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  1. Article ; Online: Comparison Between Thyroid Stimulating Immunoglobulin and TSH-Receptor Antibodies in the Management of Graves' Orbitopathy.

    Khamisi, Selwan / Lundqvist, Martin / Engström, Britt Edén / Larsson, Anders / Karlsson, F Anders / Ljunggren, Östen

    Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association

    2023  Volume 131, Issue 4, Page(s) 236–241

    Abstract: Objectives: TSH-receptor antibodies (TRAb) targeting the TSH receptor (TSH-R) induce hyperthyroidism in Graves´ disease (GD). Graves´ orbitopathy (GO) is influenced by stimulation of the TSH-R in the orbita. GO has been, among other factors, linked to ... ...

    Abstract Objectives: TSH-receptor antibodies (TRAb) targeting the TSH receptor (TSH-R) induce hyperthyroidism in Graves´ disease (GD). Graves´ orbitopathy (GO) is influenced by stimulation of the TSH-R in the orbita. GO has been, among other factors, linked to high TRAb levels. Thyroid stimulating immunoglobulins (TSI) is a relatively new method for assessing TSH-receptor antibodies. The aim of this study was to investigate the role of TSI in the management of GO.
    Methods: Patients with newly diagnosed GD (n=30, median age 55 years (range 35-72), 29 women) received pharmacological therapy (methimazole+++thyroxine) for up to 24 months. GO was identified by clinical signs and symptoms. Eleven patients had GO at diagnosis, and another six developed GO during treatment. Blood samples for TSI and other thyroidal biomarkers were obtained at baseline and on five occasions during the 24-month follow-up. Twenty-two subjects completed the drug regimen without surgery or radioiodine treatment.
    Results: At baseline, TSI was highly correlated with TRAb (
    Conclusion: The present study does not support any added benefit of TSI compared to TRAb for the prediction and management of GO.
    MeSH term(s) Humans ; Female ; Adult ; Middle Aged ; Aged ; Graves Ophthalmopathy/drug therapy ; Receptors, Thyrotropin ; Iodine Radioisotopes/therapeutic use ; Immunoglobulins, Thyroid-Stimulating ; Graves Disease/drug therapy ; Thyrotropin ; Autoantibodies
    Chemical Substances Receptors, Thyrotropin ; Iodine Radioisotopes ; Immunoglobulins, Thyroid-Stimulating ; Thyrotropin (9002-71-5) ; Autoantibodies
    Language English
    Publishing date 2023-01-27
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 1225416-2
    ISSN 1439-3646 ; 0947-7349
    ISSN (online) 1439-3646
    ISSN 0947-7349
    DOI 10.1055/a-2021-0596
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  2. Article ; Online: Increased plasma levels of soluble programmed death ligand 1 (sPD-L1) and fibroblast growth factor 23 (FGF-23) in patients with Graves' ophthalmopathy in comparison to hyperthyroid patients without Graves' ophthalmopathy.

    Khamisi, Selwan / Anders Karlsson, F / Ljunggren, Östen / Thulin, Mans / Larsson, Anders

    Cytokine

    2023  Volume 169, Page(s) 156269

    Abstract: Background: Management of Graves' ophthalmopathy (GO) is still a challenge in Graves' disease (GD). Moreover, 40% of GD patients show radiological muscle enlargement without clinically apparent GO. Delayed treatment of GO may lead to deterioration in ... ...

    Abstract Background: Management of Graves' ophthalmopathy (GO) is still a challenge in Graves' disease (GD). Moreover, 40% of GD patients show radiological muscle enlargement without clinically apparent GO. Delayed treatment of GO may lead to deterioration in prognosis.
    Methods: Thirty GD patients with overt hyperthyroidism were included in this study, 17 of whom either had GO at diagnosis or developed GO during the study period. Samples were collected at the beginning of the study, at 6 months, and at 24 months. Plasma samples were analyzed for 92 cytokines using the Olink Target 96 inflammation panel.
    Results: After adjustment for multiplicity testing using the false discovery rate approach, soluble programmed death ligand 1 (sPD-L1) and fibroblast growth factor 23 (FGF-23) were significantly elevated in GO patients.
    Conclusion: Using a broad cytokine panel we show that patients with Graves' ophthalmopathy have elevated PD-L1 and FGF-23 levels. The findings support previous suggestions that PD-L1 may serve as a treatment target.
    MeSH term(s) Humans ; B7-H1 Antigen ; Fibroblast Growth Factor-23 ; Graves Ophthalmopathy ; Hyperthyroidism ; Graves Disease
    Chemical Substances CD274 protein, human ; B7-H1 Antigen ; Fibroblast Growth Factor-23 (7Q7P4S7RRE)
    Language English
    Publishing date 2023-06-10
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1018055-2
    ISSN 1096-0023 ; 1043-4666
    ISSN (online) 1096-0023
    ISSN 1043-4666
    DOI 10.1016/j.cyto.2023.156269
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  3. Article ; Online: Complications and adverse effects related to surgical and medical treatment in patients with inflammatory bowel disease in a prospectively recruited population-based cohort.

