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Eeva M Ryhänen
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Ilkka Heiskanen
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Harri Sintonen Endocrinology, Department of Public Health, Group Administration, Helsinki University Hospital, University of Eastern Finland, Abdominal Center, University of Helsinki and Helsinki University Hospital, Post Box 340, FI-00290 Helsinki, Finland

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Matti J Välimäki
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Risto P Roine Endocrinology, Department of Public Health, Group Administration, Helsinki University Hospital, University of Eastern Finland, Abdominal Center, University of Helsinki and Helsinki University Hospital, Post Box 340, FI-00290 Helsinki, Finland
Endocrinology, Department of Public Health, Group Administration, Helsinki University Hospital, University of Eastern Finland, Abdominal Center, University of Helsinki and Helsinki University Hospital, Post Box 340, FI-00290 Helsinki, Finland
Endocrinology, Department of Public Health, Group Administration, Helsinki University Hospital, University of Eastern Finland, Abdominal Center, University of Helsinki and Helsinki University Hospital, Post Box 340, FI-00290 Helsinki, Finland

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Camilla Schalin-Jäntti
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Health-related quality of life (HRQoL) is frequently impaired in primary hyperparathyroidism (PHPT) but it is unclear if surgery is beneficial. The objective was to prospectively assess HRQoL in PHPT (n=124) with the 15D instrument before and after surgery, to compare it with that of a comparable sample of the general population (n=4295), and search for predictors of HRQoL and its change. HRQoL, and clinical and laboratory parameters were measured before and at 6 and 12 months after surgery. Regression techniques were used to search for predictors of HRQoL and gains from treatment. Before surgery, PHPT patients had significantly lower mean 15D score compared to controls (0.813 vs 0.904, P<0.001). Excretion, mental function, discomfort and symptoms, distress, depression, vitality, and sexual activity were most impaired (all P<0.001). Number of medications (P=0.001) and subjective symptoms (P<0.05) but not calcium or parathyroid hormone (PTH) predicted impaired HRQoL. Serum 25-hydroxyvitamin D (25OHD) was of borderline significance (P=0.051). Compared to baseline, mean 15D score improved significantly 6 months after surgery (0.813 vs 0.865, P<0.001) and the effect sustained at 1 year (0.878, P<0.001). The improvement was clinically important in 77.4% of patients (P<0.001). Educational level independently predicted improvement (P<0.005). HRQoL is severely impaired in PHPT but improves significantly after surgery. The 15D is a sensitive tool for assessing HRQoL and recognizing patients likely to benefit from surgery.

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Maria Angela D'amico Section of Human Morphology, Department of Medicine and Aging Sciences, G. d'Annunzio University of Chieti–Pescara, Via Dei Vestini 31, 66013 Chieti, Italy

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Barbara Ghinassi Section of Human Morphology, Department of Medicine and Aging Sciences, G. d'Annunzio University of Chieti–Pescara, Via Dei Vestini 31, 66013 Chieti, Italy

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Pascal Izzicupo Section of Human Morphology, Department of Medicine and Aging Sciences, G. d'Annunzio University of Chieti–Pescara, Via Dei Vestini 31, 66013 Chieti, Italy

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Lamberto Manzoli Section of Human Morphology, Department of Medicine and Aging Sciences, G. d'Annunzio University of Chieti–Pescara, Via Dei Vestini 31, 66013 Chieti, Italy

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A Di Baldassarre Section of Human Morphology, Department of Medicine and Aging Sciences, G. d'Annunzio University of Chieti–Pescara, Via Dei Vestini 31, 66013 Chieti, Italy

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Chromogranin A (CgA (CHGA)) is the major soluble protein co-stored and co-released with catecholamines and can function as a pro-hormone by giving rise to several bioactive peptides. This review summarizes the physiological functions, the pathogenic implications, and the recent use of these molecules as biomarkers in several pathological conditions. A thorough literature review of the electronic healthcare databases MEDLINE, from January 1985 to September 2013, was conducted to identify articles and studies concerned with CgA and its processing. The search strategies utilized keywords such as chromogranin A, vasostatins 1 and 2, chromofungin, chromacin, pancreastatin, catestatin, WE14, chromostatin, GE25, parastatin, and serpinin and was supplemented by the screening of references from included papers and review articles. A total of 209 English-language, peer-reviewed original articles or reviews were examined. The analysis of the retrospective literature suggested that CgA and its several bioactive fragments exert a broad spectrum of regulatory activities by influencing the endocrine, the cardiovascular, and the immune systems and by affecting the glucose or calcium homeostasis. As some peptides exert similar effects, but others elicit opposite responses, the regulation of the CgA processing is critical to maintain homeostasis, whereas an unbalanced production of peptides that exert opposing effects can have a pathogenic role in several diseases. These clinical implications entail that CgA and its derived peptides are now used as diagnostic and prognostic markers or to monitor the response to pharmacological intervention not only in endocrine tumors, but also in cardiovascular, inflammatory, and neuropsychiatric diseases.

