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Yamaguchi M, Yoshiyama T, Maruyama R, Ohashi M, Nishizono S, Kobayashi T, Miyatake M, Sameshima H. Citrus tamurana Hort. ex Tanaka (Hyuganatsu orange)-derived arabinogalactan suppresses bone turnover in postmenopausal women: A randomized placebo-controlled study. J Obstet Gynaecol Res 2024; 50:2299-2308. [PMID: 39419484 DOI: 10.1111/jog.16116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Accepted: 09/27/2024] [Indexed: 10/19/2024]
Abstract
AIM To evaluate Hyuganatsu oranges (Citrus tamurana Hort. Ex Tanaka) derived arabinogalactan for bone turnover, we performed a randomized placebo-controlled trial. METHODS Sixty-three postmenopausal women were age-stratified and randomly assigned to receive arabinogalactan-rich hyuganatsu juice (study group) or a placebo drink (control group) for 90 days. We measured blood tartrate-resistant acid phosphatase 5b (TRACP5b), type I procollagen N-terminal propeptide (P1NP), and other bone turnover biomarker levels at baseline, days 45 and 90 (T90) of the intervention, and day 30 of recovery. Cumulative effects were compared between groups using repeated-measures linear mixed model analysis. The primary endpoint was the difference between the pre- and post-intervention TRACP5b and P1NP levels. RESULTS Using repeated measures linear mixed model analysis, the study group had significantly lower TRACP5b and P1NP levels at day 90 than the control group (mean [95% confidence interval]; TRACP5b: 310.0 [269.2-350.9] vs. 386.4 [341.2-431.6] mU/dL; P1NP: 53.7 [48.6-58.7] vs. 70.3 [64.1-76.4] ng/mL), whereas other biomarker levels showed no change. CONCLUSION Arabinogalactan-rich Hyuganatsu juice suppressed bone mineral turnover and potentially improved ovarian hormone deficiency-induced osteoporosis in postmenopausal women.
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Affiliation(s)
- Masatoshi Yamaguchi
- Department of Obstetrics and Gynecology, University of Miyazaki, Faculty of Medicine, Miyazaki, Japan
| | | | - Ruriko Maruyama
- Department of Obstetrics and Gynecology, University of Miyazaki, Faculty of Medicine, Miyazaki, Japan
| | - Masanao Ohashi
- Department of Obstetrics and Gynecology, Kawakita General Hospital, Tokyo, Japan
| | - Shoko Nishizono
- Faculty of Biotechnology and Life Science, Sojo University, Kumamoto, Japan
| | - Taichi Kobayashi
- Center for Collaborative Research & Community Cooperation, University of Miyazaki, Miyazaki, Japan
| | - Munetoshi Miyatake
- Faculty of Engineering, University of Miyazaki, University of Miyazaki, Miyazaki, Japan
| | - Hiroshi Sameshima
- Department of Obstetrics and Gynecology, University of Miyazaki, Faculty of Medicine, Miyazaki, Japan
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Heinrichs L, Fluegen G, Loosen SH, Loberg C, Wittig L, Quaas A, Plum PS, Große Hokamp N, Minko P, Krieg A, Antoch G, Knoefel WT, Luedde T, Roderburg C, Jördens MS. Bone mineral density as a prognostic marker in patients with biliary tract cancer undergoing surgery. BJC REPORTS 2024; 2:72. [PMID: 39323978 PMCID: PMC11420066 DOI: 10.1038/s44276-024-00094-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Revised: 08/19/2024] [Accepted: 08/21/2024] [Indexed: 09/27/2024]
Abstract
Background Biliary tract cancer (BTC) is one of the most aggressive malignancies and surgery represents the only curative treatment approach. However, even in patients with complete tumor resection 5-year survival rates are below 30%. So far, prognostic markers to assess the outcome of these patients are lacking. We therefore evaluated bone mineral density (BMD) as a prognostic tool in patients receiving surgery for BTC. methods 76 BTC patients undergoing tumor resection in our clinic (Duesseldorf cohort) as well as an external validation cohort of 34 BTC patients (Cologne cohort) were included. BMD was analyzed at the first lumbar vertebra, using routine CT scans which has been proven comparable to DXA. Results Median overall survival (OS) of the Duesseldorf cohort after surgery was 527 days, one- and five-year survival probabilities were 62 and 18%. Patients with BMD above 156.5 HU had significantly improved OS (1435 days vs. 459 days; p = 0.002). The prognostic value for BMD was confirmed using Cox-regression analysis, as well as an external validation cohort. In subgroup analysis the prognostic effect of BMD was only present in female patients, suggesting sex specific differences. Conclusion BMD is a valuable, easily accessible and independent prognostic marker in patients receiving liver surgery for BTC.
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Affiliation(s)
- Lisa Heinrichs
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany
| | - Georg Fluegen
- Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, 40225 Duesseldorf, Germany
| | - Sven H. Loosen
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany
| | - Christina Loberg
- Department of Diagnostic and Interventional Radiology, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany
| | - Linda Wittig
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany
| | - Alexander Quaas
- Institute of Pathology, University Hospital Cologne and Medical Faculty, University of Cologne, 50937 Cologne, Germany
| | - Patrick S. Plum
- Department of General, Visceral, Cancer and Transplantation Surgery, University Hospital Cologne, 50937 Cologne, Germany
| | - Nils Große Hokamp
- Institute for Diagnostic and Interventional Radiology, University Hospital Cologne, 50937 Cologne, Germany
| | - Peter Minko
- Department of Diagnostic and Interventional Radiology, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany
| | - Andreas Krieg
- Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, 40225 Duesseldorf, Germany
| | - Gerald Antoch
- Department of Diagnostic and Interventional Radiology, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany
| | - Wolfram T. Knoefel
- Department of Surgery (A), Heinrich-Heine-University and University Hospital Duesseldorf, 40225 Duesseldorf, Germany
| | - Tom Luedde
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany
| | - Christoph Roderburg
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany
| | - Markus S. Jördens
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany
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Quester J, Nethander M, Coward E, Reimann E, Mägi R, Pettersson-Kymmer U, Hveem K, Ohlsson C. High SHBG and Low Bioavailable Testosterone are Strongly Causally Associated with Increased Forearm Fracture Risk in Women: An MR Study Leveraging Novel Female-Specific Data. Calcif Tissue Int 2024; 115:648-660. [PMID: 39412545 PMCID: PMC11531422 DOI: 10.1007/s00223-024-01301-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Accepted: 09/27/2024] [Indexed: 11/03/2024]
Abstract
The effects of androgens on women's bone health are not fully understood. Mendelian randomization (MR) studies using sex-combined data suggest that sex hormone-binding globulin (SHBG) and bioavailable testosterone (BioT) causally affect bone traits. Given significant sex differences in hormone regulation and effects, female-specific MR studies are necessary. In the current study, we explored the causal relationships of SHBG, BioT, and total testosterone (TT) with forearm fracture (FAFx) risk in women using two-sample MR analyses. We utilized a unique female-specific FAFx outcome dataset from three European biobanks (UFO, HUNT, Estonian Biobank) comprising 111,351 women and 8823 FAFx cases, along with female-specific genetic instruments of SHBG, BioT, and TT identified in the UK Biobank. We also assessed bone mineral density (BMD) at the forearm (FA), femoral neck (FN), and lumbar spine (LS) using female-specific GWAS data from the GEFOS consortium. High SHBG (odds ratio per standard deviation increase (OR/SD): 1.53, 95% confidence intervals (CIs): 1.34-1.75), low BioT (OR/SD: 0.77, 0.71-0.84) and low TT (OR/SD 0.90, 0.83-0.98) were causally associated with increased FAFx risk. BioT was positively, and SHBG inversely, causally associated with especially FA-BMD, but also LS-BMD and FN-BMD, while TT was only significantly positively associated with FA-BMD and LS-BMD. We propose that endogenous androgens and SHBG are important for women's bone health at distal trabecular-rich bone sites such as the distal forearm and may serve as predictors for FAFx risk.
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Affiliation(s)
- Johan Quester
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
- Department of Drug Treatment, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden.
| | - Maria Nethander
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Bioinformatics Core Facility, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Eivind Coward
- HUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, 7491, Trondheim, Norway
| | - Ene Reimann
- Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia
| | - Reedik Mägi
- Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia
| | - Ulrika Pettersson-Kymmer
- Department of Medical and Translational Biology, Clinical Pharmacology, Umea University, Umea, Sweden
| | - Kristian Hveem
- HUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, 7491, Trondheim, Norway
- HUNT Research Centre, Department of Public Health and Nursing, Norwegian University of Science and Technology, Postboks 8905, 7491, Trondheim, Norway
- Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway
| | - Claes Ohlsson
- Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Drug Treatment, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden
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Li T, Yuan J, Xu P, Jia J, Zhao J, Zhang J, Ding R, Zhao X, He D, Wu T, Cheng X. PMAIP1, a novel diagnostic and potential therapeutic biomarker in osteoporosis. Aging (Albany NY) 2024; 16:3694-3715. [PMID: 38372699 PMCID: PMC10929792 DOI: 10.18632/aging.205553] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2023] [Accepted: 12/26/2023] [Indexed: 02/20/2024]
Abstract
BACKGROUND Osteoporosis is a common endocrine metabolic bone disease, which may lead to severe consequences. However, the unknown molecular mechanism of osteoporosis, the observable side effects of present treatments and the inability to fundamentally improve bone metabolism seriously restrict the impact of prevention and treatment. The study aims to identify potential biomarkers from osteoclast progenitors, specifically peripheral blood monocytes on predicting the osteoporotic phenotype. METHODS Datasets were obtained from Gene Expression Omnibus (GEO). Based on the differentially expressed genes (DEGs) and GSEA results, GO and KEGG analyses were performed using the DAVID database and Metascape database. PPI network, TF network, drug-gene interaction network, and ceRNA network were established to determine the hub genes. Its osteogenesis, migration, and proliferation abilities in bone marrow mesenchymal stem cells (BMSCs) were validated through RT-qPCR, WB, ALP staining, VK staining, wound healing assay, transwell assay, and CCK-8 assay. RESULTS A total of 63 significant DEGs were screened. Functional and pathway enrichment analysis discovered that the functions of the significant DEGs (SDEGs) are mainly related to immunity and metal ions. A comprehensive evaluation of all the network analyses, PMAIP1 was defined as osteoporosis's core gene. This conclusion was further confirmed in clinical cohort data. A series of experiments demonstrated that the PMAIP1 gene can promote the osteogenesis, migration and proliferation of BMSC cells. CONCLUSIONS All of these outcomes showed a new theoretical basis for further research in the treatment of osteoporosis, and PMAIP1 was identified as a potential biomarker for osteoporosis diagnosis and treatment.
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Affiliation(s)
- Tao Li
- Institute of Orthopaedics of Jiangxi Province, Nanchang, Jiangxi, China
| | - Jinghong Yuan
- Institute of Orthopaedics of Jiangxi Province, Nanchang, Jiangxi, China
- Department of Osteoporosis, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Peichuan Xu
- Institute of Orthopaedics of Jiangxi Province, Nanchang, Jiangxi, China
| | - Jingyu Jia
- Institute of Orthopaedics of Jiangxi Province, Nanchang, Jiangxi, China
- Department of Osteoporosis, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Jiangminghao Zhao
- Department of Osteoporosis, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Jian Zhang
- Institute of Orthopaedics of Jiangxi Province, Nanchang, Jiangxi, China
- Department of Osteoporosis, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Rui Ding
- Institute of Orthopaedics of Jiangxi Province, Nanchang, Jiangxi, China
- Department of Orthopaedics, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Xiaokun Zhao
- Department of Osteoporosis, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Dingwen He
- Institute of Orthopaedics of Jiangxi Province, Nanchang, Jiangxi, China
| | - Tianlong Wu
- Institute of Orthopaedics of Jiangxi Province, Nanchang, Jiangxi, China
- Department of Orthopaedics, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Xigao Cheng
- Institute of Orthopaedics of Jiangxi Province, Nanchang, Jiangxi, China
- Department of Osteoporosis, The Second Affiliated Hospital of Nanchang University, Nanchang, China
- Department of Orthopaedics, The Second Affiliated Hospital of Nanchang University, Nanchang, China
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Reder SR, Fritzen I, Brockmann MA, Hardt J, Elsner K, Petrowski K, Bjelopavlovic M. Comparing a common clavicle maturation-based age estimation method to ordinary regression analyses with quadratic and sex-specific interaction terms in adolescents. Sci Rep 2024; 14:2754. [PMID: 38307929 PMCID: PMC10837444 DOI: 10.1038/s41598-024-52980-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Accepted: 01/25/2024] [Indexed: 02/04/2024] Open
Abstract
Established methods of age estimation are based on correlating defined maturation stages of bony structures with tables representing the observed range of biological ages in the majority of cases. In this retrospective monocentric study in southwestern Germany, common age estimation methodology was assessed in n = 198 subjects at the age of 25 or younger by analyzing the influence of age, quadratic age, biological sex and age-sex interaction on the ossification stages of the medial epiphysis fugue. Three readers (ICC ≥ 0.81 for left/right side) evaluated routine care computed tomography images of the clavicle with a slice thickness of 1 mm. By using least square regression analyses, to determine the real biological age a quadratic function was determined corrected for the age estimated by established methods and sex (R2 = 0.6 each side), reducing the mean absolute error and root mean squared error in the age estimation of women (2.57 and 3.19) and men (2.57 and 3.47) to 1.54 and 1.82 for women, and 1.54 and 2.25 for men. In women, the medial clavicle epiphysis seem to fuse faster, which was particularly observable from approximately 18 years of age. Before that age, the estimation method was relatively close to the ideal correlation between assessed and real age. To conclude, the presented new method enables more precise age estimation in individuals and facilitates the determination and quantification of additional variables, quantifying their influence on the maturation of the medial clavicle epiphysis based on the established ossification stages.
