uu.seUppsala University Publications
Change search
Refine search result
12 51 - 86 of 86
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 51.
    Lewerin, Catharina
    et al.
    Univ Gothenburg, Sect Hematol & Coagulat, Dept Internal Med, Inst Med,Sahlgrenska Acad, Gothenburg, Sweden..
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Nilsson-Ehle, Herman
    Univ Gothenburg, Sect Hematol & Coagulat, Dept Internal Med, Inst Med,Sahlgrenska Acad, Gothenburg, Sweden..
    Karlsson, Magnus K.
    Lund Univ, Clin & Mol Osteoporosis Res Unit, Dept Clin Sci & Orthoped, Malmo, Sweden..
    Herlitz, Hans
    Univ Gothenburg, Dept Mol & Clin Med, Sahlgrenska Acad, Gothenburg, Sweden..
    Lorentzon, Mattias
    Univ Gothenburg, CBAR, Dept Internal Med, Inst Med,Sahlgrenska Acad, Gothenburg, Sweden.;Univ Gothenburg, Dept Geriatr Med, Internal Med, Inst Med,Sahlgrenska Acad, Gothenburg, Sweden..
    Ohlsson, Claes
    Univ Gothenburg, CBAR, Dept Internal Med, Inst Med,Sahlgrenska Acad, Gothenburg, Sweden..
    Mellström, Dan
    Univ Gothenburg, CBAR, Dept Internal Med, Inst Med,Sahlgrenska Acad, Gothenburg, Sweden.;Univ Gothenburg, Dept Geriatr Med, Internal Med, Inst Med,Sahlgrenska Acad, Gothenburg, Sweden..
    Low serum iron is associated with high serum intact FGF23 in elderly men: The Swedish MrOS study2017In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 98, p. 1-8Article in journal (Refereed)
    Abstract [en]

    Background: Fibroblast growth factor (FGF23) is a protein that is produced by osteoblasts and osteocytes. Increased serum levels of FGF23 have been associated with increased risks of osteoporotic fractures and cardiovascular disease, particularly in participants with poor renal function. Serum iron (Fe) has been suggested as a regulator of FGF23 homeostasis. Objective: To determine whether Fe and iron status are determinants of the levels of intact FGF23 (iFGF23) in elderly men. Methods: The MrOS study is a population-based study of elderly men (N = 1010; mean age, 75.3 years; range, 69-81 years). The levels of Fe, transferrin saturation (TS), and ferritin were evaluated in relation to the serum concentrations of iFGF23 before and after adjustments for confounders. Results: TS<15% was found in 3.5% (34/977) of the participants, who had a higher median level iFGF23 compared with the remaining subjects (47.4 mu rnol/L vs. 41.9 mu mol/L, p = 0.008). The levels of iFGF23 correlated negatively (un-adjusted) with the levels of Fe (r = -0.17, p < 0.001), TS (r = -0.16, p < 0.001) and serum ferritin (r = -0.07, p = 0.022). In addition, in participants with estimated glomerular filtration rate eGFRCystatin C > 60 mL/min, the levels of iFGF23 correlated (age-adjusted) negatively with the levels of Fe (r = -0.15, p < 0.001) and TS (r = -0.17, p < 0.001). The level of iFGF23 correlated positively (un-adjusted) with lumbar spine bone mineral density (BMD) (r = 0.14, p < 0.001), total body BMD (r = 0.11, p = 0.001), and total hip BMD (r = 0.09, p = 0.004). The corresponding correlations, when adjusted for age, weight, and height were: r = 0.08, p = 0.018; r = 0.05, p = 0.120; and r = 0.02, p = 0.624, respectively. No associations were found between BMD and the levels of Fe or TS. Multiple step-wise linear regression analyses [adjusting for age, body mass index (BMI), comorbidity index, cystatin C, C-reactive protein (hs-CRP), serum vitamin D 25-OH (25OHD), phosphate, calcium, parathyroid hormone (PTH), erythropoietin, hemoglobin, lumbar spine BMD, apolipoprotein B/A1 ratio] were performed in three separate models with Fe, TS or ferritin as potential explanatory variables. Fe and TS, but not ferritin, were independent predictors of iFGF23 level (standardized beta-values: -0.10, p <0.001; 0.10, p <0.001; and -0.05, p = 0.062, respectively). Conclusion: Low levels of Fe in elderly men are associated with high levels of iFGF23, independently of markers of inflammation and renal function, suggesting an iron-related pathway for FGF23 regulation. (C) 2017 Elsevier Inc. All rights reserved.

  • 52.
    Lindahl, Katarina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Astrom, Eva
    Karolinska Univ Hosp, Pediat Neurol, Astrid Lindgren Childrens Hosp, Stockholm, Sweden;Karolinska Inst, Dept Woman & Child Hlth, Stockholm, Sweden.
    Dragomir, Anca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Symoens, Sofie
    Univ Hosp Ghent, Dept Med Genet, Ghent, Belgium.
    Coucke, Paul
    Univ Hosp Ghent, Dept Med Genet, Ghent, Belgium.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Paschalis, Eleftherios
    Ludwig Boltzmann Inst Osteol, Hanusch Hosp WGKK, Vienna, Austria;Hanusch Hosp, Med Dept 1, AUVA Trauma Ctr Meidling, Vienna, Austria.
    Roschger, Paul
    Ludwig Boltzmann Inst Osteol, Hanusch Hosp WGKK, Vienna, Austria;Hanusch Hosp, Med Dept 1, AUVA Trauma Ctr Meidling, Vienna, Austria.
    Gamsjaeger, Sonja
    Ludwig Boltzmann Inst Osteol, Hanusch Hosp WGKK, Vienna, Austria;Hanusch Hosp, Med Dept 1, AUVA Trauma Ctr Meidling, Vienna, Austria.
    Klaushofer, Klaus
    Ludwig Boltzmann Inst Osteol, Hanusch Hosp WGKK, Vienna, Austria;Hanusch Hosp, Med Dept 1, AUVA Trauma Ctr Meidling, Vienna, Austria.
    Fratzl-Zelman, Nadja
    Ludwig Boltzmann Inst Osteol, Hanusch Hosp WGKK, Vienna, Austria;Hanusch Hosp, Med Dept 1, AUVA Trauma Ctr Meidling, Vienna, Austria.
    Kindmark, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Homozygosity for CREB3L1 premature stop codon in first case of recessive osteogenesis imperfecta associated with OASIS-deficiency to survive infancy2018In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 114, p. 268-277Article in journal (Refereed)
    Abstract [en]

    Background: Mutations of the endoplasmic reticulum (ER) stress transducer OASIS (encoded by CREB3L1), cause severe recessive osteogenesis imperfecta (OI) not compatible with surviving the neonatal period, as has been shown in two unrelated families through a whole gene deletion vs. a qualitative alteration of OASIS Heterozygous carriers in the described families have exhibited a mild phenotype. OASIS is a transcription factor highly expressed in osteoblasts, and OASIS(-/-) mice exhibit severe osteopenia and spontaneous fractures. Here, we expand the clinical spectrum by a detailed phenotypic characterization of the first case of OASIS-associated OI surviving the neonatal period, with heterozygous family members being unaffected.

    Methods: All OI-associated genes were sequenced. Primary human osteoblast-like cell (hOB) and fibroblast (FB) cultures were obtained for qPCR, and steady-state collagen biochemistry. FB, hOB and skin biopsies were ultrastructurally analyzed. Bone was analyzed by |mu CT, histomorphometry, quantitative backscattered electron imaging (qBEI), and Raman microspectroscopy.

    Results: The proband, a boy with severe OI, had blue sclera and tooth agenesis A homozygous CREB3L1 stop codon mutation was detected by sequencing, while several family members were heterozygotes Markedly low levels of CREB3L1 mRNA were confirmed by qPCR in hOBs (16%) and FB (21%), however, collagen I levels were only reduced in hOBs (5-10%) Electron microscopy of hOBs showed pronounced alterations, with numerous myelin figures and diminished RER vs. normal ultrastructure of FB. Bone histomorphometry and qBEI were similar to collagen I OI, with low trabecular thickness and mineral apposition rate, and increased bone matrix mineralization. Raman microspectroscopy revealed low level of glycosaminoglycans. Clinical response to lifelong bisphosphonate treatment was as expected in severe OI with steadily increasing bone mineral density, but despite this the boy suffered repeated childhood fractures.

    Conclusions: Deficiency of OASIS can cause severe OI compatible with surviving the neonatal period A marked decrease of collagen type I transcription was noted in bone tissue, but not in skin, and ultrastructure of hOBs was pathological. Results also suggested OASIS involvement in glycosaminoglycan secretion in bone.

  • 53.
    Lindahl, Katarina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Astrom, Eva
    Rubin, Carl-Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Grigelioniene, Giedre
    Malmgren, Barbro
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Kindmark, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Genetic epidemiology, prevalence, and genotype-phenotype correlations in the Swedish population with osteogenesis imperfecta2015In: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438, Vol. 23, no 8, p. 1042-1050Article in journal (Refereed)
    Abstract [en]

    Osteogenesis imperfecta (OI) is a rare hereditary bone fragility disorder, caused by collagen I mutations in 90% of cases. There are no comprehensive genotype-phenotype studies on 4100 families outside North America, and no population-based studies determining the genetic epidemiology of OI. Here, detailed clinical phenotypes were recorded, and the COL1A1 and COL1A2 genes were analyzed in 164 Swedish OI families (223 individuals). Averages for bone mineral density (BMD), height and yearly fracture rate were calculated and related to OI and mutation type. N-terminal helical mutations in both the alpha 1-and alpha 2-chains were associated with the absence of dentinogenesis imperfecta (P<0.0001 vs 0.0049), while only those in the alpha 1-chain were associated with blue sclera (P = 0.0110). Comparing glycine with serine substitutions, alpha 1-alterations were associated with more severe phenotype (P = 0.0031). Individuals with type I OI caused by qualitative vs quantitative mutations were shorter (P < 0.0001), but did not differ considering fractures or BMD. The children in this cohort were estimated to represent >95% of the complete Swedish pediatric OI population. The prevalence of OI types I, III, and IV was 5.16, 0.89, and 1.35/100 000, respectively (7.40/100 000 overall), corresponding to what has been estimated but not unequivocally proven in any population. Collagen I mutation analysis was performed in the family of 97% of known cases, with causative mutations found in 87%. Qualitative mutations caused 32% of OI type I. The data reported here may be helpful to predict phenotype, and describes for the first time the genetic epidemiology in > 95% of an entire OI population.

  • 54.
    Lindahl, Katarina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Kindmark, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Rubin, Carl-Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Malmgren, B.
    Karolinska Inst, Dept Dent Med, Div Pediat Dent, Stockholm, Sweden..
    Grigelioniene, G.
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.;Karolinska Univ Hosp Stockholm, Dept Clin Genet, Stockholm, Sweden..
    Soderhall, S.
    Karolinska Univ Hosp, Neuropediat Unit, Stockholm, Sweden.;Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Åstrom, E.
    Karolinska Univ Hosp, Neuropediat Unit, Stockholm, Sweden.;Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Decreased fracture rate, pharmacogenetics and BMD response in 79 Swedish children with osteogenesis imperfecta types I, III and IV treated with Pamidronate2016In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 87, p. 11-18Article in journal (Refereed)
    Abstract [en]

    Background: Osteogenesis imperfecta (OI) is an inherited heterogeneous bone fragility disorder, usually caused by collagen I mutations. It is well established that bisphosphonate treatment increases lumbar spine (LS) bone mineral density (BMD), as well as improves vertebral geometry in severe 01; however, fracture reduction has been difficult to prove, pharmacogenetic studies are scarce, and it is not known at which age, or severity of disease, treatment should be initiated.

    Materials and methods: COL1A1 and COL1A2 were analyzed in 79 children with OI (type I n = 33, type III n = 25 and type IV n = 21) treated with Pamidronate. Data on LS BMD, height, and radiologically confirmed non vertebral and vertebral fractures were collected prior to, and at several time points during treatment.

    Results: An increase in LS BMD Z-score was observed for all types of OI, and a negative correlation to A LS BMD was observed for both age and LS BMD Z-score at treatment initiation. Supine height Z-scores were not affected by Pamidronate treatment, The fracture rate was reduced for all OI types at all time points during treatment (overall p < 0.0003, < 0.0001 and 0.0003 for all 01 types 1, III and IV respectively). The reduced fracture rate was maintained for types I and IV, while an additional decrease was observed over time for type III. The fracture rate was reduced also in individuals with continued low BMD after >4 yrs Pamidronate. Twice as many boys as girls with 01 type I were treated with Pamidronate, and the fracture rate the year prior treatment was 2.2 times higher for boys (p = 0.0236). Greater Delta LS BMD, but smaller Delta fracture numbers were observed on Pamidronate for helical glycine mutations in COL1A1 vs. COL1A2. Vertebral compression fractures did not progress in any individual during treatment; however, they did not improve in 9%, and these individuals were all >11 years of age at treatment initiation. (p < 0.0001).

