Search Results
Search for other papers by Eva Novoa in
Google Scholar
PubMed
Search for other papers by Marcel Gärtner in
Google Scholar
PubMed
Search for other papers by Christoph Henzen in
Google Scholar
PubMed
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.
Search for other papers by Lu Liu in
Google Scholar
PubMed
Search for other papers by Chunyan Li in
Google Scholar
PubMed
Search for other papers by Peng Yang in
Google Scholar
PubMed
Search for other papers by Jian Zhu in
Google Scholar
PubMed
Search for other papers by Dongmei Gan in
Google Scholar
PubMed
Search for other papers by Le Bu in
Google Scholar
PubMed
Search for other papers by Manna Zhang in
Google Scholar
PubMed
Search for other papers by Chunjun Sheng in
Google Scholar
PubMed
Search for other papers by Hong Li in
Google Scholar
PubMed
Search for other papers by Shen Qu in
Google Scholar
PubMed
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.
Search for other papers by Kaisa K Ivaska in
Google Scholar
PubMed
Search for other papers by Maikki K Heliövaara in
Google Scholar
PubMed
Search for other papers by Pertti Ebeling in
Google Scholar
PubMed
Search for other papers by Marco Bucci in
Google Scholar
PubMed
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
Search for other papers by Ville Huovinen in
Google Scholar
PubMed
Search for other papers by H Kalervo Väänänen in
Google Scholar
PubMed
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
Search for other papers by Pirjo Nuutila in
Google Scholar
PubMed
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
Search for other papers by Heikki A Koistinen in
Google Scholar
PubMed
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.
Search for other papers by Sarah Zaheer in
Google Scholar
PubMed
Search for other papers by Kayla Meyer in
Google Scholar
PubMed
Search for other papers by Rebecca Easly in
Google Scholar
PubMed
Search for other papers by Omar Bayomy in
Google Scholar
PubMed
Search for other papers by Janet Leung in
Google Scholar
PubMed
Search for other papers by Andrew W Koefoed in
Google Scholar
PubMed
Search for other papers by Mahyar Heydarpour in
Google Scholar
PubMed
Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
Search for other papers by Roy Freeman in
Google Scholar
PubMed
Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA
Harvard Medical School, Boston, Massachusetts, USA
Search for other papers by Gail K Adler in
Google Scholar
PubMed
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
Search for other papers by Yaqian Mao in
Google Scholar
PubMed
Search for other papers by Lizhen Xu in
Google Scholar
PubMed
Search for other papers by Ting Xue in
Google Scholar
PubMed
Search for other papers by Jixing Liang in
Google Scholar
PubMed
Search for other papers by Wei Lin in
Google Scholar
PubMed
Search for other papers by Junping Wen in
Google Scholar
PubMed
Search for other papers by Huibin Huang in
Google Scholar
PubMed
Search for other papers by Liantao Li in
Google Scholar
PubMed
Department of Endocrinology, Fujian Provincial Hospital, Fujian, China
Fujian Provincial Key Laboratory of Medical Analysis, Fujian Academy of Medical, Fujian, China
Search for other papers by Gang Chen in
Google Scholar
PubMed
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.
Search for other papers by Lijuan Fu in
Google Scholar
PubMed
Search for other papers by Jinhuan Ma in
Google Scholar
PubMed
Search for other papers by Sumei Yan in
Google Scholar
PubMed
Search for other papers by Qijun Si in
Google Scholar
PubMed
Background:
Whether polymorphisms in VDR gene affect the risk of postmenopausal osteoporosis or not remain unclear. Thus, the authors performed a meta-analysis to more robustly assess associations between polymorphisms in VDR gene and the risk of postmenopausal osteoporosis by integrating the results of previous literature.
Methods:
Medline, Embase, Wanfang, VIP and CNKI were searched comprehensively for eligible literature, and 67 genetic association studies were finally selected to be included in this meta-analysis.
Results:
We found that ApaI rs7975232 (dominant comparison: OR = 0.77, P = 0.007; allele comparison: OR = 0.81, P = 0.04), BsmI rs1544410 (dominant comparison: OR = 0.69, P = 0.002; allele comparison: OR = 0.78, P = 0.008) and TaqI rs731236 (recessive comparison: OR = 1.32 , P = 0.01) polymorphisms were significantly associated with the risk of postmenopausal osteoporosis in Caucasians, whereas FokI rs10735810 polymorphism was significantly associated with the risk of postmenopausal osteoporosis in Asians (dominant comparison: OR = 0.61, P = 0.0001; recessive comparison: OR = 2.02, P = 0.001; allele comparison: OR = 0.68, P = 0.002).
Conclusions:
This meta-analysis shows that ApaI rs7975232, BsmI rs1544410 and TaqI rs731236 polymorphisms may affect the risk of postmenopausal osteoporosis in Caucasians, while BsmI rs1544410 polymorphism may affect the risk of postmenopausal osteoporosis in Asians.