    Rönnblom, Anders / Ljunggren, Östen / Karlbom, Urban

    Scandinavian journal of gastroenterology

    2021  Volume 56, Issue 11, Page(s) 1296–1303

    Abstract: Background: Medical adverse effects and surgical complications have been reported during treatment of patients with inflammatory bowel diseases (IBDs). There is however a shortage of studies describing these in the same cohort of patients.: Aim: To ... ...

    Abstract Background: Medical adverse effects and surgical complications have been reported during treatment of patients with inflammatory bowel diseases (IBDs). There is however a shortage of studies describing these in the same cohort of patients.
    Aim: To describe medical adverse effects and surgical complications in a prospectively followed population-based cohort of patients followed for at least 10 years.
    Methods: All newly diagnosed patients with ulcerative colitis (UC) and Crohn's disease (CD) in the county of Uppsala between 2005 and 2009 were prospectively followed. At the end of 2019, the medical notes were scrutinised and all medical adverse effects and postoperative surgical complications were registered.
    Results: A total of 330 patients with UC and 153 patients with CD in all age groups were included in the cohort. Four hundred and forty-two of these (91.5%) could be followed for 10 years or until death. One hundred and twenty-two patients (26.9%) experienced one or more adverse effects during the pharmacological treatment, and 25 of these could be classified as serious. Fifty-seven malignancies were diagnosed during the observation time. Surgery was performed in 16/330 UC and 33/153 CD patients. Frequency of early postoperative complications was 31% for UC patients and 36% for CD patients. Most complications were minor but two patients were re-operated, two needed intensive care and one patient died postoperatively.
    Conclusions: Adverse effects related to medical therapy were experienced by approximately every fourth patient, and by every third patient that was operated.
    MeSH term(s) Cohort Studies ; Colitis, Ulcerative/drug therapy ; Colitis, Ulcerative/surgery ; Crohn Disease/drug therapy ; Crohn Disease/surgery ; Drug-Related Side Effects and Adverse Reactions ; Humans ; Inflammatory Bowel Diseases/drug therapy ; Inflammatory Bowel Diseases/surgery
    Language English
    Publishing date 2021-08-08
    Publishing country England
    Document type Journal Article
    ZDB-ID 82042-8
    ISSN 1502-7708 ; 0036-5521
    ISSN (online) 1502-7708
    ISSN 0036-5521
    DOI 10.1080/00365521.2021.1961309
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  4. Article ; Online: The association between peripheral arterial disease and risk for hip fractures in elderly men is not explained by low hip bone mineral density. Results from the MrOS Sweden study.

    Bokrantz, Tove / Manhem, Karin / Lorentzon, Mattias / Karlsson, Magnus / Ljunggren, Östen / Ohlsson, Claes / Mellström, Dan

    Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA

    2022  Volume 33, Issue 12, Page(s) 2607–2617

    Abstract: In this prospective study in Swedish elderly men, PAD based on an ABI < 0.9 was associated with an increased risk of hip fracture, independent of age and hip BMD. However, after further adjustments for comorbidity, medications, physical function, and ... ...

