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Natacha Driessens Université libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (HUB), CUB Hôpital Erasme, Department of Endocrinology, Route de Lennik, Brussels, Belgium

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Madhu Prasai Université libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (HUB), CUB Hôpital Erasme, Department of Endocrinology, Route de Lennik, Brussels, Belgium

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Orsalia Alexopoulou Department of Endocrinology, Cliniques Universitaires Saint Luc, Brussels, Belgium

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Christophe De Block Department of Endocrinology-Diabetology-Metabolism, Universitair Ziekenhuis Antwerpen & University of Antwerp, Drie Eikenstraat, Edegem, Belgium

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Eva Van Caenegem Department of Endocrinology, Academisch Ziekenhuis Sint-Jan Brugge – Oostende AV, Ruddershove, Brugge, Belgium

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Guy T’Sjoen Department of Endocrinology, Ghent Universitary Hospital, C. Heymanslaan, Gent, Belgium

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Frank Nobels Department of Endocrinology, Onze-Lieve Vrouw Ziekenhuis, Moorselbaan, Aalst, Belgium

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Christophe Ghys Department of Endocrinology, Universitair Ziekenhuis Brussel, Laarbeeklaan, Brussels, Belgium

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Laurent Vroonen Department of Endocrinology, Cliniques Universitaires de Liège, Avenue de l’hôpital, Liège, Belgium

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Corinne Jonas Department of Endocrinology, CHU UCL Namur - Godinne, Avenue Docteur Gaston Thérasse, Yvoir, Belgium

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Bernard Corvilain Université libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (HUB), CUB Hôpital Erasme, Department of Endocrinology, Route de Lennik, Brussels, Belgium

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Dominique Maiter Department of Endocrinology, Cliniques Universitaires Saint Luc, Brussels, Belgium

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Objective

Primary adrenal insufficiency (PAI) is a rare disease with an increasing prevalence, which may be complicated by life-threatening adrenal crisis (AC). Good quality epidemiological data remain scarce. We performed a Belgian survey to describe the aetiology, clinical characteristics, treatment regimens, comorbidities and frequency of AC in PAI.

Methods

A nationwide multicentre study involving 10 major university hospitals in Belgium collected data from adult patients with known PAI.

Results

Two hundred patients were included in this survey. The median age at diagnosis was 38 years (IQR 25–48) with a higher female prevalence (F/M sex ratio = 1.53). The median disease duration was 13 years (IQR 7–25). Autoimmune disease was the most common aetiology (62.5%) followed by bilateral adrenalectomy (23.5%) and genetic variations (8.5%). The majority (96%) of patients were treated with hydrocortisone at a mean daily dose of 24.5 ± 7.0 mg, whereas 87.5% of patients also received fludrocortisone. About one-third of patients experienced one or more AC over the follow-up period, giving an incidence of 3.2 crises per 100 patient-years. There was no association between the incidence of AC and the maintenance dose of hydrocortisone. As high as 27.5% of patients were hypertensive, 17.5% had diabetes and 17.5% had a diagnosis of osteoporosis.

Conclusion

This study provides the first information on the management of PAI in large clinical centres in Belgium, showing an increased frequency of postsurgical PAI, a nearly normal prevalence of several comorbidities and an overall good quality of care with a low incidence of adrenal crises, compared with data from other registries.

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Giuseppe Grande Unit of Andrology and Reproductive Medicine, University Hospital of Padova, Padova, Italy

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Andrea Graziani Department of Medicine, University of Padova, Padova, Italy

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Antonella Di Mambro Unit of Andrology and Reproductive Medicine, University Hospital of Padova, Padova, Italy

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Riccardo Selice Unit of Andrology and Reproductive Medicine, University Hospital of Padova, Padova, Italy

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Alberto Ferlin Unit of Andrology and Reproductive Medicine, University Hospital of Padova, Padova, Italy
Department of Medicine, University of Padova, Padova, Italy