Center for Healthy Aging, Technische Universität Dresden, Dresden, Germany
Search for other papers by Sylvia Thiele in
Google Scholar
PubMed
Search for other papers by Anke Hannemann in
Google Scholar
PubMed
Center for Healthy Aging, Technische Universität Dresden, Dresden, Germany
Search for other papers by Maria Winzer in
Google Scholar
PubMed
Center for Healthy Aging, Technische Universität Dresden, Dresden, Germany
Search for other papers by Ulrike Baschant in
Google Scholar
PubMed
Center for Healthy Aging, Technische Universität Dresden, Dresden, Germany
Search for other papers by Heike Weidner in
Google Scholar
PubMed
Search for other papers by Matthias Nauck in
Google Scholar
PubMed
Search for other papers by Rajesh V Thakker in
Google Scholar
PubMed
DFG Research Center and Cluster of Excellence for Regenerative Therapies, Technical University, Dresden, Germany
Search for other papers by Martin Bornhäuser in
Google Scholar
PubMed
Center for Healthy Aging, Technische Universität Dresden, Dresden, Germany
DFG Research Center and Cluster of Excellence for Regenerative Therapies, Technical University, Dresden, Germany
Search for other papers by Lorenz C Hofbauer in
Google Scholar
PubMed
Center for Healthy Aging, Technische Universität Dresden, Dresden, Germany
Search for other papers by Martina Rauner in
Google Scholar
PubMed
Glucocorticoids (GC) are used for the treatment of inflammatory diseases, including various forms of arthritis. However, their use is limited, amongst others, by adverse effects on bone. The Wnt and bone formation inhibitor sclerostin was recently implicated in the pathogenesis of GC-induced osteoporosis. However, data are ambiguous. The aim of this study was to assess the regulation of sclerostin by GC using several mouse models with high GC levels and two independent cohorts of patients treated with GC. Male 24-week-old C57BL/6 and 18-week-old DBA/1 mice exposed to GC and 12-week-old mice with endogenous hypercortisolism displayed reduced bone formation as indicated by reduced levels of P1NP and increased serum sclerostin levels. The expression of sclerostin in femoral bone tissue and GC-treated bone marrow stromal cells, however, was not consistently altered. In contrast, GC dose- and time-dependently suppressed sclerostin at mRNA and protein levels in human mesenchymal stromal cells, and this effect was GC receptor dependent. In line with the human cell culture data, patients with rheumatoid arthritis (RA, n = 101) and polymyalgia rheumatica (PMR, n = 21) who were exposed to GC had lower serum levels of sclerostin than healthy age- and sex-matched controls (−40%, P < 0.01 and −26.5%, P < 0.001, respectively). In summary, sclerostin appears to be differentially regulated by GC in mice and humans as it is suppressed by GCs in humans but is not consistently altered in mice. Further studies are required to delineate the differences between GC regulation of sclerostin in mice and humans and assess whether sclerostin mediates GC-induced osteoporosis in humans.
Search for other papers by Rimesh Pal in
Google Scholar
PubMed
Search for other papers by Sanjay Kumar Bhadada in
Google Scholar
PubMed
Search for other papers by Awesh Singhare in
Google Scholar
PubMed
Search for other papers by Anil Bhansali in
Google Scholar
PubMed
Search for other papers by Sadishkumar Kamalanathan in
Google Scholar
PubMed
Search for other papers by Manoj Chadha in
Google Scholar
PubMed
Search for other papers by Phulrenu Chauhan in
Google Scholar
PubMed
Search for other papers by Ashwani Sood in
Google Scholar
PubMed
Search for other papers by Vandana Dhiman in
Google Scholar
PubMed
Search for other papers by Dinesh Chandra Sharma in
Google Scholar
PubMed
Search for other papers by Uma Nahar Saikia in
Google Scholar
PubMed
Search for other papers by Debajyoti Chatterjee in
Google Scholar
PubMed
Search for other papers by Vikas Agashe in
Google Scholar
PubMed
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by recalcitrant hypophosphatemia. Reports from the Indian subcontinent are scarce, with most being single center experiences involving few patients. Herein, we conducted a retrospective analysis of 30 patients of TIO diagnosed at three tertiary care hospitals in India. Patients with persistent hypophosphatemia (despite correction of hypovitaminosis D), normocalcemia, elevated alkaline phosphatase, low TmP/GFR and elevated or ‘inappropriately normal’ FGF23 levels were labeled as having TIO. They were sequentially subjected to functional followed by anatomical imaging. Patients with a well-localized tumor underwent excision; others were put on phosphorous and calcitriol supplementation. The mean age at presentation was 39.6 years with female:male ratio of 3:2. Bone pain (83.3%) and proximal myopathy (70%) were the chief complaints; 40% of cases had fractures. The mean delay in diagnosis was 3.8 years. Tumors were clinically detectable in four patients (13.3%). The mean serum phosphate was 0.50 mmol/L with a median serum FGF23 level of 518 RU/mL. Somatostatin receptor-based scintigraphy was found to be superior to FDG-PET in tumor localization. Lower extremities were the most common site of the tumor (72%). Tumor size was positively correlated with serum FGF23 levels. Twenty-two patients underwent tumor resection and 16 of them had phosphaturic mesenchymal tumors. Surgical excision led to cure in 72.7% of patients whereas disease persistence and disease recurrence were seen in 18.2% and 9.1% of cases, respectively. At the last follow-up, serum phosphate in the surgically treated group was significantly higher than in the medically managed group.