    Abstract In this prospective study in Swedish elderly men, PAD based on an ABI < 0.9 was associated with an increased risk of hip fracture, independent of age and hip BMD. However, after further adjustments for comorbidity, medications, physical function, and socioeconomic factors, the association diminished and was no longer statistically significant.
    Introduction: To examine if peripheral arterial disease (PAD) is associated with an increased risk for hip fracture in men independent of hip BMD.
    Methods: Ankle-brachial index (ABI) was assessed in the Swedish MrOS (Osteoporotic Fractures in Men) study, a prospective observational study including 3014 men aged 69-81 years at baseline. PAD was defined as ABI < 0.90. Incident fractures were assessed in computerized X-ray archives. The risk for hip fractures was calculated using Cox proportional hazard models. At baseline, BMD was assessed using DXA (Lunar Prodigy and Hologic QDR 4500) and functional measurements and blood samples were collected. Standardized questionnaires were used to collect information about medical history, falls, and medication.
    Results: During 10 years of follow-up, 186 men had an incident hip fracture. The hazard ratio (HR) for hip fracture in men with PAD was 1.70 (95% CI 1.14-2.54), adjusted for age and study site. Additional adjustment for total hip BMD marginally affected this association (HR 1.64; 95% CI 1.10-2.45). In a final multivariate model, the HR attenuated to a non-significant HR 1.38 (95% CI 0.91-2.11) adjusted for age, site, hip BMD, BMI, falls, smoking, eGFR, handgrip strength, walking speed, former hip fracture, antihypertensive treatment, diabetes, education, and history of cardiovascular disease.
    Conclusion: This study suggests that PAD is associated with an increased risk for hip fracture independently of hip BMD in elderly Swedish men. However, the high frequency of comorbidity and lower physical performance among men with PAD might partly explain this association.
    MeSH term(s) Aged ; Male ; Humans ; Bone Density ; Sweden/epidemiology ; Hand Strength ; Prospective Studies ; Risk Factors ; Hip Fractures/epidemiology ; Hip Fractures/etiology ; Bone Diseases, Metabolic/complications ; Peripheral Arterial Disease/complications ; Peripheral Arterial Disease/epidemiology ; Osteoporotic Fractures/etiology ; Osteoporotic Fractures/complications
    Language English
    Publishing date 2022-08-19
    Publishing country England
    Document type Observational Study ; Journal Article
    ZDB-ID 1064892-6
    ISSN 1433-2965 ; 0937-941X
    ISSN (online) 1433-2965
    ISSN 0937-941X
    DOI 10.1007/s00198-022-06535-3
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  5. Article ; Online: 3D Finite Element Models Reconstructed From 2D Dual-Energy X-Ray Absorptiometry (DXA) Images Improve Hip Fracture Prediction Compared to Areal BMD in Osteoporotic Fractures in Men (MrOS) Sweden Cohort.

    Grassi, Lorenzo / Väänänen, Sami P / Jehpsson, Lars / Ljunggren, Östen / Rosengren, Björn E / Karlsson, Magnus K / Isaksson, Hanna

    Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

    2023  Volume 38, Issue 9, Page(s) 1258–1267

    Abstract: Bone strength is an important contributor to fracture risk. Areal bone mineral density (aBMD) derived from dual-energy X-ray absorptiometry (DXA) is used as a surrogate for bone strength in fracture risk prediction tools. 3D finite element (FE) models ... ...

    Abstract Bone strength is an important contributor to fracture risk. Areal bone mineral density (aBMD) derived from dual-energy X-ray absorptiometry (DXA) is used as a surrogate for bone strength in fracture risk prediction tools. 3D finite element (FE) models predict bone strength better than aBMD, but their clinical use is limited by the need for 3D computed tomography and lack of automation. We have earlier developed a method to reconstruct the 3D hip anatomy from a 2D DXA image, followed by subject-specific FE-based prediction of proximal femoral strength. In the current study, we aim to evaluate the method's ability to predict incident hip fractures in a population-based cohort (Osteoporotic Fractures in Men [MrOS] Sweden). We defined two subcohorts: (i) hip fracture cases and controls cohort: 120 men with a hip fracture (<10 years from baseline) and two controls to each hip fracture case, matched by age, height, and body mass index; and (ii) fallers cohort: 86 men who had fallen the year before their hip DXA scan was acquired, 15 of which sustained a hip fracture during the following 10 years. For each participant, we reconstructed the 3D hip anatomy and predicted proximal femoral strength in 10 sideways fall configurations using FE analysis. The FE-predicted proximal femoral strength was a better predictor of incident hip fractures than aBMD for both hip fracture cases and controls (difference in area under the receiver operating characteristics curve, ΔAUROC = 0.06) and fallers (ΔAUROC = 0.22) cohorts. This is the first time that FE models outperformed aBMD in predicting incident hip fractures in a population-based prospectively followed cohort based on 3D FE models obtained from a 2D DXA scan. Our approach has potential to notably improve the accuracy of fracture risk predictions in a clinically feasible manner (only one single DXA image is needed) and without additional costs compared to the current clinical approach. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
    MeSH term(s) Male ; Humans ; Absorptiometry, Photon/methods ; Finite Element Analysis ; Osteoporotic Fractures/diagnostic imaging ; Osteoporotic Fractures/epidemiology ; Sweden/epidemiology ; Hip Fractures/diagnostic imaging ; Hip Fractures/epidemiology ; Bone Density
    Language English
    Publishing date 2023-08-07
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 632783-7
    ISSN 1523-4681 ; 0884-0431
    ISSN (online) 1523-4681
    ISSN 0884-0431
    DOI 10.1002/jbmr.4878
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  6. Article: [No title information]