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Affiliation(s)
- Sebastian R Reder
- Department of Neuroradiology, University Medical Center, Johannes Gutenberg-University of Mainz, 55131, Mainz, Germany.
| | - Isabel Fritzen
- Department of Prosthetic Dentistry, University Medical Center of the Johannes Gutenberg-University Mainz, Augustusplatz 2, 55131, Mainz, Germany
| | - Marc A Brockmann
- Department of Neuroradiology, University Medical Center, Johannes Gutenberg-University of Mainz, 55131, Mainz, Germany
| | - Jochen Hardt
- Department of Medical Psychology and Medical Sociology, University Medical Center of the Johannes Gutenberg-University Mainz, Duesbergweg 6, 55131, Mainz, Germany
| | - Katrin Elsner
- Institute of Legal Medicine, University Medical Center of the Johannes Gutenberg-University of Mainz, Am Pulverturm 9, 55131, Mainz, Germany
| | - Katja Petrowski
- Department of Medical Psychology and Medical Sociology, University Medical Center of the Johannes Gutenberg-University Mainz, Duesbergweg 6, 55131, Mainz, Germany
| | - Monika Bjelopavlovic
- Department of Prosthetic Dentistry, University Medical Center of the Johannes Gutenberg-University Mainz, Augustusplatz 2, 55131, Mainz, Germany
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Kulpa J, Eglit G, Hill ML, MacNair L, Yardley H, Ware MA, Bonn-Miller MO, Peters EN. Serum Markers of Bone Turnover Following Controlled Administration of Two Medical Cannabis Products in Healthy Adults. Cannabis Cannabinoid Res 2024; 9:300-309. [PMID: 36346322 PMCID: PMC10874824 DOI: 10.1089/can.2022.0181] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
Introduction: Cannabidiol (CBD) has been shown to maintain bone integrity in pre-clinical models, but little is known about the effects of delta-9-tetrahydrocannabinol (THC) on bone turnover. In this study we explored the effects of two oral medical cannabis products on normal bone homeostasis through evaluation of markers of bone resorption (carboxyl-terminal collagen crosslinks, CTx) and bone formation (procollagen type 1 N-terminal propeptide, P1NP; alkaline phosphatase, ALP). Methods: This study is an analysis of secondary data from two Phase 1 double-blind, placebo-controlled trials of Spectrum Yellow (0.9 mg THC, 20 mg CBD/mL of oil) and Spectrum Red (2.5 mg THC, 0.3 mg CBD/softgel). Healthy participants (n=38 men, 45 women) were randomized to receive 5-20 mg THC (CBD levels varied as a function of administered product) or placebo daily (BID) for 7 days. Bone markers were assessed at baseline, upon completion of product administration (day 8), and after a 5-day washout (day 13). Results: All bone markers were significantly higher in men at baseline (p≤0.008). For CTx, there was a significant day×group interaction (F=3.23, p=0.04); CTx levels were significantly lower in participants treated with Spectrum Red (b=-164.28; 95% confidence interval [CI], -328 to -0.29; p=0.04) and marginally lower in participants treated with Spectrum Yellow (b=-157.31; 95% CI, -323 to 8.68; p=0.06) versus placebo on day 8. For P1NP and ALP, there were no significant differences between treatments across study days. Bone marker values outside the reference range (RR) were observed; CTx > RR (n=71) was predominantly (85.9%) observed in male participants, whereas P1NP > RR (n=100) was more evenly distributed between sexes (53.0% in men). These were not considered clinically significant and did not differ between treatment groups. Conclusions: These are the first interventional human data on the effect of cannabinoids on biomarkers of bone turnover. Short-term treatment with CBD- or THC-dominant medical cannabis products resulted in attenuation of a marker of bone resorption. Although the attenuation was not clinically significant, this finding may be indicative of protective properties of cannabinoids in bone. Further research over longer dosing durations in individuals exhibiting bone-specific conditions (e.g., osteoporosis) is warranted. ClinicalTrials.gov IDs: ACTRN12619001723178 and ACTRN12619001450101.
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Affiliation(s)
| | | | - Melanie L. Hill
- School of Medicine, University of California, San Diego, La Jolla, California, USA
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Rouge M, Legendre F, Elkhatib R, Delalande C, Cognié J, Reigner F, Barrière P, Deleuze S, Hanoux V, Galéra P, Bouraïma-Lelong H. Early Castration in Horses Does Not Impact Osteoarticular Metabolism. Int J Mol Sci 2023; 24:16778. [PMID: 38069100 PMCID: PMC10706761 DOI: 10.3390/ijms242316778] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 11/17/2023] [Accepted: 11/20/2023] [Indexed: 12/18/2023] Open
Abstract
The castration of stallions is traditionally performed after puberty, at around the age of 2 years old. No studies have focused on the effects of early castration on osteoarticular metabolism. Thus, we aimed to compare early castration (3 days after birth) with traditional castration (18 months of age) in horses. Testosterone and estradiol levels were monitored from birth to 33 months in both groups. We quantified the levels of biomarkers of cartilage and bone anabolism (CPII and N-MID) and catabolism (CTX-I and CTX-II), as well as of osteoarthritis (HA and COMP) and inflammation (IL-6 and PGE2). We observed a lack of parallelism between testosterone and estradiol synthesis after birth and during puberty in both groups. The extra-gonadal synthesis of steroids was observed around the 28-month mark, regardless of the castration age. We found the expression of estrogen receptor (ESR1) in cartilage and bone, whereas androgen receptor (AR) expression appeared to be restricted to bone. Nevertheless, with respect to osteoarticular metabolism, steroid hormone deprivation resulting from early castration had no discernable impact on the levels of biomarkers related to bone and cartilage metabolism, nor on those associated with OA and inflammation. Consequently, our research demonstrated that early castration does not disrupt bone and cartilage homeostasis.
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Affiliation(s)
- Marion Rouge
- Université de Caen-Normandie, OeReCa, 14000 Caen, France; (M.R.); (R.E.); (C.D.); (V.H.)
| | - Florence Legendre
- Université de Caen Normandie BIOTARGEN, 14000 Caen, France; (F.L.); (P.G.)
| | - Razan Elkhatib
- Université de Caen-Normandie, OeReCa, 14000 Caen, France; (M.R.); (R.E.); (C.D.); (V.H.)
| | - Christelle Delalande
- Université de Caen-Normandie, OeReCa, 14000 Caen, France; (M.R.); (R.E.); (C.D.); (V.H.)
| | - Juliette Cognié
- INRAE, Université de Tours, Centre de Recherche de Tours, UMR PRC, 37380 Nouzilly, France;
| | - Fabrice Reigner
- INRAE, Université de Tours, Centre de Recherche de Tours, UEPAO, 37380 Nouzilly, France; (F.R.); (P.B.)
| | - Philippe Barrière
- INRAE, Université de Tours, Centre de Recherche de Tours, UEPAO, 37380 Nouzilly, France; (F.R.); (P.B.)
| | | | - Vincent Hanoux
- Université de Caen-Normandie, OeReCa, 14000 Caen, France; (M.R.); (R.E.); (C.D.); (V.H.)
| | - Philippe Galéra
- Université de Caen Normandie BIOTARGEN, 14000 Caen, France; (F.L.); (P.G.)
| | - Hélène Bouraïma-Lelong
- Université de Caen-Normandie, OeReCa, 14000 Caen, France; (M.R.); (R.E.); (C.D.); (V.H.)
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8
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Huang T, Howse FM, Stachenfeld NS, Usselman CW. Correlations between salivary- and blood-derived gonadal hormone assessments and implications for inclusion of female participants in research studies. Am J Physiol Heart Circ Physiol 2023; 324:H33-H46. [PMID: 36426884 DOI: 10.1152/ajpheart.00399.2022] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Even in the 21st century, female participants continue to be underrepresented in human physiology research. This underrepresentation is attributable in part to the perception that the inclusion of females is more time consuming, less convenient, and more expensive relative to males because of the need to account for the menstrual cycle in cardiovascular study designs. Accounting for menstrual cycle-induced fluctuations in gonadal hormones is important, given established roles in governing vascular function and evidence that failure to consider gonadal hormone fluctuations can result in misinterpretations of biomarkers of cardiovascular disease. Thus, for cardiovascular researchers, the inclusion of females in research studies implies a necessity to predict, quantify, and/or track indexes of menstrual cycle-induced changes in hormones. It is here that methodologies are lacking. Gold standard measurement requires venous blood samples, but this technique is invasive and can become both expensive and technically preclusive when serial measurements are required. To this end, saliva-derived measures of gonadal hormones provide a means of simple, noninvasive hormone tracking. To investigate the feasibility of this technique as a means of facilitating research designs that take the menstrual cycle into account, the purpose of this review was to examine literature comparing salivary and blood concentrations of the primary gonadal hormones that fluctuate across the menstrual cycle: estradiol and progesterone. The data indicate that there appear to be valid and promising applications of salivary gonadal hormone monitoring, which may aid in the inclusion of female participants in cardiovascular research studies.
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Affiliation(s)
- Tingyu Huang
- Cardiovascular Health and Autonomic Regulation Laboratory, Department of Kinesiology and Physical Education, McGill University, Montreal, Quebec, Canada
| | - Fiona M Howse
- Cardiovascular Health and Autonomic Regulation Laboratory, Department of Kinesiology and Physical Education, McGill University, Montreal, Quebec, Canada
| | - Nina S Stachenfeld
- The John B. Pierce Laboratory, New Haven, Connecticut.,Yale School of Medicine, New Haven, Connecticut
| | - Charlotte W Usselman
- Cardiovascular Health and Autonomic Regulation Laboratory, Department of Kinesiology and Physical Education, McGill University, Montreal, Quebec, Canada.,McGill Research Centre for Physical Activity and Health, McGill University, Montreal, Quebec, Canada
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9
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David K, Narinx N, Antonio L, Evenepoel P, Claessens F, Decallonne B, Vanderschueren D. Bone health in ageing men. Rev Endocr Metab Disord 2022; 23:1173-1208. [PMID: 35841491 DOI: 10.1007/s11154-022-09738-5] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/20/2022] [Indexed: 01/11/2023]
Abstract
Osteoporosis does not only affect postmenopausal women, but also ageing men. The burden of disease is projected to increase with higher life expectancy both in females and males. Importantly, osteoporotic men remain more often undiagnosed and untreated compared to women. Sex steroid deficiency is associated with bone loss and increased fracture risk, and circulating sex steroid levels have been shown to be associated both with bone mineral density and fracture risk in elderly men. However, in contrast to postmenopausal osteoporosis, the contribution of relatively small decrease of circulating sex steroid concentrations in the ageing male to the development of osteoporosis and related fractures, is probably only minor. In this review we provide several clinical and preclinical arguments in favor of a 'bone threshold' for occurrence of hypogonadal osteoporosis, corresponding to a grade of sex steroid deficiency that in general will not occur in many elderly men. Testosterone replacement therapy has been shown to increase bone mineral density in men, however data in osteoporotic ageing males are scarce, and evidence on fracture risk reduction is lacking. We conclude that testosterone replacement therapy should not be used as a sole bone-specific treatment in osteoporotic elderly men.
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Affiliation(s)
- Karel David
- Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Herestraat 49, ON1bis box 902, 3000 , Leuven, Belgium
- Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium
| | - Nick Narinx
- Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Herestraat 49, ON1bis box 902, 3000 , Leuven, Belgium
- Department of Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium
| | - Leen Antonio
- Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Herestraat 49, ON1bis box 902, 3000 , Leuven, Belgium
- Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium
| | - Pieter Evenepoel
- Nephrology and Renal Transplantation Research Group, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
- Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium
| | - Frank Claessens
- Laboratory of Molecular Endocrinology, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium
| | - Brigitte Decallonne
- Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Herestraat 49, ON1bis box 902, 3000 , Leuven, Belgium
- Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium
| | - Dirk Vanderschueren
- Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Herestraat 49, ON1bis box 902, 3000 , Leuven, Belgium.
- Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium.
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Sanchez MM, Bagdasarian IA, Darch W, Morgan JT. Organotypic cultures as aging associated disease models. Aging (Albany NY) 2022; 14:9338-9383. [PMID: 36435511 PMCID: PMC9740367 DOI: 10.18632/aging.204361] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Accepted: 10/21/2022] [Indexed: 11/24/2022]
Abstract
Aging remains a primary risk factor for a host of diseases, including leading causes of death. Aging and associated diseases are inherently multifactorial, with numerous contributing factors and phenotypes at the molecular, cellular, tissue, and organismal scales. Despite the complexity of aging phenomena, models currently used in aging research possess limitations. Frequently used in vivo models often have important physiological differences, age at different rates, or are genetically engineered to match late disease phenotypes rather than early causes. Conversely, routinely used in vitro models lack the complex tissue-scale and systemic cues that are disrupted in aging. To fill in gaps between in vivo and traditional in vitro models, researchers have increasingly been turning to organotypic models, which provide increased physiological relevance with the accessibility and control of in vitro context. While powerful tools, the development of these models is a field of its own, and many aging researchers may be unaware of recent progress in organotypic models, or hesitant to include these models in their own work. In this review, we describe recent progress in tissue engineering applied to organotypic models, highlighting examples explicitly linked to aging and associated disease, as well as examples of models that are relevant to aging. We specifically highlight progress made in skin, gut, and skeletal muscle, and describe how recently demonstrated models have been used for aging studies or similar phenotypes. Throughout, this review emphasizes the accessibility of these models and aims to provide a resource for researchers seeking to leverage these powerful tools.
