple factors may affect bone mineral density (BMD). Our objective was to identify the correlates of age-related differences in BMD among men and women.

Methods: We performed a cross-sectional study involving 490 men and 517 women between the age of 29 and 87 years that were free of medication and diseases known to affect bone metabolism. BMD was measured at various sites using dual-energy X-ray absorptiometry, and factors possibly associated with skeletal status were assessed by direct measurements and a detailed questionnaire.

Results: BMD was lower with advancing age at all BMD measurement sites, the greatest difference being for the femoral neck where in women BMD was 37.5 % lower in the oldest compared to that in the youngest age group, but the difference was 22.9 % in men. Levels of free estradiol were sharply lower after age of 40 among women; free testosterone declined gradually with age among men but was not independently associated with BMD. Factors including lean mass, physical activity, ionized calcium, C-terminal telopeptide (CTX), serum sodium, free estradiol, and smoking explained a large fraction of difference in BMD in different age groups but to a varying degree in men and women. Lean mass was the strongest independent factor associated with BMD at all sites among men and women.

Conclusions: Age-related decline in BMD is more pronounced in women than in men, but determinants of BMD are multiple and interrelated. Our study indicates that different factors may be important for bone health of men and women and at different ages.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11657-015-0214-7DOI Listing
July 2016

Enhanced interpretation of newborn screening results without analyte cutoff values.

Genet Med 2012 Jul 16;14(7):648-55. Epub 2012 Feb 16.

Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, MN, USA.

Purpose: To improve quality of newborn screening by tandem mass spectrometry with a novel approach made possible by the collaboration of 154 laboratories in 49 countries.

Methods: A database of 767,464 results from 12,721 cases affected with 60 conditions was used to build multivariate pattern recognition software that generates tools integrating multiple clinically significant results into a single score. This score is determined by the overlap between normal and disease ranges, penetration within the disease range, differences between conditions, and weighted correction factors.

Results: Ninety tools target either a single condition or the differential diagnosis between multiple conditions. Scores are expressed as the percentile rank among all cases with the same condition and are compared to interpretation guidelines. Retrospective evaluation of past cases suggests that these tools could have avoided at least half of 279 false-positive outcomes caused by carrier status for fatty-acid oxidation disorders and could have prevented 88% of known false-negative events.

Conclusion: Application of this computational approach to raw data is independent from single analyte cutoff values. In Minnesota, the tools have been a major contributing factor to the sustained achievement of a false-positive rate below 0.1% and a positive predictive value above 60%.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/gim.2012.2DOI Listing
July 2012

A compendium of inborn errors of metabolism mapped onto the human metabolic network.

Mol Biosyst 2012 Oct;8(10):2545-58

Center for Systems Biology, University of Iceland, Iceland.

Inborn errors of metabolism (IEMs) are hereditary metabolic defects, which are encountered in almost all major metabolic pathways occurring in man. Many IEMs are screened for in neonates through metabolomic analysis of dried blood spot samples. To enable the mapping of these metabolomic data onto the published human metabolic reconstruction, we added missing reactions and pathways involved in acylcarnitine (AC) and fatty acid oxidation (FAO) metabolism. Using literary data, we reconstructed an AC/FAO module consisting of 352 reactions and 139 metabolites. When this module was combined with the human metabolic reconstruction, the synthesis of 39 acylcarnitines and 22 amino acids, which are routinely measured, was captured and 235 distinct IEMs could be mapped. We collected phenotypic and clinical features for each IEM enabling comprehensive classification. We found that carbohydrate, amino acid, and lipid metabolism were most affected by the IEMs, while the brain was the most commonly affected organ. Furthermore, we analyzed the IEMs in the context of metabolic network topology to gain insight into common features between metabolically connected IEMs. While many known examples were identified, we discovered some surprising IEM pairs that shared reactions as well as clinical features but not necessarily causal genes. Moreover, we could also re-confirm that acetyl-CoA acts as a central metabolite. This network based analysis leads to further insight of hot spots in human metabolism with respect to IEMs. The presented comprehensive knowledge base of IEMs will provide a valuable tool in studying metabolic changes involved in inherited metabolic diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c2mb25075fDOI Listing
October 2012

[Phenylketonuria (PKU) in Iceland].

Laeknabladid 2011 06;97(6):349-52

Læknadeild Háskóla Íslands.

Introduction: PKU is a metabolic disorder caused by a mutation in the phenylalanine hydroxylase (PAH) gene. Icelandic neonatal screening for PKU started in 1972. The mutation causes a variable [corrected] dysfunction in PAH, that metabolizes phenylalanine (Phe) to tyrosine (Tyr) with the cofactor tetrahydrobiopterin (BH4). Accumulation of Phe causes mental retardation and seizures. Current therapy focuses on Phe-restrictive diet and newer methods like BH4 in large doses. The primary aim was to collect data about PKU in Iceland and evaluate therapy and screening. Additional focus was on BH4 therapy.

