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- Abstract: Hypoparathyroidism x
- Abstract: Osteo* x
- Abstract: Vitamin D x
Faculté de Chirurgie Dentaire, Université de Toulouse III, Toulouse, France
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CHU de Toulouse, Laboratoire d’Hématologie, Toulouse, France
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Faculté de Chirurgie Dentaire, Université de Toulouse III, Toulouse, France
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Estrogen–progestin therapy was previously considered as the standard of care for managing bothersome symptoms associated with menopause, but it increases risks of breast cancer and of thromboembolism. The combination of conjugated estrogen (CE) with bazedoxifene (BZA) named tissue-selective estrogen complex (TSEC) was designed to minimize or even abrogate the undesirable effects on breast, while maintaining the beneficial effects such as prevention of osteoporosis and suppression of climacteric symptoms. The risk on thromboembolism associated with TSEC is unknown, although the clinical available data are reassuring. The aim of this study was to define the impact of a chronic administration of CE, BZA or CE + BZA on hemostasis and thrombosis in ovariectomized mice. As expected, CE, but not BZA neither CE + BZA, induced uterine and vagina hypertrophy. As previously demonstrated for 17β-estradiol (E2), we found that CE (i) increased tail-bleeding time, (ii) prevented occlusive thrombus formation in injured carotid artery and (iii) protected against collagen/epinephrine-induced thromboembolism. Thus, whereas BZA antagonized CE action on reproductive tissues, it had no impact on the effect of CE on hemostasis, thromboembolism and arterial thrombosis in mice. CE + BZA shared the anti-thrombotic actions of CE in these mouse models. If a similar process is at work in women, CE combined with BZA could contribute to minimize the risk of thrombosis associated with hormone replacement therapy.
Musculoskeletal Research Laboratory and Bone Quality and Health Assessment Centre, Department of Orthopedics & Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, Hong Kong
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Department of Endocrinology, The First Affiliated Hospital of Shanxi Medical University, Taiyuan, Shanxi, China
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Background
Primary hypertrophic osteoarthropathy (PHO) is a rare genetic multi-organic disease characterized by digital clubbing, periostosis and pachydermia. Two genes, HPGD and SLCO2A1, which encodes 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and prostaglandin transporter (PGT), respectively, have been reported to be related to PHO. Deficiency of aforementioned two genes leads to failure of prostaglandin E2 (PGE2) degradation and thereby elevated levels of PGE2. PGE2 plays an important role in tumorigenesis. Studies revealed a tumor suppressor activity of 15-PGDH in tumors, such as lung, bladder and breast cancers. However, to date, no HPGD-mutated PHO patients presenting concomitant tumor has been documented. In the present study, we reported the first case of HPGD-mutated PHO patient with soft tissue giant tumors at lower legs and evaluated the efficacy of selective COX-2 inhibitor (etoricoxib) treatment in the patient.
Methods
In this study, we summarized the clinical data, collected the serum and urine samples for biochemical test and analyzed the HPGD gene in our patient.
Results
A common HPGD mutation c.310_311delCT was identified in the patient. In addition to typical clinical features (digital clubbing, periostosis and pachydermia), the patient demonstrated a new clinical manifestation, a giant soft tissue tumor on the left lower leg which has not been reported in HPGD-mutated PHO patient before. After 6-month treatment with etoricoxib, the patient showed decreased PGE2 levels and improved PHO-related symptoms. Though the soft tissue tumor persisted, it seemed to be controlled under the etoricoxib treatment.
Conclusion
This finding expanded the clinical spectrum of PHO and provided unique insights into the HPGD-mutated PHO.
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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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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 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.
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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.