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Affiliation(s)
- Martina M. Sanchez
- Department of Bioengineering, University of California, Riverside, CA 92521, USA
| | | | - William Darch
- Department of Bioengineering, University of California, Riverside, CA 92521, USA
| | - Joshua T. Morgan
- Department of Bioengineering, University of California, Riverside, CA 92521, USA
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11
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Jördens MS, Wittig L, Loberg C, Heinrichs L, Keitel V, Schulze-Hagen M, Antoch G, Knoefel WT, Fluegen G, Loosen SH, Roderburg C, Luedde T. Bone Mineral Density Is a Predictor of Mortality in Female Patients with Cholangiocellular Carcinoma Undergoing Palliative Treatment. Biomedicines 2022; 10:biomedicines10071660. [PMID: 35884968 PMCID: PMC9313370 DOI: 10.3390/biomedicines10071660] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 07/05/2022] [Accepted: 07/07/2022] [Indexed: 01/02/2023] Open
Abstract
Background: Cholangiocellular adenocarcinoma (CCA) is a rare and aggressive malignancy originating from the bile ducts. Its general prognosis is poor as therapeutic options are limited. Many patients present with advanced stages of disease, and palliative chemotherapy remains the only treatment option. Prognostic markers to assess the outcome of chemotherapeutic treatment in CCA are limited. We therefore evaluated bone mineral density (BMD) as a prognostic tool in patients with advanced CCA. Patients and Methods: We included 75 patients with advanced CCA that were treated at our academic tumor center. Prior to treatment, bone mineral density was analyzed at the first lumbar vertebra using routine CT scans in the venous phase and the local PACS (IntelliSpace PACS, Philips, Amsterdam, The Netherlands). Results: BMD was not significantly different between male and female patients but decreased with age. Patients with BMD above 167 HU have a significantly improved overall survival (474 days vs. 254 days; log-rank X2(1) = 6.090; p = 0.014). The prognostic value of BMD was confirmed using univariate (HR 2.313 (95%CI: 1.170–4.575); p = 0.016) and multivariate (HR 4.143 (95%CI: 1.197–14.343); p = 0.025) Cox regression analyses. Subgroup analysis revealed that the prognostic value of BMD was only present in female patients and not in male patients, suggesting sex-specific differences. Conclusions: Our data suggest that BMD is a valuable, easily accessible, and independent prognostic marker for overall survival in patients with advanced CCA. Furthermore, subgroup analysis showed the sex specificity of this marker, which demonstrated relevance only in female patients.
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Affiliation(s)
- Markus S. Jördens
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany; (L.W.); (L.H.); (V.K.); (S.H.L.); (C.R.); (T.L.)
- Correspondence: ; Tel.: +49-211-81-18940
| | - Linda Wittig
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany; (L.W.); (L.H.); (V.K.); (S.H.L.); (C.R.); (T.L.)
| | - Christina Loberg
- Department of Diagnostic and Interventional Radiology, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany; (C.L.); (G.A.)
| | - Lisa Heinrichs
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany; (L.W.); (L.H.); (V.K.); (S.H.L.); (C.R.); (T.L.)
| | - Verena Keitel
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany; (L.W.); (L.H.); (V.K.); (S.H.L.); (C.R.); (T.L.)
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty of Otto-von-Guericke-University, 39120 Magdeburg, Germany;
| | - Maximilian Schulze-Hagen
- Department for Diagnostic and Interventional Radiology, University Hospital Aachen, 52074 Aachen, Germany;
| | - Gerald Antoch
- Department of Diagnostic and Interventional Radiology, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany; (C.L.); (G.A.)
| | - Wolfram T. Knoefel
- Department of General, Visceral and Pediatric Surgery, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany;
| | - Georg Fluegen
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty of Otto-von-Guericke-University, 39120 Magdeburg, Germany;
| | - Sven H. Loosen
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany; (L.W.); (L.H.); (V.K.); (S.H.L.); (C.R.); (T.L.)
| | - Christoph Roderburg
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany; (L.W.); (L.H.); (V.K.); (S.H.L.); (C.R.); (T.L.)
| | - Tom Luedde
- Department of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany; (L.W.); (L.H.); (V.K.); (S.H.L.); (C.R.); (T.L.)
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12
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Xu L, Zhao Q, Li K, Zhang Y, Wang C, Hind K, Wang L, Liu Y, Cheng X. The Role of Sex Hormones on Bone Mineral Density, Marrow Adiposity, and Muscle Adiposity in Middle-Aged and Older Men. Front Endocrinol (Lausanne) 2022; 13:817418. [PMID: 35265038 PMCID: PMC8899107 DOI: 10.3389/fendo.2022.817418] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Accepted: 01/31/2022] [Indexed: 02/05/2023] Open
Abstract
PURPOSE The etiology of age-related bone loss is less clear in men. This study is aimed to observe the variations of endogenous sex hormone concentrations with increasing of age in men, and investigate their relations to bone mass, marrow adiposity, and muscle adiposity. METHODS A total of 199 community-dwelling Chinese men (aged 41 to 82 years) were included and measured of serum total estradiol, total testosterone, and follicle-stimulating hormone (FSH) concentrations by enzyme-linked immunosorbent assay (ELISA). Vertebral trabecular volumetric bone mineral density (vBMD) was measured by quantitative computed tomography for all participants, and vertebral marrow fat content and erector muscle fat content were quantified by Chemistry-shift-encoding magnetic resonance imaging in 62 participants. RESULTS In this population, FSH concentration increased (p < 0.001) gradually with aging. Lower vBMD was independently associated with higher FSH concentration (β = -0.216, p < 0.001), but not with total estradiol or total testosterone. For each standard deviation increase in FSH there was a 50% higher risk of an individual having osteopenia or osteoporosis (vBMD < 120 mg/cm3). Marrow fat content and erector muscle fat content were greater in osteopenic and osteoporotic men, but there were no associations with sex hormones concentrations. CONCLUSION In summary, FSH but not total estradiol or total testosterone is related to vertebral trabecular vBMD in middle-aged and older Chinese men. Neither marrow adiposity nor muscle adiposity is associated with sex hormones.
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Affiliation(s)
- Li Xu
- Department of Radiology, Beijing Jishuitan Hospital, Beijing, China
| | - Qian Zhao
- International Medical Center, West China Hospital, Sichuan University, Chengdu, China
| | - Kai Li
- Department of Radiology, Beijing Jishuitan Hospital, Beijing, China
| | - Yong Zhang
- Department of Radiology, Beijing Jishuitan Hospital, Beijing, China
| | - Chao Wang
- Department of Epidemiology and Biostatistics, Beijing Research Institute of Traumatology and Orthopedics, Beijing Jishuitan Hospital, Beijing, China
| | - Karen Hind
- Department of Sport and Exercise Sciences, Durham University, Durham, United Kingdom
| | - Ling Wang
- Department of Radiology, Beijing Jishuitan Hospital, Beijing, China
| | - Yandong Liu
- Department of Radiology, Beijing Jishuitan Hospital, Beijing, China
| | - Xiaoguang Cheng
- Department of Radiology, Beijing Jishuitan Hospital, Beijing, China
- *Correspondence: Xiaoguang Cheng,
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13
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Ali D, Tencerova M, Figeac F, Kassem M, Jafari A. The pathophysiology of osteoporosis in obesity and type 2 diabetes in aging women and men: The mechanisms and roles of increased bone marrow adiposity. Front Endocrinol (Lausanne) 2022; 13:981487. [PMID: 36187112 PMCID: PMC9520254 DOI: 10.3389/fendo.2022.981487] [Citation(s) in RCA: 58] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Accepted: 08/29/2022] [Indexed: 11/13/2022] Open
Abstract
Osteoporosis is defined as a systemic skeletal disease characterized by decreased bone mass and micro-architectural deterioration leading to increased fracture risk. Osteoporosis incidence increases with age in both post-menopausal women and aging men. Among other important contributing factors to bone fragility observed in osteoporosis, that also affect the elderly population, are metabolic disturbances observed in obesity and Type 2 Diabetes (T2D). These metabolic complications are associated with impaired bone homeostasis and a higher fracture risk. Expansion of the Bone Marrow Adipose Tissue (BMAT), at the expense of decreased bone formation, is thought to be one of the key pathogenic mechanisms underlying osteoporosis and bone fragility in obesity and T2D. Our review provides a summary of mechanisms behind increased Bone Marrow Adiposity (BMA) during aging and highlights the pre-clinical and clinical studies connecting obesity and T2D, to BMA and bone fragility in aging osteoporotic women and men.
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Affiliation(s)
- Dalia Ali
- Department of Molecular Endocrinology, KMEB, University of Southern Denmark and Odense University Hospital, Odense, Denmark
- *Correspondence: Dalia Ali, ; Abbas Jafari,
| | - Michaela Tencerova
- Laboratory of Molecular Physiology of Bone, Institute of Physiology of the Czech Academy of Sciences, Prague, Czechia
| | - Florence Figeac
- Department of Molecular Endocrinology, KMEB, University of Southern Denmark and Odense University Hospital, Odense, Denmark
| | - Moustapha Kassem
- Department of Molecular Endocrinology, KMEB, University of Southern Denmark and Odense University Hospital, Odense, Denmark
| | - Abbas Jafari
- Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark
- *Correspondence: Dalia Ali, ; Abbas Jafari,
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14
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He B, Lyu Q, Yin L, Zhang M, Quan Z, Ou Y. Depression and Osteoporosis: A Mendelian Randomization Study. Calcif Tissue Int 2021; 109:675-684. [PMID: 34259888 PMCID: PMC8531056 DOI: 10.1007/s00223-021-00886-5] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2021] [Accepted: 06/29/2021] [Indexed: 12/15/2022]
Abstract
Observational studies suggest a link between depression and osteoporosis, but these may be subject to confounding and reverse causality. In this two-sample Mendelian randomization analysis, we included the large meta-analysis of genome-wide association studies for depression among 807,553 individuals (246,363 cases and 561,190 controls) of European descent, the large meta-analysis to identify genetic variants associated with femoral neck bone mineral density (FN-BMD), forearm BMD (FA-BMD) and lumbar spine BMD (LS-BMD) among 53,236 individuals of European ancestry, and the GWAS summary data of heel BMD (HE-BMD) and fracture among 426,824 individuals of European ancestry. The results revealed that genetic predisposition towards depression showed no causal effect on FA-BMD (beta-estimate: 0.091, 95% confidence interval [CI] - 0.088 to 0.269, SE:0.091, P value = 0.320), FN-BMD (beta-estimate: 0.066, 95% CI - 0.016 to 0.148, SE:0.042, P value = 0.113), LS-BMD (beta-estimate: 0.074, 95% CI - 0.029 to 0.177, SE:0.052, P value = 0.159), HE-BMD (beta-estimate: 0.009, 95% CI - 0.043 to 0.061, SE:0.027, P value = 0.727), or fracture (beta-estimate: 0.008, 95% CI - 0.071 to 0.087, SE:0.041, P value = 0.844). These results were also confirmed by multiple sensitivity analyses. Contrary to the findings of observational studies, our results do not reveal a causal role of depression in osteoporosis or fracture.
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Affiliation(s)
- Bin He
- Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yi Xue Yuan Road, Yuzhong District, Chongqing, 400016, China.
| | - Qiong Lyu
- Department of General Practice, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yi Xue Yuan Road, Yuzhong District, Chongqing, 400016, China
| | - Lifeng Yin
- Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yi Xue Yuan Road, Yuzhong District, Chongqing, 400016, China
| | - Muzi Zhang
- Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yi Xue Yuan Road, Yuzhong District, Chongqing, 400016, China
| | - Zhengxue Quan
- Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yi Xue Yuan Road, Yuzhong District, Chongqing, 400016, China
| | - Yunsheng Ou
- Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, No. 1 Yi Xue Yuan Road, Yuzhong District, Chongqing, 400016, China
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15
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Pooja, Sharma V, Meena RN, Ray K, Panjwani U, Varshney R, Sethy NK. TMT-Based Plasma Proteomics Reveals Dyslipidemia Among Lowlanders During Prolonged Stay at High Altitudes. Front Physiol 2021; 12:730601. [PMID: 34721061 PMCID: PMC8554329 DOI: 10.3389/fphys.2021.730601] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Accepted: 09/02/2021] [Indexed: 01/11/2023] Open
Abstract
Acute exposure to high altitude perturbs physiological parameters and induces an array of molecular changes in healthy lowlanders. However, activation of compensatory mechanisms and biological processes facilitates high altitude acclimatization. A large number of lowlanders stay at high altitude regions from weeks to months for work and professional commitments, and thus are vulnerable to altitude-associated disorders. Despite this, there is a scarcity of information for molecular changes associated with long-term stay at high altitudes. In the present study, we evaluated oxygen saturation (SpO2), heart rate (HR), and systolic and diastolic blood pressure (SBP and DBP) of lowlanders after short- (7 days, HA-D7) and long-term (3 months, HA-D150) stay at high altitudes, and used TMT-based proteomics studies to decipher plasma proteome alterations. We observed improvements in SpO2 levels after prolonged stay, while HR, SBP, and DBP remained elevated as compared with short-term stay. Plasma proteomics studies revealed higher levels of apolipoproteins APOB, APOCI, APOCIII, APOE, and APOL, and carbonic anhydrases (CA1 and CA2) during hypoxia exposure. Biological network analysis also identified profound alterations in lipoprotein-associated pathways like plasma lipoprotein assembly, VLDL clearance, chylomicron assembly, chylomicron remodeling, plasma lipoprotein clearance, and chylomicron clearance. In corroboration, lipid profiling revealed higher levels of total cholesterol (TC), triglycerides (TGs), low-density lipoprotein (LDL) for HA-D150 whereas high density lipoproteins (HDL) levels were lower as compared with HA-D7 and sea-level indicating dyslipidemia. We also observed higher levels of proinflammatory cytokines IL-6, TNFα, and CRP for HA-D150 along with oxidized LDL (oxLDL), suggesting vascular inflammation and proartherogenic propensity. These results demonstrate that long-term stay at high altitudes exacerbates dyslipidemia and associated disorders.