    Conclusion: Pamidronate treatment in children with all types of 01 increased LS BMD, decreased fracture rate, and improved vertebral compression fractures. Fracture reduction was prompt and maintained during treatment, irrespective of age at treatment initiation and collagen I mutation type.

  • 55.
    Lindahl, Katarina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Langdahl, Bente
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Kindmark, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Therapy of Endocrine Disease: Treatment of osteogenesis imperfecta in adults2014In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 171, no 2, p. R79-R90Article, review/survey (Refereed)
    Abstract [en]

    Background: Osteogenesis imperfecta (OI) is a heterogeneous rare connective tissue disorder commonly caused by mutations in the collagen type I genes. Pharmacological treatment has been most extensively studied in children, and there are only few studies comprising adult OI patients. Objectives: i) To review the literature on the current medical management of OI in children and adults, and thereby identify unmet medical needs and ii) to present an overview of possible future treatment options. Results: Individualization and optimization of OI treatment in adults remain a challenge, because available treatments do not target the underlying collagen defect, and available literature gives weak support for treatment decisions for adult patients. Conclusions: Bisphosphonates are still the most widely used pharmacological treatment for adult OI, but the current evidence supporting this is sparse and investigations on indications for choice and duration of treatment are needed.

  • 56.
    Ljunggren, Östen
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Benhamou, C. L.
    Dekker, J.
    Kapetanos, G.
    Kocjan, T.
    Langdahl, B. L.
    Napoli, N.
    Petto, H.
    Nikolic, T.
    Lindh, E.
    Study description and baseline characteristics of the population enrolled in a multinational observational study of extended teriparatide use (ExFOS)2014In: Current Medical Research and Opinion, ISSN 0300-7995, E-ISSN 1473-4877, Vol. 30, no 8, p. 1607-1616Article in journal (Refereed)
    Abstract [en]

    Objective: To better characterize patients who are currently being prescribed teriparatide in Europe, this article describes the study design and baseline characteristics of participants of the Extended Forsteo* Observational Study (ExFOS). Research design and methods: ExFOS is a noninterventional, multicenter, prospective, observational study in men and women with osteoporosis treated with teriparatide during the course of normal clinical practice for up to 24 months and with a post-treatment follow-up of at least 18 months. Main outcome measures: Baseline characteristics, including history of fracture and back pain, and health-related quality of life (HRQoL, assessed using the EuroQol-5 Dimension [EQ-5D]). Results: Of 1607 patients enrolled, 90.9% were women. At baseline, mean (standard deviation [SD]) age was 70.3 (9.8) years, and 85.8% of patients had a history of fracture (64.7% with >= 2 fragility fractures). Of those with historic fractures, 90.8% had vertebral fractures (67.8% had thoracic fractures). The mean (SD) of reported bone mineral density T-scores were -3.0 (1.2), -2.4 (1.0), and -2.5 (0.9) for lumbar spine, total hip (left), and femoral neck (left), respectively. Overall, 39.3% of patients had experienced >= 1 fall during the 12 months before enrollment. At baseline, 11.4% of patients were osteoporosis-treatment naive and 15% were currently using glucocorticoids. The mean (SD) visual analog scale score for back pain during the last month was 50.7 (26.9), and 62.1% of patients experienced daily or almost daily back pain. The median EQ-5D health state value at baseline was 0.62 (first and third quartiles: 0.19, 0.74). Conclusions: Baseline characteristics of the ExFOS study cohort indicate that patients prescribed teriparatide in Europe have severe osteoporosis with highly prevalent vertebral fractures, frequent and disabling back pain, and a poor HRQoL, despite previous pharmacotherapy for osteoporosis. Limitations include non-randomization, lack of a comparator group, and patient self-report for data on prior medication and fracture history.

  • 57.
    Lodefalk, Maria
    et al.
    Univ Orebro, Dept Paediat, Fac Med & Hlth, SE-70182 Orebro, Sweden.;Univ Orebro, Univ Hlth Care Res Ctr, SE-70182 Orebro, Sweden..
    Frykholm, Carina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Esbjorner, Elisabeth
    Univ Orebro, Dept Paediat, Fac Med & Hlth, SE-70182 Orebro, Sweden..
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Hypercalcaemia in a Patient with 2p13.2-p16.1 Duplication2016In: Hormone Research in Paediatrics, ISSN 1663-2818, E-ISSN 1663-2826, Vol. 85, no 3, p. 213-218Article in journal (Refereed)
    Abstract [en]

    Background: Partial duplication of 2p is a rare condition that causes facial anomalies, psychomotor delay, and growth failure. Hypercalcaemia is rare in children. So far, duplication of 2p has never been associated with hypercalcaemia. Methods: Here, we report a girl with a partial duplication of 2p presenting with moderate to severe hypercalcaemia at the age of 2 years. She also had hypercalciuria, nephrocalcinosis, decreased renal function, and secondary hyperparathyroidism at presentation. She was thoroughly investigated, including genetic testing of the CYP24A1, CASR, ALPL, and NOD2 genes, to determine the cause of hypercalcaemia. Results: 1,25-dihydroxyvitamin D levels were increased. Hypercalcaemia and hypercalciuria responded well to glucocorticoids but not to cinacalcet. Hyperparathyroidism resolved with improving renal function. Apart from the known duplication of 2p, no pathogenic variants were detected in the studied genes. The duplication of 2p contains the PPP3R1 gene, which encodes for the calcineurin B subunit. Conclusion: We conclude that partial duplication of 2p can be associated with hypercalcaemia and hypercalciuria and hypothesise that the underlying mechanism is an increased extra-renal, parathyroid hormone-independent 25-hydroxyvitamin D 1 alpha-hydroxylase activity, leading to raised amounts of 1,25-dihydroxyvitamin D. The increased enzymatic activity could possibly be caused by calcineurin B subunit-related macrophage stimulation.

  • 58.
    Malmgren, B.
    et al.
    Karolinska Inst, Div Pediat Dent, Dept Dent Med, Stockholm, Sweden..
    Andersson, K.
    Karolinska Inst, Div Pediat Dent, Dept Dent Med, Stockholm, Sweden..
    Lindahl, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Kindmark, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Grigelioniene, G.
    Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden.;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Zachariadis, V.
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Dahllof, G.
    Karolinska Inst, Div Pediat Dent, Dept Dent Med, Stockholm, Sweden..
    Astrom, E.
    Karolinska Univ Hosp, Neuropediat Unit, Stockholm, Sweden.;Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Tooth agenesis in osteogenesis imperfecta related to mutations in the collagen type I genes2017In: Oral Diseases, ISSN 1354-523X, E-ISSN 1601-0825, Vol. 23, no 1, p. 42-49Article in journal (Refereed)
    Abstract [en]

    BackgroundOsteogenesis imperfecta (OI) is a heterogeneous group of disorders of connective tissue, mainly caused by mutations in the collagen type I genes (COL1A1 and COL1A2). Tooth agenesis is a common feature of OI. We investigated the association between tooth agenesis and collagen type I mutations in individuals with OI. Subjects and methodsIn this cohort study, 128 unrelated individuals with OI were included. Panoramic radiographs were analyzed regarding dentinogenesis imperfecta (DGI) and congenitally missing teeth. The collagen I genes were sequenced in all individuals, and in 25, multiplex ligation-dependent probe amplification was performed. ResultsMutations in the COL1A1 and COL1A2 genes were found in 104 of 128 individuals. Tooth agenesis was diagnosed in 17% (hypodontia 11%, oligodontia 6%) and was more frequent in those with DGI (P=0.016), and in those with OI type III, 47%, compared to those with OI types I, 12% (P=0.003), and IV, 13% (P=0.017). Seventy-five percent of the individuals with oligodontia (6 missing teeth) had qualitative mutations, but there was no association with OI type, gender, or presence of DGI. ConclusionThe prevalence of tooth agenesis is high (17%) in individuals with OI, and OI caused by a qualitative collagen I mutation is associated with oligodontia.

  • 59.
    Manojlovic-Gacic, Emilija
    et al.
    Univ Belgrade, Inst Pathol, Sch Med, Belgrade, Serbia.
    Engström, Britt Edén
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Casar-Borota, Olivera
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical and experimental pathology.
    Histopathological classification of non-functioning pituitary neuroendocrine tumors2018In: Pituitary, ISSN 1386-341X, E-ISSN 1573-7403, Vol. 21, no 2, p. 119-129Article, review/survey (Refereed)
    Abstract [en]

    Non-functioning pituitary neuroendocrine tumors do not cause endocrine symptoms related to hypersecretion of adenohypophyseal hormones and are clinically characterized by symptoms due to growing sellar tumor mass. Histopathological classification of this tumor group has always been challenging due to their heterogeneity, limited knowledge on their biology, and diverse methodological problems. We have searched PubMed database for data related to the histopathological classification of non-functioning pituitary tumors and methods for its application. Principles of the classification and grading presented in the recently released 4th edition of the World Health Organization classification of endocrine tumors have been summarized. Based on the expression of anterior pituitary hormones and pituitary specific transcription factors, gonadotroph tumors dominate within the group of clinically non-functioning tumors, followed by corticotroph type; however, other less common types of the non-functioning tumors can be identified. Assessment of tumor cell proliferation is important to identify "high-risk adenomas." A few subtypes of non-functioning tumors belong to the category of potentially aggressive tumors, independent of the cell proliferation rate. Here, we present up to date criteria for the classification of clinically non-functioning pituitary tumors, offer a diagnostic approach for the routine clinical use, and emphasize a need for inclusion of prognostic and predictive markers in the classification.

  • 60. McCloskey, Eugene V
    et al.
    Odén, Anders
    Harvey, Nicholas C
    Leslie, William D
    Hans, Didier
    Johansson, Helena
    Barkmann, Reinhard
    Boutroy, Stephanie
    Brown, Jacques
    Chapurlat, Roland
    Elders, Petra Jm
    Fujita, Yuki
    Glüer, Claus-C
    Goltzman, David
    Iki, Masayuki
    Karlsson, Magnus
    Kindmark, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kotowicz, Mark
    Kurumatani, Norio
    Kwok, Timothy
    Lamy, Oliver
    Leung, Jason
    Lippuner, Kurt
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Lorentzon, Mattias
    Mellström, Dan
    Merlijn, Thomas
    Oei, Ling
    Ohlsson, Claes
    Pasco, Julie A.
    Rivadeneira, Fernando
    Rosengren, Björn
    Sornay-Rendu, Elisabeth
    Szulc, Pawel
    Tamaki, Junko
    Kanis, John A
    A meta-analysis of trabecular bone score in fracture risk prediction and its relationship to FRAX2016In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 31, no 5, p. 940-948Article in journal (Refereed)
    Abstract [en]

    Trabecular bone score (TBS) is a grey-level textural index of bone microarchitecture derived from lumbar spine dual-energy X-ray absorptiometry (DXA) images. TBS is a BMD-independent predictor of fracture risk. The objective of this meta-analysis was to determine whether TBS predicted fracture risk independently of FRAX probability and to examine their combined performance by adjusting the FRAX probability for TBS. We utilized individual level data from 17,809 men and women in 14 prospective population-based cohorts. Baseline evaluation included TBS and the FRAX risk variables and outcomes during follow up (mean 6.7 years) comprised major osteoporotic fractures. The association between TBS, FRAX probabilities and the risk of fracture was examined using an extension of the Poisson regression model in each cohort and for each sex and expressed as the gradient of risk (GR; hazard ratio per 1SD change in risk variable in direction of increased risk). FRAX probabilities were adjusted for TBS using an adjustment factor derived from an independent cohort (the Manitoba Bone Density Cohort). Overall, the GR of TBS for major osteoporotic fracture was 1.44 (95% CI: 1.35-1.53) when adjusted for age and time since baseline and was similar in men and women (p > 0.10). When additionally adjusted for FRAX 10-year probability of major osteoporotic fracture, TBS remained a significant, independent predictor for fracture (GR 1.32, 95%CI: 1.24-1.41). The adjustment of FRAX probability for TBS resulted in a small increase in the GR (1.76, 95%CI: 1.65, 1.87 vs. 1.70, 95%CI: 1.60-1.81). A smaller change in GR for hip fracture was observed (FRAX hip fracture probability GR 2.25 vs. 2.22). TBS is a significant predictor of fracture risk independently of FRAX. The findings support the use of TBS as a potential adjustment for FRAX probability, though the impact of the adjustment remains to be determined in the context of clinical assessment guidelines.