Beijing Key Laboratory of Diabetes Research and Care, Beijing, China
Search for other papers by Xiaoxia Jia in
Google Scholar
PubMed
Beijing Key Laboratory of Diabetes Research and Care, Beijing, China
Search for other papers by Yaxin An in
Google Scholar
PubMed
Beijing Key Laboratory of Diabetes Research and Care, Beijing, China
Search for other papers by Yuechao Xu in
Google Scholar
PubMed
Beijing Key Laboratory of Diabetes Research and Care, Beijing, China
Search for other papers by Yuxian Yang in
Google Scholar
PubMed
Beijing Key Laboratory of Diabetes Research and Care, Beijing, China
Search for other papers by Chang Liu in
Google Scholar
PubMed
Beijing Key Laboratory of Diabetes Research and Care, Beijing, China
Search for other papers by Dong Zhao in
Google Scholar
PubMed
Beijing Key Laboratory of Diabetes Research and Care, Beijing, China
Search for other papers by Jing Ke in
Google Scholar
PubMed
Background
Obesity is known as a common risk factor for osteoporosis and type 2 diabetes mellitus (T2DM). Perirenal fat, surrounding the kidneys, has been reported to be unique in anatomy and biological functions. This study aimed to explore the relationship between perirenal fat and bone metabolism in patients with T2DM.
Methods
A total of 234 patients with T2DM were recruited from September 2019 to December 2019 in the cross-sectional study. The biochemical parameters and bone turnover markers (BTMs) were determined in all participants. Perirenal fat thickness (PrFT) was performed by ultrasounds via a duplex Doppler apparatus. Associations between PrFT and bone metabolism index were determined via correlation analysis and regression models.
Results
The PrFT was significantly correlated with β-C-terminal telopeptides of type I collagen (β-CTX) (r = −0.14, P < 0.036), parathyroid hormone (iPTH) (r = −0.18, P ≤ 0.006), and 25 hydroxyvitamin D (25-OH-D) (r = −0.14, P = 0.001). Multivariate analysis confirmed that the association of PrFT and β-CTX (β = −0.136, P = 0.042) was independent of other variables.
Conclusion
This study showed a negative and independent association between PrFT and β-CTX in subjects with T2DM, suggesting a possible role of PrFT in bone metabolism. Follow-up studies and further research are necessary to validate the associations and to elucidate the underlying mechanisms.
Endocrine Unit, Royal Victoria Infirmary, Newcastle upon Tyne, UK
Search for other papers by Earn H Gan in
Google Scholar
PubMed
Search for other papers by Wendy Robson in
Google Scholar
PubMed
Search for other papers by Peter Murphy in
Google Scholar
PubMed
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
Search for other papers by Robert Pickard in
Google Scholar
PubMed
Endocrine Unit, Royal Victoria Infirmary, Newcastle upon Tyne, UK
Search for other papers by Simon Pearce in
Google Scholar
PubMed
Search for other papers by Rachel Oldershaw in
Google Scholar
PubMed
Background
The highly plastic nature of adrenal cortex suggests the presence of adrenocortical stem cells (ACSC), but the exact in vivo identity of ACSC remains elusive. A few studies have demonstrated the differentiation of adipose or bone marrow-derived mesenchymal stem cells (MSC) into steroid-producing cells. We therefore investigated the isolation of multipotent MSC from human adrenal cortex.
Methods
Human adrenals were obtained as discarded surgical material. Single-cell suspensions from human adrenal cortex (n = 3) were cultured onto either complete growth medium (CM) or MSC growth promotion medium (MGPM) in hypoxic condition. Following ex vivo expansion, their multilineage differentiation capacity was evaluated. Phenotype markers were analysed by immunocytochemistry and flow cytometry for cell-surface antigens associated with bone marrow MSCs and adrenocortical-specific phenotype. Expression of mRNAs for pluripotency markers was assessed by q-PCR.
Results
The formation of colony-forming unit fibroblasts comprising adherent cells with fibroblast-like morphology were observed from the monolayer cell culture, in both CM and MGPM. Cells derived from MGPM revealed differentiation towards osteogenic and adipogenic cell lineages. These cells expressed cell-surface MSC markers (CD44, CD90, CD105 and CD166) but did not express the haematopoietic, lymphocytic or HLA-DR markers. Flow cytometry demonstrated significantly higher expression of GLI1 in cell population harvested from MGPM, which were highly proliferative. They also exhibited increased expression of the pluripotency markers.
Conclusion
Our study demonstrates that human adrenal cortex harbours a mesenchymal stem cell-like population. Understanding the cell biology of adrenal cortex- derived MSCs will inform regenerative medicine approaches in autoimmune Addison’s disease.