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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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Huda M Elsharkasi Developmental Endocrinology Research Group, University of Glasgow, Glasgow, UK

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Suet C Chen Developmental Endocrinology Research Group, University of Glasgow, Glasgow, UK

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Lewis Steell Developmental Endocrinology Research Group, University of Glasgow, Glasgow, UK

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Shuko Joseph Developmental Endocrinology Research Group, University of Glasgow, Glasgow, UK
Paediatric Neurosciences Research Group, Royal Hospital for Children, NHS Greater Glasgow & Clyde, Glasgow, UK

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Naiemh Abdalrahaman Developmental Endocrinology Research Group, University of Glasgow, Glasgow, UK

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Christie McComb Department of Clinical Physics, NHS Greater Glasgow & Clyde, Glasgow, UK

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Blair Johnston Department of Clinical Physics, NHS Greater Glasgow & Clyde, Glasgow, UK

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John Foster Department of Clinical Physics, NHS Greater Glasgow & Clyde, Glasgow, UK

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Sze Choong Wong Developmental Endocrinology Research Group, University of Glasgow, Glasgow, UK

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S Faisal Ahmed Developmental Endocrinology Research Group, University of Glasgow, Glasgow, UK

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Objective

The aim of this study is to investigate the role of 3T-MRI in assessing musculoskeletal health in children and young people.

Design

Bone, muscle and bone marrow imaging was performed in 161 healthy participants with a median age of 15.0 years (range, 8.0, 30.0).

Methods

Detailed assessment of bone microarchitecture (constructive interference in the steady state (CISS) sequence, voxel size 0.2 × 0.2 × 0.4 mm3), bone geometry (T1-weighted turbo spin echo (TSE) sequence, voxel size 0.4 × 0.4 × 2 mm3) and bone marrow (1H-MRS, point resolved spectroscopy sequence (PRESS) (single voxel size 20 × 20 × 20 mm3) size and muscle adiposity (Dixon, voxel size 1.1 × 1.1 × 2 mm3).

Results

There was an inverse association of apparent bone volume/total volume (appBV/TV) with age (r = −0.5, P < 0.0005). Cortical area, endosteal and periosteal circumferences and muscle cross-sectional area showed a positive association to age (r > 0.49, P < 0.0001). In those over 17 years of age, these parameters were also higher in males than females (P < 0.05). This sex difference was also evident for appBV/TV and bone marrow adiposity (BMA) in the older participants (P < 0.05). AppBV/TV showed a negative correlation with BMA (r = −0.22, P =  0.01) which also showed an association with muscle adiposity (r = 0.24, P = 0.04). Cortical geometric parameters were highly correlated with muscle area (r > 0.57, P < 0.01).

Conclusions

In addition to providing deep insight into the normal relationships between bone, fat and muscle in young people, these novel data emphasize the role of MRI as a non-invasive method for performing a comprehensive and integrated assessment of musculoskeletal health in the growing skeleton.

Open access
Hsiao-Yun Yeh Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan
Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

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Hung-Ta Hondar Wu Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
Division of Musculoskeletal Section, Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan

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Hsiao-Chin Shen Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan
Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan

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Tzu-Hao Li Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Foundation, Taipei, Taiwan
School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan

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Ying-Ying Yang Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan
Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

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Kuei-Chuan Lee Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

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Yi-Hsuan Lin Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan
Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

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Chia-Chang Huang Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan
Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan

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Ming-Chih Hou Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

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Objective

Previous studies have suggested that body mass index (BMI) should be considered when assessing the relationship between fatty liver (FL) and osteoporosis. The aim of this study was to investigate future fracture events in people with FL, focusing on the effect of BMI in both sexes.

Methods

This retrospective cohort study, spanning from 2011 to 2019, enrolled 941 people, including 441 women and 500 men, aged 50 years or older who underwent liver imaging (ultrasound, computed tomography, or magnetic resonance image) and dual-energy X-ray absorptiometry (for bone mineral density measurements). The study examined predictors of osteoporosis in both sexes and the effect of different ranges of BMI (18.5–24, 24–27, and ≥27 kg/m2) on the risk of future fracture events in FL patients.

