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A Gizard Department of Pediatric Orthopedic Surgery, Besançon University Hospital, Paris, France

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A Rothenbuhler APHP, Department of Pediatric Endocrinology, Bicêtre Paris Sud, Le Kremlin Bicêtre, France
Reference Center for Rare Disorders of Calcium and Phosphate Metabolism, Le Kremlin Bicêtre, France
Plateforme d’Expertise Paris Sud Maladies Rares and Filière OSCAR, Bicêtre Paris Sud, Le Kremlin Bicêtre, France

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Z Pejin APHP, Department of Pediatric Orthopedic Surgery, Necker Hospital, Paris, France

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G Finidori APHP, Department of Pediatric Orthopedic Surgery, Necker Hospital, Paris, France

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C Glorion APHP, Department of Pediatric Orthopedic Surgery, Necker Hospital, Paris, France

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B de Billy Department of Pediatric Orthopedic Surgery, Besançon University Hospital, Paris, France

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A Linglart APHP, Department of Pediatric Endocrinology, Bicêtre Paris Sud, Le Kremlin Bicêtre, France
Reference Center for Rare Disorders of Calcium and Phosphate Metabolism, Le Kremlin Bicêtre, France
Plateforme d’Expertise Paris Sud Maladies Rares and Filière OSCAR, Bicêtre Paris Sud, Le Kremlin Bicêtre, France
INSERM U1169, Hôpital Bicêtre, Le Kremlin Bicêtre, et Université Paris-Saclay, Le Kremlin Bicêtre, France

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P Wicart Reference Center for Rare Disorders of Calcium and Phosphate Metabolism, Le Kremlin Bicêtre, France
APHP, Department of Pediatric Orthopedic Surgery, Necker Hospital, Paris, France

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Background

X-linked hypophosphatemic rickets (XLHR) is due to mutations in PHEX leading to unregulated production of FGF23 and hypophosphatemia. XLHR is characterized by leg bowing of variable severity. Phosphate supplements and oral vitamin analogs, partially or, in some cases, fully restore the limb straightness. Surgery is the alternative for severe or residual limb deformities.

Objective

To retrospectively assess the results of surgical limb correction in XLHR (osteotomies and bone alignment except for 3 transient hemiepiphysiodesis).

Methods

We analyzed the incidence of recurrence and post-surgical complications in 49 XLHR patients (29F, 20M) (mean age at diagnosis 6.0 years (± 7.1)).

Results

At first surgery, the mean age was 13.4 years (± 5.0). Recurrence was observed in 14/49 (29%) patients. The number of additional operations significantly decreased with age (2.0 (± 0.9), 1.7 (± 1.0) and 1.2 (± 0.4) in children <11 years, between 11 and 15, and >15 years; P < 0.001). Incidence of recurrence seemed to be lower in patients with good metabolic control of the rickets (25% vs 33%). Complications were observed in 57% of patients.

Conclusion

We report a large series of surgical procedures in XLHR. Our results confirm that phosphate supplements and vitamin D analog therapy is the first line of treatment to correct leg bowing. Surgery before puberty is associated with a high risk of recurrence of the limb deformity. Such procedures should only be recommended, following multidisciplinary discussions, in patients with severe distortion leading to mechanical joint and ligament complications, or for residual deformities once growth plates have fused.

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Keina Nishio Department of Obstetrics and Gynecology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki-city, Osaka 569-8686, Japan

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Akiko Tanabe Department of Obstetrics and Gynecology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki-city, Osaka 569-8686, Japan

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Risa Maruoka Department of Obstetrics and Gynecology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki-city, Osaka 569-8686, Japan

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Kiyoko Nakamura Department of Obstetrics and Gynecology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki-city, Osaka 569-8686, Japan

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Masaaki Takai Department of Obstetrics and Gynecology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki-city, Osaka 569-8686, Japan

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Tatsuharu Sekijima Department of Obstetrics and Gynecology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki-city, Osaka 569-8686, Japan

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Satoshi Tunetoh Department of Obstetrics and Gynecology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki-city, Osaka 569-8686, Japan

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Yoshito Terai Department of Obstetrics and Gynecology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki-city, Osaka 569-8686, Japan

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Masahide Ohmichi Department of Obstetrics and Gynecology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki-city, Osaka 569-8686, Japan

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Objective

Although surgical menopause may increase the risks of osteoporosis, few studies have investigated the influence of chemotherapy and radiation therapy. The aim of this study is to evaluate the effects of treatments for gynecological malignancies on bone mineral density (BMD).

Methods

This study enrolled 35 premenopausal women (15 ovarian cancers (OCs), 9 endometrial cancers (ECs), and 11 cervical cancers (CCs)) who underwent surgical treatment that included bilateral oophorectomy with or without adjuvant platinum-based chemotherapy in OC and EC patients, or concurrent chemo-radiation therapy (CCRT) in CC patients according to the established protocols at the Osaka Medical College Hospital between 2006 and 2008. The BMD of the lumbar spine (L1–L4) was measured by dual-energy X-ray absorptiometry, and urine cross-linked telopeptides of type I collagen (NTx) and bone alkaline phosphatase (BAP) were assessed for evaluation of bone resorption and bone formation respectively. These assessments were performed at baseline and 12 months after treatment.

Results

Although the serum BAP was significantly increased only in the CC group, a rapid increase in the bone resorption marker urinary NTx was observed in all groups. The BMD, 12 months after CCRT was significantly decreased in the CC group at 91.9±5.9% (P<0.05 in comparison to the baseline).

Conclusion

This research suggests that anticancer therapies for premenopausal women with gynecological malignancies increase bone resorption and may reduce BMD, particularly in CC patients who have received CCRT. Therefore, gynecologic cancer survivors should be educated about these potential risks and complications.

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Ulla Schmidt Endocrine Unit, Department of Medicine, Endocrine Unit, Faculty of Health Sciences, Department of Medicine O, Herlev University Hospital, Herlev Ringvej, DK-2730 Herlev, Denmark

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Birte Nygaard Endocrine Unit, Department of Medicine, Endocrine Unit, Faculty of Health Sciences, Department of Medicine O, Herlev University Hospital, Herlev Ringvej, DK-2730 Herlev, Denmark

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Ebbe Winther Jensen Endocrine Unit, Department of Medicine, Endocrine Unit, Faculty of Health Sciences, Department of Medicine O, Herlev University Hospital, Herlev Ringvej, DK-2730 Herlev, Denmark

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Jan Kvetny Endocrine Unit, Department of Medicine, Endocrine Unit, Faculty of Health Sciences, Department of Medicine O, Herlev University Hospital, Herlev Ringvej, DK-2730 Herlev, Denmark

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Anne Jarløv Endocrine Unit, Department of Medicine, Endocrine Unit, Faculty of Health Sciences, Department of Medicine O, Herlev University Hospital, Herlev Ringvej, DK-2730 Herlev, Denmark

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Jens Faber Endocrine Unit, Department of Medicine, Endocrine Unit, Faculty of Health Sciences, Department of Medicine O, Herlev University Hospital, Herlev Ringvej, DK-2730 Herlev, Denmark
Endocrine Unit, Department of Medicine, Endocrine Unit, Faculty of Health Sciences, Department of Medicine O, Herlev University Hospital, Herlev Ringvej, DK-2730 Herlev, Denmark

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Background

A recent randomized controlled trial suggests that hypothyroid subjects may find levothyroxine (l-T4) and levotriiodothyronine combination therapy to be superior to l-T4 monotherapy in terms of quality of life, suggesting that the brain registered increased T3 availability during the combination therapy.