  • 61.
    Mehta, Atul
    et al.
    UCL, Royal Free London NHS Fdn Trust, London, England..
    Panahloo, Zoya
    Shire, Zug, Switzerland..
    Di Rocco, Maja
    Giannina Gaslini Inst, Dept Pediat, Unit Rare Dis, Genoa, Italy..
    Goker-Alpand, Ozlem
    O&O Alpan LLC, Lysosomal Disorders Unit, Fairfax, VA USA.;O&O Alpan LLC, Ctr Clin Trials, Fairfax, VA USA..
    Hughes, Derralynn
    UCL, Royal Free London NHS Fdn Trust, London, England..
    Kindmark, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism. Uppsala Univ Hosp, Uppsala, Sweden..
    Kuter, David
    Harvard Med Sch, Massachusetts Gen Hosp, Ctr Hematol, Boston, MA USA..
    Lukina, Elena
    Natl Res Ctr Hematol, Moscow, Russia..
    Nakamura, Kimitoshi
    Kumamoto Univ Hosp, Kumamoto, Japan..
    Oliveri, Beatriz
    UBA, CONICET, INIGEMUBACONICET, Lab Osteoporosis & Enfermedades Metabol Oseas, Buenos Aires, DF, Argentina..
    Perez-Lopez, Jordi
    Hosp Valle De Hebron, Unit Rare Dis, Barcelona, Spain..
    Schwartzk, Ida V. D.
    Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil.;Univ Fed Rio Grande do Sul, Dept Genet, Porto Alegre, RS, Brazil..
    Serratrice, Christine
    Geneva Univ Hosp, Thonex, Switzerland..
    Szer, Jeff
    Royal Melbourne Hosp, Parkville, Vic, Australia..
    Zimran, Ari
    Hebrew Univ Jerusalem, Gaucher Clin, Shaare Zedek Med Ctr, Hadassah Med Sch, Jerusalem, Israel..
    Pastores, Gregory
    Univ Coll Dublin, Dublin, Ireland.;Mater Misericordiae Univ Hosp, Dublin, Ireland..
    Management goals and normalization concept for type 1 Gaucher disease: Results from a survey of expert physicians2018In: Molecular Genetics and Metabolism, ISSN 1096-7192, E-ISSN 1096-7206, Vol. 123, no 2, p. S94-S94Article in journal (Other academic)
  • 62.
    Mellstrom, D.
    et al.
    Sahlgrens Acad, Inst Med, Dept Internal Med & Clin Nutr, Geriatr Med, Molndal, Sweden..
    Ohlsson, C.
    Univ Gothenburg, Sahlgrenska Acad, CBAR, Gothenburg, Sweden..
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Lorentzon, M.
    Sahlgrens Acad, Inst Med, Dept Internal Med & Clin Nutr, Geriatr Med, Molndal, Sweden..
    Nilsson, A. G.
    Sahlgrens Acad, Inst Med, Dept Internal Med & Clin Nutr, Geriatr Med, Molndal, Sweden..
    Lewerin, C.
    Sahlgrens Univ Hosp, Sect Hematol & Coagulat, Gothenburg, Sweden..
    Smith, U.
    Inst Med, Gothenburg, Sweden..
    Karlsson, M.
    Lund Univ, Skane Univ Hosp, Dept Orthopaed & Clin Sci, Malmo, Sweden..
    Increased Risk For Incident Hip Fracture In Men With Type 2 Diabetes2017In: Osteoporosis International, ISSN 0937-941X, E-ISSN 1433-2965, Vol. 28, p. S529-S530Article in journal (Other academic)
  • 63. Moayyeri, Alireza
    et al.
    Hsu, Yi-Hsiang
    Karasik, David
    Estrada, Karol
    Xiao, Su-Mei
    Nielson, Carrie
    Srikanth, Priya
    Giroux, Sylvie
    Wilson, Scott G.
    Zheng, Hou-Feng
    Smith, Albert V.
    Pye, Stephen R.
    Leo, Paul J.
    Teumer, Alexander
    Hwang, Joo-Yeon
    Ohlsson, Claes
    McGuigan, Fiona
    Minster, Ryan L.
    Hayward, Caroline
    Olmos, Jose M.
    Lyytikaeinen, Leo-Pekka
    Lewis, Joshua R.
    Swart, Karin M. A.
    Masi, Laura
    Oldmeadow, Chris
    Holliday, Elizabeth G.
    Cheng, Sulin
    van Schoor, Natasja M.
    Harvey, Nicholas C.
    Kruk, Marcin
    Fabiola Del Greco, M.
    Igl, Wilmar
    Trummer, Olivia
    Grigoriou, Efi
    Luben, Robert
    Liu, Ching-Ti
    Zhou, Yanhua
    Oei, Ling
    Medina-Gomez, Carolina
    Zmuda, Joseph
    Tranah, Greg
    Brown, Suzanne J.
    Williams, Frances M.
    Soranzo, Nicole
    Jakobsdottir, Johanna
    Siggeirsdottir, Kristin
    Holliday, Kate L.
    Hannemann, Anke
    Go, Min Jin
    Garcia, Melissa
    Polasek, Ozren
    Laaksonen, Marika
    Zhu, Kun
    Enneman, Anke W.
    McEvoy, Mark
    Peel, Roseanne
    Sham, Pak Chung
    Jaworski, Maciej
    Johansson, Asa
    Hicks, Andrew A.
    Pludowski, Pawel
    Scott, Rodney
    Dhonukshe-Rutten, Rosalie A. M.
    van der Velde, Nathalie
    Kaehoenen, Mika
    Viikari, Jorma S.
    Sievaenen, Harri
    Raitakari, Olli T.
    Gonzalez-Macias, Jesus
    Hernandez, Jose L.
    Mellstroem, Dan
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Cho, Yoon Shin
    Voelker, Uwe
    Nauck, Matthias
    Homuth, Georg
    Voelzke, Henry
    Haring, Robin
    Brown, Matthew A.
    McCloskey, Eugene
    Nicholson, Geoffrey C.
    Eastell, Richard
    Eisman, John A.
    Jones, Graeme
    Reid, Ian R.
    Dennison, Elaine M.
    Wark, John
    Boonen, Steven
    Vanderschueren, Dirk
    Wu, Frederick C. W.
    Aspelund, Thor
    Richards, J. Brent
    Bauer, Doug
    Hofman, Albert
    Khaw, Kay-Tee
    Dedoussis, George
    Obermayer-Pietsch, Barbara
    Gyllensten, Ulf
    Pramstaller, Peter P.
    Lorenc, Roman S.
    Cooper, Cyrus
    Kung, Annie Wai Chee
    Lips, Paul
    Alen, Markku
    Attia, John
    Luisa Brandi, Maria
    de Groot, Lisette C. P. G. M.
    Lehtimaeki, Terho
    Riancho, Jose A.
    Campbell, Harry
    Liu, Yongmei
    Harris, Tamara B.
    Akesson, Kristina
    Karlsson, Magnus
    Lee, Jong-Young
    Wallaschofski, Henri
    Duncan, Emma L.
    O'Neill, Terence W.
    Gudnason, Vilmundur
    Spector, Timothy D.
    Rousseau, Francois
    Orwoll, Eric
    Cummings, Steven R.
    Wareham, Nick J.
    Rivadeneira, Fernando
    Uitterlinden, Andre G.
    Prince, Richard L.
    Kiel, Douglas P.
    Reeve, Jonathan
    Kaptoge, Stephen K.
    Genetic determinants of heel bone properties: genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium2014In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 23, no 11, p. 3054-3068Article in journal (Refereed)
    Abstract [en]

    Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 x 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 x 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 x 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.

  • 64.
    Napoli, Nicola
    et al.
    Univ Campus Biomed, Div Endocrinol & Diabet, Alvaro del Portillo 21, I-00128 Rome, Italy.
    Langdahl, Bente. L.
    Aarhus Univ Hosp, Aarhus, Denmark.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Lespessailles, Eric
    Univ Orleans, Orleans, France;Reg Hosp Orleans, Orleans, France.
    Kapetanos, George
    Papageorgiou Gen Hosp, Thessaloniki, Greece.
    Kocjan, Tomaz
    Univ Med Ctr, Ljubljana, Slovenia.
    Nikolic, Tatjana
    Univ Hosp, Zagreb, Croatia.
    Eiken, Pia
    Hillerod Hosp, Dept Cardiol Nephrol & Endocrinol, Hillerod, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.
    Petto, Helmut
    Eli Lilly & Co, Windlesham, Surrey, England.
    Moll, Thomas
    Eli Lilly & Co, Windlesham, Surrey, England.
    Lindh, Erik
    Eli Lilly & Co, Windlesham, Surrey, England.
    Marin, Fernando
    Eli Lilly & Co, Windlesham, Surrey, England.
    Effects of Teriparatide in Patients with Osteoporosis in Clinical Practice: 42-Month Results During and After Discontinuation of Treatment from the European Extended Forsteo (R) Observational Study (ExFOS)2018In: Calcified Tissue International, ISSN 0171-967X, E-ISSN 1432-0827, Vol. 103, no 4, p. 359-371Article in journal (Refereed)
    Abstract [en]

    This study aimed to describe clinical outcomes in patients prescribed teriparatide and followed up for 18months after stopping the drug in real-life conditions. The Extended Forsteo (R) Observational Study analysed incident clinical fractures in 6-month intervals using logistic regression with repeated measures. Changes in back pain (visual analogue scale) and health-related quality of life (HRQoL; EQ-5D questionnaire) were analysed using mixed models for repeated measures. Patients were analysed if they had a post-baseline visit, regardless of whether and for how long they took teriparatide. Of 1531 patients analysed (90.7% female, mean age: 70.3years), 76 (5.0%) never took teriparatide. Median treatment duration was 23.6months. The adjusted odds of clinical fracture decreased by 47% in the >12- to 18-month treatment period (p=0.013) compared with the first 6-month period, with no statistically significant reduction in the >18- to 24-month interval. The clinical fracture rate remained stable during the 18 months' post-teriparatide, when approximately 98% of patients took osteoporosis medication (51% bisphosphonates). Clinical vertebral fractures were reduced at every time period compared with the first 6months. Adjusted mean back pain scores decreased and EQ-5D scores increased significantly at each post-baseline observation. In a real-life clinical setting, the risk of clinical fractures declined during 24months of teriparatide treatment. This reduction was maintained 18months after stopping teriparatide. In parallel, patients reported significant improvements in back pain and HRQoL. The results should be interpreted in the context of the non-controlled design of this observational study.