Results

The average follow-up period was 5.3 years for women and 4.2 years for men. Multivariate analysis identified age and BMI as independent risk factors of osteoporosis in both sexes. Each unit increase in BMI decreased the risk of osteoporosis by ≥10%. In both women and men with FL, a BMI of 24–27 kg/m2 offered protection against future fractures, compared to those without FL and with a BMI of 18.5–24 kg/m2.

Conclusion

The protective effect of a higher BMI against future fractures in middle-aged and elderly female and male patients with FL is not uniform and diminishes beyond certain BMI ranges.

Open access
Fabienne A U Fox Population Health Sciences, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany

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Lennart Koch Population Health Sciences, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
University for Health Sciences, Medical Informatics and Technology (UMIT TIROL), Tirol, Austria

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Monique M B Breteler Population Health Sciences, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
Institute for Medical Biometry, Informatics and Epidemiology (IMBIE), Faculty of Medicine, University of Bonn, Bonn, Germany

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N Ahmad Aziz Population Health Sciences, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
Department of Neurology, Faculty of Medicine, University of Bonn, Bonn, Germany

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Objective

Maintaining muscle function throughout life is critical for healthy ageing. Although in vitro studies consistently indicate beneficial effects of 25-hydroxyvitamin D (25-OHD) on muscle function, findings from population-based studies remain inconclusive. We therefore aimed to examine the association between 25-OHD concentration and handgrip strength across a wide age range and assess potential modifying effects of age, sex and season.

Methods

We analysed cross-sectional baseline data of 2576 eligible participants out of the first 3000 participants (recruited from March 2016 to March 2019) of the Rhineland Study, a community-based cohort study in Bonn, Germany. Multivariate linear regression models were used to assess the relation between 25-OHD levels and grip strength while adjusting for age, sex, education, smoking, season, body mass index, physical activity levels, osteoporosis and vitamin D supplementation.

Results

Compared to participants with deficient 25-OHD levels (<30 nmol/L), grip strength was higher in those with inadequate (30 to <50 nmol/L) and adequate (≥50 to ≤125 nmol/L) levels (ß inadequate = 1.222, 95% CI: 0.377; 2.067, P = 0.005; ß adequate = 1.228, 95% CI: 0.437; 2.019, P = 0.002). Modelling on a continuous scale revealed grip strength to increase with higher 25-OHD levels up to ~100 nmol/L, after which the direction reversed (ß linear = 0.505, 95% CI: 0.179; 0.830, P = 0.002; ß quadratic = –0.153, 95% CI: –0.269; -0.038, P = 0.009). Older adults showed weaker effects of 25-OHD levels on grip strength than younger adults (ß 25OHDxAge = –0.309, 95% CI: –0.594; –0.024, P = 0.033).

Conclusions

Our findings highlight the importance of sufficient 25-OHD levels for optimal muscle function across the adult life span. However, vitamin D supplementation should be closely monitored to avoid detrimental effects.

Open access
Laurent Maïmoun Département de Médecine Nucléaire, Hôpital Lapeyronie, Centre Hospitalier Régional Universitaire (CHU) Montpellier, Montpellier, France
PhyMedExp, Université de Montpellier, INSERM, CNRS, Montpellier, France

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Denis Mariano-Goulart Département de Médecine Nucléaire, Hôpital Lapeyronie, Centre Hospitalier Régional Universitaire (CHU) Montpellier, Montpellier, France
PhyMedExp, Université de Montpellier, INSERM, CNRS, Montpellier, France

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Helena Huguet Unité de Recherche Clinique et Epidémiologie, Hôpital Lapeyronie, CHU Montpellier, Montpellier, France

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Eric Renard Departement d’Endocrinologie, Diabète, Nutrition, Hôpital Lapeyronie, CHRU Montpellier, Montpellier, France
CIC INSERM 1411, Hôpital Gui de Chauliac, CHU Montpellier, Montpellier Cedex 5, France
Institut de Génomique Fonctionnelle, CNRS UMR 5203/INSERM U661/Université Montpellier, Montpellier, France

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Patrick Lefebvre Departement d’Endocrinologie, Diabète, Nutrition, Hôpital Lapeyronie, CHRU Montpellier, Montpellier, France

