Pågående projekter

Anne Kristine Amstrup: Betydningen af melatoninbehandling til osteopenipatienter: Effekt på BMD, livskvalitet og muskelstyrke

Jakob Starup Linde: Markører for knoglestatus hos Diabetes Mellitus patienter (type 1 og type 2) og effekt af antiresorptiv behandling på glykæmiske markører. – ”Diabone”

Gitte Bloch Rasmussen: Betydningen af D-vitamintilskud til gravide for graviditetens forløb, fosterets udvikling og knoglemineraltætheden i ammeperioden: et randomiseret placebo-kontrolleret studie

Line Underbjerg: Karakterisering af patienter med idiopatisk hypoparathyreoidisme, autosomalt dominant hypocalcæmi og pseudohypoparathyreoidisme

Stine Aistrup Eriksen: Depression – can vitamin D treatment help the patients with regard to muscles and bone?

Mina Nicole Holmgaard Händel: Influence of vitamin D status in utero and at the time of birth on the risk of childhood fractures

Sofie Hertz Rønn: Betydningen af K2-vitamin for knoglemetabolisme, insulinfølsomhed og karstivhed

Ditte Beck Jepsen: PaVOS: Parathyroid Hormone and Whole-Body Vibration treatment in Osteoporosis Study

Katrine Hygum: Effekten af liraglutid på knogleomsætning og knogleudseende hos patienter med type 2 diabetes

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Anne Kristine Amstrup, læge, Medicinsk Endokrinologisk Afdeling, MEA, Aarhus Universitetshospital, Tage-Hansens Gade

Betydningen af melatoninbehandling til osteopenipatienter: Effekt på BMD, livskvalitet og muskelstyrke

Background: Melatonin is known for its regulation of circadian rhythm. The production falls with age, which explains why elderly may have disturbed sleep patterns. In vitro and vivo studies suggests that melatonin also may protect against bone loss through increased osteoblast- and inhibited osteoclast activity. However, so far human studies have not been performed.

Design and patients: Double blinded randomised controlled study. Eighty post-menopausal women (aged 55-75) with osteopenia are randomized to receive 1mg, 3mg or placebo (daily – at night time) for 12 months.

Methods and results: Effects of melatonin on BMD, bone- structure and mass will be assessed through DXA-scans, pQCT, and QCT. Quality of life, sleep, and activity level will be assessed though questionnaires. Calciumhomeostasis will be analyzed through blood and urines samples. As safety parameters, balance and muscle function will also be performed.

Conclusion: Expected improvements in BMD, quality of life and sleep.

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Jakob Starup Linde, læge, Medicinsk-Endokrinologisk Afdeling, MEA, Aarhus Universiteteshospital, Tage-Hansens Gade

Markører for knoglestatus hos Diabetes Mellitus patienter (type 1 og type 2) og effekt af antiresorptiv behandling på glykæmiske markører. – ”Diabone”

Baggrund: Diabetes Mellitus er associeret med en øget frakturrisiko, hvor odds ratio for hoftefraktur tidligere er fundet til hhv. 6 og 1,5 for henholdsvis type 1 og type 2 diabetikere. Bone mineral density (BMD) er lavere blandt type 1 diabetikere og højere blandt type 2 diabetikere end ikke diabetikere. Dog kan den lavere BMD hos type 1 diabetikerne ikke til fulde forklare den øgede fraktur risiko. Alendronat er fundet at øge BMD blandt type 2 diabetikere i løbet af tre år, men om dette er en gavnlig effekt hos diabetes patienter er uvist.

Formål: At undersøge om der er forskelle i type 1- og type 2 diabetes patienters knoglestatus samt undersøge effekten af Alendronat på hhv. knoglestatus og glykæmisk status.

Design og studiepopulation: Det kliniske forsøg er delt i to: Et tværsnitsstudie med 100 type 1 diabetes patienter og 100 type 2 diabetes patienter og et dobbeltblindet randomiseret kontrolleret studie med 64 diabetes patienter udvalgt fra tværsnitssutdiet med T-score -3,5 til -1. Deltagerne bliver randomiseret til Alendronat- eller placebobehandling i to år.

Rekruttering og studiecentre: Deltagerne bliver primært rekrutteret fra ambulatorier på de tre studiecentre: Aarhus Universitetshospital, Aalborg Universitetshospital og Odense Universitetshospital.

Metode: Undersøgelserne i studiet omfatter blodprøver, urinprøver, DXA-skanning, HRpQCT skanning og specifikt for tværsnitsstudiet knoglevævs-, muskelvævs- og fedtvævsbiopsi.