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Affiliation(s)
- Pooja
- Peptide and Proteomics Division, Defence Institute of Physiology and Allied Sciences, New Delhi, India
| | - Vandana Sharma
- Peptide and Proteomics Division, Defence Institute of Physiology and Allied Sciences, New Delhi, India
| | - Ram Niwas Meena
- Peptide and Proteomics Division, Defence Institute of Physiology and Allied Sciences, New Delhi, India
| | - Koushik Ray
- Neurophysiology Department, Defence Institute of Physiology and Allied Sciences, New Delhi, India
| | - Usha Panjwani
- Neurophysiology Department, Defence Institute of Physiology and Allied Sciences, New Delhi, India
| | - Rajeev Varshney
- Peptide and Proteomics Division, Defence Institute of Physiology and Allied Sciences, New Delhi, India
| | - Niroj Kumar Sethy
- Peptide and Proteomics Division, Defence Institute of Physiology and Allied Sciences, New Delhi, India
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16
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Fu S, Ping P, Li Y, Li B, Zhao Y, Yao Y, Zhang P. Centenarian longevity had inverse relationships with nutritional status and abdominal obesity and positive relationships with sex hormones and bone turnover in the oldest females. J Transl Med 2021; 19:436. [PMID: 34663361 PMCID: PMC8522151 DOI: 10.1186/s12967-021-03115-7] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Accepted: 10/09/2021] [Indexed: 01/13/2023] Open
Abstract
Objective The number of older people is estimated to increase from 524 million in 2010 to 1.5 billion in 2050. The factors and models of human longevity and successful aging are questions that have intrigued individuals for thousands of years. For the first time, the current study was designed to investigate the relationships between sex hormones, bone turnover, abdominal obesity, nutritional status and centenarian longevity in the oldest females. Methods The China Hainan Centenarian Cohort Study was performed in 18 cities and counties of Hainan Province using standard methodology in 500 centenarian females and 237 oldest females aged between 80 and 99 years. Results Centenarians were inversely associated with the geriatric nutritional risk index [Exp(B) (95% CI): 0.901 (0.883–0.919)] and abdominal obesity [Exp(B) (95% CI): 0.719 (0.520–0.996)] and positively associated with prolactin [Exp(B) (95% CI): 1.073 (1.044–1.103)], progesterone [Exp(B) (95% CI): 44.182 (22.036–88.584)], estradiol [Exp(B) (95% CI): 1.094 (1.071–1.119)], osteocalcin [Exp(B) (95% CI): 1.041 (1.028–1.054)], β-crossLaps [Exp(B) (95% CI): 63.141 (24.482–162.848)] and parathyroid [Exp(B) (95% CI): 1.022 (1.013–1.031)] hormone levels (P < 0.05 for all). The geriatric nutritional risk index and abdominal obesity were inversely associated with luteinizing hormone [β coefficient (95% CI): − 0.001 (− 0.002 to 0.001)]; Exp(B) (95% CI): 0.985 (0.974–0.996)], follicle-stimulating hormone [β coefficient (95% CI): 0.000 (− 0.001 to 0.000)]; Exp(B) (95% CI): 0.990 (0.985–0.996)], osteocalcin [β coefficient (95% CI): − 0.001 (− 0.001 to 0.000)]; Exp(B) (95% CI): 0.987(0.977–0.997)] and β-crossLaps [β coefficient (95% CI): − 0.100 (− 0.130 to 0.071)]; Exp(B) (95% CI): 0.338 (0.166–0.689)] levels (P < 0.05 for all). Conclusions Centenarian longevity had inverse relationships with nutritional status and abdominal obesity and positive relationships with sex hormones and bone turnover. Nutritional status and abdominal obesity had inverse relationships with sex hormones and bone turnover. Increased sex hormones and bone turnover may be representative of centenarian longevity. Optimizing nutritional status and avoiding abdominal obesity may increase sex hormones and bone turnover and promote centenarian longevity and successful aging.
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Affiliation(s)
- Shihui Fu
- Cardiology Department, Hainan Hospital of Chinese People's Liberation Army General Hospital, Sanya, China. .,Department of Geriatric Cardiology, Chinese People's Liberation Army General Hospital, Beijing, China.
| | - Ping Ping
- Pharmacy Department, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Yulong Li
- Department of Geriatric Cardiology, Chinese People's Liberation Army General Hospital, Beijing, China
| | - Bo Li
- Cardiology Department, Hainan Hospital of Chinese People's Liberation Army General Hospital, Sanya, China
| | - Yali Zhao
- Central Laboratory, Hainan Hospital of Chinese People's Liberation Army General Hospital, Sanya, China.
| | - Yao Yao
- Center for Healthy Aging and Development Studies, National School of Development, Peking University, Beijing, China.
| | - Pei Zhang
- School of Life Science, Beijing Institute of Technology, Beijing, China.
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Bibliometric analysis of global research trends on male osteoporosis: a neglected field deserves more attention. Arch Osteoporos 2021; 16:154. [PMID: 34632530 DOI: 10.1007/s11657-021-01016-2] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Accepted: 09/27/2021] [Indexed: 02/03/2023]
Abstract
UNLABELLED We analyzed the knowledge structure, current status, and future directions of 3243 publications on male osteoporosis by employing bibliometric analysis. Our results indicated that Osteoporosis International was the most influential journal in this field. And the study of epidemiology and risk factors has been recognized as a hot research topic in recent years. This study also calls for more attention to be given on male osteoporosis research. INTRODUCTION Male osteoporosis is increasing as a serious health problem worldwide with the aging of population. However, a comprehensive understanding of the current status and future trends in this field is lacking to date. The goal of the present study was to summarize and visualize the knowledge framework, research hotspots, and emerging trends of male osteoporosis research based on the bibliometric method. METHODS Scientific publications regarding male osteoporosis from 1998 to 2020 were downloaded from the SCIE database. VOSviewer, CiteSpace, and online bibliometric website were used for this study. The main analyses include cooperative relationships between countries/institutions/authors, co-citation analysis of authors/journals, and co-occurrence analysis of keywords/subject categories, as well as analyses on keyword/reference bursts. RESULTS A total of 3243 publications with 128,751 citations were identified. Despite experiencing a period of increase in the number of publications, incentives for conducting male osteoporosis research seem to have decreased during recent years. The USA has the most prominent contributions, as reflected by most publications and the highest H-index value. Oregon Health and Science University was the most prolific institution within this domain. The most influential academic journal was Osteoporosis International. Keywords were categorized into four clusters: basic research, epidemiology and risk factors, diagnostic studies, treatment and fracture prevention. Burst keyword detection suggested that the following research directions including "obesity," "zoledronic acid," "DXA," "inflammation," "fall," "microarchitecture," and "sarcopenia" remain research hotspots in the near future and deserve our further attention. CONCLUSIONS This is the first bibliometric analysis that provides a comprehensive overview of male osteoporosis research, which may provide helpful references for investigators to further explore hot issues in this field.
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Yuan S, Chen J, Zeng L, Zhou C, Yu S, Fang L. Association of bone mineral density and depression in different bone sites and ages: A meta-analysis. Food Sci Nutr 2021; 9:4780-4792. [PMID: 34531991 PMCID: PMC8441488 DOI: 10.1002/fsn3.2379] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2020] [Revised: 04/20/2021] [Accepted: 05/16/2021] [Indexed: 01/01/2023] Open
Abstract
Major depressive disorder (MDD) is considered as a risk factor for osteoporosis. Bone mineral density (BMD), as the main tool for diagnosing osteoporosis, has been reported to have correlation with MDD in different cohorts. However, the information in causative link and etiology determinants of osteoporosis in MDD is still under investigation. The results are unclear. Thus, we perform a meta-analysis to evaluate the association between altered BMD and MDD. We searched the electronic databases to find studies examining BMD in patients with MDD. Finally, 26 published studies were included in our meta-analysis up from January 1990 to January 2019. All the data were pooled analysis using RevMan software. The association between altered BMD and MDD was assessed by std. mean difference (STD) and their 95% confidence intervals (CIs) for each study. Twenty-six studies were included in this meta-analysis. Pooled results showed a significant lower BMD in spine (STD=0.51, 95% CI=0.30-0.71, p < .00001), total hip (STD=0.41, 95% CI=0.16 to 0.66, p = .001), and femoral neck (STD=0.93, 95% CI=0.32 to 1.55, p = .003) in MDD compared with controls. After stratification by mean age, gender, recruitment, diagnostic criteria, and measuring methods, no significant difference of BMD was found in bone mineral density of male total hip between MDD and controls(p > .05). Moreover, adults appear to have lower BMD than old cohorts. This is an updated meta-analysis to reveal the association of bone mineral density and depression, suggesting that BMD appears to be more susceptible to occur in spine, total hip, femoral neck in MDD, especially for adults and women. Our meta-analysis may provide clinicians and public health administrators with an important screening tool for assessing depression and avoiding osteoporosis in adult subjects and female.
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Affiliation(s)
- Shiyi Yuan
- Department of NephrologyYongchuan Hospital of Chongqing Medical UniversityChongqingChina
- Department of NephrologyThe People’s Hospital of Yongchuan DistrictChongqingChina
| | - Jianjun Chen
- College of Life SciencesChongqing Medical UniversityChongqingChina
| | - Li Zeng
- Department of NeurologyThe Second Affiliated Hospital of Chongqing Medical UniversityChongqingChina
| | - Chanjuan Zhou
- Department of NephrologyYongchuan Hospital of Chongqing Medical UniversityChongqingChina
| | - Shenrun Yu
- The People’s Hospital of Yong chuan DistrictChongqingChina
| | - Liang Fang
- Department of NephrologyYongchuan Hospital of Chongqing Medical UniversityChongqingChina
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19
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Singleton RC, Pharr GM, Nyman JS. Increased tissue-level storage modulus and hardness with age in male cortical bone and its association with decreased fracture toughness. Bone 2021; 148:115949. [PMID: 33862261 PMCID: PMC8102428 DOI: 10.1016/j.bone.2021.115949] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Revised: 04/05/2021] [Accepted: 04/06/2021] [Indexed: 11/19/2022]
Abstract
The incidence of bone fracture increases with age, due to both declining bone quantity and quality. Toward the goal of an improved understanding of the causes of the age-related decline in the fracture toughness of male cortical bone, nanoindentation experiments were performed on femoral diaphysis specimens from men aged 21-98 years. Because aged bone has less matrix-bound water and dry bone is less viscoelastic, we used a nanoindentation method that is sensitive to changes in viscoelasticity. Given the anisotropy of bone stiffness, longitudinal (n = 26) and transverse (n = 25) specimens relative to the long axis of the femur diaphysis were tested both dry in air and immersed in phosphate buffered saline solution. Indentation stiffness (storage modulus) and hardness increased with age, while viscoelasticity (loss modulus) was independent of donor age. The increases in indentation stiffness and hardness with age were best explained by increased mineralization with age. Indentation stiffness and hardness were negatively correlated with previously acquired fracture toughness parameters, which is consistent with a tradeoff between material strength and toughness. In keeping with the complex structure of bone, a combination of tissue-level storage modulus or hardness, bound water, and osteonal area in regression models best explained the variance in the fracture toughness of male human cortical bone. On the other hand, viscoelasticity was unchanged with age and was not associated with fracture toughness. In conclusion, the age-related increase in stiffness and hardness of male cortical bone may be one of the multiple tissue-level characteristics that contributes to decreased fracture toughness.
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Affiliation(s)
- Robert C Singleton
- Materials Science and Engineering Department, University of Tennessee, Knoxville, TN 37996, USA
| | - George M Pharr
- Materials Science and Engineering Department, University of Tennessee, Knoxville, TN 37996, USA; Department of Materials Science and Engineering, Texas A&M University, College Station, TX 77843-3003, USA
| | - Jeffry S Nyman
- Department of Orthopaedic Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Center for Bone Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN 37212, USA.
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20
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Trius-Soler M, Marhuenda-Muñoz M, Laveriano-Santos EP, Martínez-Huélamo M, Sasot G, Storniolo CE, Estruch R, Lamuela-Raventós RM, Tresserra-Rimbau A. Moderate Consumption of Beer (with and without Ethanol) and Menopausal Symptoms: Results from a Parallel Clinical Trial in Postmenopausal Women. Nutrients 2021; 13:nu13072278. [PMID: 34209273 PMCID: PMC8308431 DOI: 10.3390/nu13072278] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 06/26/2021] [Accepted: 06/28/2021] [Indexed: 12/28/2022] Open
Abstract
The menopausal transition can be a challenging period for women’s health and a trigger of uncomfortable symptoms. Beer is the main food source of isoxanthohumol, a precursor of 8-prenylnaringenin, the strongest phytoestrogen identified to date. As phytoestrogens are reported to reduce perimenopausal symptoms, we evaluated if a daily moderate consumption of beer with (AB) and without alcohol (NAB) could improve menopausal symptoms and modify cardiovascular risk factors. A total of 37 postmenopausal women were enrolled in a parallel controlled intervention trial and assigned to three study groups: 16 were administered AB (330 mL/day), 7 NAB (660 mL/day), and 14 were in the control group. After a 6-month follow-up of the 34 participants who finished the trial, both interventions (AB and NAB) significantly reduced the severity of the menopause-related symptoms (p-value AB vs. Control: 0.009; p-value NAB vs. Control: 0.033). Moreover, AB had a beneficial net effect on psychological menopausal discomforts compared to the control group. As the sex hormone profile did not differ significantly between the study groups, the effects of both types of beers (AB and NAB) are attributed to the non-alcoholic fraction of beer. Furthermore, moderate NAB consumption improved the lipid profile and decreased blood pressure in postmenopausal women.