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Sara Lomelino Pinheiro Serviço de Endocrinologia, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal

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Ana Saramago Unidade de Investigação em Patobiologia Molecular, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal

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Branca Maria Cavaco Unidade de Investigação em Patobiologia Molecular, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal

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Carmo Martins Unidade de Investigação em Patobiologia Molecular, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal

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Valeriano Leite Serviço de Endocrinologia e Unidade de Investigação em Patobiologia Molecular, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal

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Tiago Nunes da Silva Serviço de Endocrinologia e Unidade de Investigação em Patobiologia Molecular, Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal

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Nineteen cases of parathyroid carcinoma in patients with multiple endocrine neoplasia type 1 have been reported in the literature, of which 11 carry an inactivating germline mutation in the MEN1 gene. Somatic genetic abnormalities in these parathyroid carcinomas have never been detected. In this paper, we aimed to describe the clinical and molecular characterization of a parathyroid carcinoma identified in a patient with MEN1. A 60-year-old man was diagnosed with primary hyperparathyroidism during the postoperative period of lung carcinoid surgery. Serum calcium and parathyroid hormone levels were 15.0 mg/dL (8.4–10.2) and 472 pg/mL (12–65), respectively. The patient underwent parathyroid surgery, and histological findings were consistent with parathyroid carcinoma. Analysis of the MEN1 gene by next-generation sequencing (NGS) identified a novel germline heterozygous nonsense pathogenic variant (c.978C>A; p.(Tyr326*)), predicted to encode a truncated protein. Genetic analysis of the parathyroid carcinoma revealed a c.307del, p.(Leu103Cysfs*16) frameshift truncating somatic MEN1 variant in the MEN1 gene, which is consistent with MEN1 tumor-suppressor role, confirming its involvement in parathyroid carcinoma etiology. Genetic analysis of CDC73, GCM2, TP53, RB1, AKT1, MTOR, PIK3CA and CCND1 genes in the parathyroid carcinoma DNA did not detect any somatic mutations. To our knowledge, this is the first report of a PC case presenting both germline (first-hit) and somatic (second-hit) inactivation of the MEN1 gene.

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Victor Jing-Wei Kang Departments of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan

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Bo-Ching Lee Departments of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan

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Jia-Zheng Huang Departments of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan

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Vin-Cent Wu Departments of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

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Yen-Hung Lin Departments of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

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Chin-Chen Chang Departments of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan

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TAIPAI group
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Primary aldosteronism (PA) is associated with urolithiasis as it causes hypercalciuria and hypocitraturia. However, the influence of different subtypes of PA on urinary stone formation remains unclear. This study aimed to evaluate the association between aldosterone-producing adenoma (APA) and the burden of urolithiasis in patients with PA. In the present study, we enrolled 312 patients with PA from a prospectively maintained database, of whom 179 had APA. Clinical, biochemical, and imaging data (including the presence, volume, and density of urinary stones on abdominal computed tomography) were compared between groups, with employment of propensity score matching (PSM) analysis to balance possible confounding factors. Kaplan–Meier analysis was used to estimate the acute renal colic event during follow-up. After PSM for age, sex, serum calcium, phosphate, blood urea nitrogen, creatinine, and uric acid, the APA and non-APA groups had 106 patients each. Patients with APA had higher serum intact parathyroid hormone (iPTH) (79.1 ± 45.0 vs 56.1 ± 30.3, P < 0.001) and a higher prevalence of urolithiasis (27.4% vs 12.3%, P = 0.006) than non-APA patients. During follow-up, a higher incidence of acute renal colic events was noted in the APA group than the non-APA group (P = 0.011); this association remained significant (P = 0.038) after adjustment for age and sex in Cox-regression analysis. Our data suggest that APA is associated with a heavier burden of urolithiasis and higher incidence of renal colic events compared to the non-APA subtype of PA.