  • 65.
    Nilsson, Anna G.
    et al.
    Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Endocrinol, Gothenburg, Sweden;Univ Gothenburg, Inst Med, Sahlgrenska Acad, Gothenburg, Sweden.
    Bergthorsdottir, Ragnhildur
    Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Endocrinol, Gothenburg, Sweden;Univ Gothenburg, Inst Med, Sahlgrenska Acad, Gothenburg, Sweden.
    Burman, Pia
    Lund Univ, Skane Univ Hosp Malmo, Dept Endocrinol, Lund, Sweden.
    Dahlqvist, Per
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
    Ekman, Bertil
    Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden;Linkoping Univ, Dept Endocrinol, Linkoping, Sweden.
    Engström, Britt E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Ragnarsson, Oskar
    Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Endocrinol, Gothenburg, Sweden;Univ Gothenburg, Inst Med, Sahlgrenska Acad, Gothenburg, Sweden.
    Skrtic, Stanko
    Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Endocrinol, Gothenburg, Sweden;AstraZeneca R&D, Molndal, Sweden;Univ Gothenburg, Inst Med, Sahlgrenska Acad, Gothenburg, Sweden.
    Wahlberg, Jeanette
    Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden;Linkoping Univ, Dept Endocrinol, Linkoping, Sweden.
    Achenbach, Heinrich
    Shire Int GmbH, Zug, Switzerland.
    Uddin, Sharif
    Shire, Lexington, MA USA.
    Marelli, Claudio
    Shire Int GmbH, Zug, Switzerland.
    Johannsson, Gudmundur
    Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Endocrinol, Gothenburg, Sweden;Univ Gothenburg, Inst Med, Sahlgrenska Acad, Gothenburg, Sweden.
    Long-term safety of once-daily, dual-release hydrocortisone in patients with adrenal insufficiency: a phase 3b, open-label, extension study2017In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 176, no 6, p. 715-725Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate the long-term safety and tolerability of a once-daily, dual-release hydrocortisone (DR-HC) tablet as oral glucocorticoid replacement therapy in patients with primary adrenal insufficiency (AI). Design: Prospective, open-label, multicenter, 5-year extension study of DR-HC conducted at five university clinics in Sweden. Methods: Seventy-one adult patients diagnosed with primary AI who were receiving stable glucocorticoid replacement therapy were recruited. Safety and tolerability outcomes included adverse events (AEs), intercurrent illness episodes, laboratory parameters and vital signs. Quality of life (QoL) was evaluated using generic questionnaires. Results: Total DR-HC exposure was 328 patient-treatment years. Seventy patients reported 1060 AEs (323 per 100 patient-years); 85% were considered unrelated to DR-HC by the investigator. The most common AEs were nasopharyngitis (70%), fatigue (52%) and gastroenteritis (48%). Of 65 serious AEs reported by 32 patients (20 per 100 patient-years), four were considered to be possibly related to DR-HC: acute AI (n = 2), gastritis (n = 1) and syncope (n = 1). Two deaths were reported (fall from height and subarachnoid hemorrhage), both considered to be unrelated to DR-HC. From baseline to 5 years, intercurrent illness episodes remained relatively stable (mean 2.6-5.4 episodes per patient per year), fasting plasma glucose (0.7 mmol/L; P < 0.0001) and HDL cholesterol (0.2 mmol/L; P < 0.0001) increased and patient-/investigator-assessed tolerability improved. QoL total scores were unchanged but worsening physical functioning was recorded (P = 0.008). Conclusions: In the first prospective study evaluating the long-term safety of glucocorticoid replacement therapy in patients with primary AI, DR-HC was well tolerated with no safety concerns observed during 5-year treatment.

  • 66. Oei, Ling
    et al.
    Estrada, Karol
    Duncan, Emma L.
    Christiansen, Claus
    Liu, Ching-Ti
    Langdahl, Bente L.
    Obermayer-Pietsch, Barbara
    Riancho, Jose A.
    Prince, Richard L.
    van Schoor, Natasja M.
    McCloskey, Eugene
    Hsu, Yi-Hsiang
    Evangelou, Evangelos
    Ntzani, Evangelia
    Evans, David M.
    Alonso, Nerea
    Husted, Lise B.
    Valero, Carmen
    Hernandez, Jose L.
    Lewis, Joshua R.
    Kaptoge, Stephen K.
    Zhu, Kun
    Cupples, L. Adrienne
    Medina-Gomez, Carolina
    Vandenput, Liesbeth
    Kim, Ghi Su
    Lee, Seung Hun
    Castano-Betancourt, Martha C.
    Oei, Edwin H. G.
    Martinez, Josefina
    Daroszewska, Anna
    van der Klift, Marjolein
    Mellstrom, Dan
    Herrera, Lizbeth
    Karlsson, Magnus K.
    Hofman, Albert
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Pols, Huibert A. P.
    Stolk, Lisette
    van Meurs, Joyce B. J.
    Ioannidis, John P. A.
    Zillikens, M. Carola
    Lips, Paul
    Karasik, David
    Uitterlinden, Andre G.
    Styrkarsdottir, Unnur
    Brown, Matthew A.
    Koh, Jung-Min
    Richards, J. Brent
    Reeve, Jonathan
    Ohlsson, Claes
    Ralston, Stuart H.
    Kiel, Douglas P.
    Rivadeneira, Fernando
    Genome-wide association study for radiographic vertebral fractures: A potential role for the 16q24 BMD locus2014In: Bone, ISSN 8756-3282, E-ISSN 1873-2763, Vol. 59, p. 20-27Article in journal (Refereed)
    Abstract [en]

    Vertebral fracture risk is a heritable complex trait. The aim of this study was to identify genetic susceptibility factors for osteoporotic vertebral fracture applying a genome-wide association study (GWAS) approach. The GWAS discovery was based on the Rotterdam Study, a population-based study of elderly Dutch individuals aged >55 years; and comprising 329 cases and 2666 controls with radiographic scoring (McCloskey-Kanis) and genetic data. Replication of one top-associated SNP was pursued by de-novo genotyping of 15 independent studies across Europe, the United States, and Australia and one Asian study. Radiographic vertebral fracture assessment was performed using McCloskey-Kanis or Genant semi-quantitative definitions. SNPs were analyzed in relation to vertebral fracture using logistic regression models corrected for age and sex. Fixed effects inverse variance and Han-Eskin alternative random effects meta-analyses were applied. Genome-wide significance was set at p<5 x 10(-8). In the discovery, a SNP (rs11645938) on chromosome 16q24 was associated with the risk for vertebral fractures at p = 4.6 x 10(-8). However, the association was not significant across 5720 cases and 21,791 controls from 14 studies. Fixed-effects meta-analysis summary estimate was 1.06 (95% Cl: 0.98-1.14; p = 0.17), displaying high degree of heterogeneity (I-2= 57%; Q(het)p = 0.0006). Under Han-Eskin alternative random effects model the summary effect was significant (p = 0.0005). The SNP maps to a region previously found associated with lumbar spine bone mineral density (LS-BMD) in two large meta-analyses from the GEFOS consortium. A false positive association in the GWAS discovery cannot be excluded, yet, the low-powered setting of the discovery and replication settings (appropriate to identify risk effect size >1.25) may still be consistent with an effect size <1.10, more of the type expected in complex traits. Larger effort in studies with standardized phenotype definitions is needed to confirm or reject the involvement of this locus on the risk for vertebral fractures.

  • 67.
    Ohlsson, Claes
    et al.
    Univ Gothenburg, Ctr Bone & Arthrit Res, Sahlgrenska Acad, Dept Internal Med & Clin Nutr,Inst Med, Vita Straket 11, SE-41345 Gothenburg, Sweden.
    Nethander, Maria
    Univ Gothenburg, Sahlgrenska Acad, Bioinformat Core Facil, Gothenburg, Sweden.
    Kindmark, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Lorentzon, Mattias
    Univ Gothenburg, Ctr Bone & Arthrit Res, Sahlgrenska Acad, Dept Internal Med & Clin Nutr,Inst Med, Vita Straket 11, SE-41345 Gothenburg, Sweden;Univ Gothenburg, Sahlgrenska Acad, Inst Med, Geriatr Med, Gothenburg, Sweden.
    Rosengren, Bjorn E.
    Lund Univ, Dept Clin Sci, Clin & Mol Osteoporosis Res Unit, Lund, Sweden;Skane Univ Hosp, Dept Orthopaed, Malmo, Sweden.
    Karlsson, Magnus K.
    Lund Univ, Dept Clin Sci, Clin & Mol Osteoporosis Res Unit, Lund, Sweden;Skane Univ Hosp, Dept Orthopaed, Malmo, Sweden.
    Mellstrom, Dan
    Univ Gothenburg, Ctr Bone & Arthrit Res, Sahlgrenska Acad, Dept Internal Med & Clin Nutr,Inst Med, Vita Straket 11, SE-41345 Gothenburg, Sweden;Univ Gothenburg, Sahlgrenska Acad, Inst Med, Geriatr Med, Gothenburg, Sweden.
    Vandenput, Liesbeth
    Univ Gothenburg, Ctr Bone & Arthrit Res, Sahlgrenska Acad, Dept Internal Med & Clin Nutr,Inst Med, Vita Straket 11, SE-41345 Gothenburg, Sweden.
    Low Serum DHEAS Predicts Increased Fracture Risk in Older Men: The MrOS Sweden Study2017In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 32, no 8, p. 1607-1614Article in journal (Refereed)
    Abstract [en]

    The adrenal-derived hormones dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are the most abundant circulating hormones and their levels decline substantially with age. DHEAS is considered an inactive precursor, which is converted into androgens and estrogens via local metabolism in peripheral target tissues. The predictive value of serum DHEAS for fracture risk is unknown. The aim of this study was, therefore, to assess the associations between baseline DHEAS levels and incident fractures in a large cohort of older men. Serum DHEAS levels were analyzed with mass spectrometry in the population-based Osteoporotic Fractures in Men study in Sweden (n = 2568, aged 69 to 81 years). Incident X-ray validated fractures (all, n = 594; non-vertebral major osteoporotic, n = 255; hip, n = 175; clinical vertebral, n = 206) were ascertained during a median follow-up of 10.6 years. DHEAS levels were inversely associated with the risk of any fracture (hazard ratio [HR] per SD decrease = 1.14, 95% confidence interval [CI] 1.05-1.24), non-vertebral major osteoporotic fractures (HR = 1.31, 95% CI 1.16-1.48), and hip fractures (HR = 1.18, 95% CI 1.02-1.37) but not clinical vertebral fractures (HR = 1.09, 95% CI 0.95-1.26) in Cox regression models adjusted for age, body mass index (BMI) and prevalent fractures. Further adjustment for traditional risk factors for fracture, bone mineral density (BMD), and/or physical performance variables as well as serum sex steroid levels only slightly attenuated the associations between serum DHEAS and fracture risk. Similarly, the point estimates were only marginally reduced after adjustment for FRAX estimates with BMD. The inverse association between serum DHEAS and all fractures or major osteoporotic fractures was nonlinear, with a substantial increase in fracture risk (all fractures 22%, major osteoporotic fractures 33%) for those participants with serum DHEAS levels below the median (0.60 mg/mL). In conclusion, low serum DHEAS levels are a risk marker of mainly non-vertebral fractures in older men, of whom those with DHEAS levels below 0.60 mg/mL are at highest risk.

  • 68.
    Orwoll, Eric S.
    et al.
    Oregon Hlth & Sci Univ, Sch Med, Bone & Mineral Unit, Div Endocrinol Diabet & Clin Nutr, 3181 SW Sam Jackson Pk Rd CR 113, Portland, OR 97201 USA..
    Lapidus, Jodi
    Oregon Hlth & Sci Univ, Div Biostat, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA..
    Wang, Patty Y.
    Oregon Hlth & Sci Univ, Sch Med, Bone & Mineral Unit, Div Endocrinol Diabet & Clin Nutr, 3181 SW Sam Jackson Pk Rd CR 113, Portland, OR 97201 USA..
    Vandenput, Liesbeth
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Ctr Bone & Arthrit Res, Gothenburg, Sweden..
    Hoffman, Andrew
    Stanford Univ, Dept Med, Stanford, CA 94305 USA..
    Fink, Howard A.
    VA Med Ctr, Geriatr Res Educ & Clin Ctr, Minneapolis, MN USA.;Univ Minnesota, Dept Med, Box 736 UMHC, Minneapolis, MN 55455 USA..
    Laughlin, Gail A.
    Univ Calif San Diego, Sch Med, Dept Family Med & Publ Hlth, Div Epidemiol, La Jolla, CA 92093 USA..
    Nethander, Maria
    Univ Gothenburg, Sahlgrenska Acad, Bioinformat Core Facil, Gothenburg, Sweden..
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Kindmark, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Lorentzon, Mattias
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Ctr Bone & Arthrit Res, Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Geriatr Med, Gothenburg, Sweden..
    Karlsson, Magnus K.
    Lund Univ, Dept Clin Sci, Clin & Mol Osteoporosis Res Unit, Malmo, Sweden.;Malmo Univ, Dept Orthopaed, Malmo, Sweden..
    Mellström, Dan
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Ctr Bone & Arthrit Res, Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Geriatr Med, Gothenburg, Sweden..
    Kwok, Anthony
    Chinese Univ Hong Kong, Dept Orthopaed & Traumatol, Hong Kong, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Jockey Club Ctr Osteoporosis Care & Control, Hong Kong, Hong Kong, Peoples R China..
    Khosla, Sundeep
    Mayo Clin, Div Endocrinol, Rochester, MN USA..
    Kwok, Timothy
    Chinese Univ Hong Kong, Jockey Club Ctr Osteoporosis Care & Control, Hong Kong, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China..
    Ohlsson, Claes
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Ctr Bone & Arthrit Res, Gothenburg, Sweden..
    The Limited Clinical Utility of Testosterone, Estradiol, and Sex Hormone Binding Globulin Measurements in the Prediction of Fracture Risk and Bone Loss in Older Men2017In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 32, no 3, p. 633-640Article in journal (Refereed)
    Abstract [en]

    Measurement of serum testosterone (T) levels is recommended in the evaluation of osteoporosis in older men and estradiol (E2) and sex hormone binding globulin (SHBG) levels are associated with the rate of bone loss and fractures, but the clinical utility of sex steroid and SHBG measurements for the evaluation of osteoporosis in men has not been examined. To evaluate whether measurements of T, E2, and/or SHBG are useful for the prediction of fracture risk or the rate of bone loss in older men, we analyzed longitudinal data from 5487 community-based men participating in the Osteoporotic Fractures in Men (MrOS) study in the United States, Sweden, and Hong Kong. Serum T, E2, and SHBG levels were assessed at baseline; incident fractures were self-reported at 4-month intervals with radiographic verification (US), or ascertained via national health records (Sweden, Hong Kong). Rate of bone loss was assessed by serial measures of hip bone mineral density (BMD). We used receiver operating characteristic (ROC) curves, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) to assess improvement in prediction. Mean age at baseline was 72 to 75 years and the prevalence of low T levels (<300 ng/dL) was 7.6% to 21.3% in the three cohorts. There were 619 incident major osteoporotic and 266 hip fractures during follow-up of approximately 10 years. Based on ROC curves, there were no improvements in fracture risk discrimination for any biochemical measure when added to models, including the Fracture Risk Assessment Tool (FRAX) with BMD. Although minor improvements in NRI were observed for the dichotomous parameters low bioavailable E2 (BioE2) (<11.4 pg/mL) and high SHBG(>59.1 nM), neither sex steroids nor SHBG provided clinically useful improvement in fracture risk discrimination. Similarly, they did not contribute to the prediction of BMD change. In conclusion, there is limited clinical utility of serum E2, T, and SHBG measures for the evaluation of osteoporosis risk in elderly men.