    Khamisi, Selwan / Lundqvist, Martin / Engström, Britt Edén / Larsson, Anders / Karlsson, F Anders / Ljunggren, Östen

    Experimental and Clinical Endocrinology & Diabetes

    2023  Volume 131, Issue 04, Page(s) 236–241

    Abstract: Objectives: TSH-receptor antibodies (TRAb) targeting the TSH receptor (TSH-R) induce hyperthyroidism in Graves´ disease (GD). Graves´ orbitopathy (GO) is influenced by stimulation of the TSH-R in the orbita. GO ... ...

    Abstract Objectives: TSH-receptor antibodies (TRAb) targeting the TSH receptor (TSH-R) induce hyperthyroidism in Graves´ disease (GD). Graves´ orbitopathy (GO) is influenced by stimulation of the TSH-R in the orbita. GO has been, among other factors, linked to high TRAb levels. Thyroid stimulating immunoglobulins (TSI) is a relatively new method for assessing TSH-receptor antibodies. The aim of this study was to investigate the role of TSI in the management of GO.
    Methods: Patients with newly diagnosed GD (n=30, median age 55 years (range 35–72), 29 women) received pharmacological therapy (methimazole+++thyroxine) for up to 24 months. GO was identified by clinical signs and symptoms. Eleven patients had GO at diagnosis, and another six developed GO during treatment. Blood samples for TSI and other thyroidal biomarkers were obtained at baseline and on five occasions during the 24-month follow-up. Twenty-two subjects completed the drug regimen without surgery or radioiodine treatment.
    Results: At baseline, TSI was highly correlated with TRAb ( r s =0.64, p<0.001), and both assays similarly correlated to fT3 values. TSI and TRAb did not differ significantly between GO and non-GO patients for visit v1 (n=30, 17 GO during the whole study) or at follow-up (n=22, 12 GO during the whole study). During follow-up, levels of TSI and TRAb decreased and normalized in both groups.
    Conclusion: The present study does not support any added benefit of TSI compared to TRAb for the prediction and management of GO.
    Keywords Graves` disease ; TRAb ; TSI
    Language English
    Publishing date 2023-01-27
    Publisher Georg Thieme Verlag KG
    Publishing place Stuttgart ; New York
    Document type Article
    ZDB-ID 1225416-2
    ISSN 1439-3646 ; 0947-7349
    ISSN (online) 1439-3646
    ISSN 0947-7349
    DOI 10.1055/a-2021-0596
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  7. Article ; Online: Fracture Incidence in Graves' Disease: A Population-Based Study.

    Khamisi, Selwan / Udumyan, Ruzan / Sjölin, Gabriel / Calissendorff, Jan / Filipsson Nyström, Helena / Holmberg, Mats / Hallengren, Bengt / Lantz, Mikael / Planck, Tereza / Wallin, Göran / Ljunggren, Östen

    Thyroid : official journal of the American Thyroid Association

    2023  Volume 33, Issue 11, Page(s) 1349–1357

    Abstract: Background: ...