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Charissa van Zwol-Janssens Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Aglaia Hage Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Kim van der Ham Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Birgitta K Velthuis Department of Radiology, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands

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Ricardo P J Budde Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands

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Maria P H Koster Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Arie Franx Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Bart C J M Fauser Department of Reproductive Medicine and Gynaecology, University Medical Center Utrecht & University of Utrecht, Utrecht, the Netherlands

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Eric Boersma Department of Cardiology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Daniel Bos Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Joop S E Laven Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Yvonne V Louwers Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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the CREW consortium
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the CREW consortium

Besides age, estrogen exposure plays a crucial role in changes in bone density (BD) in women. Premature ovarian insufficiency (POI) and polycystic ovary syndrome (PCOS) are conditions in reproductive-aged women in which the exposure to estrogen is substantially different. Women with a history of preeclampsia (PE) are expected to have normal estrogen exposure. Within the CREw-IMAGO study, we investigated if trabecular BD is different in these women because of differences in the duration of estrogen exposure. Trabecular BD was measured in thoracic vertebrae on coronary CT scans. Women with a reduced estrogen exposure (POI) have a lower BD compared to women with an intermediate exposure (PE) (mean difference (MD) −26.8, 95% CI −37.2 to −16.3). Women with a prolonged estrogen exposure (PCOS) have the highest BD (MD 15.0, 95% CI 4.3–25.7). These results support the hypothesis that the duration of estrogen exposure in these women is associated with trabecular BD.

Significance statement

Our results suggest that middle-aged women with PCOS have a higher BD and women with POI have a lower BD. We hypothesized that this is due to either a prolonged estrogen exposure, as seen in women with PCOS, or a reduced estrogen exposure, as in women with POI. In the counseling of women with reproductive disorders on long-term health issues, coronary CT provides a unique opportunity to assess both coronary artery calcium score for cardiovascular screening as well as trabecular BD.

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Niek F Dirks Atalmedial Diagnostics Centre, Spaarne Gasthuis, Haarlem, The Netherlands
Department of Clinical Chemistry, Hematology and Immunology, Noordwest Ziekenhuis, Alkmaar, The Netherlands

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Etienne Cavalier Department of Clinical Chemistry, University of Liège, CHU de Liège, Liège, Belgium

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Annemieke C Heijboer Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Clinical Chemistry, Endocrine Laboratory, Boelelaan, Amsterdam, The Netherlands
Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam, The Netherlands
Amsterdam UMC location University of Amsterdam, Department of Clinical Chemistry, Endocrine Laboratory, Amsterdam, The Netherlands
Amsterdam Reproduction & Development Research Institute, Amsterdam, The Netherlands

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The measurement of vitamin D metabolites aids in assessing vitamin D status and in diagnosing disorders of calcium homeostasis. Most laboratories measure total 25-hydroxyvitamin D (25(OH)D), while others have taken the extra effort to measure 25(OH)D2 and 25(OH)D3 separately and additional metabolites such as 1,25-dihydroxyvitamin D and 24,25-dihydroxyvitamin D. The aim of this review is to provide an updated overview of the main markers of vitamin D metabolism, define the intended measurands, and discuss the advantages and disadvantages of the two most widely used assays, automated assays and liquid chromatography–tandem mass spectrometry (LC-MS/MS). Whether using the easy and fast automated assays or the more complex LC-MS/MS, one should know the pitfalls of the used technique in order to interpret the measurements. In conclusion, automated assays are unable to accurately measure 25(OH)D in all patient groups, including persons using D2. In these cases, an LC-MS/MS method, when appropriately developed and standardized, produces a more reliable measurement.

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Budoor Alemadi Endocrinology Department, Dubai Hospital, Dubai Health, Dubai, UAE

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Fauzia Rashid Endocrinology Department, Dubai Hospital, Dubai Health, Dubai, UAE

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Ali Alzahrani King Faisal Specialist Hospital & Research Centre, Department of Medicine, Riyadh, Saudi Arabia

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Primary hyperparathyroidism has emerged as a prevalent endocrine disorder in clinical settings, necessitating in most cases, surgical intervention for the removal of the diseased gland. This condition is characterised by overactivity of the parathyroid glands, resulting in excessive parathyroid hormone production and subsequent disturbances in calcium homeostasis. The primary mode of management is surgical treatment, relying on the accurate localisation of the pathological parathyroid gland. Precise identification is paramount to ensuring that the surgical intervention effectively targets and removes the diseased gland, alleviating the hyperfunctioning state. However, localising the gland becomes challenging, as discrepancies between the clinical manifestation of active parathyroid and radiological identification are common. Based on our current knowledge, to date, no comprehensive review has been conducted that considers all factors collectively. This comprehensive review delves into the factors contributing to false-negative 99mTc-Sestamibi scans. Our research involved an exhaustive search in the PubMed database for hyperparathyroidism, with the identified literature meticulously filtered and reviewed by the authors. The results highlighted various factors, including multiple parathyroid diseases, nodular goitre, mild disease, or the presence of an ectopic gland that causes discordance. Hence, a thorough consideration of these factors is crucial during the diagnostic workup of hyperparathyroidism. Employing intraoperative PTH assays can significantly contribute to a successful cure of the disease, thereby providing a more comprehensive approach to managing this prevalent endocrine disorder.