Hypothesis

Peripheral tissue might also be stimulated during T4/T3 combination therapy compared with T4 monotherapy.

Methods

Serum levels of sex hormone-binding globulin (SHBG), pro-collagen-1-N-terminal peptide (PINP), and N-terminal pro-brain natriuretic peptide (NT-proBNP) (representing hepatocyte, osteoblast, and cardiomyocyte stimulation respectively) were measured in 26 hypothyroid subjects in a double-blind, randomized, crossover trial, which compared the replacement therapy with T4/T3 in combination (50 μg T4 was substituted with 20 μg T3) to T4 alone (once daily regimens). This was performed to obtain unaltered serum TSH levels during the trial and between the two treatment groups. Blood sampling was performed 24 h after the last intake of thyroid hormone medication.

Results

TSH remained unaltered between the groups ((median) 0.83 vs 1.18 mU/l in T4/T3 combination and T4 monotherapy respectively; P=0.534). SHBG increased from (median) 75 nmol/l at baseline to 83 nmol/l in the T4/T3 group (P=0.015) but remained unaltered in the T4 group (67 nmol/l); thus, it was higher in the T4/T3 vs T4 group (P=0.041). PINP levels were higher in the T4/T3 therapy (48 vs 40 μg/l (P<0.001)). NT-proBNP did not differ between the groups.

Conclusions

T4/T3 combination therapy in hypothyroidism seems to have more metabolic effects than the T4 monotherapy.

Open access
Eva Novoa Department of Otorhinolaryngology, Clinic of Endocrinology, Head and Neck Surgery

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Marcel Gärtner Department of Otorhinolaryngology, Clinic of Endocrinology, Head and Neck Surgery

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Christoph Henzen Department of Otorhinolaryngology, Clinic of Endocrinology, Head and Neck Surgery

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Objective

The study aimed to assess the possible systemic effects of intratympanic dexamethasone (IT-Dex) on the hypothalamic–pituitary–adrenal (HPA) axis, inflammation, and bone metabolism.

Design

A prospective cohort study including 30 adult patients of a tertiary referral ENT clinic treated with 9.6 mg IT-Dex over a period of 10 days was carried out.

Methods

Effects on plasma and salivary cortisol concentrations (basal and after low-dose (1 μg) ACTH stimulation), peripheral white blood cell count, and biomarkers for bone turnover were measured before (day 0) and after IT-Dex (day 16). Additional measurements for bone turnover were performed 5 months after therapy. Clinical information and medication with possible dexamethasone interaction were recorded.

Results

IT-Dex was well tolerated, and no effect was detected on the HPA axis (stimulated plasma and salivary cortisol concentration on day 0: 758±184 and 44.5±22.0 nmol/l; day 16: 718±154 and 39.8±12.4 nmol/l; P=0.58 and 0.24 respectively). Concentrations of osteocalcin (OC) and bone-specific alkaline phosphatase (BSAP) did not differ after dexamethasone (OC on days 0 and 16 respectively: 24.1±10.5 and 23.6±8.8 μg/l; BSAP on day 0, 16, and after 5 months respectively: 11.5±4.2, 10.3±3.4, and 12.6±5.06 μg/l); similarly, there was no difference in the peripheral white blood cell count (5.7×1012/l and 6.1×1012/l on days 0 and 16 respectively).

Conclusions

IT-Dex therapy did not interfere with endogenous cortisol secretion or bone metabolism.

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Lu Liu
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Chunyan Li
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Peng Yang
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Jian Zhu Department of Endocrinology, Department of Internal Medicine, Department of Paediatrics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Middle Road, Shanghai 200072, China

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Dongmei Gan Department of Endocrinology, Department of Internal Medicine, Department of Paediatrics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Yanchang Middle Road, Shanghai 200072, China

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Le Bu
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Manna Zhang
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Chunjun Sheng
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Hong Li
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Shen Qu
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Alendronate (ALN) is a commonly used drug for the treatment of osteoporosis. Atypical femur fractures (AFFs) have been associated with long-term use of ALN and have recently become the subject of considerable attention as ALN use increases. This meta-analysis aimed to determine the relationship between ALN and AFF. The Embase, PubMed, and Cochrane library databases were searched for relevant studies published before November 6, 2014. Studies clearly reporting the relationship between ALN and AFF were selected for our analysis. From these results, the relationship between ALN and AFF was analyzed. Weighted mean differences were calculated using a random-effects model. Five studies were included in this meta-analysis. The results revealed that the use of ALN will not increase the risk of AFF in short term (P>0.05), but there will be a risk of AFF (P<0.05) with long-term (>5 years) use of ALN. These findings indicate that long-term use of ALN is a risk factor for AFF and that more attention should be paid to the clinical applications of ALN.

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Veronica Kieffer
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Kate Davies University Hospitals of Leicester NHS Trust, Great Ormond Street Hospital for Children NHS Trust, Central Manchester University Hospitals NHS Foundation Trust, NHS Grampian, Portsmouth Hospitals NHS Trust, Salford Royal Hospitals Foundation Trust, Heart of England NHS Foundation Trust, The London Clinic, Department of Diabetes and Endocrinology, Leicester Royal Infirmary, Leicester, LE1 5WW, UK

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Christine Gibson University Hospitals of Leicester NHS Trust, Great Ormond Street Hospital for Children NHS Trust, Central Manchester University Hospitals NHS Foundation Trust, NHS Grampian, Portsmouth Hospitals NHS Trust, Salford Royal Hospitals Foundation Trust, Heart of England NHS Foundation Trust, The London Clinic, Department of Diabetes and Endocrinology, Leicester Royal Infirmary, Leicester, LE1 5WW, UK

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Morag Middleton University Hospitals of Leicester NHS Trust, Great Ormond Street Hospital for Children NHS Trust, Central Manchester University Hospitals NHS Foundation Trust, NHS Grampian, Portsmouth Hospitals NHS Trust, Salford Royal Hospitals Foundation Trust, Heart of England NHS Foundation Trust, The London Clinic, Department of Diabetes and Endocrinology, Leicester Royal Infirmary, Leicester, LE1 5WW, UK