Tidsperspektiv: Tværsnitsstudiet er opstartet pr. 01-03-2013 og forventes afsluttet d. 31-03-2014. Det randomiserede kontrollerede studie forventes afsluttet d. 31-08-2015.

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Gitte Bloch Rasmussen, læge, PhD-stud., Medicinsk-Endokrinologisk Afdeling, MEA, Aarhus Universitetshospital, Tage-Hansens Gade

Background: Vitamin D (25OHD) deficiency is common among women of childbearing age. The level of 25OHD is important for the pregnancy. Vitamin D deficiency in pregnant women is associated with low birth weight, neonatal hypocalcaemia and pre-eclampsia.
Literature is conflicting – and the effects of supplementation during pregnancy on maternal, perinatal and infant health are based on limited evidence.

Aim: To investigate effects of vitamin D supplementation in women with 25OHD < 50 nmol/L, before, during, and after pregnancy. We hypothesized that maternal vitamin D status, before and during pregnancy, is correlated with birth weight, and maternal intake of vitamin D has a positive effect on birth weight and pregnancy outcome.

Methods: A controlled, double-blinded randomized trial. Women all with wish of pregnancy and 25OHD <50 nmol/l were randomized to either supplements of 35 or 70 µg cholecalciferol daily or placebo. Treatment was administered before achieved pregnancy and continued to 4 months after birth. The study included questionnaires, blood and urine samples every 4 months. DEXA scanning was performed at baseline and at end of study. 25OHD was measured in maternal blood, the umbilical cord, breast milk and a blood sample from the new-borns 4 months after birth.

Status: 600 women screened, 200 included, 96 infant born, end of study Jan. 2014. Data analysis begins autumn 2013.

Perspective: The study will provide valuable information about vitamin D supplements. The results of the study may guide future recommendations of vitamin D supplements for pregnant women.

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Line Underbjerg, MD/Ph.D.-stud., Medicinsk-Endokrinologisk Afdeling, MEA, Aarhus Universiteteshospital, Tage-Hansens Gade

Karakterisering af patienter med idiopatisk hypoparathyreoidisme, autosomalt dominant hypocalcæmi og pseudohypoparathyreoidisme

Baggrund: Hypoparathyreoidisme (HypoPT) er en sjælden sygdom som karakteriseres ved lavt niveau af PTH og plasma calcium. Den skyldes hyppigst en komplikation til halskirurgi, men kan også være forårsaget af genetiske eller autoimmune årsager. Der findes kun sparsom viden om denne gruppe patienter.

Formål: Formålet med projektet er at foretage en deltaljeret klinisk og genetisk karakterisering af patienter med idiopatisk hypoparathyreoidisme samt pseudohypoparathyreoidisme. Endvidere ønsker vi at foretage familieopsporing i de arvelige tilfælde. Slutteligt vil prævalensen af magnesium mangel blive undersøgt.

Design og studiepopulation: Et deskriptivt tværsnitsstudie med patienter med idiopatisk HypoPT, autosomalt dominant hypocalcæmi og pseudohypoparathyreoidisme identificeret via Landspatientregisteret og receptoplysninger fra regionernes Primær Sundhed.

Metode: Undersøgelserne i studiet omfatter spørgeskemaundersøgelser, blodprøver, urinprøver, DXA-skanning, HRpQCT skanning, magnesiuminfusionstest, knoglebiopsier samt genetisk udredning.

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Stine Aistrup Eriksen, PhD-studerende, Klinisk Institut, Aalborg Universitet

Depression – can vitamin D treatment help the patients with regard to muscles and bone?

Background: In recent years it has become evident that some types of antidepressants are associated both with an increased risk of falling and decreased bone mineral density. These factors predispose patients for serious fractures such as hip fractures with substantial morbidity and mortality. The specific mechanisms involved in this negative impact on bone and postural control have not been fully elucidated. It is well known that Vitamin D plays an important role for bone health as well as muscle function and thus indirectly postural control. Furthermore, vitamin D deficiency has been observed among depressed patients.  To our knowledge no study has investigated the involvement of Vitamin D in relation to the increased risk of fractures associated with antidepressants. Aim: There-fore, this project will investigate the underlying mechanisms leading to skeletal impairment and musculoskeletal symptoms in patients receiving different types of antidepressants. Moreover, the effect of vitamin D supplementation will be investigated among patients taking these antidepres-sants.