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Affiliation(s)
- Marta Trius-Soler
- Department of Nutrition, Food Sciences and Gastronomy, XaRTA, School of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain; (M.T.-S.); (M.M.-M.); (E.P.L.-S.); (M.M.-H.); (G.S.); (C.E.S.)
- INSA-UB, Nutrition and Food Safety Research Institute, University of Barcelona, 08921 Santa Coloma de Gramanet, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain;
| | - María Marhuenda-Muñoz
- Department of Nutrition, Food Sciences and Gastronomy, XaRTA, School of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain; (M.T.-S.); (M.M.-M.); (E.P.L.-S.); (M.M.-H.); (G.S.); (C.E.S.)
- INSA-UB, Nutrition and Food Safety Research Institute, University of Barcelona, 08921 Santa Coloma de Gramanet, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain;
| | - Emily P. Laveriano-Santos
- Department of Nutrition, Food Sciences and Gastronomy, XaRTA, School of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain; (M.T.-S.); (M.M.-M.); (E.P.L.-S.); (M.M.-H.); (G.S.); (C.E.S.)
- INSA-UB, Nutrition and Food Safety Research Institute, University of Barcelona, 08921 Santa Coloma de Gramanet, Spain
| | - Miriam Martínez-Huélamo
- Department of Nutrition, Food Sciences and Gastronomy, XaRTA, School of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain; (M.T.-S.); (M.M.-M.); (E.P.L.-S.); (M.M.-H.); (G.S.); (C.E.S.)
- INSA-UB, Nutrition and Food Safety Research Institute, University of Barcelona, 08921 Santa Coloma de Gramanet, Spain
| | - Gemma Sasot
- Department of Nutrition, Food Sciences and Gastronomy, XaRTA, School of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain; (M.T.-S.); (M.M.-M.); (E.P.L.-S.); (M.M.-H.); (G.S.); (C.E.S.)
- INSA-UB, Nutrition and Food Safety Research Institute, University of Barcelona, 08921 Santa Coloma de Gramanet, Spain
| | - Carolina E. Storniolo
- Department of Nutrition, Food Sciences and Gastronomy, XaRTA, School of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain; (M.T.-S.); (M.M.-M.); (E.P.L.-S.); (M.M.-H.); (G.S.); (C.E.S.)
- INSA-UB, Nutrition and Food Safety Research Institute, University of Barcelona, 08921 Santa Coloma de Gramanet, Spain
| | - Ramon Estruch
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain;
- Department of Internal Medicine, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Spain
| | - Rosa M. Lamuela-Raventós
- Department of Nutrition, Food Sciences and Gastronomy, XaRTA, School of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain; (M.T.-S.); (M.M.-M.); (E.P.L.-S.); (M.M.-H.); (G.S.); (C.E.S.)
- INSA-UB, Nutrition and Food Safety Research Institute, University of Barcelona, 08921 Santa Coloma de Gramanet, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain;
- Correspondence: (R.M.L.-R.); (A.T.-R.); Tel.: +34-934-034-843 (R.M.L.-R. & A.T.-R.)
| | - Anna Tresserra-Rimbau
- Department of Nutrition, Food Sciences and Gastronomy, XaRTA, School of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain; (M.T.-S.); (M.M.-M.); (E.P.L.-S.); (M.M.-H.); (G.S.); (C.E.S.)
- INSA-UB, Nutrition and Food Safety Research Institute, University of Barcelona, 08921 Santa Coloma de Gramanet, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain;
- Correspondence: (R.M.L.-R.); (A.T.-R.); Tel.: +34-934-034-843 (R.M.L.-R. & A.T.-R.)
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21
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Atsumi Y, Rino Y, Aoyama T, Okuda N, Kawahara S, Kazama K, Numata M, Tamagawa H, Oshima T, Yukawa N, Masuda M. A Gender Comparison of Bone Metabolic Changes After Gastric Cancer Surgery: A Prospective Observational Study. In Vivo 2021; 35:2341-2348. [PMID: 34182516 DOI: 10.21873/invivo.12510] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Revised: 04/24/2021] [Accepted: 04/26/2021] [Indexed: 12/28/2022]
Abstract
BACKGROUND/AIM This study was designed to investigate gender-related differences in changes in bone metabolism after gastric cancer surgery. PATIENTS AND METHODS We prospectively recruited 47 patients (38 males and 9 females) who had early gastric cancer. The bone mineral density (BMD), serum levels of 1,25-dihydroxy vitamin D (1,25(OH)2VD), 25-hydroxy vitamin D (25(OH)VD), and estradiol (E2) were measured before and after surgery. RESULTS BMD significantly decreased 12 months after surgery by median degrees of 3.4% and 3.9% in male and female patients, respectively (p<0.001 and p=0.023). There was no significant difference between both genders in the rate of change in BMD after surgery. The serum E2 level in male patients significantly increased by a median value of 22 pg/ml 12 months after gastrectomy (p=0.030). Both the serum 25(OH)VD and 1,25(OH)2VD levels remained nearly within the normal range throughout the observation period in both male and female patients. CONCLUSION BMD significantly decreased within 12 months after gastrectomy in both male and female patients with gastric cancer, and there was no significant gender-related difference in the rate of change in BMD.
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Affiliation(s)
- Yosuke Atsumi
- Department of Surgery, Yokohama City University, Yokohama, Japan;
| | - Yasushi Rino
- Department of Surgery, Yokohama City University, Yokohama, Japan
| | - Toru Aoyama
- Department of Surgery, Yokohama City University, Yokohama, Japan
| | - Naoko Okuda
- Department of Surgery, Yokohama City University, Yokohama, Japan
| | | | - Keisuke Kazama
- Department of Surgery, Yokohama City University, Yokohama, Japan
| | - Masakatsu Numata
- Department of Surgery, Yokohama City University, Yokohama, Japan
| | - Hiroshi Tamagawa
- Department of Surgery, Yokohama City University, Yokohama, Japan
| | - Takashi Oshima
- Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan
| | - Norio Yukawa
- Department of Surgery, Yokohama City University, Yokohama, Japan
| | - Munetaka Masuda
- Department of Surgery, Yokohama City University, Yokohama, Japan
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22
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Zwickl H, Zwickl-Traxler E, Haushofer A, Seier J, Podar K, Weber M, Hackner K, Jacobi N, Pecherstorfer M, Vallet S. Effect of cachexia on bone turnover in cancer patients: a case-control study. BMC Cancer 2021; 21:744. [PMID: 34182958 PMCID: PMC8240310 DOI: 10.1186/s12885-021-08518-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Accepted: 06/11/2021] [Indexed: 12/18/2022] Open
Abstract
Background Increased bone turnover is frequently observed in advanced cancer and predominantly related to bone metastases or therapy. Cachexia represents an important cause of morbidity and mortality in cancer patients. Key features are weight loss, muscle wasting and chronic inflammation, which induce profound metabolic changes in several organs, including the bone. However, whether cachexia contributes to abnormal bone metabolism in cancer patients is unknown. Aim of the present study was to determine the potential correlation of bone turnover markers with body composition and laboratory parameters in treatment-naïve cancer patients. Methods In this cross-sectional study we measured the levels of carboxy terminal telopeptide of collagen (CTX), an indicator of bone resorption, as well as osteocalcin (Ocn) and procollagen type I N-terminal propeptide (PINP), indicators of bone formation, in 52 cancer patients and correlated with body composition and laboratory parameters. Univariate and multivariate logistic analysis were performed to identify determinants of negative bone remodeling balance, estimated by CTX/Ocn and CTX/PINP ratio. Results Based on weight loss, body mass index and muscle mass, patients were divided into a cachectic (59.6%) and a control (40.4%) group. After correcting for the presence of bone metastases, our results showed a significant upregulation of CTX in cachectic patients compared to non-cachectic cancer patients (median 0.38 vs 0.27 ng/mL, p < 0.05), with no difference in Ocn and PINP levels (mean 14 vs. 16 ng/ml, p = 0.2 and median 32 vs. 26 μg/L, p = 0.5, respectively). In addition, the CTX/Ocn and the CTX/PINP ratio were indicative of bone resorption in 68% and 60% of cachexia patients, respectively (vs. 20% and 31% in the control group, p = 0.002 and p = 0.06). The main determinants of the unbalanced bone turnover were hypoalbuminemia for the CTX/Ocn ratio (OR 19.8, p < 0.01) and high CRP for the CTX/PINP ratio (OR 5.3, p < 0.01) in the multivariate regression analysis. Conclusions CTX is substantially higher in cachectic patients compared to non-cachectic oncological patients and hypoalbuminemia as well as elevated CRP concentrations are independent predictors of a negative bone remodeling balance in cancer patients. These results strongly indicate that cachexia correlates with exacerbated bone turnover in cancer. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-021-08518-9.
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Affiliation(s)
- Hannes Zwickl
- Karl Landsteiner University of Health Sciences, Dr. Karl-Dorrek-Strasse 30, Krems, 3500, Austria
| | - Elisabeth Zwickl-Traxler
- Karl Landsteiner University of Health Sciences, Dr. Karl-Dorrek-Strasse 30, Krems, 3500, Austria.,Department of Internal Medicine 2, University Hospital Krems, Mitterweg 10, Krems, 3500, Austria
| | - Alexander Haushofer
- Central Laboratory, Klinikum Wels-Grieskirchen, Grieskirchner Straße 42, Wels, 4600, Austria
| | - Josef Seier
- Central Laboratory, Klinikum Wels-Grieskirchen, Grieskirchner Straße 42, Wels, 4600, Austria
| | - Klaus Podar
- Karl Landsteiner University of Health Sciences, Dr. Karl-Dorrek-Strasse 30, Krems, 3500, Austria.,Department of Internal Medicine 2, University Hospital Krems, Mitterweg 10, Krems, 3500, Austria
| | - Michael Weber
- Karl Landsteiner University of Health Sciences, Dr. Karl-Dorrek-Strasse 30, Krems, 3500, Austria
| | - Klaus Hackner
- Karl Landsteiner University of Health Sciences, Dr. Karl-Dorrek-Strasse 30, Krems, 3500, Austria.,Department of Pneumology, University Hospital Krems, Mitterweg 10, Krems, 3500, Austria
| | - Nico Jacobi
- IMC University of Applied Sciences Krems, Institute Krems Bioanalytics, Magnesitstraße 1, Krems, 3500, Austria
| | - Martin Pecherstorfer
- Karl Landsteiner University of Health Sciences, Dr. Karl-Dorrek-Strasse 30, Krems, 3500, Austria.,Department of Internal Medicine 2, University Hospital Krems, Mitterweg 10, Krems, 3500, Austria
| | - Sonia Vallet
- Karl Landsteiner University of Health Sciences, Dr. Karl-Dorrek-Strasse 30, Krems, 3500, Austria. .,Department of Internal Medicine 2, University Hospital Krems, Mitterweg 10, Krems, 3500, Austria.
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23
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Vitamin D Metabolites and Sex Steroid Indices in Postmenopausal Women with and without Low Bone Mass. Metabolites 2021; 11:metabo11020086. [PMID: 33535639 PMCID: PMC7912789 DOI: 10.3390/metabo11020086] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 01/24/2021] [Accepted: 01/29/2021] [Indexed: 01/10/2023] Open
Abstract
While the independent roles of vitamin D and sex hormones in skeletal health are well established, the associations of vitamin D and its metabolites to sex hormones and their indices are less investigated. In this observational study, clinical information of 189 Saudi postmenopausal women aged ≥50 years old [N = 80 with normal bone mineral density (BMD), aged 53.3 ± 7.7 years with body mass index (BMI)= 34.1kg/m2 ± 5.8, and N = 109 with low BMD (T-score −1.0 to −2.5), aged 57.0 ± 8.2 years, BMI = 32.4kg/m2 ± 6.2] was extracted from an existing capital-wide osteoporosis registry in Riyadh, Saudi Arabia. Data included were BMD scores, serum total 25(OH)D, sex hormones, and bone turnover markers which were measured using commercially available assays. Age- and BMI-adjusted comparisons revealed significantly higher parathyroid hormone (PTH) levels as well as significantly lower testosterone and bioavailable testosterone in the low BMD group than the normal BMD group (p-values 0.04, 0.02, and 0.03, respectively). Stepwise linear regression showed that circulating testosterone levels accounted for 9.7% and 8.9% of the variances perceived in bioavailable 25(OH)D and free 25(OH)D, respectively (p < 0.01), independent of other sex hormones, sex hormone indices, and bone turnover markers. Our study suggests that androgens are significantly associated with non-conventional vitamin D metabolites and these associations may have clinical relevance in assessing risk for low BMD and osteoporosis in Arab postmenopausal women.