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Jean Munday University Hospitals of Leicester NHS Trust, Great Ormond Street Hospital for Children NHS Trust, Central Manchester University Hospitals NHS Foundation Trust, NHS Grampian, Portsmouth Hospitals NHS Trust, Salford Royal Hospitals Foundation Trust, Heart of England NHS Foundation Trust, The London Clinic, Department of Diabetes and Endocrinology, Leicester Royal Infirmary, Leicester, LE1 5WW, UK

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Shashana Shalet University Hospitals of Leicester NHS Trust, Great Ormond Street Hospital for Children NHS Trust, Central Manchester University Hospitals NHS Foundation Trust, NHS Grampian, Portsmouth Hospitals NHS Trust, Salford Royal Hospitals Foundation Trust, Heart of England NHS Foundation Trust, The London Clinic, Department of Diabetes and Endocrinology, Leicester Royal Infirmary, Leicester, LE1 5WW, UK

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Lisa Shepherd University Hospitals of Leicester NHS Trust, Great Ormond Street Hospital for Children NHS Trust, Central Manchester University Hospitals NHS Foundation Trust, NHS Grampian, Portsmouth Hospitals NHS Trust, Salford Royal Hospitals Foundation Trust, Heart of England NHS Foundation Trust, The London Clinic, Department of Diabetes and Endocrinology, Leicester Royal Infirmary, Leicester, LE1 5WW, UK

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Phillip Yeoh University Hospitals of Leicester NHS Trust, Great Ormond Street Hospital for Children NHS Trust, Central Manchester University Hospitals NHS Foundation Trust, NHS Grampian, Portsmouth Hospitals NHS Trust, Salford Royal Hospitals Foundation Trust, Heart of England NHS Foundation Trust, The London Clinic, Department of Diabetes and Endocrinology, Leicester Royal Infirmary, Leicester, LE1 5WW, UK

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This competency framework was developed by a working group of endocrine specialist nurses with the support of the Society for Endocrinology to enhance the clinical care that adults with an endocrine disorder receive. Nurses should be able to demonstrate that they are functioning at an optimal level in order for patients to receive appropriate care. By formulating a competency framework from which an adult endocrine nurse specialist can work, it is envisaged that their development as professional practitioners can be enhanced. This is the second edition of the Competency Framework for Adult Endocrine Nursing. It introduces four new competencies on benign adrenal tumours, hypo- and hyperparathyroidism, osteoporosis and polycystic ovary syndrome. The authors and the Society for Endocrinology welcome constructive feedback on the document, both nationally and internationally, in anticipation that further developments and ideas can be incorporated into future versions.

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Karoline Winckler Department of Cardiology, Department of Research, Institute of Clinical Studies, Clinical Research Unit, Department of Paediatrics, Department of Medicine, Department of Physiology and Nuclear Medicine, Institute of Clinical Medicine, Nephrology and Endocrinology

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Lise Tarnow Department of Cardiology, Department of Research, Institute of Clinical Studies, Clinical Research Unit, Department of Paediatrics, Department of Medicine, Department of Physiology and Nuclear Medicine, Institute of Clinical Medicine, Nephrology and Endocrinology
Department of Cardiology, Department of Research, Institute of Clinical Studies, Clinical Research Unit, Department of Paediatrics, Department of Medicine, Department of Physiology and Nuclear Medicine, Institute of Clinical Medicine, Nephrology and Endocrinology
Department of Cardiology, Department of Research, Institute of Clinical Studies, Clinical Research Unit, Department of Paediatrics, Department of Medicine, Department of Physiology and Nuclear Medicine, Institute of Clinical Medicine, Nephrology and Endocrinology

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Louise Lundby-Christensen Department of Cardiology, Department of Research, Institute of Clinical Studies, Clinical Research Unit, Department of Paediatrics, Department of Medicine, Department of Physiology and Nuclear Medicine, Institute of Clinical Medicine, Nephrology and Endocrinology
Department of Cardiology, Department of Research, Institute of Clinical Studies, Clinical Research Unit, Department of Paediatrics, Department of Medicine, Department of Physiology and Nuclear Medicine, Institute of Clinical Medicine, Nephrology and Endocrinology

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Thomas P Almdal Department of Cardiology, Department of Research, Institute of Clinical Studies, Clinical Research Unit, Department of Paediatrics, Department of Medicine, Department of Physiology and Nuclear Medicine, Institute of Clinical Medicine, Nephrology and Endocrinology
Department of Cardiology, Department of Research, Institute of Clinical Studies, Clinical Research Unit, Department of Paediatrics, Department of Medicine, Department of Physiology and Nuclear Medicine, Institute of Clinical Medicine, Nephrology and Endocrinology

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Niels Wiinberg Department of Cardiology, Department of Research, Institute of Clinical Studies, Clinical Research Unit, Department of Paediatrics, Department of Medicine, Department of Physiology and Nuclear Medicine, Institute of Clinical Medicine, Nephrology and Endocrinology

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Pia Eiken Department of Cardiology, Department of Research, Institute of Clinical Studies, Clinical Research Unit, Department of Paediatrics, Department of Medicine, Department of Physiology and Nuclear Medicine, Institute of Clinical Medicine, Nephrology and Endocrinology
Department of Cardiology, Department of Research, Institute of Clinical Studies, Clinical Research Unit, Department of Paediatrics, Department of Medicine, Department of Physiology and Nuclear Medicine, Institute of Clinical Medicine, Nephrology and Endocrinology

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Trine W Boesgaard Department of Cardiology, Department of Research, Institute of Clinical Studies, Clinical Research Unit, Department of Paediatrics, Department of Medicine, Department of Physiology and Nuclear Medicine, Institute of Clinical Medicine, Nephrology and Endocrinology

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the CIMT trial group
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Despite aggressive treatment of cardiovascular disease (CVD) risk factors individuals with type 2 diabetes (T2D) still have increased risk of cardiovascular morbidity and mortality. The primary aim of this study was to examine the cross-sectional association between total (25-hydroxy vitamin D (25(OH)D)) and risk of CVD in patients with T2D. Secondary objective was to examine the association between 25(OH)D and bone health. A Danish cohort of patients with T2D participating in a randomised clinical trial were analysed. In total 415 patients (68% men, age 60±9 years (mean±s.d.), duration of diabetes 12±6 years), including 294 patients (71%) treated with insulin. Carotid intima–media thickness (IMT) and arterial stiffness (carotid artery distensibility coefficient (DC) and Young's elastic modulus (YEM)) were measured by ultrasound scan as indicators of CVD. Bone health was assessed by bone mineral density and trabecular bone score measured by dual energy X-ray absorptiometry. In this cohort, 214 patients (52%) were vitamin D deficient (25(OH)D <50 nmol/l). Carotid IMT was 0.793±0.137 mm, DC was 0.0030±0.001 mmHg, YEM was 2354±1038 mmHg and 13 (3%) of the patients were diagnosed with osteoporosis. A 25(OH)D level was not associated with carotid IMT or arterial stiffness (P>0.3) or bone health (P>0.6) after adjustment for CVD risk factors. In conclusion, 25(OH)D status was not associated with carotid IMT, arterial stiffness or bone health in this cohort of patients with T2D. To explore these associations and the association with other biomarkers further, multicentre studies with large numbers of patients are required.