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Low bone mass is common in men with Klinefelter syndrome (KS), with a prevalence of 6–15% of osteoporosis and of 25–48% of osteopenia. Reduced bone mass has been described since adolescence and it might be related to both reduced bone formation and higher bone resorption. Although reduced testosterone levels are clearly involved in the pathogenesis, this relation is not always evident. Importantly, fracture risk is increased independently from bone mineral density (BMD) and testosterone levels. Here we discuss the pathogenesis of osteoporosis in patients with KS, with a particular focus on the role of testosterone and testis function. In fact, other hormonal mechanisms, such as global Leydig cell dysfunction, causing reduced insulin-like factor 3 and 25-OH vitamin D levels, and high follicle-stimulating hormone and estradiol levels, might be involved. Furthermore, genetic aspects related to the supernumerary X chromosome might be involved, as well as androgen receptor expression and function. Notably, body composition, skeletal mass and strength, and age at diagnosis are other important aspects. Although dual-energy x-ray absorptiometry is recommended in the clinical workflow for patients with KS to measure BMD, recent evidence suggests that alterations in the microarchitecture of the bones and vertebral fractures might be present even in subjects with normal BMD. Therefore, analysis of trabecular bone score, high-resolution peripheral quantitative computed tomography and vertebral morphometry seem promising tools to better estimate the fracture risk of patients with KS. This review also summarizes the evidence on the best available treatments for osteoporosis in men with KS, with or without hypogonadism.

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Yi Chen Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China

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Wen Zhang Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China

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Chi Chen Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China

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Yuying Wang Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China

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Ningjian Wang Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China

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Yingli Lu Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China

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Objective

We aimed to evaluate whether thyroid hormones, autoimmune and thyroid homeostasis status were related to bone turnover in type 2 diabetes.

Methods

The data were obtained from a cross-sectional study, the METAL study. In this study, 4209 participants (2059 men and 2150 postmenopausal women) with type 2 diabetes were enrolled. Thyroid function, thyroid antibodies and three bone turnover markers (BTMs), including a large N-mid fragment of osteocalcin (N-MID osteocalcin), β-C-terminal cross-linked telopeptides of type I collagen (β-CTX) and procollagen type I N-terminal propeptide (P1NP), were measured. Thyroid homeostasis parameters, including the sum activity of step-up deiodinases (SPINA-GD), thyroid secretory capacity (SPINA-GT), Jostel’s TSH index (TSHI) and the thyrotroph thyroid hormone resistance index (TTSI), were calculated. The associations of thyroid parameters with BTMs were analyzed using linear regression.

Results

Free and total triiodothyronine were positively associated with N-MID osteocalcin and P1NP in both sexes and positively associated with β-CTX in postmenopausal women. Thyroid-stimulating hormone was negatively associated with β-CTX in postmenopausal women, and free thyroxine was negatively associated with N-MID osteocalcin and P1NP in men. SPINA-GD was positively associated with N-MID osteocalcin and P1NP in both sexes. There was a positive relationship of SPINA-GT with β-CTX, a negative relationship of TTSI with β-CTX, and a negative relationship of TSHI with β-CTX and P1NP in postmenopausal women.

Conclusions

Among men and postmenopausal women with type 2 diabetes, significant associations were observed between N-MID osteocalcin, β-CTX and P1NP with thyroid function and thyroid homeostasis. Further prospective studies are warranted to understand the causal relationship and underlying mechanism.