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Pal R, Aggarwal A, Sachdeva N, Ram S, Garg A, Bhansali A, Bhadada SK. Age- and sex-specific concentrations of bone remodeling markers in healthy Indian adults with and without vitamin D deficiency. Arch Osteoporos 2021; 16:10. [PMID: 33415509 DOI: 10.1007/s11657-020-00855-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Accepted: 11/09/2020] [Indexed: 02/03/2023]
Abstract
UNLABELLED Bone remodeling markers exhibit marked inter-ethnic variation; hence, population-specific data are required. Herein, we have established age- and sex-specific concentrations of serum PINP and CTX in healthy Indian adults with and without vitamin D deficiency that can be used in clinical practice for monitoring response to anti-osteoporotic therapy. OBJECTIVE The present study was undertaken to generate data on age- and sex-specific concentrations of serum procollagen type I N-propeptide (PINP) and type I collagen C-telopeptide (CTX) in healthy Indian adults with and without vitamin D deficiency. METHODS Apparently, healthy subjects aged ≥ 20 years with no prior co-morbidities were recruited from the community by door-to-door surveys. Provisionally eligible participants underwent blood sampling after overnight fast. Individuals with biochemical abnormalities that could potentially affect bone remodeling were excluded. However, subjects with vitamin D deficiency were not excluded. Serum total PINP and β-CrossLaps (CTX) were measured using electro-chemiluminescence immunoassay. RESULTS After exclusion, 677 subjects were enrolled (M:F = 2.5:4.2, mean age = 45.0 years). Median serum PINP and CTX were 55.78 ng/ml (40.27-71.70) and 0.356 ng/ml (0.238-0.499), respectively. There was no difference in PINP/CTX between men and women or between premenopausal and postmenopausal women. Decade-wise distribution of PINP/CTX showed that maximum values were attained in 3rd decade; subsequently, in men, levels declined with age while in women, there was a peak in the 6th decade coinciding with the early years of menopause. Vitamin D deficiency and severe vitamin D deficiency were seen in 417 (61.5%) and 259 subjects (38.2%), respectively. There was no significant difference in PINP/CTX in subjects with and without vitamin D deficiency. CONCLUSIONS The present study has allowed us to generate data on serum concentrations of PINP/CTX in a diverse group of healthy community-dwelling Indian adults with varying serum vitamin D levels. It might aid in monitoring response to anti-osteoporotic therapy amongst native Indians.
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Affiliation(s)
- Rimesh Pal
- Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Anshita Aggarwal
- Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Naresh Sachdeva
- Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Sant Ram
- Department of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Abhilasha Garg
- Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Anil Bhansali
- Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Sanjay Kumar Bhadada
- Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India.
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25
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Thirumalai A, Yuen F, Amory JK, Hoofnagle AN, Swerdloff RS, Liu PY, Long JE, Blithe DL, Wang C, Page ST. Dimethandrolone Undecanoate, a Novel, Nonaromatizable Androgen, Increases P1NP in Healthy Men Over 28 Days. J Clin Endocrinol Metab 2021; 106:e171-e181. [PMID: 33090208 PMCID: PMC7765650 DOI: 10.1210/clinem/dgaa761] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Indexed: 02/06/2023]
Abstract
CONTEXT Dimethandrolone undecanoate (DMAU) is being developed as a male contraceptive. Daily oral administration of DMAU, a potent androgen that is not aromatized, markedly suppresses serum testosterone (T) and estradiol (E2) in healthy men. E2 deficiency can increase bone resorption in men. OBJECTIVE This work aimed to assess changes in bone turnover markers with DMAU administration in a 28-day study. DESIGN A randomized, double-blind, placebo-controlled study was conducted. SETTING This study took place at 2 academic medical centers. PARTICIPANTS Healthy men, age 18 to50 years (n = 81), participated. INTERVENTION Men received 0, 100, 200, or 400 mg of oral DMAU for 28 days. Serum C-terminal telopeptide of type I collagen (CTX; bone resorption marker) and procollagen type I amino-terminal propeptide (P1NP; bone formation marker) were measured on days 1 and 28. MAIN OUTCOME MEASURES Changes in bone turnover markers and serum hormones over the treatment period were measured. RESULTS On day 28, median serum T and E2 were markedly suppressed in all treatment groups vs placebo (P < .001 for both). Percentage change (%) in serum P1NP significantly differed across treatment groups (P = .007): Serum P1NP significantly increased in the 200 mg (5%, interquartile range [IQR] -7% to 27%) and 400 mg (22%, IQR -1% to 40%) groups relative to placebo (-8%, IQR -20% to 0%). Change (%) in serum CTX did not differ between groups (P = .09). CONCLUSIONS DMAU administration for 28 days to healthy men leads to marked suppression of serum T and E2, yet increases P1NP, a serum marker of bone formation. Longer-term studies of the potent androgen DMAU are warranted to determine its impact on bone health in men.
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Affiliation(s)
- Arthi Thirumalai
- University of Washington, Seattle, Washington
- Correspondence and Reprint Requests: Arthi Thirumalai, MBBS, Division of Metabolism, Endocrinology and Nutrition, University of Washington, HSB C209, Box 357138, 1959 NE Pacific St, Seattle, WA 98195, USA. E-mail:
| | - Fiona Yuen
- The Lundquist Institute at Harbor UCLA Medical Center, Torrance, California
| | | | | | - Ronald S Swerdloff
- The Lundquist Institute at Harbor UCLA Medical Center, Torrance, California
| | - Peter Y Liu
- The Lundquist Institute at Harbor UCLA Medical Center, Torrance, California
| | - Jill E Long
- Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
| | - Diana L Blithe
- Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
| | - Christina Wang
- The Lundquist Institute at Harbor UCLA Medical Center, Torrance, California
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Lee N, Kang S, Lee W, Hwang SS. The Association between Community Water Fluoridation and Bone Diseases: A Natural Experiment in Cheongju, Korea. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:ijerph17249170. [PMID: 33316869 PMCID: PMC7764285 DOI: 10.3390/ijerph17249170] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Revised: 12/04/2020] [Accepted: 12/05/2020] [Indexed: 11/16/2022]
Abstract
The present study aimed to investigate the association between bone diseases and community water fluoridation (CWF). An ecological study with a natural experiment design was conducted in Cheongju, South Korea, from 1 January 2004 to 31 December 2013. The community water fluoridation program was implemented in Cheongju and divided into CWF and non-CWF areas. To observe adverse health effects related to bone diseases, we conducted a spatio-temporal analysis of the prevalence of hip fracture, osteoporosis, and bone cancer in residents who have lived in CWF and non-CWF areas using National Health Insurance Service data. First, we used standardized incidence ratios to estimate the disease risk. Second, the hierarchical Bayesian Poisson spatio-temporal regression model was used to investigate the association between the selected bone diseases and CWF considering space and time interaction. The method for Bayesian estimation was based on the R-integrated nested Laplace approximation (INLA). Comparing the CWF area with the non-CWF area, there was no clear evidence that exposure to CWF increased health risks at the town level in Cheongju since CWF was terminated after 2004. The posterior relative risks (RR) of hip fracture was 0.95 (95% confidence intervals 0.87, 1.05) and osteoporosis was 0.94 (0.87, 1.02). The RR in bone cancer was a little high because the sample size very small compared to the other bone diseases (RR = 1.20 (0.89, 1.61)). The relative risk of selected bone diseases (hip fractures, osteoporosis, and bone cancer) increased over time but did not increase in the CWF area compared to non-CWF areas. CWF has been used to reduce dental caries in all population groups and is known for its cost-effectiveness. These findings suggest that CWF is not associated with adverse health risks related to bone diseases. This study provides scientific evidence based on a natural experiment design. It is necessary to continue research on the well-designed epidemiological studies and develop public health prevention programs to help in make suitable polices.
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Bae S, Zeng S, Park-Min KH. Nuclear receptors in osteoclasts. Curr Opin Pharmacol 2020; 53:8-17. [PMID: 32569976 PMCID: PMC7669703 DOI: 10.1016/j.coph.2020.03.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2019] [Revised: 03/09/2020] [Accepted: 03/23/2020] [Indexed: 02/08/2023]
Abstract
Osteoclasts are bone-resorbing cells that play an essential role in the remodeling of bone under physiological conditions and numerous pathological conditions, such as osteoporosis, bone metastasis, and inflammatory bone erosion. Nuclear receptors are crucial to various physiological processes, including metabolism, development and inflammation, and function as transcription factors to activate target genes. Synthetic ligands of nuclear receptors are also available for the treatment of metabolic and inflammatory diseases. However, dysregulated bone phenotypes have been documented in patients who take synthetic nuclear receptor ligands as a therapy. Therefore, the effect of nuclear receptors on bone cells has become an important area of exploration; additionally, the molecular mechanisms underlying the action of nuclear receptors in osteoclasts have not been completely understood. Here, we cover the recent progress in our understanding of the roles of nuclear receptors in osteoclasts.
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Affiliation(s)
- Seyeon Bae
- Arthritis and Tissue Degeneration Program, David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, NY 10021, USA; Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
| | - Steven Zeng
- Arthritis and Tissue Degeneration Program, David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, NY 10021, USA
| | - Kyung-Hyun Park-Min
- Arthritis and Tissue Degeneration Program, David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, NY 10021, USA; Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA; BCMB Allied Program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10021, USA.
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Bhattarai HK, Shrestha S, Rokka K, Shakya R. Vitamin D, Calcium, Parathyroid Hormone, and Sex Steroids in Bone Health and Effects of Aging. J Osteoporos 2020; 2020:9324505. [PMID: 32612801 PMCID: PMC7317615 DOI: 10.1155/2020/9324505] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Accepted: 05/27/2020] [Indexed: 12/26/2022] Open
Abstract
Bone health of the elderly is a major global health concern, since about 1 in 3 women and 1 in 5 men suffer from bone loss and fractures, often called osteoporosis, in old age. Bone health is a complex issue affected by multiple hormones and minerals. Among all the hormones involved in bone health, calcitriol (also vitamin D), parathyroid, and sex hormones (especially estrogen) have been discussed in this review paper. We have discussed the metabolism of these hormones and their effects on bone health. Vitamin D can be obtained from diet or formed from 7-dehydrocholesterol found under the skin in the presence of sunlight. The active form, calcitriol, causes dimerization of vitamin D receptor and acts on the bones, intestine, and kidney to regulate the level of calcium in blood. Similarly, parathyroid hormone is secreted when the serum level of calcium is low. It helps regulate the level of blood calcium through calcitriol. Sex hormones regulate bone modeling at an early age and remodeling later in life. Loss of ovarian function and a decrement in the level of production of estrogen are marked by bone loss in elderly women. In the elderly, various changes in the calcium and vitamin D metabolism, such as decrease in the production of vitamin D, decrease in dietary vitamin D, decreased renal production, increased production of excretory products, decrease in the level of VDR, and decreased calcium absorption by the intestines, can lead to bone loss. When the elderly are diagnosed with osteoporosis, medications that directly target bone such as bisphosphonates, RANK ligand inhibitors, estrogen and estrogen analogues, estrogen receptor modulators, and parathyroid hormone receptor agonists are used. Additionally, calcium and vitamin D supplements are prescribed.
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Affiliation(s)
| | - Shreya Shrestha
- Department of Biotechnology, Kathmandu University, Dhulikhel, Nepal
| | - Kabita Rokka
- Department of Biotechnology, Kathmandu University, Dhulikhel, Nepal
| | - Rosy Shakya
- Department of Biotechnology, Kathmandu University, Dhulikhel, Nepal
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Guebeli A, Platz EA, Paller CJ, McGlynn KA, Rohrmann S. Relationship of sex steroid hormones with bone mineral density of the lumbar spine in adult men. Bone Joint Res 2020; 9:139-145. [PMID: 32435466 PMCID: PMC7229310 DOI: 10.1302/2046-3758.93.bjr-2019-0141.r1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
Abstract
Aims To examine the relationship of sex steroid hormones with osteopenia in a nationally representative sample of men in the USA. Methods Data on bone mineral density (BMD), serum sex hormones, dairy consumption, smoking status, and body composition were available for 806 adult male participants of the cross-sectional National Health and Nutrition Examination Survey (NHANES, 1999-2004). We estimated associations between quartiles of total and estimated free oestradiol (E2) and testosterone (T) and osteopenia (defined as 1 to 2.5 SD below the mean BMD for healthy 20- to 29-year-old men) by applying sampling weights and using multivariate-adjusted logistic regression. We then estimated the association between serum hormone concentrations and osteopenia by percentage of body fat, frequency of dairy intake, cigarette smoking status, age, and race/ethnicity. Results Men in the lowest quartile of total E2 concentrations (< 21.52 pg/ml) had greater odds of osteopenia compared with men in the highest quartile (odds ratio (OR) 2.29, 95% confidence interval (CI) 1.11 to 4.73; p-trend = 0.030). Total and free T were not associated with osteopenia. Low total E2 concentrations were associated with greater odds of osteopenia among non-daily dairy consumers (p-trend = 0.046), current or former smokers (p-trend = 0.032), and younger men (p-trend = 0.031). No differences were observed by race/ethnicity and obesity. Conclusion In this nationally representative study of the USA, men with lower total E2 were more likely to have osteopenia, which was particularly evident among younger men, men with less-than-daily dairy consumption, and current or former smokers. Cite this article:Bone Joint Res. 2020;9(3):139–145.
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Affiliation(s)
- Alissa Guebeli
- Department of Orthopaedic Surgery, Cantonal Hospital of Baselland, Liestal, Switzerland
| | - Elizabeth A Platz
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health; James Buchanan Brady Urological Institute, and Department of Urology, Johns Hopkins University School of Medicine, and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland, USA
| | - Channing J Paller
- Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
| | - Katherine A McGlynn
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland, USA
| | - Sabine Rohrmann
- Division of Chronic Disease Epidemiology, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland
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Lin JC, Liu ZG, Liu RR, Xie LW, Xie HL, Cai HG. The increase of osteopontin and β-carboxy-terminal cross-linking telopeptide of type I collagen enhances the risk of hip fracture in the elderly. J Clin Lab Anal 2020; 34:e23204. [PMID: 32406547 PMCID: PMC7246377 DOI: 10.1002/jcla.23204] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Revised: 11/17/2019] [Accepted: 12/22/2019] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Hip fracture in the elderly is a health burden worldwide due to its high mortality rate. This study was conducted to determine the possible mechanisms of osteopontin (OPN) and β-carboxy-terminal cross-linking telopeptide of type I collagen (β-CTX) in hip fracture in the elderly. MATERIALS AND METHODS In the study, we recruited 108 elderly patients with hip fracture diagnosed from May 2012 to May 2015 at the Third Hospital of Xiamen and 86 healthy individuals without a history of hip fracture were taken as controls. Serum levels of OPN and β-CTX were then determined. The T and Z values for bone mineral density (BMD) were also measured. Moreover, logistic regression analysis was performed to assess the risk and protective factors for hip fracture in the elderly. RESULTS Serum levels of both OPN and β-CTX were increased in elderly patients with hip fracture. OPN was positively correlated with β-CTX. In addition, the levels of OPN and β-CTX shared a positive association with the age, and a negative association with the BMD, in terms of T and Z values of the hip. In addition, increased BMD and outdoor sports might be protective factors for hip fracture, and an increase in levels of OPN and β-CTX might be associated with a higher risk of hip fracture in the elderly population. DISCUSSION Collectively, increased serum levels of OPN and β-CTX might be correlated with a higher risk of a hip fracture and have predictive values in the occurrence of hip fracture in the elderly.