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Kaisa K Ivaska
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Maikki K Heliövaara Department of Cell Biology and Anatomy, Department of Medicine, Turku PET Centre, Department of Radiology, Medical Imaging Centre of Southwest Finland, Department of Endocrinology, Abdominal Center: Endocrinology, Minerva Foundation Institute for Medical Research, Institute of Biomedicine, University of Turku, FI-20520 Turku, Finland

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Pertti Ebeling Department of Cell Biology and Anatomy, Department of Medicine, Turku PET Centre, Department of Radiology, Medical Imaging Centre of Southwest Finland, Department of Endocrinology, Abdominal Center: Endocrinology, Minerva Foundation Institute for Medical Research, Institute of Biomedicine, University of Turku, FI-20520 Turku, Finland

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Marco Bucci Department of Cell Biology and Anatomy, Department of Medicine, Turku PET Centre, Department of Radiology, Medical Imaging Centre of Southwest Finland, Department of Endocrinology, Abdominal Center: Endocrinology, Minerva Foundation Institute for Medical Research, Institute of Biomedicine, University of Turku, FI-20520 Turku, Finland

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Ville Huovinen Department of Cell Biology and Anatomy, Department of Medicine, Turku PET Centre, Department of Radiology, Medical Imaging Centre of Southwest Finland, Department of Endocrinology, Abdominal Center: Endocrinology, Minerva Foundation Institute for Medical Research, Institute of Biomedicine, University of Turku, FI-20520 Turku, Finland
Department of Cell Biology and Anatomy, Department of Medicine, Turku PET Centre, Department of Radiology, Medical Imaging Centre of Southwest Finland, Department of Endocrinology, Abdominal Center: Endocrinology, Minerva Foundation Institute for Medical Research, Institute of Biomedicine, University of Turku, FI-20520 Turku, Finland
Department of Cell Biology and Anatomy, Department of Medicine, Turku PET Centre, Department of Radiology, Medical Imaging Centre of Southwest Finland, Department of Endocrinology, Abdominal Center: Endocrinology, Minerva Foundation Institute for Medical Research, Institute of Biomedicine, University of Turku, FI-20520 Turku, Finland

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H Kalervo Väänänen
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Pirjo Nuutila Department of Cell Biology and Anatomy, Department of Medicine, Turku PET Centre, Department of Radiology, Medical Imaging Centre of Southwest Finland, Department of Endocrinology, Abdominal Center: Endocrinology, Minerva Foundation Institute for Medical Research, Institute of Biomedicine, University of Turku, FI-20520 Turku, Finland
Department of Cell Biology and Anatomy, Department of Medicine, Turku PET Centre, Department of Radiology, Medical Imaging Centre of Southwest Finland, Department of Endocrinology, Abdominal Center: Endocrinology, Minerva Foundation Institute for Medical Research, Institute of Biomedicine, University of Turku, FI-20520 Turku, Finland

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Heikki A Koistinen Department of Cell Biology and Anatomy, Department of Medicine, Turku PET Centre, Department of Radiology, Medical Imaging Centre of Southwest Finland, Department of Endocrinology, Abdominal Center: Endocrinology, Minerva Foundation Institute for Medical Research, Institute of Biomedicine, University of Turku, FI-20520 Turku, Finland
Department of Cell Biology and Anatomy, Department of Medicine, Turku PET Centre, Department of Radiology, Medical Imaging Centre of Southwest Finland, Department of Endocrinology, Abdominal Center: Endocrinology, Minerva Foundation Institute for Medical Research, Institute of Biomedicine, University of Turku, FI-20520 Turku, Finland

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Insulin signaling in bone-forming osteoblasts stimulates bone formation and promotes the release of osteocalcin (OC) in mice. Only a few studies have assessed the direct effect of insulin on bone metabolism in humans. Here, we studied markers of bone metabolism in response to acute hyperinsulinemia in men and women. Thirty-three subjects from three separate cohorts (n=8, n=12 and n=13) participated in a euglycaemic hyperinsulinemic clamp study. Blood samples were collected before and at the end of infusions to determine the markers of bone formation (PINP, total OC, uncarboxylated form of OC (ucOC)) and resorption (CTX, TRAcP5b). During 4 h insulin infusion (40 mU/m2 per min, low insulin), CTX level decreased by 11% (P<0.05). High insulin infusion rate (72 mU/m2 per min) for 4 h resulted in more pronounced decrease (−32%, P<0.01) whereas shorter insulin exposure (40 mU/m2 per min for 2 h) had no effect (P=0.61). Markers of osteoblast activity remained unchanged during 4 h insulin, but the ratio of uncarboxylated-to-total OC decreased in response to insulin (P<0.05 and P<0.01 for low and high insulin for 4 h respectively). During 2 h low insulin infusion, both total OC and ucOC decreased significantly (P<0.01 for both). In conclusion, insulin decreases bone resorption and circulating levels of total OC and ucOC. Insulin has direct effects on bone metabolism in humans and changes in the circulating levels of bone markers can be seen within a few hours after administration of insulin.