Materials And Methods: Information was gathered from Landspitali medical charts retrospectively. Serum-Phe (S-Phe) measurements, age at initiation of therapy, PAH mutation types and information on current therapy was collected. RESULTS from BH4 loading tests were collected.

Results: 27 patients have been diagnosed with PKU in Iceland since 1947. Incidence 1972-2008 is 1/8400 living births. Classic PKU is the most common presentation in Iceland. Patients diagnosed after screening started have normal intelligence. Age at initiation of therapy and S-Phe average values lower with time. 12 PAH mutation types have been found in Iceland. A novel Icelandic mutation, Y377fsdelT, did not respond to BH4 loading test. Two patients responded to a BH4 loading test and four other patients are likely to respond to BH4 loading test.

Conclusion: PKU incidence in Iceland is slightly higher than in neighboring countries. Therapy compliance is adequate and international consensuses regarding therapy are met. PKU patients in Iceland are generally in good health. Screening is efficient and save. BH4 therapy is a an optional alternative therapy in Iceland.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.17992/lbl.2011.06.376DOI Listing
June 2011

Clinical validation of cutoff target ranges in newborn screening of metabolic disorders by tandem mass spectrometry: a worldwide collaborative project.

Genet Med 2011 Mar;13(3):230-54

Mayo Clinic College of Medicine, Rochester, Minnesota, USA.

Purpose: To achieve clinical validation of cutoff values for newborn screening by tandem mass spectrometry through a worldwide collaborative effort.

Methods: Cumulative percentiles of amino acids and acylcarnitines in dried blood spots of approximately 25–30 million normal newborns and 10,742 deidentified true positive cases are compared to assign clinical significance, which is achieved when the median of a disorder range is, and usually markedly outside, either the 99th or the 1st percentile of the normal population. The cutoff target ranges of analytes and ratios are then defined as the interval between selected percentiles of the two populations. When overlaps occur, adjustments are made to maximize sensitivity and specificity taking all available factors into consideration.

Results: As of December 1, 2010, 130 sites in 45 countries have uploaded a total of 25,114 percentile data points, 565,232 analyte results of true positive cases with 64 conditions, and 5,341 cutoff values. The average rate of submission of true positive cases between December 1, 2008, and December 1, 2010, was 5.1 cases/day. This cumulative evidence generated 91 high and 23 low cutoff target ranges. The overall proportion of cutoff values within the respective target range was 42% (2,269/5,341).

Conclusion: An unprecedented level of cooperation and collaboration has allowed the objective definition of cutoff target ranges for 114 markers to be applied to newborn screening of rare metabolic disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/GIM.0b013e31820d5e67DOI Listing
March 2011

Risk factors for bone loss in the hip of 75-year-old women: a 4-year follow-up study.

Maturitas 2010 Nov 11;67(3):256-61. Epub 2010 Aug 11.

Department of Medicine, Landspitali-University Hospital, Reykjavik, Iceland.

Risk factors for bone loss among the elderly are largely unknown. The objective of the study was to examine longitudinal bone loss in the hip in one-hundred and sixty-two 75-year-old women. Bone mineral density (BMD, g/cm(2)) was measured with dual X-ray absorptiometry (DXA) at baseline and after 4 years. The relationship between changes in BMD during follow-up and the following factors; baseline BMD, baseline weight, weight change, baseline lean and fat body mass (measured with DXA), serum values of biochemical markers and hormones, nutritional and lifestyle factors according to a questionnaire was assessed. The annual mean (SD) change in femoral neck BMD was -0.31% (1.38) in total trochanter -0.35% (1.15) and total hip -0.34% (1.10) and did not differ significantly between measurement sites. Bisphosphonate users had a 2.9%, 1.7% and 1.9% mean adjusted increase in femoral neck, total trochanter and total hip BMD respectively, different from none-users (p<0.05). Subjects with more than three weekly physical activity sessions had less femoral neck bone loss than less active women (p<0.05). The proportion of the variance in BMD changes explained by multivariate models (R(2)) was 12-13%. Women gaining weight had less loss of BMD than those losing weight in the trochanter and the total hip (p<0.001), and in the femoral neck (p=0.055). Elderly women should be advised to maintain their body weight and participate in physical activity. Despite the large number of variables examined in this study, bone loss occurring with increased age is not thoroughly explained.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.maturitas.2010.07.005DOI Listing
November 2010

Association of variants at UMOD with chronic kidney disease and kidney stones-role of age and comorbid diseases.