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Affiliation(s)
- Jian-Chun Lin
- Department of Orthopaedics, The Third Hospital of Xiamen, Xiamen, China
| | - Zhong-Guo Liu
- Department of Orthopaedics, The Third Hospital of Xiamen, Xiamen, China
| | - Rui-Ren Liu
- Department of Orthopaedics, The Third Hospital of Xiamen, Xiamen, China
| | - Liang-Wen Xie
- Department of Orthopaedics, The Third Hospital of Xiamen, Xiamen, China
| | - Huang-Lin Xie
- Department of Orthopaedics, The Third Hospital of Xiamen, Xiamen, China
| | - He-Guo Cai
- Department of Orthopaedics, The Third Hospital of Xiamen, Xiamen, China
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Ackerman KE, Singhal V, Slattery M, Eddy KT, Bouxsein ML, Lee H, Klibanski A, Misra M. Effects of Estrogen Replacement on Bone Geometry and Microarchitecture in Adolescent and Young Adult Oligoamenorrheic Athletes: A Randomized Trial. J Bone Miner Res 2020; 35:248-260. [PMID: 31603998 PMCID: PMC7064307 DOI: 10.1002/jbmr.3887] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2019] [Revised: 09/27/2019] [Accepted: 10/01/2019] [Indexed: 02/04/2023]
Abstract
Oligoamenorrheic athletes (OAs) have lower bone mineral density (BMD) and greater impairment of bone microarchitecture, and therefore higher fracture rates compared to eumenorrheic athletes. Although improvements in areal BMD (aBMD; measured by dual-energy X-ray absorptiometry) in OAs have been demonstrated with transdermal estrogen treatment, effects of such treatment on bone microarchitecture are unknown. Here we explore effects of transdermal versus oral estrogen versus no estrogen on bone microarchitecture in OA. Seventy-five OAs (ages 14 to 25 years) were randomized to (i) a 100-μg 17β-estradiol transdermal patch (PATCH) administered continuously with 200 mg cyclic oral micronized progesterone; (ii) a combined 30 μg ethinyl estradiol and 0.15 mg desogestrel pill (PILL); or (iii) no estrogen/progesterone (NONE) and were followed for 12 months. Calcium (≥1200 mg) and vitamin D (800 IU) supplements were provided to all. Bone microarchitecture was assessed using high-resolution peripheral quantitative CT at the distal tibia and radius at baseline and 1 year. At baseline, randomization groups did not differ by age, body mass index, percent body fat, duration of amenorrhea, vitamin D levels, BMD, or bone microarchitecture measurements. After 1 year of treatment, at the distal tibia there were significantly greater increases in total and trabecular volumetric BMD (vBMD), cortical area and thickness, and trabecular number in the PATCH versus PILL groups. Trabecular area decreased significantly in the PATCH group versus the PILL and NONE groups. Less robust differences between groups were seen at the distal radius, where percent change in cortical area and thickness was significantly greater in the PATCH versus PILL and NONE groups, and changes in cortical vBMD were significantly greater in the PATCH versus PILL groups. In conclusion, in young OAs, bone structural parameters show greater improvement after 1 year of treatment with transdermal 17β-estradiol versus ethinyl estradiol-containing pills, particularly at the tibia. © 2019 American Society for Bone and Mineral Research.
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Affiliation(s)
- Kathryn E Ackerman
- Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.,Division of Sports Medicine, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA
| | - Vibha Singhal
- Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.,Division of Pediatric Endocrinology, Massachusetts General Hospital for Children and Harvard Medical School, Boston, MA, USA
| | - Meghan Slattery
- Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Kamryn T Eddy
- Eating Disorders Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Mary L Bouxsein
- Center for Advanced Orthopedic Studies, Beth Israel Deaconess Medical Center, Division of Endocrinology, Massachusetts General Hospital, and Harvard Medical School, Boston, MA, USA
| | - Hang Lee
- Biostatistics Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Anne Klibanski
- Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Madhusmita Misra
- Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.,Division of Pediatric Endocrinology, Massachusetts General Hospital for Children and Harvard Medical School, Boston, MA, USA
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Shieh A, Greendale GA, Cauley JA, Karvonen-Gutierrez C, Crandall CJ, Karlamangla AS. Estradiol and Follicle-Stimulating Hormone as Predictors of Onset of Menopause Transition-Related Bone Loss in Pre- and Perimenopausal Women. J Bone Miner Res 2019; 34:2246-2253. [PMID: 31442329 PMCID: PMC7963392 DOI: 10.1002/jbmr.3856] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Revised: 08/05/2019] [Accepted: 08/17/2019] [Indexed: 12/19/2022]
Abstract
The menopause transition (MT) may be an opportunity for early intervention to prevent rapid bone loss. To intervene early, we need to be able to prospectively identify pre- and perimenopausal women who are beginning to lose bone. This study examined whether estradiol (E2), or follicle-stimulating hormone (FSH), measured in pre- and perimenopausal women, can predict significant bone loss by the next year. Bone loss was considered significant if bone mineral density (BMD) decline at the lumbar spine (LS) or femoral neck (FN) from a pre- or early perimenopausal baseline to 1 year after the E2 or FSH measurement was greater than the least detectable change. We used data from 1559 participants in the Study of Women's Health Across the Nation and tested E2 and FSH as separate predictors using repeated measures modified Poisson regression. Adjusted for MT stage, age, race/ethnicity, and body mass index, women with lower E2 (and higher FSH) were more likely to lose BMD: At the LS, each halving of E2 and each doubling of FSH were associated with 10% and 39% greater risk of significant bone loss, respectively (p < 0.0001 for each). At the FN, each halving of E2 and each doubling of FSH were associated with 12% (p = 0.01) and 27% (p < 0.001) greater risk of significant bone loss. FSH was more informative than E2 (assessed by the area under the receiver-operator curve) at identifying women who were more versus less likely to begin losing bone, especially at the LS. Prediction was better when hormones were measured in pre- or early perimenopause than in late perimenopause. Tracking within-individual change in either hormone did not predict onset of bone loss better than a single measure. We conclude that measuring FSH in the MT can help prospectively identify women with imminent or ongoing bone loss at the LS. © 2019 American Society for Bone and Mineral Research.
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Affiliation(s)
- Albert Shieh
- Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles
| | - Gail A. Greendale
- Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles
| | - Jane A. Cauley
- Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh
| | | | - Carolyn J. Crandall
- Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles
| | - Arun S. Karlamangla
- Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles
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Fassler CS, Gutmark-Little I, Xie C, Giannini CM, Chandler DW, Biro FM, Pinney SM. Sex Hormone Phenotypes in Young Girls and the Age at Pubertal Milestones. J Clin Endocrinol Metab 2019; 104:6079-6089. [PMID: 31408174 PMCID: PMC6821200 DOI: 10.1210/jc.2019-00889] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2019] [Accepted: 08/07/2019] [Indexed: 01/08/2023]
Abstract
CONTEXT The age of pubertal onset is influenced by many variables in young girls. Previous studies have not examined sex hormones longitudinally around the time of breast development and their relationship to pubertal onset. OBJECTIVE We sought to use an unbiased statistical approach to identify phenotypes of sex hormones in young girls and examine their relationship with pubertal milestones. DESIGN AND SETTING Longitudinal observational study. PARTICIPANTS AND MAIN OUTCOME MEASURES In 269 girls, serum concentrations of steroid sex hormones [estradiol (E2), estrone, testosterone, and dehydroepiandrosterone sulfate] were measured by HPLC-mass spectrometry at time points before, at, and after thelarche. Girls were classified into four hormone phenotypes using objective principal components and cluster analyses of longitudinal hormone data. The association between the identified phenotypes and age of pubertal milestones was estimated using Cox proportional hazards modeling. RESULTS Mean ages at thelarche, pubarche, and menarche were 9.02, 9.85, and 12.30 years, respectively. Girls with low levels of all four hormones, phenotype 3b, were youngest at thelarche (8.67 years); those in phenotype 2, with the highest E2 levels and E2 surge 6 months after thelarche, were youngest at menarche (11.87 years) with shortest pubertal tempo. When controlling for race, maternal age of menarche, caregiver education, and body mass, different phenotypes were associated with the age of pubertal events. CONCLUSIONS Hormone phenotypic clustering can identify clinically relevant subgroups with differing ages of thelarche, pubarche, and menarche. These findings may enhance the understanding of timing of pubertal milestones and risk of adult disease.
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Affiliation(s)
- Cecily S Fassler
- Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Iris Gutmark-Little
- Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Changchun Xie
- Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Courtney M Giannini
- Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | | | - Frank M Biro
- Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Susan M Pinney
- Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, Ohio
- Correspondence and Reprint Requests: Susan M. Pinney, PhD, Department of Environmental Health, University of Cincinnati College of Medicine, 160 Panzeca Way, Kettering Laboratory Building, Room 208, Cincinnati, Ohio 45267. E-mail:
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Chen JF, Lin PW, Tsai YR, Yang YC, Kang HY. Androgens and Androgen Receptor Actions on Bone Health and Disease: From Androgen Deficiency to Androgen Therapy. Cells 2019; 8:cells8111318. [PMID: 31731497 PMCID: PMC6912771 DOI: 10.3390/cells8111318] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2019] [Revised: 10/21/2019] [Accepted: 10/22/2019] [Indexed: 12/12/2022] Open
Abstract
Androgens are not only essential for bone development but for the maintenance of bone mass. Therefore, conditions with androgen deficiency, such as male hypogonadism, androgen-insensitive syndromes, and prostate cancer with androgen deprivation therapy are strongly associated with bone loss and increased fracture risk. Here we summarize the skeletal effects of androgens—androgen receptors (AR) actions based on in vitro and in vivo studies from animals and humans, and discuss bone loss due to androgens/AR deficiency to clarify the molecular basis for the anabolic action of androgens and AR in bone homeostasis and unravel the functions of androgen/AR signaling in healthy and disease states. Moreover, we provide evidence for the skeletal benefits of androgen therapy and elucidate why androgens are more beneficial than male sexual hormones, highlighting their therapeutic potential as osteoanabolic steroids in improving bone fracture repair. Finally, the application of selective androgen receptor modulators may provide new approaches for the treatment of osteoporosis and fractures as well as building stronger bones in diseases dependent on androgens/AR status.
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Affiliation(s)
- Jia-Feng Chen
- Division of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Kaohsiung Chang-Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung 833, Taiwan;
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kaohsiung 833, Taiwan; (P.-W.L.); (Y.-R.T.); (Y.-C.Y.)
| | - Pei-Wen Lin
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kaohsiung 833, Taiwan; (P.-W.L.); (Y.-R.T.); (Y.-C.Y.)
- Center for Menopause and Reproductive Medicine Research, Department of Obstetrics and Gynecology, Kaohsiung Chang-Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung 833, Taiwan
| | - Yi-Ru Tsai
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kaohsiung 833, Taiwan; (P.-W.L.); (Y.-R.T.); (Y.-C.Y.)
- Center for Menopause and Reproductive Medicine Research, Department of Obstetrics and Gynecology, Kaohsiung Chang-Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung 833, Taiwan
- An-Ten Obstetrics and Gynecology Clinic, Kaohsiung 802, Taiwan
| | - Yi-Chien Yang
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kaohsiung 833, Taiwan; (P.-W.L.); (Y.-R.T.); (Y.-C.Y.)
- Department of Dermatology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
| | - Hong-Yo Kang
- Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kaohsiung 833, Taiwan; (P.-W.L.); (Y.-R.T.); (Y.-C.Y.)
- Center for Menopause and Reproductive Medicine Research, Department of Obstetrics and Gynecology, Kaohsiung Chang-Gung Memorial Hospital and Chang Gung University, College of Medicine, Kaohsiung 833, Taiwan
- Correspondence: ; Tel.: +886-7-731-7123 (ext. 8898)
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35
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Vlot MC, Wiepjes CM, de Jongh RT, T'Sjoen G, Heijboer AC, den Heijer M. Gender-Affirming Hormone Treatment Decreases Bone Turnover in Transwomen and Older Transmen. J Bone Miner Res 2019; 34:1862-1872. [PMID: 31099910 PMCID: PMC6852079 DOI: 10.1002/jbmr.3762] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2018] [Revised: 05/03/2019] [Accepted: 05/11/2019] [Indexed: 12/26/2022]
Abstract
Sex steroids play a key role in bone turnover and preserving BMD; hence, gender-affirming hormone treatment (HT) in transgender people affects bone metabolism. Most studies have looked into the effect of HT on changes in BMD; however, they do not provide insights into changes in bone metabolism caused by HT. This study investigated changes in bone turnover markers (BTMs) and sclerostin, as well as their correlations with change in BMD in transwomen and transmen during the first year of HT. Transwomen received estradiol and antiandrogens; transmen received testosterone. Sclerostin; P1NP; alkaline phosphatase (ALP); CTx; and BMD of the total hip, the femoral neck, and the lumbar spine were evaluated at baseline and after 1 year of HT. There were 121 transwomen (median age 30 years, interquartile range [IQR] 24 to 41 years) and 132 transmen (median age 24 years, IQR 21 to 33 years) included in the study. In transwomen, ALP decreased in 19% (95% CI, -21 to-16), CTx in 11% (95% CI, -18 to-4), and sclerostin in 8% (95%CI, -13 to-4) of study participants after 1 year of HT. In contrast, in transmen P1NP, ALP, and sclerostin increased in 33% (95% CI, 24 to 42), 16% (95% CI, 12 to 20), and 15% (95% CI, 10 to 20) of study participants, respectively, after 1 year of HT. No age differences were seen in transwomen, whereas in transmen aged ≥50 years a decrease in all BTMs was found in contrast with the other age groups. These transmen had low estrogen concentration at the start of HT based on their postmenopausal state before the start of HT; their estradiol concentrations increased during testosterone treatment. Changes in BTMs and BMD were weakly correlated (correlation coefficient all <0.30). To conclude, 1 year of HT resulted in decreased bone turnover in transwomen and older transmen, whereas it increased in younger transmen. The decrease in bone resorption in older transmen shows the importance of estrogen as a key regulator of bone turnover. © 2019 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc.