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Marie-Christine Picot Unité de Recherche Clinique et Epidémiologie, Hôpital Lapeyronie, CHU Montpellier, Montpellier, France
CIC INSERM 1411, Hôpital Gui de Chauliac, CHU Montpellier, Montpellier Cedex 5, France

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Anne-Marie Dupuy Département de Biochimie, Hôpital Lapeyronie, CHU Montpellier, Montpellier, France

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Jean-Paul Cristol PhyMedExp, Université de Montpellier, INSERM, CNRS, Montpellier, France
Département de Biochimie, Hôpital Lapeyronie, CHU Montpellier, Montpellier, France

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Philippe Courtet Institut de Génomique Fonctionnelle, CNRS, INSERM Université Montpellier, Montpellier, France
Département d’Urgence et Post-Urgence Psychiatrique, Hôpital Lapeyronie, CHU Montpellier, Montpellier, France

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Vincent Boudousq Département de Médecine Nucléaire, Hôpital Carémeau, CHU Nîmes, Nîmes, France

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Antoine Avignon Département Endocrinologie, Nutrition, Diabète, Equipe Nutrition, Diabète, CHU Montpellier, Montpellier, France

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Sébastien Guillaume Institut de Génomique Fonctionnelle, CNRS, INSERM Université Montpellier, Montpellier, France
Département d’Urgence et Post-Urgence Psychiatrique, Hôpital Lapeyronie, CHU Montpellier, Montpellier, France

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Ariane Sultan PhyMedExp, Université de Montpellier, INSERM, CNRS, Montpellier, France
Département Endocrinologie, Nutrition, Diabète, Equipe Nutrition, Diabète, CHU Montpellier, Montpellier, France

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Objectives

The two-fold aim of this study was: (i) to determine the effects of undernutrition on the myokines in patients with restrictive anorexia nervosa (AN) and (ii) to examine the potential link between myokines and bone parameters.

Methods

In this study, 42 young women with restrictive AN and 42 age-matched controls (CON) (mean age, 18.5 ± 4.2 years and 18.6 ± 4.2 years, respectively) were enrolled. aBMD and body composition were determined with DXA. Resting energy expenditure (REEm), a marker of energy status, was indirectly assessed by calorimetry. Bone turnover markers and myokines (follistatin, myostatin and irisin) were concomitantly evaluated.

Results

AN patients presented low aBMD at all bone sites. REEm, bone formation markers, myostatin and IGF-1 were significantly lower, whereas the bone resorption marker and follistatin were higher in AN compared with controls. No difference was observed between groups for irisin levels. When the whole population was studied, among myokines, only myostatin was positively correlated with aBMD at all bone sites. However, multiple regression analyses showed that in the AN group, the independent variables for aBMD were principally amenorrhoea duration, lean tissue mass (LTM) and procollagen type I N-terminal propeptide (PINP). For CON, the independent variables for aBMD were principally LTM, age and PINP. Whatever the group analysed, none of the myokines appeared as explicative independent variables of aBMD.

Conclusion

This study demonstrated that despite the altered myokine levels in patients with AN, their direct effect on aBMD loss and bone turnover alteration seems limited in comparison with other well-known disease-related factors such as oestrogen deprivation.

Open access
Behnaz Abiri Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

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Majid Valizadeh Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

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Amirhossein Ramezani Ahmadi Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

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Shirin Amini Department of Nutrition, Shoushtar Faculty of Medical Sciences, Shoushtar, Iran

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Mohammad Nikoohemmat Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

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Faeze Abbaspour Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

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Farhad Hosseinpanah Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

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Objectives

It has not been established whether vitamin D deficiency is associated with anthropometric state; therefore, this systematic review examined the relationship between serum vitamin D levels with anthropometrics and adiposity across different ages.

Methods

Studies that examined vitamin D deficiency with adiposity measures in different age groups were searched in the PubMed, Scopus, Embase, and Google Scholar databases until November 2023. Two investigators independently reviewed titles and abstracts, examined full-text articles, extracted data, and rated the quality in accordance with the Newcastle–Ottawa criteria.