PLoS Genet 2010 Jul 29;6(7):e1001039. Epub 2010 Jul 29.

deCODE genetics, Reykjavik, Iceland.

Chronic kidney disease (CKD) is a worldwide public health problem that is associated with substantial morbidity and mortality. To search for sequence variants that associate with CKD, we conducted a genome-wide association study (GWAS) that included a total of 3,203 Icelandic cases and 38,782 controls. We observed an association between CKD and a variant with 80% population frequency, rs4293393-T, positioned next to the UMOD gene (GeneID: 7369) on chromosome 16p12 (OR = 1.25, P = 4.1x10(-10)). This gene encodes uromodulin (Tamm-Horsfall protein), the most abundant protein in mammalian urine. The variant also associates significantly with serum creatinine concentration (SCr) in Icelandic subjects (N = 24,635, P = 1.3 x 10(-23)) but not in a smaller set of healthy Dutch controls (N = 1,819, P = 0.39). Our findings validate the association between the UMOD variant and both CKD and SCr recently discovered in a large GWAS. In the Icelandic dataset, we demonstrate that the effect on SCr increases substantially with both age (P = 3.0 x 10(-17)) and number of comorbid diseases (P = 0.008). The association with CKD is also stronger in the older age groups. These results suggest that the UMOD variant may influence the adaptation of the kidney to age-related risk factors of kidney disease such as hypertension and diabetes. The variant also associates with serum urea (P = 1.0 x 10(-6)), uric acid (P = 0.0064), and suggestively with gout. In contrast to CKD, the UMOD variant confers protection against kidney stones when studied in 3,617 Icelandic and Dutch kidney stone cases and 43,201 controls (OR = 0.88, P = 5.7 x 10(-5)).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pgen.1001039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2912386PMC
July 2010

Discrepancies between creatinine- and cystatin C-based equations: implications for identification of chronic kidney disease in the general population.

Scand J Urol Nephrol 2010 Sep;44(4):242-50

Division of Nephrology and Hypertension, Department of Medicine, University of Kansas School of Medicine, Kansas City, Kansas, USA.

Objective: Early detection and treatment of chronic kidney disease (CKD) is important for slowing the progression of the disease and decreasing the associated risk of cardiovascular disease. This study examined how two creatinine-based and two cystatin C-based equations for calculating estimated glomerular filtration rate (eGFR) perform relative to each other in identifying CKD in a large cohort of community-dwelling individuals.

Material And Methods: A total of 1630 adults were recruited from the Reykjavik area. Each subject's eGFR was calculated using the Modification of Diet in Renal Disease (MDRD) Study and Cockroft-Gault equations, and two cystatin C-based equations. The prevalence of decreased eGFR obtained by the four equations was compared and the relative performance of the equations examined.

Results: The MDRD equation labelled significantly fewer individuals as having CKD (5.3%) relative to the other equations (12.8-19.7%). Agreement between equations was limited, with up to one-third of subjects diagnosed as having CKD by the MDRD equation being classified as normal by other equations. Correlations between creatinine- and cystatin C-based equations varied with age, gender and diuretic use.

Conclusions: The MDRD equation results in lower population-wide estimates of CKD relative to the other equations tested. An understanding of the performance of these equations is critical when they are used for estimating the prevalence of CKD in a population-wide setting or for diagnosing the disorder in clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/00365591003709450DOI Listing
September 2010

Sequence variants in the CLDN14 gene associate with kidney stones and bone mineral density.

Nat Genet 2009 Aug 28;41(8):926-30. Epub 2009 Jun 28.

DeCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland.

Kidney stone disease is a common condition. To search for sequence variants conferring risk of kidney stones, we conducted a genome-wide association study in 3,773 cases and 42,510 controls from Iceland and The Netherlands. We discovered common, synonymous variants in the CLDN14 gene that associate with kidney stones (OR = 1.25 and P = 4.0 x 10(-12) for rs219780[C]). Approximately 62% of the general population is homozygous for rs219780[C] and is estimated to have 1.64 times greater risk of developing the disease compared to noncarriers. The CLDN14 gene is expressed in the kidney and regulates paracellular permeability at epithelial tight junctions. The same variants were also found to associate with reduced bone mineral density at the hip (P = 0.00039) and spine (P = 0.0077).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/ng.404DOI Listing
August 2009

[Bone mineral density and bone turnover in systemic sclerosis].

Laeknabladid 2007 Jul-Aug;93(7-8):535-41

Laeknadeild Háskóla Islands.

Aims: To elucidate bone mineral density (BMD) and bone turnover in an un-selected group of patients with Systemic Sclerosis (SSc) in national based registry.

