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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.
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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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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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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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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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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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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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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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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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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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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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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.
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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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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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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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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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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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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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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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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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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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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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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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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Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
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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.
Department of Endocrinology, Fujian Provincial Hospital, Fujian, China
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Department of Endocrinology, Fujian Provincial Hospital, Fujian, China
Fujian Provincial Key Laboratory of Medical Analysis, Fujian Academy of Medical, Fujian, China
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Objective
To establish a rapid, cost-effective, accurate, and acceptable osteoporosis (OP) screening model for the Chinese male population (age ≥ 40 years) based on data mining technology.
Materials and methods
This was a 3-year retrospective cohort study, which belonged to the sub-cohort of the Chinese Reaction Study. The research period was from March 2011 to December 2014. A total of 1834 subjects who did not have OP at the baseline and completed a 3-year follow-up were included in this study. All subjects underwent quantitative ultrasound examinations for calcaneus at the baseline and follow-ups that lasted for 3 years. We utilized the least absolute shrinkage and selection operator (LASSO) regression model to select feature variables. The characteristic variables selected in the LASSO regression were analyzed by multivariable logistic regression (MLR) to construct the predictive model. This predictive model was displayed through a nomogram. We used the receiver operating characteristic (ROC) curve, C-index, calibration curve, and clinical decision curve analysis (DCA) to evaluate model performance and the bootstrapping validation to internally validate the model.
Results
The predictive factors included in the prediction model were age, neck circumference, waist-to-height ratio, BMI, triglyceride, impaired fasting glucose, dyslipidemia, osteopenia, smoking history, and strenuous exercise. The area under the ROC (AUC) curve of the risk nomogram was 0.882 (95% CI, 0.858–0.907), exhibiting good predictive ability and performance. The C-index for the risk nomogram was 0.882 in the prediction model, which presented good refinement. In addition, the nomogram calibration curve indicated that the prediction model was consistent. The DCA showed that when the threshold probability was between 1 and 100%, the nomogram had a good clinical application value. More importantly, the internally verified C-index of the nomogram was still very high, at 0.870.
Conclusions
This novel nomogram can effectively predict the 3-year incidence risk of OP in the male population. It also helps clinicians to identify groups at high risk of OP early and formulate personalized intervention measures.
Laboratory for Anthropology and Skeletal Biology, Institute of Anatomy, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
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An increasing number of patients worldwide suffer from bone fractures that occur after low intensity trauma. Such fragility fractures are usually associated with advanced age and osteoporosis but also with long-term immobilization, corticosteroid therapy, diabetes mellitus, and other endocrine disorders. It is important to understand the skeletal origins of increased bone fragility in these conditions for preventive and therapeutic strategies to combat one of the most common health problems of the aged population. This review summarizes current knowledge pertaining to the phenomenon of micropetrosis (osteocyte lacunar mineralization). As an indicator of former osteocyte death, micropetrosis is more common in aged bone and osteoporotic bone. Considering that the number of mineralized osteocyte lacunae per bone area can distinguish healthy, untreated osteoporotic and bisphosphonate-treated osteoporotic patients, it could be regarded as a novel structural marker of impaired bone quality. Further research is needed to clarify the mechanism of lacunar mineralization and to explore whether it could be an additional target for preventing or treating bone fragility related to aging and various endocrine diseases.