  • 69.
    Ragnarsson, Oskar
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med & Clin Nutr, Grona Straket 8, S-41345 Gothenburg, Sweden;Sahlgrens Univ Hosp, Dept Endocrinol, Grona Straket 8, S-41345 Gothenburg, Sweden.
    Olsson, Daniel S.
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med & Clin Nutr, Grona Straket 8, S-41345 Gothenburg, Sweden;Sahlgrens Univ Hosp, Dept Endocrinol, Grona Straket 8, S-41345 Gothenburg, Sweden.
    Chantzichristos, Dimitrios
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med & Clin Nutr, Grona Straket 8, S-41345 Gothenburg, Sweden;Sahlgrens Univ Hosp, Dept Endocrinol, Grona Straket 8, S-41345 Gothenburg, Sweden.
    Papakokkinou, Eleni
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med & Clin Nutr, Grona Straket 8, S-41345 Gothenburg, Sweden;Sahlgrens Univ Hosp, Dept Endocrinol, Grona Straket 8, S-41345 Gothenburg, Sweden.
    Dahlqvist, Per
    Umea Univ, Dept Med, S-90187 Umea, Sweden.
    Segerstedt, Elin
    Umea Univ, Dept Med, S-90187 Umea, Sweden.
    Olsson, Tommy
    Umea Univ, Dept Med, S-90187 Umea, Sweden.
    Petersson, Maria
    Karolinska Univ Hosp, Patient Area Endocrinol & Nephrol, Inflammat & Infect Theme, S-17176 Solna, Sweden;Karolinska Inst, Dept Mol Med & Surg, S-17177 Stockholm, Sweden.
    Berinder, Katarina
    Karolinska Univ Hosp, Patient Area Endocrinol & Nephrol, Inflammat & Infect Theme, S-17176 Solna, Sweden;Karolinska Inst, Dept Mol Med & Surg, S-17177 Stockholm, Sweden.
    Bensing, Sophie
    Karolinska Univ Hosp, Patient Area Endocrinol & Nephrol, Inflammat & Infect Theme, S-17176 Solna, Sweden;Karolinska Inst, Dept Mol Med & Surg, S-17177 Stockholm, Sweden.
    Höybye, Charlotte
    Karolinska Univ Hosp, Patient Area Endocrinol & Nephrol, Inflammat & Infect Theme, S-17176 Solna, Sweden;Karolinska Inst, Dept Mol Med & Surg, S-17177 Stockholm, Sweden.
    Engström, Britt E
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Burman, Pia
    Skane Univ Hosp, Dept Endocrinol, S-21428 Malmo, Sweden;Lund Univ, S-22350 Lund, Sweden.
    Bonelli, Lorenza
    Skane Univ Hosp, Dept Endocrinol, S-21428 Malmo, Sweden;Lund Univ, S-22350 Lund, Sweden.
    Follin, Cecilia
    Skane Univ Hosp, Dept Endocrinol, S-22242 Lund, Sweden.
    Petranek, David
    Skane Univ Hosp, Dept Endocrinol, S-22242 Lund, Sweden.
    Erfurth, Eva Marie
    Skane Univ Hosp, Dept Endocrinol, S-22242 Lund, Sweden.
    Wahlberg, Jeanette
    Linkoping Univ, Dept Endocrinol, Dept Med & Hlth Sci, S-58183 Linkoping, Sweden.
    Ekman, Bertil
    Linkoping Univ, Dept Endocrinol, Dept Med & Hlth Sci, S-58183 Linkoping, Sweden.
    Åkerman, Anna-Karin
    Orebro Univ, Sch Med Sci, Dept Internal Med, S-70281 Orebro, Sweden.
    Schwarcz, Erik
    Orebro Univ, Sch Med Sci, Dept Internal Med, S-70281 Orebro, Sweden.
    Bryngelsson, Ing-Liss
    Orebro Univ Hosp, Dept Occupat & Environm Med, S-70281 Orebro, Sweden.
    Johannsson, Gudmundur
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med & Clin Nutr, Grona Straket 8, S-41345 Gothenburg, Sweden;Sahlgrens Univ Hosp, Dept Endocrinol, Grona Straket 8, S-41345 Gothenburg, Sweden.
    The incidence of Cushing's disease: a nationwide Swedish study2019In: Pituitary, ISSN 1386-341X, E-ISSN 1573-7403, Vol. 22, no 2, p. 179-186Article in journal (Refereed)
    Abstract [en]

    Background: Studies on the incidence of Cushing's disease (CD) are few and usually limited by a small number of patients. The aim of this study was to assess the annual incidence in a nationwide cohort of patients with presumed CD in Sweden.

    Methods: Patients registered with a diagnostic code for Cushing's syndrome (CS) or CD, between 1987 and 2013 were identified in the Swedish National Patient Registry. The CD diagnosis was validated by reviewing clinical, biochemical, imaging, and histopathological data.

    Results: Of 1317 patients identified, 534 (41%) had confirmed CD. One-hundred-and-fifty-six (12%) patients had other forms of CS, 41 (3%) had probable but unconfirmed CD, and 334 (25%) had diagnoses unrelated to CS. The mean (95% confidence interval) annual incidence between 1987 and 2013 of confirmed CD was 1.6 (1.4-1.8) cases per million. 1987-1995, 1996-2004, and 2005-2013, the mean annual incidence was 1.5 (1.1-1.8), 1.4 (1.0-1.7) and 2.0 (1.7-2.3) cases per million, respectively. During the last time period the incidence was higher than during the first and second time periods (P<0.05).

    Conclusion: The incidence of CD in Sweden (1.6 cases per million) is in agreement with most previous reports. A higher incidence between 2005 and 2013 compared to 1987-2004 was noticed. Whether this reflects a truly increased incidence of the disease, or simply an increased awareness, earlier recognition, and earlier diagnosis can, however, not be answered. This study also illustrates the importance of validation of the diagnosis of CD in epidemiological research.

  • 70.
    Ragnarsson, Oskar
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med & Clin Nutr, SE-41345 Gothenburg, Sweden;Sahlgrens Univ Hosp, Dept Endocrinol, SE-41345 Gothenburg, Sweden.
    Olsson, Daniel S.
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med & Clin Nutr, SE-41345 Gothenburg, Sweden;Sahlgrens Univ Hosp, Dept Endocrinol, SE-41345 Gothenburg, Sweden.
    Papakokkinou, Eleni
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med & Clin Nutr, SE-41345 Gothenburg, Sweden;Sahlgrens Univ Hosp, Dept Endocrinol, SE-41345 Gothenburg, Sweden.
    Chantzichristos, Dimitrios
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med & Clin Nutr, SE-41345 Gothenburg, Sweden;Sahlgrens Univ Hosp, Dept Endocrinol, SE-41345 Gothenburg, Sweden.
    Dahlqvist, Per
    Umea Univ, Dept Publ Hlth & Clin Med, SE-90187 Umea, Sweden.
    Segerstedt, Elin
    Umea Univ, Dept Publ Hlth & Clin Med, SE-90187 Umea, Sweden.
    Olsson, Tommy
    Umea Univ, Dept Publ Hlth & Clin Med, SE-90187 Umea, Sweden.
    Petersson, Maria
    Karolinska Inst, Dept Mol Med & Surg, SE-17176 Stockholm, Sweden;Karolinska Univ Hosp, Dept Endocrinol Metab & Diabetol, SE-17177 Stockholm, Sweden.
    Berinder, Katarina
    Karolinska Inst, Dept Mol Med & Surg, SE-17176 Stockholm, Sweden;Karolinska Univ Hosp, Dept Endocrinol Metab & Diabetol, SE-17177 Stockholm, Sweden.
    Bensing, Sophie
    Karolinska Inst, Dept Mol Med & Surg, SE-17176 Stockholm, Sweden;Karolinska Univ Hosp, Dept Endocrinol Metab & Diabetol, SE-17177 Stockholm, Sweden.
    Höybye, Charlotte
    Karolinska Inst, Dept Mol Med & Surg, SE-17176 Stockholm, Sweden;Karolinska Univ Hosp, Dept Endocrinol Metab & Diabetol, SE-17177 Stockholm, Sweden.
    Edén Engström, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Burman, Pia
    Lund Univ, Skane Univ Hosp, Dept Endocrinol, SE-21428 Malmo, Sweden.
    Bonelli, Lorenza
    Lund Univ, Skane Univ Hosp, Dept Endocrinol, SE-21428 Malmo, Sweden.
    Follin, Cecilia
    Skane Univ Hosp, Dept Endocrinol, SE-22242 Lund, Sweden.
    Petranek, David
    Skane Univ Hosp, Dept Endocrinol, SE-22242 Lund, Sweden.
    Erfurth, Eva Marie
    Skane Univ Hosp, Dept Endocrinol, SE-22242 Lund, Sweden.
    Wahlberg, Jeanette
    Linkoping Univ, Dept Endocrinol, SE-58183 Linkoping, Sweden;Linkoping Univ, Dept Med & Hlth Sci, SE-58183 Linkoping, Sweden.
    Ekman, Bertil
    Linkoping Univ, Dept Endocrinol, SE-58183 Linkoping, Sweden;Linkoping Univ, Dept Med & Hlth Sci, SE-58183 Linkoping, Sweden.
    Åkerman, Anna-Karin
    Orebro Univ, Sch Hlth & Med Sci, Dept Internal Med, SE-70281 Orebro, Sweden.
    Schwarcz, Erik
    Orebro Univ, Sch Hlth & Med Sci, Dept Internal Med, SE-70281 Orebro, Sweden.
    Bryngelsson, Ing-Liss
    Orebro Univ Hosp, Dept Occupat & Environm Med, SE-70281 Orebro, Sweden.
    Johannsson, Gudmundur
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med & Clin Nutr, SE-41345 Gothenburg, Sweden;Sahlgrens Univ Hosp, Dept Endocrinol, SE-41345 Gothenburg, Sweden.
    Overall and Disease-Specific Mortality in Patients With Cushing Disease: A Swedish Nationwide Study2019In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 104, no 6, p. 2375-2384Article in journal (Refereed)
    Abstract [en]

    Context: Whether patients with Cushing disease (CD) in remission have increased mortality is still debatable. Objective: To study overall and disease-specific mortality and predictive factors in an unselected nationwide cohort of patients with CD. Design, Patients, and Methods: A retrospective study of patients diagnosed with CD, identified in the Swedish National Patient Registry between 1987 and 2013. Medical records were systematically reviewed to verify the diagnosis. Standardized mortality ratios (SMRs) with 95% CIs were calculated and Cox regression models were used to identify predictors of mortality. Results: Of 502 identified patients with CD (n = 387 women; 77%), 419 (83%) were confirmed to be in remission. Mean age at diagnosis was 43 (SD, 16) years and median follow-up was 13 (interquartile range, 6 to 23) years. The observed number of deaths was 133 vs 54 expected, resulting in an overall SMR of 2.5 (95% CI, 2.1 to 2.9). The commonest cause of death was cardiovascular diseases (SMR, 3.3; 95% CI, 2.6 to 4.3). Excess mortality was also found associated with infections and suicide. For patients in remission, the SMR was 1.9 (95% CI, 1.5 to 2.3); bilateral adrenalectomy and glucocorticoid replacement therapy were independently associated with increased mortality, whereas GH replacement was associated with improved outcome. Conclusion: Findings from this large nationwide study indicate that patients with CD have excess mortality. The findings illustrate the importance of achieving remission and continued active surveillance, along with adequate hormone replacement and evaluation of cardiovascular risk and mental health.