Material And Methods: All patients who have been diagnosed with SSc in Iceland were invited to participate in the study. Participants underwent standardized interview and delivered urine and blood samples for measurements of various bone metabolites (e.g. PTH, osteocalcin, Cross Laps, PINP, IGF-1, Cystatin-C and 25-OH-vitamin-D), before they underwent measurement of BMD with DEXA (QDR 4500 Elite).

Results: Twenty-four individuals, 20 female and four male, of 29 diagnosed patients with SSc in Iceland accepted to participate in the study (83%). The mean age was 60 +/- 15 years. Seventeen of 20 females were postmenopausal. Twelve patients had history of fractures. Only four patients were on treatment with bisphosphonate. All measured bone metabolites were in normal ranges, but U-calcium was in the lower ranges. According to DEXA, eight patients had osteopenia (T-value = -1.0 - -2.5) and three osteoporosis (T-value <---2.5), while six patients had BMD more than one standard deviation below the mean of age matched controls.

Conclusion: Although the majority of patients with SSc have normal bone turnover and BMD, every fourth patient may have low BMD. No single pathogenic factor was observed, however, several individuals are in calcium saving stages reflected in low urinary calcium excretion. This may be result of defects in intestinal absorption of calcium due to gastrointestinal involvement of the disease. This study does not give opportunity to evaluate effects of treatment on BMD in this group of patients. Thus, individual evaluation concerning osteoporosis is recommended in patients with SSc.
View Article and Find Full Text PDF

Download full-text PDF

Source
September 2007

[Assessment of age-related changes in parathyroid hormone levels by different methods.].

Laeknabladid 2003 Mar;89(3):191-7

Landspitali University Hospital, Fossvogi, 108 Reykjavík, Iceland.

Background: Current assays measuring intact PTH may not only measure the active form, PTH(1-84), but also some large breakdown products, including PTH(7-84). A new method is believed to measure only PTH(1-84). The purpose of this study was to examine whether increases in intact PTH that accompany age, weight and worsening renal function could be related to breakdown products interfering with traditional assays.

Methods: We used data from an ongoing cross-sectional study on bone health in 40-85 years old Icelanders. Over a 12 month period, 1096 subjects were invited for a DEXA scan, blood test, height and weight measurements and each subject answered a questionnaire on health and medication. For the current analysis we excluded those who were taking medications affecting bone and mineral metabolism. PTH was measured using PTH elecsys (Roche) and the new PTH cap (Scantibodies). We used kappa statistic to assess agreement with regard to levels above upper reference values for each assay and ANOVA, Pearson's and Spearman's correlation coefficients for other analysis. Women and men were analyzed separately.

Results: Of 746 individuals who came for the study, after exclusion, 247 women and 209 men remained for this analysis. PTH was on the average roughly 40% lower with the new PTH cap assay. The correlation between the assays was 0.787 (P<0.001) for women and 0.69 (P<0.001) for men. Kappa statistic was 0.486 (P<0.001) for women and 0.283 (P<0.001) for men, indicating fair to good agreement. PTH elecsys increased with age (P=0.03 and P=0.01 for women and men, respectively) but not PTH cap (P=0.7 and P=0.09 for women and men, respectively). PTH elecsys was positively associated with cystatin C (P<0.05 for both genders), but the correlation between PTH cap and Cystatin C was not statistically significant. The association with body mass index was similar for the two assays (r=0.16 to 0.24, P<0.05) for both genders.

Conclusions: There is a significant difference between these two PTH assays. It is likely that increases in intact PTH observed with age and worsening renal function are related to large breakdown products of PTH whereas the PTH increase seen with higher weight seems to be related to PTH(1-84) itself.
View Article and Find Full Text PDF

Download full-text PDF

Source
March 2003

[The relationship between physical activity, body mass index, body composition and grip strength in an Icelandic population.].

Laeknabladid 2004 Jun;90(6):479-86

Iceland University Hospital, Fossvogi, 108 Reykjavík, Iceland.

Objective: To study physical activity among Icelandic adults and the relationship with anthropometric factors and grip strength.

Material And Methods: Randomly selected participants, 30-85 years of age, answered questions regarding exercise and diet. Body composition was measured with DXA, which detects the proportions of different body tissues. Height, weight and grip strength were measured and the body mass index (kg/m(2)) was calculated. The prevalence of regular physical activity was studied for men and women in the age groups of 30-45 years, 50-65 years and 70-85 years and the relationship to body mass index, body composition and grip strength examined. The possible preventive effect of exercise on overweight and obesity was also studied.