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Agnès Linglart Service d'Endocrinologie et Diabétologie de l'Enfant, Service de Pédiatrie générale – Consultation de rhumatologie, Service d'Endocrinologie et des Maladies de la Reproduction, Service d'ORL et chirurgie cervico-maxillo-faciale, Université Paris 11, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphore, Service d'Odontologie-Maladies Rares Hôpital Bretonneau 2 rue Carpeaux, Université Paris Descartes 12 Rue de l'École de Médecine, Service Rhumatologie B Hôpital Cochin, Centre de Référence des Maladies Rares des Maladies Auto-Inflammatoires Rares de l'Enfant, Service d'explorations fonctionnelles rénales, Service de Chirurgie infantile orthopédique, Association de patients RVRH-XLH, Hôpital Bicêtre, APHP, 78 rue du Général Leclerc, 94270 Le Kremlin Bicêtre, France
Service d'Endocrinologie et Diabétologie de l'Enfant, Service de Pédiatrie générale – Consultation de rhumatologie, Service d'Endocrinologie et des Maladies de la Reproduction, Service d'ORL et chirurgie cervico-maxillo-faciale, Université Paris 11, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphore, Service d'Odontologie-Maladies Rares Hôpital Bretonneau 2 rue Carpeaux, Université Paris Descartes 12 Rue de l'École de Médecine, Service Rhumatologie B Hôpital Cochin, Centre de Référence des Maladies Rares des Maladies Auto-Inflammatoires Rares de l'Enfant, Service d'explorations fonctionnelles rénales, Service de Chirurgie infantile orthopédique, Association de patients RVRH-XLH, Hôpital Bicêtre, APHP, 78 rue du Général Leclerc, 94270 Le Kremlin Bicêtre, France
Service d'Endocrinologie et Diabétologie de l'Enfant, Service de Pédiatrie générale – Consultation de rhumatologie, Service d'Endocrinologie et des Maladies de la Reproduction, Service d'ORL et chirurgie cervico-maxillo-faciale, Université Paris 11, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphore, Service d'Odontologie-Maladies Rares Hôpital Bretonneau 2 rue Carpeaux, Université Paris Descartes 12 Rue de l'École de Médecine, Service Rhumatologie B Hôpital Cochin, Centre de Référence des Maladies Rares des Maladies Auto-Inflammatoires Rares de l'Enfant, Service d'explorations fonctionnelles rénales, Service de Chirurgie infantile orthopédique, Association de patients RVRH-XLH, Hôpital Bicêtre, APHP, 78 rue du Général Leclerc, 94270 Le Kremlin Bicêtre, France

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Martin Biosse-Duplan Service d'Endocrinologie et Diabétologie de l'Enfant, Service de Pédiatrie générale – Consultation de rhumatologie, Service d'Endocrinologie et des Maladies de la Reproduction, Service d'ORL et chirurgie cervico-maxillo-faciale, Université Paris 11, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphore, Service d'Odontologie-Maladies Rares Hôpital Bretonneau 2 rue Carpeaux, Université Paris Descartes 12 Rue de l'École de Médecine, Service Rhumatologie B Hôpital Cochin, Centre de Référence des Maladies Rares des Maladies Auto-Inflammatoires Rares de l'Enfant, Service d'explorations fonctionnelles rénales, Service de Chirurgie infantile orthopédique, Association de patients RVRH-XLH, Hôpital Bicêtre, APHP, 78 rue du Général Leclerc, 94270 Le Kremlin Bicêtre, France
Service d'Endocrinologie et Diabétologie de l'Enfant, Service de Pédiatrie générale – Consultation de rhumatologie, Service d'Endocrinologie et des Maladies de la Reproduction, Service d'ORL et chirurgie cervico-maxillo-faciale, Université Paris 11, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphore, Service d'Odontologie-Maladies Rares Hôpital Bretonneau 2 rue Carpeaux, Université Paris Descartes 12 Rue de l'École de Médecine, Service Rhumatologie B Hôpital Cochin, Centre de Référence des Maladies Rares des Maladies Auto-Inflammatoires Rares de l'Enfant, Service d'explorations fonctionnelles rénales, Service de Chirurgie infantile orthopédique, Association de patients RVRH-XLH, Hôpital Bicêtre, APHP, 78 rue du Général Leclerc, 94270 Le Kremlin Bicêtre, France
Service d'Endocrinologie et Diabétologie de l'Enfant, Service de Pédiatrie générale – Consultation de rhumatologie, Service d'Endocrinologie et des Maladies de la Reproduction, Service d'ORL et chirurgie cervico-maxillo-faciale, Université Paris 11, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphore, Service d'Odontologie-Maladies Rares Hôpital Bretonneau 2 rue Carpeaux, Université Paris Descartes 12 Rue de l'École de Médecine, Service Rhumatologie B Hôpital Cochin, Centre de Référence des Maladies Rares des Maladies Auto-Inflammatoires Rares de l'Enfant, Service d'explorations fonctionnelles rénales, Service de Chirurgie infantile orthopédique, Association de patients RVRH-XLH, Hôpital Bicêtre, APHP, 78 rue du Général Leclerc, 94270 Le Kremlin Bicêtre, France

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Karine Briot Service d'Endocrinologie et Diabétologie de l'Enfant, Service de Pédiatrie générale – Consultation de rhumatologie, Service d'Endocrinologie et des Maladies de la Reproduction, Service d'ORL et chirurgie cervico-maxillo-faciale, Université Paris 11, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphore, Service d'Odontologie-Maladies Rares Hôpital Bretonneau 2 rue Carpeaux, Université Paris Descartes 12 Rue de l'École de Médecine, Service Rhumatologie B Hôpital Cochin, Centre de Référence des Maladies Rares des Maladies Auto-Inflammatoires Rares de l'Enfant, Service d'explorations fonctionnelles rénales, Service de Chirurgie infantile orthopédique, Association de patients RVRH-XLH, Hôpital Bicêtre, APHP, 78 rue du Général Leclerc, 94270 Le Kremlin Bicêtre, France
Service d'Endocrinologie et Diabétologie de l'Enfant, Service de Pédiatrie générale – Consultation de rhumatologie, Service d'Endocrinologie et des Maladies de la Reproduction, Service d'ORL et chirurgie cervico-maxillo-faciale, Université Paris 11, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphore, Service d'Odontologie-Maladies Rares Hôpital Bretonneau 2 rue Carpeaux, Université Paris Descartes 12 Rue de l'École de Médecine, Service Rhumatologie B Hôpital Cochin, Centre de Référence des Maladies Rares des Maladies Auto-Inflammatoires Rares de l'Enfant, Service d'explorations fonctionnelles rénales, Service de Chirurgie infantile orthopédique, Association de patients RVRH-XLH, Hôpital Bicêtre, APHP, 78 rue du Général Leclerc, 94270 Le Kremlin Bicêtre, France