    Abstract Background:
    MeSH term(s) Humans ; Male ; Female ; Spinal Fractures/complications ; Incidence ; Retrospective Studies ; Fractures, Bone/epidemiology ; Fractures, Bone/etiology ; Graves Disease/complications ; Graves Disease/drug therapy ; Graves Disease/epidemiology ; Hyperthyroidism/complications ; Osteoporosis/complications ; Osteoporosis/epidemiology ; Adrenal Cortex Hormones
    Chemical Substances Adrenal Cortex Hormones
    Language English
    Publishing date 2023-10-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1086044-7
    ISSN 1557-9077 ; 1050-7256
    ISSN (online) 1557-9077
    ISSN 1050-7256
    DOI 10.1089/thy.2023.0162
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  8. Article ; Online: Osteoprotegerin predicts cardiovascular events in patients treated with haemodialysis.

    Wu, Ping-Hsun / Glerup, Rie Io / Svensson, My Hanna Sofia / Eriksson, Niclas / Christensen, Jeppe Hagstrup / Linde, Torbjörn / Ljunggren, Östen / Fellström, Bengt

    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

    2021  Volume 37, Issue 6, Page(s) 1162–1170

    Abstract: Background: Disturbances in bone mineral metabolism are associated with increased mortality and cardiovascular events (CVEs). However, the association between bone-associated protein biomarkers, mortality and CVEs independent of cytokine activation ... ...

    Abstract Background: Disturbances in bone mineral metabolism are associated with increased mortality and cardiovascular events (CVEs). However, the association between bone-associated protein biomarkers, mortality and CVEs independent of cytokine activation remains unknown. This study aimed to investigate bone-associated protein biomarkers and the association with inflammatory cytokines and cardiovascular (CV) outcomes.
    Methods: This prospective study enrolled haemodialysis patients in Denmark between December 2010 and March 2011. Using a proximity extension proteomics assay, nine bone-associated proteins were examined: cathepsin D (CTSD), cathepsin L1 (CTSL1), dickkopf-related protein 1, fibroblast growth factor 23, leptin, osteoprotegerin (OPG), receptor activator of nuclear factor kappa-Β ligand, TNF-related apoptosis-inducing ligand (TRAIL) and TRAIL receptor 2 (TRAIL-R2). The importance of the bone-associated protein markers was evaluated by a random forest (RF) algorithm. The association between bone-associated proteins with all-cause death, CV death and CVEs was analysed in multivariable Cox models adjusted for age, gender, comorbidities, laboratory data and dialysis duration.
    Results: We enrolled 331 patients [63.7% men; mean age, 65 years (standard deviation 14.6)] in a prospective cohort study with 5 years of follow-up. When adjusting for confounders, CTSL1 remained associated with all-cause death and four biomarkers were associated with CVEs. However, the association between bone markers and the outcomes was attenuated after adjusting for inflammatory proteins and only OPG remained associated with CVEs in the adjusted model. Evaluating the importance of bone markers by RF, OPG was the most important marker related to CVEs. OPG also improved the prediction of CVEs in integrated discrimination improvement and net reclassification improvement analyses.
    Conclusions: OPG, a well-known bone biomarker, was associated with CVEs independent of cytokine activity. In contrast, the association between CVEs and the remaining three bone-associated proteins (TRAIL-R2, CTSD and CTSL1) was affected by cytokine inflammation activity.
    MeSH term(s) Aged ; Biomarkers ; Cardiovascular Diseases/etiology ; Cytokines ; Female ; Humans ; Male ; Osteoprotegerin/blood ; Prospective Studies ; Receptors, TNF-Related Apoptosis-Inducing Ligand ; Renal Dialysis/adverse effects ; TNF-Related Apoptosis-Inducing Ligand
    Chemical Substances Biomarkers ; Cytokines ; Osteoprotegerin ; Receptors, TNF-Related Apoptosis-Inducing Ligand ; TNF-Related Apoptosis-Inducing Ligand ; TNFRSF10B protein, human ; TNFRSF11B protein, human ; TNFSF10 protein, human
    Language English
    Publishing date 2021-06-03
    Publishing country England
    Document type Journal Article
    ZDB-ID 90594-x
    ISSN 1460-2385 ; 0931-0509
    ISSN (online) 1460-2385
    ISSN 0931-0509
    DOI 10.1093/ndt/gfab192
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  9. Article ; Online: Serum Glycine Levels Are Associated With Cortical Bone Properties and Fracture Risk in Men.