Results: Of 2310 invited, 1630 subjects (70.6%) participated. Mean participation in regular physical activity was 3-4 times a week but 19% of the women and 24% of the men did no exercise at all. In general, swimming, walking and calisthenics of various types and intensities were the most common forms of exercise and in the age group 30-45 year old 16% of the women and 8% of the men did strength training. 50.4% of women 30-45 years of age and 68.2% of 50-65 year old men were overweight or obese. Mean fat mass was highest in 70-85 year old women (38%) and men (27%). Occupational activity was not related to body mass index, body composition or grip strength. Significant negative relationship was found between frequency of exercise and fat mass. The relationship between grip strength and lean mass or exercise was non-significant. The odds ratio of being overweight or obesity was 0.5 (CI was 0.37-0.77 for women and 0.37-0.94 for men) for those who exercised five or more days per week compared to those who exercised less frequently.

Conclusion: One of four Icelandic men and one of five women do not participate in regular physical activity despite of strong scientific indications of various positive health effects of exercise. More than half of adult Icelanders are overweight or obese but the risk is halved among those who exercise at least five days per week, compared to those who exercise less frequently. Sedentary lifestyle is more common amongst Icelanders than in the neighboring countries and realistic goals need to be set to increase the participation in regular physical activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
June 2004

[Vitamin-D homeostasis amongst adult Icelandic population.].

Laeknabladid 2004 Jan;90(1):29-36

Division of endocrinology and metabolism, Iceland University Hospital, Fossvogi, 108 Reykjavík, Iceland.

Background: The purpose of this study was to examine the effect of vitamin D intake and production in skin on vitamin D homeostasis in adult Icelanders.

Methods: Participants were 30-85 years old, randomly selected from the registry of the Reykjavik area (64 degrees N) and answered a thorough questionnaire on diet and vitamin supplements. Concentrations of 25(OH)-vitamin D [25(OH)D] in peripheral blood were examined based on season during the study period February 2001-January 2003, vitamin D intake and age (age groups 30-45, 50-65, and 70-85 years old). We defined vitamin D deficiency as either [25(OH)D] <25 nmol/l or as [25(OH)D] where the inverse relationship between serum iPTH and [25(OH)D] became statistically significant.

Results: Of 2310 invited, 1630 subjects participated (70,6% participation) but 21 individuals were excluded due to primary hyperparathyroidism. Mean [25(OH)D] was 46.5-/+20 nmol/l but varied by season, age and vitamin D intake, highest in June-July, 52.1-/+19.8 and lowest in February-March, 42.0-/+20.5 (p<0.001). [25(OH)D] was highest in the oldest age group, 50.8-/+19.7, but lowest in the youngest, 42.5-/+20 as was the intake 16.6-/+10 microg/day compared to 9.9-/+9 microg/day in the youngest. The correlation between vitamin D intake and [25(OH)D] was highest for the oldest group, r=0.41, p<0.001 but lowest in the youngest, r=0.24, p<0.001. [25(OH)D] was significantly higher among users of vitamin supplements (45.4-/+19.7) or fish oil (53.0-/+18.4) than among non-users (38.0-/+18.9). Vitamin D insufficiency was seen among 14.5% of those participating according to traditional definition, but 50% were below [25(OH)D] of 45 nmol/l where negative correlation between [25(OH)D] and PTH became statistically significant.

Conclusions: The serum concentration of 25(OH)D at which vitamin D deficiency becomes biochemically significant is higher than traditionally thought. A daily intake of 15-20 microg/day during wintertime would be required to maintain normal homeostasis in Icelandic adults, which is considerably higher than present recommendations of 7-10 microg/day for adults. Further research is needed to define the limit for vitamin-D sufficiency.
View Article and Find Full Text PDF

Download full-text PDF

Source
January 2004

Relationship between serum parathyroid hormone levels, vitamin D sufficiency, and calcium intake.

JAMA 2005 Nov;294(18):2336-41

Public Health Institute of Iceland.

Context: Adequate vitamin D status for optimum bone health has received increased recognition in recent years; however, the ideal intake is not known. Serum 25-hydroxyvitamin D is the generally accepted indicator of vitamin D status, but no universal reference level has been reached.

Objective: To investigate the relative importance of high calcium intake and serum 25-hydroxyvitamin D for calcium homeostasis, as determined by serum intact parathyroid hormone (PTH).

Design, Setting, And Participants: Cross-sectional study of 2310 healthy Icelandic adults who were divided equally into 3 age groups (30-45 years, 50-65 years, or 70-85 years) and recruited from February 2001 to January 2003. They were administered a semi-quantitative food frequency questionnaire, which assessed vitamin D and calcium intake. Participants were further divided into groups according to calcium intake (<800 mg/d, 800-1200 mg/d, and >1200 mg/d) and serum 25-hydroxyvitamin D level (<10 ng/mL, 10-18 ng/mL, and >18 ng/mL).

Main Outcome Measure: Serum intact PTH as determined by calcium intake and vitamin D.