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Nekoo Panahi Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
Osteoporosis Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

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Sahar Saeedi Moghaddam Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
Kiel Institute for the World Economy, Kiel, Germany

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Noushin Fahimfar Osteoporosis Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Science, Tehran, Iran

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Negar Rezaei Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

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Mahnaz Sanjari Osteoporosis Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

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Mohammad-Mahdi Rashidi Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

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Parnian Shobeiri Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

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Bagher Larijani Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

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Afshin Ostovar Osteoporosis Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

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Background

We aimed to document the current state of exposure to low bone mineral density (BMD) and trends in attributable burdens between 2000 and 2019 globally and in different World Health Organization (WHO) regions using the Global Burden of Disease (GBD) study 2019.

Methods

We reviewed the sex-region-specific summary exposure value (SEV) of low BMD and the all-ages numbers and age-standardized rates of disability-adjusted life years (DALYs), years lived with disability (YLDs), years of life lost (YLLs), and deaths attributed to low BMD. We compared different WHO regions (Africa, the Eastern Mediterranean Region, Europe, Region of the Americas, Southeast Asia, and Western Pacific), age categories, and sexes according to the estimates of the GBD 2019 report.

Results

The global age-standardized SEV of low BMD is estimated to be 20.7% in women and 11.3% in men in 2019. Among the WHO regions, Africa had the highest age-standardized SEV of low BMD in women (28.8% (95% uncertainty interval 22.0–36.3)) and men (16.8% (11.5–23.8)). The lowest SEV was observed in Europe in both women (14.7% (9.9–21.0)) and men (8.0% (4.3–13.4)). An improving trend in the global rate of DALY, death, and YLL was observed during 2000–2019 (−5.7%, −4.7%, and −11.9% change, respectively); however, the absolute numbers increased with the highest increase observed in global YLD (70.9%) and death numbers (67.6%). Southeast Asia Region had the highest age-standardized rates of DALY (303.4 (249.2–357.2)), death (10.6 (8.5–12.3)), YLD (133.5 (96.9–177.3)), and YLL (170.0 (139–197.7)).

Conclusions

Overall, the highest-burden attributed to low BMD was observed in the Southeast Asia Region. Knowledge of the SEV of low BMD and the attributed burden can increase the awareness of healthcare decision-makers to adopt appropriate strategies for early screening, and also strategies to prevent falls and fragility fractures and their consequent morbidity and mortality.

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I M A A van Roessel Department of Pediatric Neuro-oncology, Princess Máxima Center, Heidelberglaan, CS Utrecht, The Netherlands
Department of Pediatric Endocrinology, Wilhelmina Children’s Hospital, University Medical Center, Lundlaan, EA Utrecht, The Netherlands

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J E Gorter Department of Pediatric Neuro-oncology, Princess Máxima Center, Heidelberglaan, CS Utrecht, The Netherlands
Department of Pediatric Endocrinology, Wilhelmina Children’s Hospital, University Medical Center, Lundlaan, EA Utrecht, The Netherlands

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B Bakker Department of Pediatric Neuro-oncology, Princess Máxima Center, Heidelberglaan, CS Utrecht, The Netherlands
Department of Pediatric Endocrinology, Wilhelmina Children’s Hospital, University Medical Center, Lundlaan, EA Utrecht, The Netherlands

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M M van den Heuvel-Eibrink Princess Máxima Center, Heidelberglaan, CS Utrecht, The Netherlands
Wilhelmina Children’s Hospital, University Medical Center, Lundlaan, EA Utrecht, The Netherlands

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M H Lequin Department of Radiology, Princess Máxima Center, Heidelberglaan, CS Utrecht, The Netherlands
Department of Radiology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands

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J van der Lugt Department of Pediatric Neuro-oncology, Princess Máxima Center, Heidelberglaan, CS Utrecht, The Netherlands

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L Meijer Department of Pediatric Neuro-oncology, Princess Máxima Center, Heidelberglaan, CS Utrecht, The Netherlands

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A Y N Schouten-van Meeteren Department of Pediatric Neuro-oncology, Princess Máxima Center, Heidelberglaan, CS Utrecht, The Netherlands

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H M van Santen Department of Pediatric Neuro-oncology, Princess Máxima Center, Heidelberglaan, CS Utrecht, The Netherlands
Department of Pediatric Endocrinology, Wilhelmina Children’s Hospital, University Medical Center, Lundlaan, EA Utrecht, The Netherlands

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Objective

Children with a supratentorial midline low-grade glioma (LGG) may be at risk for impaired bone health due to hypothalamic-pituitary dysfunction, obesity, exposure to multiple treatment modalities, and/or decreased mobility. The presence of impaired bone health and/or its severity in this population has been understudied. We aimed to identify the prevalence and risk factors for bone problems in children with supratentorial midline LGG.