Results

Seventy-two studies, with a total of 59,430 subjects, were included. Of these studies, 27 cross-sectional studies and one longitudinal study (with 25,615 participants) evaluated the possible link between 25(OH)D serum concentrations and anthropometric/adiposity indices in the pediatric population. Forty-two cross-sectional studies and two cohort investigations (with 33,815 participants) investigated the relationship between serum 25(OH)D levels and adiposity measures in adults and/or the elderly population. There is evidence supporting links between vitamin D deficiency and obesity, and revealed an inverse association between vitamin D and adiposity indicators, specifically in female subjects. However, the effects of several confounding factors should also be considered.

Conclusion

Most published studies, most of which were cross-sectional, reported a negative association between vitamin D and female adiposity indicators. Therefore, serum vitamin D levels should be monitored in overweight/obese individuals.

Open access
Marília D’Elboux Guimarães Brescia Endocrine Genetics Unit (LIM-25), Endocrinology Division, University of São Paulo School of Medicine (FMUSP), Faculdade de Medicina da Universidade de São Paulo (FMUSP), Hospital das Clinicas (HCFMUSP), São Paulo, São Paulo, Brazil
Parathyroid Unit – LIM-28, Laboratório de Cirurgia de Cabeça e Pescoço, Division of Head and Neck Surgery, Department of Surgery, Hospital das Clinicas (HCFMUSP), University of São Paulo School of Medicine (FMUSP), Faculdade de Medicina, Universidade de São Paulo, São Paulo, São Paulo, Brazil

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Karine Candido Rodrigues Endocrine Genetics Unit (LIM-25), Endocrinology Division, University of São Paulo School of Medicine (FMUSP), Faculdade de Medicina da Universidade de São Paulo (FMUSP), Hospital das Clinicas (HCFMUSP), São Paulo, São Paulo, Brazil
Endocrine Oncology Division, Institute of Cancer of the State of São Paulo (ICESP), University of São Paulo School of Medicine (FMUSP), Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, São Paulo, Brazil

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André Fernandes d’Alessandro Parathyroid Unit – LIM-28, Laboratório de Cirurgia de Cabeça e Pescoço, Division of Head and Neck Surgery, Department of Surgery, Hospital das Clinicas (HCFMUSP), University of São Paulo School of Medicine (FMUSP), Faculdade de Medicina, Universidade de São Paulo, São Paulo, São Paulo, Brazil

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Wellington Alves Filho Department of Surgery, Walter Cantidio University Hospital, Federal University of Ceara School of Medicine (FAMED-UFC), Fortaleza, Brazil

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Willemijn Y van der Plas Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

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Schelto Kruijff Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

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Sergio Samir Arap Parathyroid Unit – LIM-28, Laboratório de Cirurgia de Cabeça e Pescoço, Division of Head and Neck Surgery, Department of Surgery, Hospital das Clinicas (HCFMUSP), University of São Paulo School of Medicine (FMUSP), Faculdade de Medicina, Universidade de São Paulo, São Paulo, São Paulo, Brazil

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Sergio Pereira de Almeida Toledo Endocrine Genetics Unit (LIM-25), Endocrinology Division, University of São Paulo School of Medicine (FMUSP), Faculdade de Medicina da Universidade de São Paulo (FMUSP), Hospital das Clinicas (HCFMUSP), São Paulo, São Paulo, Brazil

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Fábio Luiz de Menezes Montenegro Parathyroid Unit – LIM-28, Laboratório de Cirurgia de Cabeça e Pescoço, Division of Head and Neck Surgery, Department of Surgery, Hospital das Clinicas (HCFMUSP), University of São Paulo School of Medicine (FMUSP), Faculdade de Medicina, Universidade de São Paulo, São Paulo, São Paulo, Brazil

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Delmar Muniz Lourenço Jr Endocrine Genetics Unit (LIM-25), Endocrinology Division, University of São Paulo School of Medicine (FMUSP), Faculdade de Medicina da Universidade de São Paulo (FMUSP), Hospital das Clinicas (HCFMUSP), São Paulo, São Paulo, Brazil
Endocrine Oncology Division, Institute of Cancer of the State of São Paulo (ICESP), University of São Paulo School of Medicine (FMUSP), Faculdade de Medicina da Universidade de São Paulo (FMUSP), São Paulo, São Paulo, Brazil

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Background

Potential influences of parathyroidectomy (PTx) on the quality of life (QoL) in multiple endocrine neoplasia type 1-related primary hyperparathyroidism (HPT/MEN1) are unknown.