Results: A total of 944 healthy participants completed all parts of the study. After adjusting for relevant factors, serum PTH was lowest in the group with a serum 25-hydroxyvitamin D level of more than 18 ng/mL but highest in the group with a serum 25-hydroxyvitamin D level of less than 10 ng/mL. At the low serum 25-hydroxyvitamin D level (<10 ng/mL), calcium intake of less than 800 mg/d vs more than 1200 mg/d was significantly associated with higher serum PTH (P = .04); and at a calcium intake of more than 1200 mg/d, there was a significant difference between the lowest and highest vitamin D groups (P = .04).

Conclusions: As long as vitamin D status is ensured, calcium intake levels of more than 800 mg/d may be unnecessary for maintaining calcium metabolism. Vitamin D supplements are necessary for adequate vitamin D status in northern climates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jama.294.18.2336DOI Listing
November 2005

[Prevalence of secondary hyperparathyroidism (SHPT) and causal factors in adult population in Reykjavík area].

Laeknabladid 2005 Feb;91(2):161-9

Iceland University Hospital, Fossvogi, 108 Reykjavík.

Introduction: SHPT is a consequence of decreased concentration of ionized calcium in blood, which may have many causes. The purpose of this study was to assess the prevalence and contributing factors of SHPT in an adult Icelandic population and explore the relationship between PTH and other variables which might explain age related increase in PTH. Such knowledge might be helpful in evaluating the results of PTH measurements. METHODS AND STUDY GROUP: The study group was a random sample of men and women in the Reykjavik area, 30-85 years of age. Serum PTH was measured by ECLIA (Roche Diagnostics), serum 25(OH)D by RIA (DiaSorin), and body composition by DXA. SHPT was defined as PTH >65 ng/l and ionized calcium <1.25 mmol/l. Inadequate vitamin D was defined as serum 25(OH)D 25-45 nmol/l and vitamin D deficiency <25 nmol/l, inadequate calcium intake <800 mg/day (from questionnaire) and reduced kidney function as serum cystatin-C >1.55 ng/l. The relationship between PTH and other variables was assessed by Spearman?s correlation coefficient and linear regression.

Results: Of 2,310 individuals invited 1,630 attended (70%), 586 men and 1,023 women. Further 21 were excluded because of primary hyperparathyroidism. Of the total group 6.6% did have SHPT, 7.7% of the women and 4.6% of men (p<0.01 by gender). Underlying causes were identified in 90% of cases, most commonly inadequate vitamin D (73%). Other important causes were obesity, inadequate calcium intake, reduced kidney function and furosemide intake. Many individuals did have more than one possible underlying cause. The concentration of PTH was found in a multivariate linear regression to be associated with age, ionized calcium, 25(OH)D, cystatin-C, smoking, and BMI, especially fat mass. Testosterone did have a weak negative relationship with PTH in men.

Conclusions: Most cases of SHPT could be explained by known causes and far the commonest was inadequate vitamin D. The prevalence of SHPT in Iceland is probably higher than described elsewhere, possibly due to less sunlight exposure. These results would suggest that a greater intake of vitamin D is needed in Iceland. The relationship of PTH with body composition, especially fat mass, sex hormones and smoking, needs further evaluation.
View Article and Find Full Text PDF

Download full-text PDF

Source
February 2005

Serum osteoprotegerin and its relationship with bone mineral density and markers of bone turnover.

Osteoporos Int 2005 Apr 20;16(4):417-23. Epub 2004 Jul 20.

Department of Medicine, Landspitali-University Hospital, Reykjavik, Iceland.

Introduction: The purpose of this study was to compare age-related differences in osteoprotegerin (OPG) in relationship with BMD and the serum bone markers osteocalcin (OC), collagen crosslinks (CTX), and tartrate-resistant acid phosphatase 5b (TRACP-5b).

Methods: Data were derived from a cross-sectional study on bone health in a random sample of community-dwelling adults aged 30 to 85 years in the Reykjavik area in Iceland. All subjects had whole body, hip, and lumbar spine BMD measured (by DXA), gave blood samples, and answered a thorough questionnaire on medications and medical history. We assessed relationships using the Spearman correlation coefficient, partial correlation, and multivariable linear regression. Men and women were analyzed separately.

Results: Of 2,310 subjects invited over 2 years, 1,630 participated. After excluding individuals with diseases and medications affecting bone metabolism, 517 women (age 56.1 +/- 16.9 years) and 491 men (age 58.7 +/- 14.9 years) remained for analysis. OPG increased steadily with age in both genders without a gender difference. In women, BMD at all sites declined steadily after age 50. In men, BMD remained relatively stable until age 70, after which it declined significantly. After controlling for age, BMI, and other confounding variables, OPG showed only a borderline positive relationship with whole body BMD in men (P = 0.10), but the relationship was nonsignificant in women. In multivariable models, OPG was inversely related to TRACP-5b (P = 0.002) and positively with OC (P = 0.007), the OC/TRACP-5b (P = 0.001) and OC/CTX (P = 0.02) ratios in women. Among men, multivariable models showed a positive association between OPG and OC (P = 0.05) and OC/TRACP-5b (P < 0.009).