Open access
Gabriella Oliveira Lima Laboratory of Pharmacology and Toxicology of Natural Products, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil

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Alex Luiz Menezes da Silva Laboratory of Pharmacology and Toxicology of Natural Products, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil

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Julianne Elba Cunha Azevedo Laboratory of Pharmacology and Toxicology of Natural Products, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil

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Chirlene Pinheiro Nascimento Laboratory of Pharmacology and Toxicology of Natural Products, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil

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Luana Rodrigues Vieira Laboratory of Pharmacology and Toxicology of Natural Products, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil

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Akira Otake Hamoy Laboratory of Pharmacology and Toxicology of Natural Products, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil

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Luan Oliveira Ferreira Laboratory of Experimental Neuropathology, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil

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Verônica Regina Lobato Oliveira Bahia Multidisciplinary Laboratory of Animal Morphology, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil

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Nilton Akio Muto Amazon Bioactive Compounds Valorization Center, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil

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Dielly Catrina Favacho Lopes Laboratory of Experimental Neuropathology, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil

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Moisés Hamoy Laboratory of Pharmacology and Toxicology of Natural Products, Institute of Biological Sciences, Federal University of Pará, Belém, Pará, Brazil

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Low plasma levels of vitamin D causes bone mineral change that can precipitate osteopenia and osteoporosis and could aggravate autoimmune diseases, hypertension and diabetes. The demand for vitamin D supplementation becomes necessary; however, the consumption of vitamin D is not without risks, which its toxicity could have potentially serious consequences related to hypervitaminosis D, such as hypercalcemia and cerebral alterations. Thus, the present study describes the electroencephalographic changes caused by supraphysiological doses of vitamin D in the brain electrical dynamics and the electrocardiographic changes. After 4 days of treatment with vitamin D at a dose of 25,000 IU/kg, the serum calcium levels found were increased in comparison with the control group. The electrocorticogram analysis found a reduction in wave activity in the delta, theta, alpha and beta frequency bands. For ECG was observed changes with shortened QT follow-up, which could be related to serum calcium concentration. This study presented important evidence about the cerebral and cardiac alterations caused by high doses of vitamin D, indicating valuable parameters in the screening and decision-making process for diagnosing patients with symptoms suggestive of intoxication.

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Victoria Chatzimavridou-Grigoriadou Department of Endocrinology, Christie Hospital NHS Foundation Trust, Manchester, UK
Department of Endocrinology, University of Manchester, School of Medical Sciences, Manchester, UK

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Lisa H Barraclough Department of Endocrinology, Christie Hospital NHS Foundation Trust, Manchester, UK
Department of Endocrinology, University of Manchester, School of Medical Sciences, Manchester, UK

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Rohit Kochhar Department of Clinical Oncology, Christie Hospital NHS Foundation Trust, Manchester, UK

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Lucy Buckley Department of Radiology, Christie Hospital NHS Foundation Trust, Manchester, UK

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Nooreen Alam Department of Radiotherapy, Christie Hospital NHS Foundation Trust, Manchester, UK

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Claire E Higham Department of Endocrinology, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK

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Background

Radiotherapy-related insufficiency fractures (RRIFs) represent a common, burdensome consequence of pelvic radiotherapy. Their underlying mechanisms remain unclear, and data on the effect of osteoporosis are contradictory, with limited studies assessing bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA).

Methods

BMD by DXA (Hologic) scan and fracture risk following pelvic RRIF were retrospectively assessed in 39 patients (median age 68 years) at a tertiary cancer centre. Patient characteristics and treatment history are presented narratively; correlations were explored using univariate regression analyses.

Results

Additional cancer treatments included chemotherapy (n = 31), surgery (n = 20) and brachytherapy (n = 19). Median interval between initiation of radiotherapy and RRIF was 11 (7.5–20.8) and that between RRIF and DXA 3 was (1–6) months. Three patients had normal BMD, 16 had osteopenia and 16 osteoporosis, following World Health Organization classification. Four patients were <40 years at the time of DXA (all Z-scores > –2). Median 10-year risk for hip and major osteoporotic fracture was 3.1% (1.5–5.7) and 11.5% (7.1–13.8), respectively. Only 33.3% of patients had high fracture risk (hip fracture >4% and/or major osteoporotic >20%), and 31% fell above the intervention threshold per National Osteoporosis Guidelines Group (NOGG) guidance (2017). Higher BMD was predicted by lower pelvic radiotherapy dose (only in L3 and L4), concomitant chemotherapy and higher body mass index.