  • 71.
    Ribom, Eva L.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Rehabilitation Medicine.
    Kindmark, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Hyperkyphosis and back pain are not associated with prevalent vertebral fractures in women with osteoporosis2015In: Physiotherapy Theory and Practice, ISSN 0959-3985, E-ISSN 1532-5040, Vol. 31, no 3, p. 182-185Article in journal (Refereed)
    Abstract [en]

    Vertebral fractures (VFs) are the clinical consequence of spinal osteoporosis and may be associated with back pain and aggravated kyphosis. However, the relative importance of VFs as an underlying cause of kyphosis and chronic back pain is not known. The aim of this study was to investigate the relationship between prevalent VFs and the size of kyphosis, and back pain in osteoporotic women. Thirty-six women, aged 74.6 +/- 8.3 years, were consecutively recruited from the osteoporosis unit at Uppsala University Hospital. The patients had 1-9 radiographic verified VFs. Tragus wall distance (TWD) and numeric rating scale were used to measure kyphosis and pain. All patients had a hyperkyphosis (TWD >= 10 cm). Notably, there were no associations between numbers or location of VFs versus size of kyphosis (rho = 0.15, p = 0.4; rho = -0.27, p = 0.12) or severity of back pain (rho = -0.08, p = 0.66; rho = 0.16, p = 0.35). Furthermore, no association was evident between kyphosis and back pain (rho = -0.02, p = 0.89). There was, however, an association between size of kyphosis and age (R = 0.44, p = 0.008). In conclusion, these data suggest that prevalent VFs are not significantly associated with kyphosis or chronic back pain, in patients with manifest spinal osteoporosis.

  • 72.
    Robinson-Cohen, Cassianne
    et al.
    Vanderbilt Univ, Med Ctr, Dept Med, Div Nephrol, Nashville, TN 37232 USA.
    Bartz, Traci M.
    Univ Washington, Cardiovasc Hlth Res Unit, Dept Biostat, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA.
    Lai, Dongbing
    Indiana Univ, Dept Med, Indianapolis, IN 46204 USA;Indiana Univ, Dept Mol Genet, Indianapolis, IN 46204 USA.
    Ikizler, T. Alp
    Vanderbilt Univ, Med Ctr, Dept Med, Div Nephrol, Nashville, TN 37232 USA.
    Peacock, Munro
    Imel, Erik A.
    Michos, Erin D.
    Johns Hopkins Sch Med, Div Cardiol, Baltimore, MD USA.
    Foroud, Tatiana M.
    Indiana Univ, Dept Med, Indianapolis, IN 46204 USA;Indiana Univ, Dept Mol Genet, Indianapolis, IN 46204 USA.
    Åkesson, Kristina
    Lund Univ, Dept Clin Sci Malmo, Clin & Mol Osteoporosis Res Unit, Malmo, Sweden;Skane Univ Hosp, Dept Orthopaed, Malmo, Sweden.
    Taylor, Kent D.
    Harbor Univ Calif, Los Angeles Med Ctr, Los Angeles Biomed Res Inst Harbor, Dept Pediat,Inst Translat Gen & Populat Sci, Torrance, CA USA.
    Malmgren, Linnea
    Lund Univ, Dept Clin Sci Malmo, Clin & Mol Osteoporosis Res Unit, Malmo, Sweden;Skane Univ Hosp, Dept Orthopaed, Malmo, Sweden.
    Matsushita, Kunihiro
    Johns Hopkins Sch Med, Div Cardiol, Baltimore, MD USA;Johns Hopkins Univ, Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA;Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
    Nethander, Maria
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Med,Bioinformat Core Facil, Gothenburg, Sweden.
    Eriksson, Joel
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Ctr Bone & Arthrit Res,Dept Internal Med & Clin N, Gothenburg, Sweden.
    Ohlsson, Claes
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Ctr Bone & Arthrit Res,Dept Internal Med & Clin N, Gothenburg, Sweden.
    Mellström, Daniel
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Ctr Bone & Arthrit Res,Dept Internal Med & Clin N, Gothenburg, Sweden.
    Wolf, Myles
    Duke Univ, Sch Med, Div Nephrol, Dept Med, Durham, NC USA;Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    McGuigan, Fiona
    Lund Univ, Dept Clin Sci Malmo, Clin & Mol Osteoporosis Res Unit, Malmo, Sweden;Skane Univ Hosp, Dept Orthopaed, Malmo, Sweden.
    Rotter, Jerome I.
    Harbor Univ Calif, Los Angeles Med Ctr, Los Angeles Biomed Res Inst Harbor, Dept Pediat,Inst Translat Gen & Populat Sci, Torrance, CA USA.
    Karlsson, Magnus
    Lund Univ, Dept Clin Sci Malmo, Clin & Mol Osteoporosis Res Unit, Malmo, Sweden;Skane Univ Hosp, Dept Orthopaed, Malmo, Sweden.
    Econs, Michael J.
    Indiana Univ, Dept Med, Indianapolis, IN 46204 USA;Indiana Univ, Dept Mol Genet, Indianapolis, IN 46204 USA.
    Ix, Joachim H.
    Univ Calif San Diego, Dept Med, Div Nephrol Hypertens, San Diego, CA 92103 USA;Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA USA.
    Lutsey, Pamela L.
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
    Psaty, Bruce M.
    Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Hlth Serv, Seattle, WA 98195 USA;Kaiser Permanente, Washington Hlth Res Inst, Seattle, WA USA.
    de Boer, Ian H.
    Univ Washington, Kidney Res Inst, Div Nephrol, Dept Med, Seattle, WA 98195 USA.
    Kestenbaum, Bryan R.
    Univ Washington, Kidney Res Inst, Div Nephrol, Dept Med, Seattle, WA 98195 USA.
    Genetic Variants Associated with Circulating Fibroblast Growth Factor 232018In: Journal of the American Society of Nephrology, ISSN 1046-6673, E-ISSN 1533-3450, Vol. 29, no 10, p. 2583-2592Article in journal (Refereed)
    Abstract [en]

    Background: Fibroblast growth factor 23 (FGF23), a bone-derived hormone that regulates phosphorus and vitamin D metabolism, contributes to the pathogenesis of mineral and bone disorders in CKD and is an emerging cardiovascular risk factor. Central elements of FGF23 regulation remain incompletely understood; genetic variation may help explain interindividual differences.

    Methods: We performed a meta-analysis of genome-wide association studies of circulating FGF23 concentrations among 16,624 participants of European ancestry from seven cohort studies, excluding participants with eGFR<30 ml/min per 1.73 m(2) to focus on FGF23 under normal conditions. We evaluated the association of single-nucleotide polymorphisms (SNPs) with natural log-transformed FGF23 concentration, adjusted for age, sex, study site, and principal components of ancestry. A second model additionally adjusted for BMI and eGFR.

    Results: We discovered 154 SNPs from five independent regions associated with FGF23 concentration. The SNP with the strongest association, rs17216707 (P=3.0x10(-24)), lies upstream of CYP24A1, which encodes the primary catabolic enzyme for 1,25-dihydroxyvitamin D and 25-hydroxyvitamin D. Each additional copy of the T allele at this locus is associated with 5% higher FGF23 concentration. Another locus strongly associated with variations in FGF23 concentration is rs11741640, within RGS14 and upstream of SLC34A1 (a gene involved in renal phosphate transport). Additional adjustment for BMI and eGFR did not materially alter the magnitude of these associations. Another top locus (within ABO, the ABO blood group transferase gene) was no longer statistically significant at the genome-wide level.

    Conclusions: Common genetic variants located near genes involved in vitamin D metabolism and renal phosphate transport are associated with differences in circulating FGF23 concentrations.

  • 73. Rosengren, Björn
    et al.
    Ribom, Eva L.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Nilsson, Jan-Åke
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Ohlsson, Claes
    Mellstrom, Dan
    Lorentzon, Mattias
    Mallmin, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Stefanick, Marcia L.
    Lapidus, Jodi
    Leung, Ping Chung
    Kwok, Anthony
    Barrett-Connor, Elizabeth
    Orwoll, Eric
    Karlsson, Magnus K.
    There is in elderly men a group difference between fallers and non-fallers in physical performance tests2011In: Age and Ageing, ISSN 0002-0729, E-ISSN 1468-2834, Vol. 40, no 6, p. 744-749Article in journal (Refereed)
  • 74.
    Spangeus, A.
    et al.
    Linkoping Univ Hosp, Linkoping, Sweden..
    Akesson, K.
    Lund Univ, Skane Univ Hosp, Malmo, Sweden..
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Banefelt, J.
    Quantify Res, Stockholm, Sweden..
    Karlsson, L.
    Quantify Res, Stockholm, Sweden..
    Ortsater, G.
    Quantify Res, Stockholm, Sweden..
    Libanati, C.
    UCB Pharma, Brussels, Belgium..
    Toth, E.
    UCB Pharma, Brussels, Belgium..
    Strom, O.
    Quantify Res, Stockholm, Sweden.;Karolinska Inst, Stockholm, Sweden..
    The Treatment Gap After Fracture In Osteoporosis Patients In Sweden2017In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, p. 72-72Article in journal (Other academic)
  • 75.
    Sten, Sabine
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of Archaeology and Ancient History, Archaeology.
    Lovén, Christian
    Riksarkivet,Box 12541, SE-10229 Stockholm, Sweden..
    Kjellström, Anna
    Stockholms Univ, Inst Arkeologi Antikens kultur, Osteologiska Skningslab, SE-10691 Stockholm, Sweden..
    Liden, Kerstin
    Stockholms Univ, Inst Arkeologi Antikens kultur, Arkeologiska Skningslabo, SE-10691 Stockholm, Sweden..
    Vretemark, Maria
    Västergotlands Museum, SE-53232 Skara, Sweden..
    Hongslo Vala, Cecilie
    Univ Goteborgs, Enheten Geriatrik Inst Medicin, Sahlgrenska Akademin, SE-40530 Gothenburg, Sweden..
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Fjällstrom, Markus
    Uppsala Univ, Arkeol Forskningslab, SE-75185 Uppsala, Sweden..
    Shalabi, Adel
    Bild­ och funktionsmedicinskt centrum, Akademiska sjukhuset, Uppsala, Sweden..
    Duvernoy, Olov
    Bild­ och funktionsmedicinskt centrum, Akademiska sjukhuset, Uppsala, Sweden..
    Segelsjö, Monica
    Bild­ och funktionsmedicinskt centrum, Akademiska sjukhuset, Uppsala, Sweden..
    Malmström, Helena
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Jakobsson, Mattias
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Erik den heliges skelett2016In: Fornvännen, ISSN 0015-7813, E-ISSN 1404-9430, Vol. 111, no 1, p. 27-40Article in journal (Refereed)
    Abstract [en]

    Saint Erik was King of Sweden for a few years up to 1160, when he was killed. A skeleton attributed to him is kept in Uppsala Cathedral. It underwent scientific reappraisal in 2014. The analyses included computer tomography, Xray absorptiometry, isotope analysis and DNA sampling. Radiocarbon confirms the alleged age of the bones. They belong to a 35-40-year-old man in excellent physical shape. The many wounds that he received in connection with his death fit surprisingly well with the saint's legend, whose preserved version was written 130 years after the event.