Conclusions: We conclude that serum OPG levels are associated with a profile of bone turnover markers favoring bone formation, suggesting that OPG may be protective against age-related bone loss. Longitudinal studies are needed to address that issue.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00198-004-1699-xDOI Listing
April 2005

Age-related decline in bone mass measured by dual-energy X-ray absorptiometry and quantitative ultrasound in a population-based sample of both sexes: identification of useful ultrasound thresholds for osteoporosis screening.

J Clin Densitom 2005 ;8(1):80-6

Department of Endocrinology & Metabolism, Landspitali-University Hospital, Fossvogur, IS-108 Reykjavik, Iceland.

Quantitative ultrasound (QUS) can be used as a screening tool for low bone mineral density (BMD), but clinical guidelines have not been set. The aim of this population-based, cross-sectional study was to compare age-related changes in bone mass measured by QUS (Lunar, Achilles Plus) and dual-energy X-ray absorptiometry (DXA) in a random sample of 1630 individuals (1041 females, 589 males) 30-85 yr of age. Individuals with DXA T-scores < or =-2.5 at the femoral neck or total hip were identified and receiver operating curves (ROCs) were used to calculate cutoff points for QUS. Sensitivity, specificity, and kappa statistics were calculated. Age-related bone loss was significantly larger with QUS than DXA at all sites in women. For men, the curves were similar for QUS and DXA in the hip. Similar correlations were found between QUS and DXA in different age groups of both sexes (0.36-0.60). For women aged 50-65 yr, a QUS T-score >-1.0 was found to be the most applicable for identifying normal BMD. In the 70-85 yr age group, a T-score <-2.5 for women and a T-score <-0.5 for men seemed reasonable cutoffs for identifying normal BMD (sensitivity: 86-93%; specificity: 28-44%; discordance: 33-73%). Calcaneal QUS cannot be used for the diagnosis of osteoporosis according to WHO criteria, but it can be of use to exclude osteoporosis in 30-40% of our cases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1385/jcd:8:1:080DOI Listing
July 2005

The effect of raloxifene on markers of bone turnover in older women living in long-term care facilities.

J Am Geriatr Soc 2004 May;52(5):779-83

Department of Geriatrics, Landspitali University Hospital, Reykjavik, Iceland.

Objectives: To examine the effect of raloxifene on bone turnover in elderly women.

Design: Clinical intervention.

Setting: Long-term care facilities.

Participants: Nineteen women completed the study, mean age 85 (range 76-99).

Intervention: Raloxifene 60 mg was given daily for 12 weeks.

Measurements: Markers of bone turnover were plasma C-telopeptides of type I collagen (CTx), urine cross-linked N-telopeptides of type I collagen (NTx) and serum tartrate-resistant acid phosphatase (TRAP 5b), plasma osteocalcin, and serum bone alkaline phosphatase. Other markers were serum 25-OH vitamin D, parathyroid hormone, ionized calcium, and phosphate. Markers were measured at baseline, after calcium and vitamin D had been taken for 6 weeks, after raloxifene had been taken for 12 weeks, and 6 weeks after raloxifene had been stopped. Paired sample t test was used to examine changes in markers at each time point.

Results: Plasma CTx decreased on average by 31%, urinary NTx by 35%, plasma osteocalcin by 25%, serum bone alkaline phosphatase by 15% (P<.01), and serum TRAP 5b by 10% (P<.05) on treatment.

Conclusion: Raloxifene reduces bone turnover in elderly women living in long-term care facilities. The effect of raloxifene on bone turnover is comparable with that seen in younger postmenopausal women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1532-5415.2004.52218.xDOI Listing
May 2004

Hyperphagia modifies FA profiles of plasma phospholipids, plasma FFA, and adipose tissue TAG.

Lipids 2003 Nov;38(11):1127-32

Department of Physiology, University of Iceland, Reykjavik, Iceland.