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Catherine Chaussain Service d'Endocrinologie et Diabétologie de l'Enfant, Service de Pédiatrie générale – Consultation de rhumatologie, Service d'Endocrinologie et des Maladies de la Reproduction, Service d'ORL et chirurgie cervico-maxillo-faciale, Université Paris 11, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphore, Service d'Odontologie-Maladies Rares Hôpital Bretonneau 2 rue Carpeaux, Université Paris Descartes 12 Rue de l'École de Médecine, Service Rhumatologie B Hôpital Cochin, Centre de Référence des Maladies Rares des Maladies Auto-Inflammatoires Rares de l'Enfant, Service d'explorations fonctionnelles rénales, Service de Chirurgie infantile orthopédique, Association de patients RVRH-XLH, Hôpital Bicêtre, APHP, 78 rue du Général Leclerc, 94270 Le Kremlin Bicêtre, France
Service d'Endocrinologie et Diabétologie de l'Enfant, Service de Pédiatrie générale – Consultation de rhumatologie, Service d'Endocrinologie et des Maladies de la Reproduction, Service d'ORL et chirurgie cervico-maxillo-faciale, Université Paris 11, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphore, Service d'Odontologie-Maladies Rares Hôpital Bretonneau 2 rue Carpeaux, Université Paris Descartes 12 Rue de l'École de Médecine, Service Rhumatologie B Hôpital Cochin, Centre de Référence des Maladies Rares des Maladies Auto-Inflammatoires Rares de l'Enfant, Service d'explorations fonctionnelles rénales, Service de Chirurgie infantile orthopédique, Association de patients RVRH-XLH, Hôpital Bicêtre, APHP, 78 rue du Général Leclerc, 94270 Le Kremlin Bicêtre, France
Service d'Endocrinologie et Diabétologie de l'Enfant, Service de Pédiatrie générale – Consultation de rhumatologie, Service d'Endocrinologie et des Maladies de la Reproduction, Service d'ORL et chirurgie cervico-maxillo-faciale, Université Paris 11, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphore, Service d'Odontologie-Maladies Rares Hôpital Bretonneau 2 rue Carpeaux, Université Paris Descartes 12 Rue de l'École de Médecine, Service Rhumatologie B Hôpital Cochin, Centre de Référence des Maladies Rares des Maladies Auto-Inflammatoires Rares de l'Enfant, Service d'explorations fonctionnelles rénales, Service de Chirurgie infantile orthopédique, Association de patients RVRH-XLH, Hôpital Bicêtre, APHP, 78 rue du Général Leclerc, 94270 Le Kremlin Bicêtre, France

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Laure Esterle Service d'Endocrinologie et Diabétologie de l'Enfant, Service de Pédiatrie générale – Consultation de rhumatologie, Service d'Endocrinologie et des Maladies de la Reproduction, Service d'ORL et chirurgie cervico-maxillo-faciale, Université Paris 11, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphore, Service d'Odontologie-Maladies Rares Hôpital Bretonneau 2 rue Carpeaux, Université Paris Descartes 12 Rue de l'École de Médecine, Service Rhumatologie B Hôpital Cochin, Centre de Référence des Maladies Rares des Maladies Auto-Inflammatoires Rares de l'Enfant, Service d'explorations fonctionnelles rénales, Service de Chirurgie infantile orthopédique, Association de patients RVRH-XLH, Hôpital Bicêtre, APHP, 78 rue du Général Leclerc, 94270 Le Kremlin Bicêtre, France
Service d'Endocrinologie et Diabétologie de l'Enfant, Service de Pédiatrie générale – Consultation de rhumatologie, Service d'Endocrinologie et des Maladies de la Reproduction, Service d'ORL et chirurgie cervico-maxillo-faciale, Université Paris 11, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphore, Service d'Odontologie-Maladies Rares Hôpital Bretonneau 2 rue Carpeaux, Université Paris Descartes 12 Rue de l'École de Médecine, Service Rhumatologie B Hôpital Cochin, Centre de Référence des Maladies Rares des Maladies Auto-Inflammatoires Rares de l'Enfant, Service d'explorations fonctionnelles rénales, Service de Chirurgie infantile orthopédique, Association de patients RVRH-XLH, Hôpital Bicêtre, APHP, 78 rue du Général Leclerc, 94270 Le Kremlin Bicêtre, France

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Séverine Guillaume-Czitrom Service d'Endocrinologie et Diabétologie de l'Enfant, Service de Pédiatrie générale – Consultation de rhumatologie, Service d'Endocrinologie et des Maladies de la Reproduction, Service d'ORL et chirurgie cervico-maxillo-faciale, Université Paris 11, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphore, Service d'Odontologie-Maladies Rares Hôpital Bretonneau 2 rue Carpeaux, Université Paris Descartes 12 Rue de l'École de Médecine, Service Rhumatologie B Hôpital Cochin, Centre de Référence des Maladies Rares des Maladies Auto-Inflammatoires Rares de l'Enfant, Service d'explorations fonctionnelles rénales, Service de Chirurgie infantile orthopédique, Association de patients RVRH-XLH, Hôpital Bicêtre, APHP, 78 rue du Général Leclerc, 94270 Le Kremlin Bicêtre, France
Service d'Endocrinologie et Diabétologie de l'Enfant, Service de Pédiatrie générale – Consultation de rhumatologie, Service d'Endocrinologie et des Maladies de la Reproduction, Service d'ORL et chirurgie cervico-maxillo-faciale, Université Paris 11, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphore, Service d'Odontologie-Maladies Rares Hôpital Bretonneau 2 rue Carpeaux, Université Paris Descartes 12 Rue de l'École de Médecine, Service Rhumatologie B Hôpital Cochin, Centre de Référence des Maladies Rares des Maladies Auto-Inflammatoires Rares de l'Enfant, Service d'explorations fonctionnelles rénales, Service de Chirurgie infantile orthopédique, Association de patients RVRH-XLH, Hôpital Bicêtre, APHP, 78 rue du Général Leclerc, 94270 Le Kremlin Bicêtre, France

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Peter Kamenicky Service d'Endocrinologie et Diabétologie de l'Enfant, Service de Pédiatrie générale – Consultation de rhumatologie, Service d'Endocrinologie et des Maladies de la Reproduction, Service d'ORL et chirurgie cervico-maxillo-faciale, Université Paris 11, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphore, Service d'Odontologie-Maladies Rares Hôpital Bretonneau 2 rue Carpeaux, Université Paris Descartes 12 Rue de l'École de Médecine, Service Rhumatologie B Hôpital Cochin, Centre de Référence des Maladies Rares des Maladies Auto-Inflammatoires Rares de l'Enfant, Service d'explorations fonctionnelles rénales, Service de Chirurgie infantile orthopédique, Association de patients RVRH-XLH, Hôpital Bicêtre, APHP, 78 rue du Général Leclerc, 94270 Le Kremlin Bicêtre, France
Service d'Endocrinologie et Diabétologie de l'Enfant, Service de Pédiatrie générale – Consultation de rhumatologie, Service d'Endocrinologie et des Maladies de la Reproduction, Service d'ORL et chirurgie cervico-maxillo-faciale, Université Paris 11, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphore, Service d'Odontologie-Maladies Rares Hôpital Bretonneau 2 rue Carpeaux, Université Paris Descartes 12 Rue de l'École de Médecine, Service Rhumatologie B Hôpital Cochin, Centre de Référence des Maladies Rares des Maladies Auto-Inflammatoires Rares de l'Enfant, Service d'explorations fonctionnelles rénales, Service de Chirurgie infantile orthopédique, Association de patients RVRH-XLH, Hôpital Bicêtre, APHP, 78 rue du Général Leclerc, 94270 Le Kremlin Bicêtre, France
Service d'Endocrinologie et Diabétologie de l'Enfant, Service de Pédiatrie générale – Consultation de rhumatologie, Service d'Endocrinologie et des Maladies de la Reproduction, Service d'ORL et chirurgie cervico-maxillo-faciale, Université Paris 11, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphore, Service d'Odontologie-Maladies Rares Hôpital Bretonneau 2 rue Carpeaux, Université Paris Descartes 12 Rue de l'École de Médecine, Service Rhumatologie B Hôpital Cochin, Centre de Référence des Maladies Rares des Maladies Auto-Inflammatoires Rares de l'Enfant, Service d'explorations fonctionnelles rénales, Service de Chirurgie infantile orthopédique, Association de patients RVRH-XLH, Hôpital Bicêtre, APHP, 78 rue du Général Leclerc, 94270 Le Kremlin Bicêtre, France