  • 76.
    Sundh, D.
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med & Clin Nutr, Geriatr Med, Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Ctr Bone & Arthrit Res, Inst Med, Gothenburg, Sweden..
    Mellstrom, D.
    Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med & Clin Nutr, Geriatr Med, Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Ctr Bone & Arthrit Res, Inst Med, Gothenburg, Sweden..
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Karlsson, M. K.
    Lund Univ, Dept Clin Sci, Clin & Mol Osteoporosis Res Unit, Lund, Sweden.;Skane Univ Hosp, Dept Orthopaed, Malmo, Sweden..
    Ohlsson, C.
    Univ Gothenburg, Sahlgrenska Acad, Ctr Bone & Arthrit Res, Inst Med, Gothenburg, Sweden..
    Nilsson, M.
    Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med & Clin Nutr, Geriatr Med, Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Ctr Bone & Arthrit Res, Inst Med, Gothenburg, Sweden..
    Nilsson, A. G.
    Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med & Clin Nutr, Geriatr Med, Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Ctr Bone & Arthrit Res, Inst Med, Gothenburg, Sweden..
    Lorentzon, M.
    Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med & Clin Nutr, Geriatr Med, Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Ctr Bone & Arthrit Res, Inst Med, Gothenburg, Sweden..
    Low serum vitamin D is associated with higher cortical porosity in elderly men2016In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 280, no 5, p. 496-508Article in journal (Refereed)
    Abstract [en]

    BackgroundBone loss at peripheral sites in the elderly is mainly cortical and involves increased cortical porosity. However, an association between bone loss at these sites and 25-hydroxyvitamin D has not been reported. ObjectiveTo investigate the association between serum levels of 25-hydroxyvitamin D, bone microstructure and areal bone mineral density (BMD) in elderly men. MethodsA population-based cohort of 444 elderly men (mean SD age 80.2 3.5 years) was investigated. Bone microstructure was measured by high-resolution peripheral quantitative computed tomography, areal BMD by dual-energy X-ray absorptiometry and serum 25-hydroxyvitamin D and parathyroid hormone levels by immunoassay. ResultsMean cortical porosity at the distal tibia was 14.7% higher (12.5 +/- 4.3% vs. 10.9 +/- 4.1%, P < 0.05) whilst cortical volumetric BMD, area, trabecular bone volume fraction and femoral neck areal BMD were lower in men in the lowest quartile of vitamin D levels compared to the highest. In men with vitamin D deficiency (<25 nmol L-1) or insufficiency [25-49 nmol L-1, in combination with an elevated serum level of parathyroid hormone (>6.8 pmol L-1)], cortical porosity was 17.2% higher than in vitamin D-sufficient men (P < 0.01). A linear regression model including age, weight, height, daily calcium intake, physical activity, smoking vitamin D supplementation and parathyroid hormone showed that 25-hydroxyvitamin D independently predicted cortical porosity (standardized = -0.110, R-2 = 1.1%, P = 0.024), area ( = 0.123, R-2 = 1.4%, P = 0.007) and cortical volumetric BMD ( = 0.125, R-2 = 1.4%, P = 0.007) of the tibia as well as areal BMD of the femoral neck ( = 0.102, R-2 = 0.9%, P = 0.04). ConclusionSerum vitamin D is associated with cortical porosity, area and density, indicating that bone fragility as a result of low vitamin D could be due to changes in cortical bone microstructure and geometry.

  • 77. Svensson, Johan
    et al.
    Karlsson, Magnus K.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Tivesten, Asa
    Mellstrom, Dan
    Moverare-Skrtic, Sofia
    Leukocyte telomere length is not associated with mortality in older men2014In: Experimental Gerontology, ISSN 0531-5565, E-ISSN 1873-6815, Vol. 57, p. 6-12Article in journal (Refereed)
    Abstract [en]

    Leukocyte telomere length (LTL) is related to the aging of somatic cells. We hypothesized that LTL is inversely associated with mortality in elderly men. LTL was measured in 2744 elderly men (mean age 75.5, range 69-81 years) included in the prospective population-based MrOS-Sweden study. Mortality data were obtained from national health registers with no loss of follow-up. During the follow-up (mean 6.0 years), 556 (20%) of the participants died. Using Cox proportional hazards regression, tertile of LTL did not associate with all-cause mortality [tertile 1 (shortest) or 2 (middle) vs. tertile 3 (longest); hazard ratio (HR) = 1.05, 95% confidence interval (CI) 0.85-1.28 and HR = 0.97, 95% CI 0.79-1.19, respectively]. Furthermore, LTL did not associate with cancer (197 events) or cardiovascular disease (CVD, 206 events) mortality (tertile 1 vs. tertile 3; HR = 0.94, 95% CI 0.67-1.34 and HR = 0.94, 95% CI 0.68-1.30, respectively). The lack of association between LTL and mortality remained also after adjustment for multiple covariates. Our results demonstrate that LTL is not associated with all-cause mortality or mortality due to cancer or CVD in elderly men. Further studies are needed to determine whether LTL can predict the risk of mortality in elderly women.  

  • 78. Tivesten, Asa
    et al.
    Vandenput, Liesbeth
    Carlzon, Daniel
    Nilsson, Maria
    Karlsson, Magnus K.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Barrett-Connor, Elizabeth
    Mellstrom, Dan
    Ohlsson, Claes
    Dehydroepiandrosterone and its Sulfate Predict the 5-Year Risk of Coronary Heart Disease Events in Elderly Men2014In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 64, no 17, p. 1801-1810Article in journal (Refereed)
    Abstract [en]

    BACKGROUND The adrenal sex hormone dehydroepiandrosterone (DHEA), which is present in serum mainly as the sulfate DHEA-S, is the most abundant steroid hormone in human blood. Its levels decline dramatically with age. Despite the great amount of literature on vascular and metabolic actions of DHEA/-S, evidence for an association between DHEA/-S levels and cardiovascular events is contradictory. OBJECTIVES This study tested the hypothesis that serum DHEA and DHEA-S are predictors of major coronary heart disease (CHD) and/or cerebrovascular disease (CBD) events in a large cohort of elderly men. METHODS We used gas and liquid chromatography-mass spectrometry to analyze baseline levels of DHEA and DHEA-S in the prospective population-based Osteoporotic Fractures in Men study in Sweden (2,416 men, ages 69 to 81 years). Complete cardiovascular clinical outcomes were available from national Swedish registers. RESULTS During the 5-year follow-up, 302 participants experienced a CHD event, and 225 had a CBD event. Both DHEA and DHEA-S levels were inversely associated with the age-adjusted risk of a CHD event; the hazard ratios and 95% confidence intervals per SD increase were 0.82 (0.73 to 0.93) and 0.86 (0.77 to 0.97), respectively. In contrast, DHEA/-S showed no statistically significant association with the risk of CBD events. The association between DHEA and CHD risk remained significant after adjustment for traditional cardiovascular risk factors, serum total testosterone and estradiol, C-reactive protein, and renal function, and remained unchanged after exclusion of the first 2.6 years of follow-up to reduce reverse causality. CONCLUSIONS Low serum levels of DHEA and its sulfate predict an increased risk of CHD, but not CBD, events in elderly men.

  • 79.
    Törring, Ove
    et al.
    Karolinska Inst, Dept Clin Sci & Educ, Stockholm, Sweden; Söderdsjukhuset, Dept Internal Med, Div Endocrinol, Stockholm, Sweden.
    Watt, Torquil
    Rigshosp, Dept Med Endocrinol, Copenhagen, Denmark; Copenhagen Univ Hosp, Internal Med Herlev Gentofte Hosp, Copenhagen, Denmark.
    Sjölin, Gabriel
    Örebro Univ, Fac Med & Hlth, Dept Surg, Örebro, Sweden.
    Byström, Kristina
    Univ Hosp, Dept Med, Örebro, Sweden; Örebro Univ, Örebro, Sweden.
    Abraham-Nordling, Mirna
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    Calissendorff, Jan
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden; Karolinska Univ Hosp, Dept Endocrinol Metab & Diabet, Stockholm, Sweden.
    Cramon, Per Karkov
    Rigshosp, Dept Med Endocrinol, Copenhagen, Denmark; Copenhagen Univ Hosp, Internal Med Herlev Gentofte Hosp, Copenhagen, Denmark.
    Nystrom, Helena Filipsson
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Gothenburg, Sweden; Sahlgrens Univ Hosp, Dept Endocrinol, Gothenburg, Sweden.
    Hallengren, Bengt
    Skåne Univ Hosp, Dept Endocrinol, Malmö, Sweden; Lund Univ, Dept Clin Sci, Malmö, Sweden.
    Holmberg, Mats
    Karolinska Univ Hosp, ANOVA, Stockholm, Sweden; Univ Gothenburg, Sahlgrenska Acad, Inst Med, Gothenburg, Sweden.
    Khamisi, Selwan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism. Uppsala Univ, Inst Internal Med, Uppsala, Sweden.
    Lantz, Mikael
    Skåne Univ Hosp, Dept Endocrinol, Malmö, Sweden; Lund Univ, Dept Clin Sci, Malmö, Sweden.
    Wallin, Goran
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden; Örebro Univ, Fac Med & Hlth, Dept Surg, Örebro, Sweden.
    Impaired Quality of Life After Radioiodine Therapy Compared to Antithyroid Drugs or Surgical Treatment for Graves' Hyperthyroidism: A Long-Term Follow-Up with the Thyroid-Related Patient-Reported Outcome Questionnaire and 36-Item Short Form Health Status Survey2019In: Thyroid, ISSN 1050-7256, E-ISSN 1557-9077, Vol. 29, no 3, p. 322-331Article in journal (Refereed)
    Abstract [en]

    Background: Hyperthyroidism is known to have a significant impact on quality of life (QoL), at least in the short term. The purpose of the present study was to assess QoL in patients 6–10 years after treatment for Graves' disease (GD) with radioiodine (RAI) compared to those treated with thyroidectomy or antithyroid drugs (ATD) as assessed with both thyroid-specific Thyroid-Related Patient-Reported Outcome (ThyPRO) questionnaire and general (36-item Short Form Health Status) QoL survey.

    Methods: The study evaluated 1186 GD patients in a sub-cohort from an incidence study 2003–2005 who had been treated according to routine clinical practice at seven participating centers. Patients were included if they had returned the ThyPRO (n = 975) and/or the 36-item Short Form Health Status survey questionnaire (n = 964) and informed consent at follow-up. Scores from ThyPRO were compared to scores from a general population sample (n = 712) using multiple linear regression adjusting for age and sex as well as multiple testing. Treatment-related QoL outcome for ATD, RAI, and surgery were compared, including adjustment for the number of treatments received, sex, age, and comorbidity.

    Results: Regardless of treatment modality, patients with GD had worse thyroid-related QoL 6–10 years after diagnosis compared to the general population. Patients treated with RAI had worse thyroid-related and general QoL than patients treated with ATD or thyroidectomy on the majority of QoL scales. Sensitivity analyses supported the relative negative comparative effects of RAI treatment on QoL in patients with hyperthyroidism.

    Conclusions: GD is associated with a lower QoL many years after treatment compared to the general population. In a previous small randomized controlled trial, no difference was found in patient satisfaction years after ATD, RAI, or surgery. Now, it is reported that in a large non-randomized cohort, patients who received RAI had adverse scores on ThyPRO and 36-item Short Form Health Status survey. These findings in a Swedish population are limited by comparison to normative data from Denmark, older age, and possibly a more prolonged course in those patients who received RAI, and a lack of information regarding thyroid status at the time of evaluation. The way RAI may adversely affect QoL is unknown, but since the results may be important for future considerations regarding treatment options for GD, they need to be substantiated in further studies.