Hyperphagia was achieved by continuous intracerebroventricular infusion of a melanocortin receptor antagonist (HS024; Neosystem, Strasbourg, France) in rats. The effects of hyperphagia on FA composition and concentration of plasma phospholipids (PL), plasma FFA, and adipose tissue TAG were studied in rats for 8 d [short-term hyperphagia (STH); n = 8], or 28 d [long-term hyperphagia (LTH); n = 9]. The control rats were treated with artificial cerebrospinal fluid for 8 d (n = 8) or 28 d (n = 10). The rats were fed the same regular diet. In STH rats the plasma PL and fasting plasma FFA contained higher concentrations of saturated FA (SFA) and monounsaturated FA (MUFA), and plasma FFA contained lower n-6 PUFA than in the control rats. In LTH rats the plasma PL contained higher concentrations of SFA, MUFA, and n-3 PUFA and higher proportions of 16:1n-7 and 18:1n-9 at the expense of 18:2n-6 than in the control rats. In LTH rats the abundant dietary intake of 18:2n-6 did not enrich 18:2n-6 of the plasma PL or adipose tissue TAG. In LTH rats the fasting plasma FFA contained more than twofold higher concentrations of SFA and MUFA, and higher proportions of 16:1n-7 and 18:1n-9 at the expense of 18:2n-6 than in the control rats. This animal obesity model shows that LTH affects the FA composition and concentration of plasma PL, plasma FFA, and adipose tissue TAG, a result consistent with changes associated with increased risk of various diseases in humans. These results also demonstrate that LTH alters the FA composition of plasma PL and adipose tissue TAG in a way that does not reflect the FA composition of dietary fat.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11745-003-1170-1DOI Listing
November 2003

Multicenter evaluation of a new immunoassay for intact PTH measurement on the Elecsys System 2010 and 1010.

Clin Lab 2002 ;48(3-4):131-41

Department of Clinical Chemistry and Laboratory Diagnostics, Heinrich-Heine-University, Düsseldorf, Germany.

Background And Objective: The determination of parathyroid hormone (PTH) is of great clinical relevance in the assessment of calcium metabolic disorders. Although PTH was one of the first hormones measured by immunoassays, there are still many difficulties in its determination due to the low concentration of the hormone in blood and due to the heterogeneity of PTH resulting from different circulating hormone fragments. The aim of our multicenter-study was to evaluate the technical performance and the clinical validity of a new immunoassay for intact PTH measurement on the Elecsys Systems 2010 and 1010.

Methods And Results: The multicenter evaluation was performed in 11 clinical laboratories. The Elecsys PTH assay is a one step sandwich electrochemiluminescence immunoassay based upon the streptavidin-biotin technology. Two monoclonal antibodies are used in the assay providing detection of intact PTH. The imprecision study yielded within-run and between-days coefficients of variation of 3.1% - 6.6% and 3.4% - 15.6%, respectively using a three level control (PreciControl Bone, Roche Diagnostics) and human pool sera at two different concentrations (HS-low: 20 - 60 pg/ml, HS-high > 65 pg/ml). The analytical sensitivity calculated as the mean value plus 2 standard deviations of a within-run imprecision was below 2.70 pg/ml using zero calibrator matrix. Dilution linearity was observed up to 4890 pg/ml using zero calibrator matrix or human pool sera. Recoveries ranged between 85% - 115%. Serum, EDTA- and heparin plasma were evaluated for PTH measurement. Due to a better analyte stability (48h at 21 degrees C; 3d at 4 degrees C) EDTA plasma was recommended for PTH measurement. Results of the Elec sys PTH immunoassay correlated well (r = 0.926 - 0.994) with three different immunoradiometric assays (N-tact PTH SP, DiaSorin; Nichols Allegro Intact PTH, Nichols Institute Diagnostics; ELSA-PTH, CISBio International) and two different immunochemiluminometric assays (PTH-Intact-Immulite, DPC Biermann; Nichols Advantage Intact PTH, Nichols Institute Diagnostics) in technical and clinical method comparisons. The Passing/Bablok regression analysis yielded slopes of 0.692 - 1.729 and intercepts of -13.982 - +15.763 pg/ml. Deviations from slope 1.0 and intercept 0.0 were not unexpected due to differences in immunoassay standardization and probably due to the presence of different PTH fragments and a variable affinity of the used antibodies to these PTH fragments. Highly similar PTH concentration pattern of the Elecsys immunoassay and the Quick-Intraoperative Intact PTH immunoassay (Nichols Institute Diagnostics) obtained from specimens taken intraoperatively support the applicability of the Elecsys immunoassay to monitor the success of parathyroid resection. A reference range of 12.3 - 56.0 pg/ml calculated from PTH values of 43 apparently healthy individuals confirms reference limits published in the literature. The partition of collectives according to age showed, that individuals > 50 years have slightly higher PTH concentrations, independently of gender. This shift could be due to age itself or to an increased prevalence of individuals without obvious calcium metabolic disorders in this collective.

Conclusion: The Elecsys PTH assay is a useful and reliable tool for determination of intact PTH. Our data support the intended use of the assay in clinical applications related to disorders of calcium metabolism.
View Article and Find Full Text PDF

Download full-text PDF

Source
July 2003
-->