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Jerome Nevoux Service d'Endocrinologie et Diabétologie de l'Enfant, Service de Pédiatrie générale – Consultation de rhumatologie, Service d'Endocrinologie et des Maladies de la Reproduction, Service d'ORL et chirurgie cervico-maxillo-faciale, Université Paris 11, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphore, Service d'Odontologie-Maladies Rares Hôpital Bretonneau 2 rue Carpeaux, Université Paris Descartes 12 Rue de l'École de Médecine, Service Rhumatologie B Hôpital Cochin, Centre de Référence des Maladies Rares des Maladies Auto-Inflammatoires Rares de l'Enfant, Service d'explorations fonctionnelles rénales, Service de Chirurgie infantile orthopédique, Association de patients RVRH-XLH, Hôpital Bicêtre, APHP, 78 rue du Général Leclerc, 94270 Le Kremlin Bicêtre, France
Service d'Endocrinologie et Diabétologie de l'Enfant, Service de Pédiatrie générale – Consultation de rhumatologie, Service d'Endocrinologie et des Maladies de la Reproduction, Service d'ORL et chirurgie cervico-maxillo-faciale, Université Paris 11, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphore, Service d'Odontologie-Maladies Rares Hôpital Bretonneau 2 rue Carpeaux, Université Paris Descartes 12 Rue de l'École de Médecine, Service Rhumatologie B Hôpital Cochin, Centre de Référence des Maladies Rares des Maladies Auto-Inflammatoires Rares de l'Enfant, Service d'explorations fonctionnelles rénales, Service de Chirurgie infantile orthopédique, Association de patients RVRH-XLH, Hôpital Bicêtre, APHP, 78 rue du Général Leclerc, 94270 Le Kremlin Bicêtre, France

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Dominique Prié Service d'Endocrinologie et Diabétologie de l'Enfant, Service de Pédiatrie générale – Consultation de rhumatologie, Service d'Endocrinologie et des Maladies de la Reproduction, Service d'ORL et chirurgie cervico-maxillo-faciale, Université Paris 11, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphore, Service d'Odontologie-Maladies Rares Hôpital Bretonneau 2 rue Carpeaux, Université Paris Descartes 12 Rue de l'École de Médecine, Service Rhumatologie B Hôpital Cochin, Centre de Référence des Maladies Rares des Maladies Auto-Inflammatoires Rares de l'Enfant, Service d'explorations fonctionnelles rénales, Service de Chirurgie infantile orthopédique, Association de patients RVRH-XLH, Hôpital Bicêtre, APHP, 78 rue du Général Leclerc, 94270 Le Kremlin Bicêtre, France
Service d'Endocrinologie et Diabétologie de l'Enfant, Service de Pédiatrie générale – Consultation de rhumatologie, Service d'Endocrinologie et des Maladies de la Reproduction, Service d'ORL et chirurgie cervico-maxillo-faciale, Université Paris 11, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphore, Service d'Odontologie-Maladies Rares Hôpital Bretonneau 2 rue Carpeaux, Université Paris Descartes 12 Rue de l'École de Médecine, Service Rhumatologie B Hôpital Cochin, Centre de Référence des Maladies Rares des Maladies Auto-Inflammatoires Rares de l'Enfant, Service d'explorations fonctionnelles rénales, Service de Chirurgie infantile orthopédique, Association de patients RVRH-XLH, Hôpital Bicêtre, APHP, 78 rue du Général Leclerc, 94270 Le Kremlin Bicêtre, France

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Anya Rothenbuhler Service d'Endocrinologie et Diabétologie de l'Enfant, Service de Pédiatrie générale – Consultation de rhumatologie, Service d'Endocrinologie et des Maladies de la Reproduction, Service d'ORL et chirurgie cervico-maxillo-faciale, Université Paris 11, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphore, Service d'Odontologie-Maladies Rares Hôpital Bretonneau 2 rue Carpeaux, Université Paris Descartes 12 Rue de l'École de Médecine, Service Rhumatologie B Hôpital Cochin, Centre de Référence des Maladies Rares des Maladies Auto-Inflammatoires Rares de l'Enfant, Service d'explorations fonctionnelles rénales, Service de Chirurgie infantile orthopédique, Association de patients RVRH-XLH, Hôpital Bicêtre, APHP, 78 rue du Général Leclerc, 94270 Le Kremlin Bicêtre, France
Service d'Endocrinologie et Diabétologie de l'Enfant, Service de Pédiatrie générale – Consultation de rhumatologie, Service d'Endocrinologie et des Maladies de la Reproduction, Service d'ORL et chirurgie cervico-maxillo-faciale, Université Paris 11, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphore, Service d'Odontologie-Maladies Rares Hôpital Bretonneau 2 rue Carpeaux, Université Paris Descartes 12 Rue de l'École de Médecine, Service Rhumatologie B Hôpital Cochin, Centre de Référence des Maladies Rares des Maladies Auto-Inflammatoires Rares de l'Enfant, Service d'explorations fonctionnelles rénales, Service de Chirurgie infantile orthopédique, Association de patients RVRH-XLH, Hôpital Bicêtre, APHP, 78 rue du Général Leclerc, 94270 Le Kremlin Bicêtre, France