Conclusion

At the time of RRIF, most patients did not have osteoporosis, some had normal BMD and overall had low fracture risk. Whilst low BMD is a probable risk factor, it is unlikely to be the main mechanism underlying RRIFs, and further studies are required to understand the predictive value of BMD.

Open access
Hans Valdemar López Krabbe Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Jørgen Holm Petersen Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
Section of Biostatistics, University of Copenhagen, Copenhagen, Denmark

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Louise Laub Asserhøj Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
Department of Fertility, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark

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Trine Holm Johannsen Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Peter Christiansen Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Rikke Beck Jensen Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

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Line Hartvig Cleemann Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Casper P Hagen Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Lærke Priskorn Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Niels Jørgensen Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Katharina M Main Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

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Anders Juul Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

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Lise Aksglaede Department of Growth and Reproduction, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Adult patients with Klinefelter syndrome (KS) are characterized by a highly variable phenotype, including tall stature, obesity, and hypergonadotropic hypogonadism, as well as an increased risk of developing insulin resistance, metabolic syndrome, and osteoporosis. Most adults need testosterone replacement therapy (TRT), whereas the use of TRT during puberty has been debated. In this retrospective, observational study, reproductive hormones and whole-body dual-energy x-ray absorptiometry-derived body composition and bone mineral content were standardized to age-related standard deviation scores in 62 patients with KS aged 5.9–20.6 years. Serum concentrations of total testosterone and inhibin B were low, whereas luteinizing hormone and follicle-stimulating hormone were high in patients before TRT. Despite normal body mass index, body fat percentage and the ratio between android fat percentage and gynoid fat percentage were significantly higher in the entire group irrespective of treatment status. In patients evaluated before and during TRT, a tendency toward a more beneficial body composition with a significant reduction in the ratio between android fat percentage and gynoid fat percentage during TRT was found. Bone mineral content (BMC) did not differ from the reference, but BMC corrected for bone area was significantly lower when compared to the reference. This study confirms that patients with KS have an unfavorable body composition and an impaired bone mineral status already during childhood and adolescence. Systematic studies are needed to evaluate whether TRT during puberty will improve these parameters.

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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
Milou Cecilia Madsen Department of Internal Medicine and Center of Expertise on Gender Dysphoria, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands

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Martin den Heijer Department of Internal Medicine and Center of Expertise on Gender Dysphoria, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands

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Claudia Pees Walaeus Library, Leiden University Medical Center, Leiden, the Netherlands

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Nienke R Biermasz Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands

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Leontine E H Bakker Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, the Netherlands

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Testosterone therapy is the cornerstone in the care of men with hypogonadism and transgender males. Gel and intramuscular injections are most frequently used and are registered and included in the international guidelines. The specific preparation should be selected according to the patient’s preference, cost, availability, and formulation-specific properties. As the majority of men with hypogonadism and transgender males require lifelong treatment with testosterone, it is important to utilize a regimen that is effective, safe, inexpensive, and convenient to use with optimal mimicking of the physiological situation. This systematic review reviews current literature on differences between the three most used testosterone preparations in adult men with hypogonadism and transgender males. Although it appeared hardly any comparative studies have been carried out, there are indications of differences between the preparations, for example, on the stability of testosterone levels, hematocrit, bone mineral density, and patient satisfaction. However, there are no studies on the effects of testosterone replacement on endpoints such as cardiovascular disease in relation to hematocrit or osteoporotic fractures in relation to bone mineral density. The effect of testosterone therapy on health-related quality of life is strongly underexposed in the reviewed studies, while this is a highly relevant outcome measure from a patient perspective. In conclusion, current recommendations on testosterone treatment appear to be based on data primarily from non-randomized clinical studies and observational studies. The availability of reliable comparative data between the different preparations will assist in the process of individual decision-making to choose the most suitable formula.

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.

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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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