  • 80.
    Vandenput, Liesbeth
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med & Clin Nutr, Ctr Bone & Arthrit Res,Inst Med, Vita Straket 11, SE-41345 Gothenburg, Sweden..
    Mellstrom, Dan
    Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med & Clin Nutr, Ctr Bone & Arthrit Res,Inst Med, Vita Straket 11, SE-41345 Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Med, Geriatr Med, Gothenburg, Sweden..
    Laughlin, Gail A.
    Univ Calif San Diego, Sch Med, Dept Family Med & Publ Hlth, Div Epidemiol, La Jolla, CA 92093 USA..
    Cawthon, Peggy M.
    Univ Calif San Francisco, Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94143 USA.;Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA..
    Cauley, Jane A.
    Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA..
    Hoffman, Andrew R.
    Stanford Univ, Dept Med, Stanford, CA 94305 USA..
    Karlsson, Magnus K.
    Lund Univ, Dept Clin Sci, Clin & Mol Osteoporosis Res Unit, Lund, Sweden.;Skane Univ Hosp, Dept Orthopaed, Malmo, Sweden..
    Rosengren, Bjorn E.
    Lund Univ, Dept Clin Sci, Clin & Mol Osteoporosis Res Unit, Lund, Sweden.;Skane Univ Hosp, Dept Orthopaed, Malmo, Sweden..
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Nethander, Maria
    Univ Gothenburg, Sahlgrenska Acad, Bioinformat Core Facil, Gothenburg, Sweden..
    Eriksson, Anna L.
    Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med & Clin Nutr, Ctr Bone & Arthrit Res,Inst Med, Vita Straket 11, SE-41345 Gothenburg, Sweden..
    Lorentzon, Mattias
    Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med & Clin Nutr, Ctr Bone & Arthrit Res,Inst Med, Vita Straket 11, SE-41345 Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Med, Geriatr Med, Gothenburg, Sweden..
    Leung, Jason
    Chinese Univ Hong Kong, Prince Wales Hosp, Jockey Club Ctr Osteoporosis Care & Control, Shatin, Hong Kong, Peoples R China..
    Kwok, Timothy
    Chinese Univ Hong Kong, Prince Wales Hosp, Jockey Club Ctr Osteoporosis Care & Control, Shatin, Hong Kong, Peoples R China..
    Orwoll, Eric S.
    Oregon Hlth & Sci Univ, Dept Med, Bone & Mineral Unit, Portland, OR 97201 USA..
    Ohlsson, Claes
    Univ Gothenburg, Sahlgrenska Acad, Dept Internal Med & Clin Nutr, Ctr Bone & Arthrit Res,Inst Med, Vita Straket 11, SE-41345 Gothenburg, Sweden..
    Low Testosterone, but Not Estradiol, Is Associated With Incident Falls in Older Men: The International MrOS Study2017In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 32, no 6, p. 1174-1181Article in journal (Refereed)
    Abstract [en]

    Fracture risk is determined by bone strength and the risk of falls. The relationship between serum sex steroids and bone strength parameters in men is well known, whereas the predictive value of sex steroids for falls is less studied. The aim of this study was to assess the associations between serum testosterone (T) and estradiol (E2) and the likelihood of falls. Older men (aged > 65 years) from the United States (n = 1919), Sweden (n = 2495), and Hong Kong (n = 1469) participating in the Osteoporotic Fractures in Men Study had baseline T and E2 analyzed by mass spectrometry. Bioavailable (Bio) levels were calculated using mass action equations. Incident falls were ascertained every 4 months during a mean follow-up of 5.7 years. Associations between sex steroids and falls were estimated by generalized estimating equations. Fall rate was highest in the US and lowest in Hong Kong (US 0.50, Sweden 0.31, Hong Kong 0.12 fall reports/person/year). In the combined cohort of 5883 men, total T (odds ratio [OR] per SD increase = 0.88, 95% confidence interval [CI] 0.86-0.91) and BioT (OR = 0.86, 95% CI 0.83-0.88) were associated with incident falls in models adjusted for age and prevalent falls. These associations were only slightly attenuated after simultaneous adjustment for physical performance variables (total T: OR = 0.94, 95% CI 0.91-0.96; BioT: OR = 0.91, 95% CI 0.89-0.94). E2, BioE2, and sex hormone-binding globulin (SHBG) were not significantly associated with falls. Analyses in the individual cohorts showed that both total T and BioT were associated with falls in MrOS US and Sweden. No association was found in MrOS Hong Kong, and this may be attributable to environmental factors rather than ethnic differences because total T and BioT predicted falls in MrOS US Asians. In conclusion, low total T and BioT levels, but not E2 or SHBG, are associated with increased falls in older men.

  • 81. Vandenput, Liesbeth
    et al.
    Mellström, Dan
    Kindmark, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Johansson, Helena
    Lorentzon, Mattias
    Leung, Jason
    Redlund-Johnell, Inga
    Rosengren, Björn E
    Karlsson, Magnus K
    Wang, Yi-Xiang
    Kwok, Timothy
    Ohlsson, Claes
    High Serum SHBG Predicts Incident Vertebral Fractures in Elderly Men.2016In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 31, no 3, p. 683-689Article in journal (Refereed)
    Abstract [en]

    Previous prospective cohort studies have shown that serum levels of sex steroids and sex hormone-binding globulin (SHBG) associate with non-vertebral fracture risk in men. The predictive value of sex hormones and SHBG for vertebral fracture risk specifically is, however, less studied. Elderly men (aged ≥65 years) from Sweden and Hong Kong participating in the MrOS study had baseline estradiol and testosterone analyzed by GC-MS and SHBG by IRMA. Incident clinical vertebral fractures (n = 242 cases) were evaluated in 4324 men during an average follow-up of 9.1 years. In a subsample of these men (n = 2256), spine X-rays were obtained at baseline and after an average follow-up of 4.3 years to identify incident radiographic vertebral fractures (n = 157 cases). The likelihood of incident clinical and radiographic vertebral fractures was estimated by Cox proportional hazards models and logistic regression models, respectively. Neither serum estradiol (HR per SD increase, 95% CI: 0.93, 0.80-1.08) nor testosterone (1.05, 0.91-1.21) predicted incident clinical vertebral fractures in age-adjusted models in the combined data set. High serum SHBG, however, associated with increased clinical vertebral fracture risk (1.24, 1.12-1.37). This association remained significant after further adjustment for FRAX with or without BMD. SHBG also associated with increased incident radiographic vertebral fracture risk (combined data set; OR per SD increase, 95% CI: 1.23, 1.05-1.44). This association remained significant after adjustment for FRAX with or without BMD. In conclusion, high SHBG predicts incident clinical and radiographic vertebral fractures in elderly men and adds moderate information beyond FRAX with BMD for vertebral fracture risk prediction.

  • 82. Vimaleswaran, Karani S
    et al.
    Cavadino, Alana
    Berry, Diane J
    Jorde, Rolf
    Dieffenbach, Aida Karina
    Lu, Chen
    Alves, Alexessander Couto
    Heerspink, Hiddo J Lambers
    Tikkanen, Emmi
    Eriksson, Joel
    Wong, Andrew
    Mangino, Massimo
    Jablonski, Kathleen A
    Nolte, Ilja M
    Houston, Denise K
    Ahluwalia, Tarunveer Singh
    van der Most, Peter J
    Pasko, Dorota
    Zgaga, Lina
    Thiering, Elisabeth
    Vitart, Veronique
    Fraser, Ross M
    Huffman, Jennifer E
    de Boer, Rudolf A
    Schöttker, Ben
    Saum, Kai-Uwe
    McCarthy, Mark I
    Dupuis, Josée
    Herzig, Karl-Heinz
    Sebert, Sylvain
    Pouta, Anneli
    Laitinen, Jaana
    Kleber, Marcus E
    Navis, Gerjan
    Lorentzon, Mattias
    Jameson, Karen
    Arden, Nigel
    Cooper, Jackie A
    Acharya, Jayshree
    Hardy, Rebecca
    Raitakari, Olli
    Ripatti, Samuli
    Billings, Liana K
    Lahti, Jari
    Osmond, Clive
    Penninx, Brenda W
    Rejnmark, Lars
    Lohman, Kurt K
    Paternoster, Lavinia
    Stolk, Ronald P
    Hernandez, Dena G
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mellström, Dan
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Tzoulaki, Ioanna
    McLachlan, Stela
    Theodoratou, Evropi
    Tiesler, Carla M T
    Jula, Antti
    Navarro, Pau
    Wright, Alan F
    Polasek, Ozren
    Wilson, James F
    Rudan, Igor
    Salomaa, Veikko
    Heinrich, Joachim
    Campbell, Harry
    Price, Jacqueline F
    Karlsson, Magnus
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Bandinelli, Stefania
    Frayling, Timothy M
    Hartman, Catharina A
    Sørensen, Thorkild I A
    Kritchevsky, Stephen B
    Langdahl, Bente Lomholt
    Eriksson, Johan G
    Florez, Jose C
    Spector, Tim D
    Lehtimäki, Terho
    Kuh, Diana
    Humphries, Steve E
    Cooper, Cyrus
    Ohlsson, Claes
    März, Winfried
    de Borst, Martin H
    Kumari, Meena
    Kivimaki, Mika
    Wang, Thomas J
    Power, Chris
    Brenner, Hermann
    Grimnes, Guri
    van der Harst, Pim
    Snieder, Harold
    Hingorani, Aroon D
    Pilz, Stefan
    Whittaker, John C
    Järvelin, Marjo-Riitta
    Hyppönen, Elina
    Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study2014In: The Lancet Diabetes and Endocrinology, ISSN 2213-8587, E-ISSN 2213-8595, Vol. 2, no 9, p. 719-729Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk.

    METHODS: In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium.

    FINDINGS: In phenotypic analyses (up to n=49 363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, -0·12 mm Hg, 95% CI -0·20 to -0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97-0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, -0·02 mm Hg, -0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of -0·10 mm Hg in systolic blood pressure (-0·21 to -0·0001; p=0·0498) and a change of -0·08 mm Hg in diastolic blood pressure (-0·15 to -0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96-0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of -0·29 mm Hg in diastolic blood pressure (-0·52 to -0·07; p=0·01), a change of -0·37 mm Hg in systolic blood pressure (-0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87-0·97; p=0·002).

    INTERPRETATION: Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.

  • 83.
    Vouzouneraki, Konstantina
    et al.
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
    Franklin, Karl A.
    Umea Univ, Dept Surg & Perioperat Sci, Umea, Sweden.
    Forsgren, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Warn, Maria
    Karolinska Inst, Dept Mol Med & Surg, Patient Area Endocrinol & Nephrol Inflammat & Inf, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden.
    Persson, Jenny Tiberg
    Univ Gothenburg, Dept Endocrinol, Inst Med, Sahlgrenska Acad, Gothenburg, Sweden;Sahlgrens Univ Hosp, Gothenburg, Sweden.
    Wik, Helena
    Univ Gothenburg, Dept Endocrinol, Inst Med, Sahlgrenska Acad, Gothenburg, Sweden;Sahlgrens Univ Hosp, Gothenburg, Sweden.
    Dahlgren, Christina
    Linkoping Univ, Dept Endocrinol, Dept Med & Hlth Sci, Dept Clin & Expt Med, Linkoping, Sweden.
    Nilsson, Ann-Sofie
    Lund Univ, Dept Clin Sci, Malmo, Sweden;Lund Univ, Dept Endocrinol, Malmo, Sweden;Skane Univ Hosp, Malmo, Sweden.
    Alkebro, Caroline
    Orebro Univ Hosp, Div Diabetol & Endocrinol, Dept Med, Orebro, Sweden.
    Burman, Pia
    Lund Univ, Dept Clin Sci, Malmo, Sweden;Lund Univ, Dept Endocrinol, Malmo, Sweden;Skane Univ Hosp, Malmo, Sweden.
    Erfurth, Eva-Marie
    Lund Univ, Dept Clin Sci, Malmo, Sweden;Lund Univ, Dept Endocrinol, Malmo, Sweden;Skane Univ Hosp, Malmo, Sweden.
    Wahlberg, Jeanette
    Linkoping Univ, Dept Endocrinol, Dept Med & Hlth Sci, Dept Clin & Expt Med, Linkoping, Sweden.
    Akerman, Anna-Karin
    Orebro Univ Hosp, Div Diabetol & Endocrinol, Dept Med, Orebro, Sweden.
    Hoybye, Charlotte
    Karolinska Inst, Dept Mol Med & Surg, Patient Area Endocrinol & Nephrol Inflammat & Inf, Stockholm, Sweden;Karolinska Univ Hosp, Stockholm, Sweden.
    Ragnarsson, Oskar
    Univ Gothenburg, Dept Endocrinol, Inst Med, Sahlgrenska Acad, Gothenburg, Sweden;Sahlgrens Univ Hosp, Gothenburg, Sweden.
    Edén Engström, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Dahlqvist, Per
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
    Temporal relationship of sleep apnea and acromegaly: a nationwide study2018In: Endocrine (Basingstoke), ISSN 1355-008X, E-ISSN 1559-0100, Vol. 62, no 2, p. 456-463Article in journal (Refereed)
    Abstract [en]

    Purpose: Patients with acromegaly have an increased risk of sleep apnea, but reported prevalence rates vary largely. Here we aimed to evaluate the sleep apnea prevalence in a large national cohort of patients with acromegaly, to examine possible risk factors, and to assess the proportion of patients diagnosed with sleep apnea prior to acromegaly diagnosis.

    Methods: Cross-sectional multicenter study of 259 Swedish patients with acromegaly. At patients' follow-up visits at the endocrine outpatient clinics of all seven university hospitals in Sweden, questionnaires were completed to assess previous sleep apnea diagnosis and treatment, cardiovascular diseases, smoking habits, anthropometric data, and S-IGF-1 levels. Daytime sleepiness was evaluated using the Epworth Sleepiness Scale. Patients suspected to have undiagnosed sleep apnea were referred for sleep apnea inves