Material & Methods: 150 subjects will participate in this study: 50 of which is diagnosed with depression and receive Citalopram (class of antidepressant termed Selective Serotonin Reuptake Inhibitors (SSRIs)); 50 depressed subjects receiving Mirtazapine (the class termed Noradrenergic and Specific Serotonergic Antidepressants (NaSSAs)); and 50 controls. Through randomisation half of the subjects in each group will receive daily Vitamin D supplementation for a period of one year. Through this period all 150 subjects will be followed through different measurements including blood tests to assess vitamin D levels, and bone scans to assess bone density. Moreover, muscle function tests and balance tests will be performed to assess strength and functionality of muscles as well as sensory motor interaction expressed as balance. Pain tests will be conducted in concordance to the muscle function tests to assess nociceptive perception among SSRIs and NaSSAs users compared to healthy controls. Quality of life is assessed through questionnaire surveys and depression severity is assessed using standard depression scales.

Perspectives: It is expected that results from this study will provide increasing awareness and knowledge of the side effect profile of antidepressants on bone metabolism. This may prompt clinicians to screen patients at high risk of drug-induced osteopenia or osteoporosis and accordingly provide treatment, which may reduce the incidence of potentially avoidable fractures. Moreover, some types of anti-depressants may show to produce a minimal or even no effect on bone turnover, and should be considered as first line treatment in the group of patients at risk of fractures.

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Mina Nicole Holmgaard Händel, Ph.D-studerende, Research Unit for Dietary Studies/Institut for Sygdomsforebyggelse, Frederiksberg Hospital

Influence of vitamin D status in utero and at the time of birth on the risk of childhood fractures

The aim of the PhD project is to examine the influence of prenatal vitamin D exposure on the risk of bone fractures during childhood and to examine if exposure to vitamin D fortified foods beneficially affects the risk of fractures in childhood.

The overall hypothesis is that individuals who are exposed to sufficient vitamin D prenatally will have a lower risk of fractures compared to individuals with lower prenatal exposure to vitamin D. As vitamin D can be obtained from both dietary sources (affected by fortification programs) and through exposing skin to UVB-radiation from the sun (influenced by season) the PhD project includes both exposure types and their effect on childhood fractures.

The study design is based on commencement and termination of a mandatory vitamin D fortification program, that was applied in Denmark from 1961-85. The main study outcome is fracture of the forearm, wrist or scaphoid bone, clavicle and ankle in the period of vitamin D fortification. Using the civil registration numbers, individuals will be individually linked to the Danish National Patient Registry (Landspatientregistret) for incident and recurrent diseases.

To validate the effect of fortification and for cases of fractures residual dried blod spots cards, stored in the Biological Specimen Bank for Neonatal Screening at Statens Serum Institute, will be used from individuals who had fractures entities and their time and gender-matched controls. The aim is to examine actual exposure differences at birth and we hypothesize that serum 25(OH)D3 levels at the time of birth is significantly lower among children who go on to sustain fractures in childhood.

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Sofie Rønn, læge, Medicinsk Endokrinologisk Afdeling, MEA, Aarhus Universitetshospital, Tage-Hansens Gade

Betydningen af K2-vitamin for knoglemetabolisme, insulinfølsomhed og karstivhed

Baggrund: K-vitamin kan have en vigtig betydning for knoglemineraliseringen og knoglekvaliteten. Effekten af K-vitamin antages at gå gennem en aktivering af matrix-proteinet osteocalcin, der menes at have en vigtig rolle i mineraliseringen af knoglevævet. Osteocalcin produceres af osteoblasten i en undercarboxyleret form, og undergår en carboxylering faciliteret af K-vitamin, hvorved det opnår sin aktive form. Carboxyleret osteocalcin har høj affinitet for calcium og hydroxyappatit, og formodes at bidrage til mineraliseringen.

Flere kliniske studier har fundet en positiv sammenhæng mellem K-vitamin og BMD, og nedsat frakturrisiko. Der er dog også studier, der ikke viser nogen effekt.

Formål: Formålet med det kliniske forsøg er at undersøge effekten af K2-vitamin på knoglemetabolisme, insulinfølsomhed og karstivhed.

Hypotese: K2-vitamin formodes, gennem en carboxylering af osteocalcin, at fastholde eller øge BMD, sammenlignet med placebo. Desuden formodes K2-vitamin gennem carboxyleringen af osteocalcin at bedre insulinfølsomheden, og gennem carboxylering af Matrix Gla Protein, at nedsætte karstivheden.

Metoder og design: Forsøget er designet som et randomiseret dobbeltblindet placebo-kontrolleret klinisk studie. Deltagerne er 142 postmenopausale kvinder med osteopeni. De behandles med 375 mikrogram K2-vitamin eller placebo, og alle modtager tilskud af kalk og D-vitamin.