Materials and methods

A retrospective study was performed in children with supratentorial midline (suprasellar or thalamic) LGG between 1 January 2003 and 1 January 2022, visiting the Princess Máxima Center for Pediatric Oncology. Impaired bone health was defined as the presence of vertebral fractures and/or very low bone mineral density (BMD).

Results

In total, 161 children were included, with a median age at tumor diagnosis of 4.7 years (range: 0.1–17.9) and a median follow-up of 6.1 years (range: 0.1–19.9). Five patients (3.1%) had vertebral fractures. In 99 patients, BMD was assessed either by Dual Energy X-ray Absorptiometry (n = 12) or Bone Health Index (n = 95); 34 patients (34.3%) had a low BMD (≤ −2.0). Impaired visual capacity was associated with bone problems in multivariable analysis (OR: 6.63, 95% CI: 1.83–24.00, P = 0.004).

Conclusion

In this retrospective evaluation, decreased BMD was prevalent in 34.3% of children with supratentorial midline LGG. For the risk of developing bone problems, visual capacity seems highly relevant. Surveillance of bone health must be an aspect of awareness in the care and follow-up of children with a supratentorial midline LGG.

Significance statement

Patients with supratentorial midline LGG may encounter various risk factors for impaired bone health. Bone problems in survivors of childhood supratentorial midline LGG are, however, understudied. This is the first paper to address the prevalence of bone problems in this specific patient population, revealing visual problems as an important risk factor. Diencephalic syndrome historyand/or weight problems associated with hypothalamic dysfunction were related to bone problems in univariate analyses. The results of this study can be used in the development of guidelines to adequately screen and treat these patients to subsequently minimizing bone problems as one of the endocrine complications.

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Anouar Aznou Department of Internal Medicine, Amsterdam University Medical Centers, MB Amsterdam, the Netherlands

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Rick Meijer Department of Internal Medicine, Amsterdam University Medical Centers, MB Amsterdam, the Netherlands

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Daniel van Raalte Department of Internal Medicine, Amsterdam University Medical Centers, MB Amsterdam, the Netherlands

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Martin den Heijer Department of Internal Medicine, Amsterdam University Medical Centers, MB Amsterdam, the Netherlands

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Annemieke Heijboer Endocrine Laboratory, Department of Clinical Chemistry, Amsterdam University Medical Centers, MB Amsterdam, the Netherlands

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Renate de Jongh Department of Internal Medicine, Amsterdam University Medical Centers, MB Amsterdam, the Netherlands

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Objective

The mechanisms underlying the development of peripheral insulin resistance are complex. Several studies have linked sclerostin, an osteocyte-derived inhibitor of the Wnt/β-catenin pathway, to obesity and insulin resistance. The aim of this study was to investigate (1) whether serum sclerostin is associated with insulin sensitivity in lean and/or obese women; and (2) whether hyperinsulinaemia affects serum sclerostin concentrations.

Design

A cross-sectional study.

Methods

Insulin sensitivity was measured in lean (BMI < 25 kg/m2) and obese (BMI > 30 kg/m2) women using a hyperinsulinaemic–euglycaemic clamp. Serum sclerostin was measured at baseline and during the clamp procedure.

Results

We studied 21 lean and 22 obese women with a median age of 40 and 43 years and a median BMI of 22.4 and 33.5 kg/m2, respectively. Obese women had higher serum sclerostin than lean women (122 ± 33 vs 93 ± 33 nmol/L, P < 0.01). Higher serum sclerostin was associated with lower insulin sensitivity in obese, but not in lean individuals (difference in M-value between highest and lowest quartile: −7.02 mg/kg/min, P = 0.03 and 1.59 mg/kg/min, P = 0.50, respectively). Hyperinsulinaemia did not affect serum sclerostin in lean nor obese women (P > 0.5).

Conclusion

Serum sclerostin is negatively associated with insulin sensitivity as measured with the hyperinsulinaemic–euglycaemic clamp in obese, but not lean women. This indicates a potential role of the Wnt/β-catenin pathway in regulating insulin sensitivity particularly in obese individuals. Our findings remain hypothesis-generating and should be confirmed by additional studies.

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