Bone and Mineral Metabolism

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Mohammed S Razzaque Department of Pathology, Lake Erie College of Osteopathic Medicine, Erie, Pennsylvania, USA

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Fibroblast growth factor‐23 (FGF23) controls the homeostasis of both phosphate and vitamin D. Bone-derived FGF23 can suppress the transcription of 1α‐hydroxylase (1α(OH)ase) to reduce renal activation of vitamin D (1,25(OH)2D3). FGF23 can also activate the transcription of 24‐hydroxylase to enhance the renal degradation process of vitamin D. There is a counter-regulation for FGF23 and vitamin D; 1,25(OH)2D3 induces the skeletal synthesis and the release of FGF23, while FGF23 can suppress the production of 1,25(OH)2D3 by inhibiting 1α(OH)ase synthesis. Genetically ablating FGF23 activities in mice resulted in higher levels of renal 1α(OH)ase, which is also reflected in an increased level of serum 1,25(OH)2D3, while genetically ablating 1α(OH)ase activities in mice reduced the serum levels of FGF23. Similar feedback control of FGF23 and vitamin D is also detected in various human diseases. Further studies are required to understand the subcellular molecular regulation of FGF23 and vitamin D in health and disease.

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Marcela Moraes Mendes Department of Nutrition, Faculty of Health Sciences, University of Brasília, Distrito Federal, Brazil
Department of Nutrition, Institute of Life Sciences, Federal University of Juiz de Fora, Governador Valadares, Minas Gerais, Brazil
Department of Nutrition, Faculty of Health and Medical Sciences, University of Surrey, University of Surrey, Guildford, UK

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Patricia Borges Botelho Department of Nutrition, Faculty of Health Sciences, University of Brasília, Distrito Federal, Brazil

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Helena Ribeiro Department of Environmental Health, Faculty of Public Health, University of São Paulo, São Paulo, Brazil

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Vitamin D enhances calcium absorption and bone mineralisation, promotes maintenance of muscle function, and is crucial for musculoskeletal health. Low vitamin D status triggers secondary hyperparathyroidism, increases bone loss, and leads to muscle weakness. The primary physiologic function of vitamin D and its metabolites is maintaining calcium homeostasis for metabolic functioning, signal transduction, and neuromuscular activity. A considerable amount of human evidence supports the well-recognised contribution of adequate serum 25-hydroxyvitamin D concentrations for bone homeostasis maintenance and prevention and treatment strategies for osteoporosis when combined with adequate calcium intake. This paper aimed to review the literature published, mainly in the last 20 years, on the effect of vitamin D and its supplementation for musculoskeletal health in order to identify the aspects that remain unclear or controversial and therefore require further investigation and debate. There is a clear need for consistent data to establish realistic and meaningful recommendations of vitamin D status that consider different population groups and locations. Moreover, there is still a lack of consensus on thresholds for vitamin D deficiency and optimal status as well as toxicity, optimal intake of vitamin D, vitamin D supplement alone as a strategy to prevent fractures and falls, recommended sun exposure at different latitudes and for different skin pigmentations, and the extra skeletal effects of vitamin D.

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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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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.

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Keiko Ohkuwa Department of Surgery, Ito Hospital, Tokyo, Japan

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Kiminori Sugino Department of Surgery, Ito Hospital, Tokyo, Japan

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Ryohei Katoh Department of Pathology, Ito Hospital, Tokyo, Japan

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Mitsuji Nagahama Department of Surgery, Ito Hospital, Tokyo, Japan

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Wataru Kitagawa Department of Surgery, Ito Hospital, Tokyo, Japan

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Kenichi Matsuzu Department of Surgery, Ito Hospital, Tokyo, Japan

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Akifumi Suzuki Department of Surgery, Ito Hospital, Tokyo, Japan

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Chisato Tomoda Department of Surgery, Ito Hospital, Tokyo, Japan

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Kiyomi Hames Department of Surgery, Ito Hospital, Tokyo, Japan

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Junko Akaishi Department of Surgery, Ito Hospital, Tokyo, Japan

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Chie Masaki Department of Surgery, Ito Hospital, Tokyo, Japan

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Kana Yoshioka Department of Surgery, Ito Hospital, Tokyo, Japan

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Koichi Ito Department of Surgery, Ito Hospital, Tokyo, Japan

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Objective

Parathyroid carcinoma is a rare tumor among parathyroid tumors. Aspiration cytology and needle biopsy are generally not recommended for diagnostic purposes because they cause dissemination. Therefore, it is commonly diagnosed by postoperative histopathological examination. In this study, we investigated whether preoperative inflammatory markers can be used as predictors of cancer in patients with primary hyperparathyroidism.

Design

This was a retrospective study.

Methods

Thirty-six cases of parathyroid carcinoma and 50 cases of parathyroid adenoma (PA) operated with the diagnosis of primary hyperparathyroidism and confirmed histopathologically at Ito Hospital were included in this study. Preoperative clinical characteristics and inflammatory markers (neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio (LMR)) were compared and their values in preoperative prediction were evaluated and analyzed.