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Philippe Wicart Service d'Endocrinologie et Diabétologie de l'Enfant, Service de Pédiatrie générale – Consultation de rhumatologie, Service d'Endocrinologie et des Maladies de la Reproduction, Service d'ORL et chirurgie cervico-maxillo-faciale, Université Paris 11, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphore, Service d'Odontologie-Maladies Rares Hôpital Bretonneau 2 rue Carpeaux, Université Paris Descartes 12 Rue de l'École de Médecine, Service Rhumatologie B Hôpital Cochin, Centre de Référence des Maladies Rares des Maladies Auto-Inflammatoires Rares de l'Enfant, Service d'explorations fonctionnelles rénales, Service de Chirurgie infantile orthopédique, Association de patients RVRH-XLH, Hôpital Bicêtre, APHP, 78 rue du Général Leclerc, 94270 Le Kremlin Bicêtre, France
Service d'Endocrinologie et Diabétologie de l'Enfant, Service de Pédiatrie générale – Consultation de rhumatologie, Service d'Endocrinologie et des Maladies de la Reproduction, Service d'ORL et chirurgie cervico-maxillo-faciale, Université Paris 11, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphore, Service d'Odontologie-Maladies Rares Hôpital Bretonneau 2 rue Carpeaux, Université Paris Descartes 12 Rue de l'École de Médecine, Service Rhumatologie B Hôpital Cochin, Centre de Référence des Maladies Rares des Maladies Auto-Inflammatoires Rares de l'Enfant, Service d'explorations fonctionnelles rénales, Service de Chirurgie infantile orthopédique, Association de patients RVRH-XLH, Hôpital Bicêtre, APHP, 78 rue du Général Leclerc, 94270 Le Kremlin Bicêtre, France
Service d'Endocrinologie et Diabétologie de l'Enfant, Service de Pédiatrie générale – Consultation de rhumatologie, Service d'Endocrinologie et des Maladies de la Reproduction, Service d'ORL et chirurgie cervico-maxillo-faciale, Université Paris 11, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphore, Service d'Odontologie-Maladies Rares Hôpital Bretonneau 2 rue Carpeaux, Université Paris Descartes 12 Rue de l'École de Médecine, Service Rhumatologie B Hôpital Cochin, Centre de Référence des Maladies Rares des Maladies Auto-Inflammatoires Rares de l'Enfant, Service d'explorations fonctionnelles rénales, Service de Chirurgie infantile orthopédique, Association de patients RVRH-XLH, Hôpital Bicêtre, APHP, 78 rue du Général Leclerc, 94270 Le Kremlin Bicêtre, France

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Pol Harvengt Service d'Endocrinologie et Diabétologie de l'Enfant, Service de Pédiatrie générale – Consultation de rhumatologie, Service d'Endocrinologie et des Maladies de la Reproduction, Service d'ORL et chirurgie cervico-maxillo-faciale, Université Paris 11, Centre de Référence des Maladies Rares du Métabolisme du Calcium et du Phosphore, Service d'Odontologie-Maladies Rares Hôpital Bretonneau 2 rue Carpeaux, Université Paris Descartes 12 Rue de l'École de Médecine, Service Rhumatologie B Hôpital Cochin, Centre de Référence des Maladies Rares des Maladies Auto-Inflammatoires Rares de l'Enfant, Service d'explorations fonctionnelles rénales, Service de Chirurgie infantile orthopédique, Association de patients RVRH-XLH, Hôpital Bicêtre, APHP, 78 rue du Général Leclerc, 94270 Le Kremlin Bicêtre, France

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In children, hypophosphatemic rickets (HR) is revealed by delayed walking, waddling gait, leg bowing, enlarged cartilages, bone pain, craniostenosis, spontaneous dental abscesses, and growth failure. If undiagnosed during childhood, patients with hypophosphatemia present with bone and/or joint pain, fractures, mineralization defects such as osteomalacia, entesopathy, severe dental anomalies, hearing loss, and fatigue. Healing rickets is the initial endpoint of treatment in children. Therapy aims at counteracting consequences of FGF23 excess, i.e. oral phosphorus supplementation with multiple daily intakes to compensate for renal phosphate wasting and active vitamin D analogs (alfacalcidol or calcitriol) to counter the 1,25-diOH-vitamin D deficiency. Corrective surgeries for residual leg bowing at the end of growth are occasionally performed. In absence of consensus regarding indications of the treatment in adults, it is generally accepted that medical treatment should be reinitiated (or maintained) in symptomatic patients to reduce pain, which may be due to bone microfractures and/or osteomalacia. In addition to the conventional treatment, optimal care of symptomatic patients requires pharmacological and non-pharmacological management of pain and joint stiffness, through appropriated rehabilitation. Much attention should be given to the dental and periodontal manifestations of HR. Besides vitamin D analogs and phosphate supplements that improve tooth mineralization, rigorous oral hygiene, active endodontic treatment of root abscesses and preventive protection of teeth surfaces are recommended. Current outcomes of this therapy are still not optimal, and therapies targeting the pathophysiology of the disease, i.e. FGF23 excess, are desirable. In this review, medical, dental, surgical, and contributions of various expertises to the treatment of HR are described, with an effort to highlight the importance of coordinated care.

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Sarah Zaheer Division of Endocrinology, Metabolism, and Nutrition, Duke University Medical Center, Durham, North Carolina, USA

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Kayla Meyer Division of Endocrinology, Diabetes and Hypertension, Brigham and Women’s Hospital, Boston, Massachusetts, USA

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Rebecca Easly Division of Endocrinology, Diabetes and Hypertension, Brigham and Women’s Hospital, Boston, Massachusetts, USA

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Omar Bayomy Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA

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Janet Leung Section of Endocrinology, Virginia Mason Medical Center, Seattle, Washington, USA

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Andrew W Koefoed Division of Endocrinology, Diabetes and Hypertension, Brigham and Women’s Hospital, Boston, Massachusetts, USA

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Mahyar Heydarpour Division of Endocrinology, Diabetes and Hypertension, Brigham and Women’s Hospital, Boston, Massachusetts, USA

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Roy Freeman Harvard Medical School, Boston, Massachusetts, USA
Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA

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Gail K Adler Division of Endocrinology, Diabetes and Hypertension, Brigham and Women’s Hospital, Boston, Massachusetts, USA
Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA
Harvard Medical School, Boston, Massachusetts, USA

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Glucocorticoid use is the most common cause of secondary osteoporosis. Poor skeletal health related to glucocorticoid use is thought to involve inhibition of the Wnt/β-catenin signaling pathway, a key pathway in osteoblastogenesis. Sclerostin, a peptide produced primarily by osteocytes, is an antagonist of the Wnt/β-catenin signaling pathway, raising the possibility that sclerostin is involved in glucocorticoids’ adverse effects on bone. The aim of this study was to determine whether an acute infusion of cosyntropin (i.e. ACTH(1–24)), which increases endogenous cortisol, increases serum sclerostin levels as compared to a placebo infusion. This study was performed using blood samples obtained from a previously published, double-blind, placebo-controlled, randomized, cross-over study among healthy men and women who received infusions of placebo or cosyntropin after being supine and fasted overnight (ClinicalTrials.gov NCT02339506). A total of 17 participants were analyzed. There was a strong correlation (R2 = 0.65, P < 0.0001) between the two baseline sclerostin measurements measured at the start of each visit, and men had a significantly higher average baseline sclerostin compared to women. As anticipated, cosyntropin significantly increased serum cortisol levels, whereas cortisol levels fell during placebo infusion, consistent with the diurnal variation in cortisol. There was no significant effect of cosyntropin as compared to placebo infusions on serum sclerostin over 6–24 h (P = 0.10). In conclusion, this randomized, placebo-controlled study was unable to detect a significant effect of a cosyntropin infusion on serum sclerostin levels in healthy men and women.

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