Knoglemetabolismen undersøges med DXA- og HRpQCT-skanninger, knoglemarvsprøver, samt biokemiske knoglemarkører. Insulinfølsomheden undersøges med HOMA-indeks og HgbA1c. Karstivheden vurderes med pulsbølgehastighedsundersøgelser, samt biokemiske markører for åreforkalkning.

Perspektiver: Projektet vil give ny viden om K-vitamins betydning for knogler, insulinfølsomhed og åreforkalkning. Desuden vil osteocalcins rolle i ovenstående blive tydeligere. Det vil også blive klarere, om K-vitamin udgør en mulighed for at forebygge bl.a. osteoporose.

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Ditte Beck Jepsen, læge, Forskningsenheden for Geriatri, Geriatrisk Afdeling G, Odense Universitetshospital

PaVOS: Parathyroid Hormone and Whole-Body Vibration treatment in Osteoporosis Study

Background: Parathyroid hormone (PTH) is an effective but expensive anabolic treatment for osteoporosis. Whole Body Vibration (WBV) has been found to stimulate muscles and bones. Animal studies have shown a beneficial effect on bone when combining PTH with mechanical loading. A combined treatment with PTH and WBV might have beneficial effects on bone and muscles, thereby reducing important fracture risks.

Aim: To investigate if the use of WBV in combination with PTH has beneficial effects on bone metabolism, muscle strength, function and balance in osteoporosis patients.

Methods: PaVOS is a multicentre, two-armed, non-blinded, RCT. Postmenopausal women (N= 40, 50 + years) starting PTH according to the Danish osteoporosis guidelines will be recruited, and assigned to a WBV-exercise group, or normal care. WBV-participants will undergo 3 weekly sessions (12-min each, including 1:1 ratio of exercise: rest) for a 12 months exercise intervention period. After 12 months the WBV-participants will be re-randomized to continue WBV for additionally 12 months or to stop the WBV.

The study will investigate BMD and bone microarchitecture with DXA and HRpQCT baseline and during the study. Bone biomarkers and functional biomarkers (Timed Up and Go, Short Physical Performance Battery, grip strength and leg extension power) will be measured to assess the effect on bone turnover, muscle strength, balance and functionality. Quality of Life, physical activity and fear of falling will be assessed by the means of the questionnaire.

Perspectives: PaVOS is the first study to investigate the effects of WBV-exercise in combination with PTH in postmenopausal women.

The study started recruiting participants in November 2015.

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Katrine Hygum, læge, Medicinsk Endokrinologisk Afdeling, MEA, Aarhus Universitetshospital, Tage-Hansens Gade

Effekten af liraglutid på knogleomsætning og knogleudseende hos patienter med type 2 diabetes

Formål: Vi ønsker at undersøge effekten af liraglutid på knoglernes omsætning og struktur hos patienter med type 2 diabetes (T2D).

Baggrund: T2D kan medføre alvorlige følgesygdomme herunder ændringer i knoglerne. Patienter med diabetes har en øget frakturrisiko. Liraglutid med handelsnavnet ”Victoza” er et godkendt stof, der ofte benyttes som lægemiddel til behandling af T2D. Liraglutid er et syntetisk hormon, der i sin naturlige form kaldes Glucagon Like Peptide 1 (GLP-1) og frigives i tarmen i forbindelse med fødeindtag. Hormonet kan bruges til behandling af T2D, da det blandt andet nedsætter blodsukkeret. Det er kendt viden, at både kostens sammensætning og hormonet GLP-1 har effekt på balancen mellem knoglenedbrydning og knoglenydannelse og også på knoglestrukturen, og undersøgelser i dyr viser, at GLP-1 styrker knoglerne. Det er dog ikke undersøgt, hvorvidt behandling med liraglutid har en direkte effekt på knoglerne hos diabetikere.

Metode: Vi vil lave et klinisk, randomiseret, dobbeltblindet, placebokontrolleret forsøg med 60 deltagere, der randomiseres til enten liraglutid 1,8 mg dagligt eller placebo (saltvand) i 180 dage. Primære endepunkt er fald i collagen I krydsbundet C-terminal telopeptid (CTX). Sekundære endepunkter er ændringer i knogleformationsmarkører, ændringer i bone mineral density (DXA-skanning), ændring i knoglestruktur (QCT- og HRpQCT-skaninger) samt ændring i HbA1c.

Perspektiver: Studiet bidrager med viden om GLP-1 analogers eventuelle effekt på knoglerne. Finder vi ved forsøget ud af, at liraglutid har en potentielt gavnlig indflydelse knoglerne, vil man på samme tid kunne behandle både T2D og forebygge en øget frakturrisiko.