Method

Short Form 36 Health Survey Questionnaire was prospectively applied to 30 HPT/MEN1 patients submitted to PTx (20, subtotal; 10, total with autograft) before, 6 and 12 months after surgery. Parameters that were analyzed included QoL, age, HPT-related symptoms, general pain, comorbidities, biochemical/hormonal response, PTx type and parathyroid volume.

Results

Asymptomatic patients were younger (30 vs 38 years; P = 0.04) and presented higher QoL scores than symptomatic ones: Physical Component Summary score (PCS) 92.5 vs 61.2, P = 0.0051; Mental Component Summary score (MCS) 82.0 vs 56.0, P = 0.04. In both groups, QoL remained stable 1 year after PTx, independently of the number of comorbidities. Preoperative general pain was negatively correlated with PCS (r = −0.60, P = 0.0004) and MCS (r = −0.57, P = 0.0009). Also, moderate/intense pain was progressively (6/12 months) more frequent in cases developing hypoparathyroidism. The PTx type and hypoparathyroidism did not affect the QoL at 12 months although remnant parathyroid tissue volume did have a positive correlation (P = 0.0490; r = 0.3625) to PCS 12 months after surgery. Patients with one to two comorbidities had as pre-PTx PCS (P = 0.0015) as 12 months and post-PTx PCS (P = 0.0031) and MCS (P = 0.0365) better than patients with three to four comorbidities.

Conclusion

A variable QoL profile was underscored in HPT/MEN1 reflecting multiple factors associated with this complex disorder as comorbidities, advanced age at PTx and presence of preoperative symptoms or of general pain perception. Our data encourage the early indication of PTx in HPT/MEN1 by providing known metabolic benefits to target organs and avoiding potential negative impact on QoL.

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Francesca Marini Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy
F.I.R.M.O. Italian Foundation for the Research on Bone Diseases, Florence, Italy

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Francesca Giusti Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy

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Teresa Iantomasi Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy

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Federica Cioppi University Hospital of Florence, Azienda Ospedaliero Universitaria Careggi (AOUC), Florence, Italy

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Maria Luisa Brandi F.I.R.M.O. Italian Foundation for the Research on Bone Diseases, Florence, Italy

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Multiple endocrine neoplasia type 1 (MEN1) is a rare, inherited cancer syndrome characterized by the development of multiple endocrine and non-endocrine tumors. MEN1 patients show a reduction of bone mass and a higher prevalence of early onset osteoporosis, compared to healthy population of the same age, gender, and ethnicity. During the monitoring and follow-up of MEN1 patients, the attention of clinicians is primarily focused on the diagnosis and therapy of tumors, while the assessment of bone health and mineral metabolism is, in many cases, marginally considered. In this study, we retrospectively analyzed bone and mineral metabolism features in a series of MEN1 patients from the MEN1 Florentine database. Biochemical markers of bone and mineral metabolism and densitometric parameters of bone mass were retrieved from the database and were analyzed based on age ranges and genders of patients and presence/absence of the three main MEN1-related endocrine tumor types. Our evaluation confirmed that patients with a MEN1 diagnosis have a high prevalence of earlyonset osteopenia and osteoporosis, in association with levels of serum and urinary markers of bone turnover higher than the normal reference values, regardless of their different MEN1 tumors. Fifty percent of patients younger than 26 years manifested osteopenia and 8.3% had osteoporosis, in at least one of the measured bone sites. These data suggest the importance of including biochemical and instrumental monitoring of bone metabolism and bone mass in the routine medical evaluation and follow-up of MEN1 patients and MEN1 carriers as important clinical aspects in the management of the syndrome.