Results

Preoperative intact-parathyroid hormone (P  = 0.0003), serum calcium (P  = 0.0048), and tumor diameter (P  = 0.0002) were significantly higher in parathyroid carcinoma than in PA. LMR showed a significant decrease in parathyroid carcinoma (P  = 0.0062). In multivariate analysis, LMR and tumor length diameter were independent predictors. In the receiver operating characteristics analysis, the cut-off values for LMR and tumor length diameter were 4.85 and 28.0 mm, respectively, for parathyroid cancer prediction. When the two extracted factors were stratified by the number of factors held, the predictive ability improved as the number of factors increased.

Conclusion

In the preoperative evaluation, a combination of tumor length diameter of more than 28 mm and LMR of less than 4.85 was considered to have a high probability of cancer.

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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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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.

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Glenville Jones Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, Ontario, Canada

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Vitamin D has many physiological functions including upregulation of intestinal calcium and phosphate absorption, mobilization of bone resorption, renal reabsorption of calcium as well as actions on a variety of pleiotropic functions. It is believed that many of the hormonal effects of vitamin D involve a 1,25-dihydroxyvitamin D3-vitamin D receptor-mediated transcriptional mechanism involving binding to the cellular chromatin and regulating hundreds of genes in many tissues. This comprehensive historical review provides a unique perspective of the many steps of the discovery of vitamin D and its deficiency disease, rickets, stretching from 1650 until the present. The overview is divided into four distinct historical phases which cover the major developments in the field and in the process highlighting the: (a) first recognition of rickets or vitamin D deficiency; (b) discovery of the nutritional factor, vitamin D and its chemical structure; (c) elucidation of vitamin D metabolites including the hormonal form, 1,25-dihydroxyvitamin D3; (d) delineation of the vitamin D cellular machinery, functions and vitamin D-related diseases which focused on understanding the mechanism of action of vitamin D in its many target cells.

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Johanna Öberg Tromso Endocrine Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway

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Rolf Jorde Tromso Endocrine Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway

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Yngve Figenschau Tromso Endocrine Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway
Diagnostic Clinic, University Hospital of North Norway, Tromso, Norway

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Per Medbøe Thorsby Hormone Laboratory, Department of Medical Biochemistry and Biochemical Endocrinology and Metabolism Research Group, Oslo University Hospital, Aker, Oslo, Norway

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Sandra Rinne Dahl Hormone Laboratory, Department of Medical Biochemistry and Biochemical Endocrinology and Metabolism Research Group, Oslo University Hospital, Aker, Oslo, Norway

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Anne Winther Division of Neurosciences, Orthopedics and Rehabilitation Services, University Hospital of North Norway, Tromso, Norway

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Guri Grimnes Tromso Endocrine Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway
Division of Internal Medicine, University Hospital of North Norway, Tromso, Norway

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Objective

Combined hormonal contraceptive (CHC) use has been associated with higher total 25-hydroxyvitamin D (25(OH)D) levels. Here, we investigate the relation between CHC use and vitamin D metabolism to elucidate its clinical interpretation.

Methods

The cross-sectional Fit Futures 1 included 1038 adolescents. Here, a subgroup of 182 girls with available 25(OH)D, 1,25-dihydroxyvitamin D (1,25(OH)2D), 24,25-dihydroxyvitamin D (24,25(OH)2D), vitamin D-binding protein (DBP) and measured free 25(OH)D levels, in addition to parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23), was investigated. Vitamin D metabolites were compared between girls using (CHC+) and not using CHC (CHC−). Further, the predictability of CHC on 25(OH)D levels was assessed in a multiple regression model including lifestyle factors. The ratios 1,25(OH)2D/25(OH)D and 24,25(OH)2D/25(OH)D (vitamin D metabolite ratio (VMR)) in relation to 25(OH)D were presented in scatterplots.

Results

CHC+ (n  = 64; 35% of the girls) had higher 25(OH)D levels (mean ± s.d., 60.3 ± 22.2) nmol/L) than CHC- (n  = 118; 41.8 ± 19.3 nmol/L), P -values <0.01. The differences in 25(OH)D levels between CHC+ and CHC− were attenuated but remained significant after the adjustment of lifestyle factors. CHC+ also had higher levels of 1,25(OH)2D, 24,25(OH)2D, DBP and calcium than CHC−, whereas 1,25(OH)2D/25(OH)D, PTH, FGF23 and albumin were significantly lower. Free 25(OH)D and VMR did not statistically differ, and both ratios appeared similar in relation to 25(OH)D, irrespective of CHC status.

Conclusion

This confirms a clinical impact of CHC on vitamin D levels in adolescents. Our observations are likely due to an increased DBP-concentration, whereas the free 25(OH)D appears unaltered.

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