    Eriksson, Anna L / Friedrich, Nele / Karlsson, Magnus K / Ljunggren, Östen / Lorentzon, Mattias / Nethander, Maria / Wallaschofski, Henri / Mellström, Dan / Ohlsson, Claes

    The Journal of clinical endocrinology and metabolism

    2021  Volume 106, Issue 12, Page(s) e5021–e5029

    Abstract: Context: In a recent study a pattern of 27 metabolites, including serum glycine, associated with bone mineral density (BMD).: Objective: To investigate associations for serum and urinary glycine levels with BMD, bone microstructure, and fracture risk ...

    Abstract Context: In a recent study a pattern of 27 metabolites, including serum glycine, associated with bone mineral density (BMD).
    Objective: To investigate associations for serum and urinary glycine levels with BMD, bone microstructure, and fracture risk in men.
    Methods: In the population-based Osteoporotic Fractures in Men (MrOS) Sweden study (men, 69-81 years) serum glycine and BMD were measured at baseline (n = 965) and 5-year follow-up (n = 546). Cortical and trabecular bone parameters of the distal tibia were measured at follow-up using high-resolution peripheral quantitative computed tomography. Urinary (n = 2682) glycine was analyzed at baseline. X-ray-validated fractures (n = 594) were ascertained during a median follow-up of 9.6 years. Associations were evaluated using linear regression (bone parameters) or Cox regression (fractures).
    Results: Circulating glycine levels were inversely associated with femoral neck (FN)-BMD. A meta-analysis (n = 7543) combining MrOS Sweden data with data from 3 other cohorts confirmed a robust inverse association between serum glycine levels and FN-BMD (P = 7.7 × 10-9). Serum glycine was inversely associated with the bone strength parameter failure load in the distal tibia (P = 0.002), mainly as a consequence of an inverse association with cortical cross-sectional area and a direct association with cortical porosity. Both serum and urinary glycine levels predicted major osteoporotic fractures (serum: hazard ratio [HR] per SD increase = 1.22, 95% CI, 1.05-1.43; urine: HR = 1.13, 95% CI, 1.02-1.24). These fracture associations were only marginally reduced in models adjusted by FRAX with BMD.
    Conclusions: Serum and urinary glycine are indirectly associated with FN-BMD and cortical bone strength, and directly associated with fracture risk in men.
    MeSH term(s) Aged ; Aged, 80 and over ; Biomarkers/blood ; Bone Density ; Cortical Bone/metabolism ; Cortical Bone/pathology ; Cross-Sectional Studies ; Follow-Up Studies ; Glycine/blood ; Humans ; Male ; Osteoporotic Fractures/blood ; Osteoporotic Fractures/epidemiology ; Osteoporotic Fractures/pathology ; Prognosis ; Prospective Studies ; Risk Assessment/methods ; Sweden/epidemiology
    Chemical Substances Biomarkers ; Glycine (TE7660XO1C)
    Language English
    Publishing date 2021-07-23
    Publishing country United States
    Document type Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
    ZDB-ID 3029-6
    ISSN 1945-7197 ; 0021-972X
    ISSN (online) 1945-7197
    ISSN 0021-972X
    DOI 10.1210/clinem/dgab544
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  10. Article ; Online: Hypercalcaemia in a Patient with 2p13.2-p16.1 Duplication.

    Lodefalk, Maria / Frykholm, Carina / Esbjörner, Elisabeth / Ljunggren, Östen

    Hormone research in paediatrics

    2016  Volume 85, Issue 3, Page(s) 213–218

    Abstract: 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, ...

    Abstract 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 1α-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.
    MeSH term(s) Child, Preschool ; Chromosome Duplication ; Chromosomes, Human, Pair 2/genetics ; Female ; Humans ; Hypercalcemia/blood ; Hypercalcemia/genetics ; Hypercalcemia/urine
    Language English
    Publishing date 2016
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2537278-6
    ISSN 1663-2826 ; 1663-2818
    ISSN (online) 1663-2826
    ISSN 1663-2818
    DOI 10.1159/000442747
    Database MEDical Literature Analysis and Retrieval System OnLINE

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