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Souad Daamouch Department of Medicine III and Center for Healthy Aging, Technische Universität Dresden, Dresden, Germany

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Sylvia Thiele Department of Medicine III and Center for Healthy Aging, Technische Universität Dresden, Dresden, Germany

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Lorenz Hofbauer Department of Medicine III and Center for Healthy Aging, Technische Universität Dresden, Dresden, Germany

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Martina Rauner Department of Medicine III and Center for Healthy Aging, Technische Universität Dresden, Dresden, Germany

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The link between obesity and low bone strength has become a significant medical concern. The canonical Wnt signaling pathway is a key regulator of mesenchymal stem cell differentiation into either osteoblasts or adipocytes with active Wnt signaling promoting osteoblastogenesis. Our previous research indicated that Dickkopf-1 (Dkk1), a Wnt inhibitor, is upregulated in bone tissue in obesity and that osteoblast-derived Dkk1 drives obesity-induced bone loss. However, Dkk1 is also produced by adipocytes, but the impact of adipogenic Dkk1 on bone remodeling and its role in obesity-induced bone loss remain unclear. Thus, in this study, we investigated the influence of adipogenic Dkk1 on bone homeostasis and obesity-induced bone loss in mice. To that end, deletion of Dkk1 in adipocytes was induced by tamoxifen administration into 8-week-old male Dkk1fl/fl;AdipoQcreERT2 mice. Bone and fat mass were analyzed at 12 and 20 weeks of age. Obesity was induced in 8-week-old male Dkk1fl/fl;AdipoQcre mice with a high-fat diet (HFD) rich in saturated fats for 12 weeks. We observed that 12-week-old male mice without adipogenic Dkk1 had a significant increase in trabecular bone volume in the vertebrae and femoral bones. While histological and serological bone formation markers were not different, the number of osteoclasts and adipocytes was decreased in the vertebral bones of Dkk1fl/fl;AdipoQcre-positive mice. Despite the increased bone mass in 12-week-old male mice, at 20 weeks of age, there was no difference in the bone volume between the controls and Dkk1fl/fl;AdipoQcre-positive mice. Also, Dkk1fl/fl;AdipoQcre-positive mice were not protected from HFD-induced bone loss. Even though mRNA expression levels of Sost, another important Wnt inhibitor, in bone from Dkk1-deficient mice fed with HFD were decreased compared to Dkk1-sufficient mice on an HFD, this did not prevent the HFD-induced suppression of bone formation. In conclusion, adipogenic Dkk1 may play a transient role in bone mass regulation during adolescence, but it does not contribute to bone homeostasis or obesity-induced bone loss later in life.

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Shu-Meng Hu Department of Nephrology, West China Hospital, Sichuan University, Chengdu, Sichuan, China

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Yang-Juan Bai Department of Laboratory Medicine/Research Centre of Clinical Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China

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Ya-Mei Li Department of Laboratory Medicine/Research Centre of Clinical Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China

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Ye Tao Department of Nephrology, West China Hospital, Sichuan University, Chengdu, Sichuan, China

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Xian-Ding Wang Department of Urology/Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China

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Tao Lin Department of Urology/Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, China

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Lan-Lan Wang Department of Laboratory Medicine/Research Centre of Clinical Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China

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Yun-Ying Shi Department of Nephrology, West China Hospital, Sichuan University, Chengdu, Sichuan, China

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Introduction

Tertiary hyperparathyroidism (THPT) and vitamin D deficiency are commonly seen in kidney transplant recipients, which may result in persistently elevated fibroblast growth factor 23 (FGF23) level after transplantation and decreased graft survival. The aim of this study is to evaluate the effect of vitamin D supplementation on THPT, FGF23-alpha Klotho (KLA) axis and cardiovascular complications after transplantation.

Materials and methods

Two hundred nine kidney transplant recipients were included and further divided into treated and untreated groups depending on whether they received vitamin D supplementation. We tracked the state of THPT, bone metabolism and FGF23–KLA axis within 12 months posttransplant and explored the predictors and risk factors for intact FGF23 levels, KLA levels, THPT and cardiovascular complications in recipients.

Results

Vitamin D supplementation significantly improved FGF23 resistance, THPT and high bone turnover status, preserved better graft function and prevented coronary calcification in the treated group compared to the untreated group at month 12. The absence of vitamin D supplementation was an independent risk factor for THPT and a predictor for intact FGF23 and KLA levels at month 12. Age and vitamin D deficiency were independent risk factors for coronary calcification in recipients at month 12.

Conclusion

Vitamin D supplementation effectively improved THPT, FGF23 resistance and bone metabolism, preserved graft function and prevented coronary calcification after transplantation.

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