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Affiliation(s)
- Mariska C Vlot
- Department of Internal Medicine and Center of Expertise on Gender Dysphoria, Amsterdam UMC, Vrije Universiteit Amsterdam, A, msterdam, The Netherlands.,Department of Clinical Chemistry, Endocrine laboratory, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Chantal M Wiepjes
- Department of Internal Medicine and Center of Expertise on Gender Dysphoria, Amsterdam UMC, Vrije Universiteit Amsterdam, A, msterdam, The Netherlands
| | - Renate T de Jongh
- Department of Internal Medicine and Center of Expertise on Gender Dysphoria, Amsterdam UMC, Vrije Universiteit Amsterdam, A, msterdam, The Netherlands
| | - Guy T'Sjoen
- Department of Endocrinology, Center for Sexology and Gender, Ghent University Hospital, Ghent, Belgium
| | - Annemieke C Heijboer
- Department of Clinical Chemistry, Endocrine laboratory, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Martin den Heijer
- Department of Internal Medicine and Center of Expertise on Gender Dysphoria, Amsterdam UMC, Vrije Universiteit Amsterdam, A, msterdam, The Netherlands
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Adami G, Rahn EJ, Saag KG. Glucocorticoid-induced osteoporosis: from clinical trials to clinical practice. Ther Adv Musculoskelet Dis 2019; 11:1759720X19876468. [PMID: 31565078 PMCID: PMC6755635 DOI: 10.1177/1759720x19876468] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2019] [Accepted: 08/26/2019] [Indexed: 01/15/2023] Open
Abstract
Glucocorticoid-induced osteoporosis (GIOP) is the most common form of secondary
osteoporosis. To date, six large randomized controlled clinical trials on the
efficacy of pharmaceutical treatment in GIOP have been conducted. All of these
studies have focused predominately on bone mineral density outcomes, and none of
them have been statistically powered to address fracture endpoints. The purpose
of this review is to highlight differences in the design and results within
these large randomized GIOP clinical trials, and how these differences might
affect clinical decisions. Differences between studies in trial design,
populations studied, and variable efficacy impact the comparability and
generalizability of these findings, and ultimately should affect practitioners’
behavior. We review the clinical trials that provide the best quality evidence
on comparative efficacy and safety of GIOP treatments. We also propose
suggestions on the design of future GIOP clinical trials with attention to
improved generalizability, and, ideally, study designs that might achieve
fracture outcomes.
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Affiliation(s)
- Giovanni Adami
- Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, 510 20th Street South, Faculty Office Tower 820D, Birmingham, AL 35294, USA
| | - Elizabeth J Rahn
- Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Kenneth G Saag
- Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, USA
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Ghanim H, Dhindsa S, Green K, Abuaysheh S, Batra M, Makdissi A, Chaudhuri A, Dandona P. Increase in Osteocalcin Following Testosterone Therapy in Men With Type 2 Diabetes and Subnormal Free Testosterone. J Endocr Soc 2019; 3:1617-1630. [PMID: 31403089 PMCID: PMC6682410 DOI: 10.1210/js.2018-00426] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2019] [Accepted: 06/25/2019] [Indexed: 01/16/2023] Open
Abstract
Context One-third of men with type 2 diabetes have subnormal free testosterone concentrations. We evaluated the following: (i) whether bone mineral density (BMD) and bone strength are affected by gonadal status in type 2 diabetes and (ii) the effect of testosterone replacement on markers of osteoblast and osteoclast activity. Design This is a secondary analysis of a previously completed, randomized, placebo-controlled trial. Ninety-four men with type 2 diabetes were recruited; 44 had subnormal free testosterone concentrations. Men with subnormal free testosterone concentrations were randomized to receive intramuscular injections of testosterone or placebo every 2 weeks for 22 weeks. Dual energy X-ray absorptiometry scans were performed at baseline and at 23 weeks. Results Men with subnormal free testosterone had similar BMD compared with men with normal free testosterone. However, bone strength indices were lower in men with subnormal free testosterone. BMD was related to free estradiol concentrations (r = 0.37, P = 0.004 at hip), whereas bone strength was related to free testosterone concentrations (r = 0.41, P < 0.001). Testosterone replacement increased osteocalcin concentrations [mean change (95% CI), 3.52 (0.45, 6.59), P = 0.008]. C-Terminal telopeptide (CTx) concentrations also increased at 15 weeks but reverted to baseline following that. There were no changes in other bone turnover markers or BMD. Conclusion We conclude that testosterone replacement resulted in an increase in osteocalcin and a transient increase in CTx, indicating an increase in osteoblastic activity and transient increase in bone breakdown. Therefore, a major action of testosterone is to increase bone turnover in men with type 2 diabetes.
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Affiliation(s)
- Husam Ghanim
- Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Williamsville, New York
| | - Sandeep Dhindsa
- Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Williamsville, New York.,Division of Endocrinology, Diabetes and Metabolism, Saint Louis University, St. Louis, Missouri
| | - Kelly Green
- Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Williamsville, New York
| | - Sanaa Abuaysheh
- Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Williamsville, New York
| | - Manav Batra
- Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Williamsville, New York
| | - Antoine Makdissi
- Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Williamsville, New York
| | - Ajay Chaudhuri
- Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Williamsville, New York
| | - Paresh Dandona
- Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Williamsville, New York
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38
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[Influence of hormone or hormone replacement therapy on bone healing]. Unfallchirurg 2019; 122:512-517. [PMID: 31172230 DOI: 10.1007/s00113-019-0677-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
Since the observations of Fuller Albright in 1940, it is well documented that estrogen deficiency is one of the major causes of osteoporosis. Osteoporosis increases not only the risk of fracture and consecutively the number of fractures but can also induce a disorder of fracture healing. This raises the question whether estrogen deficiency negatively influences bone healing in addition to fragility. The currently available literature on this topic provides indications that estrogen deficiency negatively influences fracture healing in the various stages of healing. Furthermore, there is evidence that the administration of estrogen antagonizes these negative effects. Future clinical investigations are needed to find out whether the experimental data can be transferred to the patients.
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Shi TT, Min M, Zhang Y, Sun CY, Liang MM, Sun YH. Depression and risk of hip fracture: a systematic review and meta-analysis of cohort studies. Osteoporos Int 2019; 30:1157-1165. [PMID: 30972449 DOI: 10.1007/s00198-019-04951-6] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2019] [Accepted: 03/21/2019] [Indexed: 12/13/2022]
Abstract
Recently published studies on the association between depression and hip fracture (HF) are inconsistent. Therefore, we performed this meta-analysis with the main aim to clarify the association between depression and HF, and also to identify possible susceptible groups. Relevant literature published until February 2019 was obtained and screened according to established inclusion criteria. Two researchers independently processed quality assessment and data extraction prior to the meta-analysis. Pooled hazard ratios (HRs) with 95%CI (confidence intervals) were calculated. To explore the sources of heterogeneity, subgroup analyses were performed based on study design, study region, NOS scores, follow-up duration, diagnostic criteria, sex, national income level, and adjustments (bone mineral density (BMD), antidepressant, calcium intake, and smoking). Ten studies with 13 estimates, involving 375,438 participants and 4576 HFs, were included. It was found that patients with depression had a higher risk of HF than non-depressed patients (HR = 1.21; 95%CI 1.11-1.31). Sensitivity analysis results show that the association is relatively stable. The studies that were not adjusted for confounders (e.g., antidepressant, BMD, calcium intake, and smoking) had higher overall HR compared to the studies that adjusted for the corresponding confounding factors. HFs are more likely to occur in European and male depression patients. This meta-analysis provided evidence of a modest positive association between depression and the risk of HFs, and the association is stronger in European and male patients. Implementation of practical measures to prevent and treat depression is of great public health significance.
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Affiliation(s)
- T T Shi
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei, 230032, Anhui, China
| | - M Min
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei, 230032, Anhui, China
| | - Y Zhang
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei, 230032, Anhui, China
| | - C Y Sun
- AMITA Health Saint Joseph Hospital Chicago, Chicago, 60657, Illinois, USA
| | - M M Liang
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei, 230032, Anhui, China
| | - Y H Sun
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, No. 81 Meishan Road, Hefei, 230032, Anhui, China.
- Center for Evidence-Based Practice, Anhui Medical University, No. 81 Meishan Road, Hefei, 230032, Anhui, China.
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Abstract
Cellular senescence refers to a process induced by various types of stress that causes irreversible cell cycle arrest and distinct cellular alterations, including profound changes in gene expression, metabolism, and chromatin organization as well as activation/reinforcement of anti-apoptotic pathways and development of a pro-inflammatory secretome or senescence-associated secretory phenotype (SASP). However, because of challenges and technical limitations in identifying and characterizing senescent cells in living organisms, only recently have some of the diverse in vivo roles of these unique cells been discovered. New findings indicate that senescent cells and their SASP can have acute beneficial functions, such as in tissue regeneration and wound healing. However, in contrast, when senescent cells accumulate in excess chronically at sites of pathology or in old tissues they drive multiple age-associated chronic diseases. Senotherapeutics that selectively eliminate senescent cells ("senolytics") or inhibit their detrimental SASP ("senomorphics") have been developed and tested in aged preclinical models. These studies have established that targeting senescence is a powerful anti-aging strategy to improve "healthspan" - i.e., the healthy period of life free of chronic disease. The roles of senescence in mediating age-related bone loss have been a recent focus of rigorous investigation. Studies in mice and humans demonstrate that with aging, at least a subset of most cell types in the bone microenvironment become senescent and develop a heterogeneous SASP. Furthermore, age-related bone loss can be alleviated in old mice, with apparent advantages over anti-resorptive therapy, by reducing the senescent cell burden genetically or pharmacologically with the first class of senolytics or a senomorphic. Collectively, these findings point to targeting senescence as a transformational strategy to extend healthspan, therefore providing strong rationale for identifying and optimizing senotherapeutics to alleviate multiple chronic diseases of aging, including osteoporosis, and set the stage for translating senotherapeutics to humans, with clinical trials currently ongoing.
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Affiliation(s)
- Joshua N Farr
- Division of Endocrinology and Metabolism and Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.
| | - Sundeep Khosla
- Division of Endocrinology and Metabolism and Kogod Center on Aging, Mayo Clinic, Rochester, MN, USA.
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41
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Wiepjes CM, de Jongh RT, de Blok CJ, Vlot MC, Lips P, Twisk JW, den Heijer M. Bone Safety During the First Ten Years of Gender-Affirming Hormonal Treatment in Transwomen and Transmen. J Bone Miner Res 2019; 34:447-454. [PMID: 30537188 PMCID: PMC7816092 DOI: 10.1002/jbmr.3612] [Citation(s) in RCA: 74] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2018] [Revised: 09/18/2018] [Accepted: 10/09/2018] [Indexed: 01/24/2023]
Abstract
Concerns about the effects of gender-affirming hormonal treatment (HT) on bone mineral density (BMD) in transgender people exist, particularly regarding the decrease in estrogen concentrations in transmen. Although it is known that HT is safe for BMD in the short term, long-term follow-up studies are lacking. Therefore this study aimed to investigate the change in BMD during the first 10 years of HT, to determine whether HT is safe and if assessing BMD during HT is necessary. A follow-up study was performed in adult transgender people receiving HT at the VU University Medical Center Amsterdam between 1998 and 2016. People were included if they were HT naive and had a dual-energy X-ray absorptiometry (DXA) scan at the start of HT. Follow-up DXA scans performed after 2, 5, and/or 10 years of HT were used for analyses. The course of BMD of the lumbar spine during the first 10 years of HT was analyzed using multilevel analyses. A total of 711 transwomen (median age 35 years; IQR, 26 to 46 years) and 543 transmen (median age 25 years; IQR, 21 to 34 years) were included. Prior to the start of HT, 21.9% of transwomen and 4.3% of transmen had low BMD for age (Z-score < -2.0). In transwomen lumbar spine BMD did not change (+0.006; 95% CI, -0.005 to +0.017), but lumbar spine Z-score increased by +0.22 (95% CI, +0.12 to +0.32) after 10 years of HT. Also in transmen lumbar spine BMD did not change (+0.008; 95% CI, -0.004 to +0.019), but lumbar spine Z-score increased by +0.34 (95% CI, +0.23 to +0.45) after 10 years of HT. This study showed that HT does not have negative effects on BMD, indicating that regularly assessing BMD during HT is not necessary. However, a high percentage of low BMD was found prior to HT, especially in transwomen. Therefore, evaluation of BMD before start of HT may be considered. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.
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Affiliation(s)
- Chantal M Wiepjes
- Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands.,Center of Expertise on Gender Dysphoria, VU University Medical Center, Amsterdam, the Netherlands
| | - Renate T de Jongh
- Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands
| | - Christel Jm de Blok
- Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands.,Center of Expertise on Gender Dysphoria, VU University Medical Center, Amsterdam, the Netherlands
| | - Mariska C Vlot
- Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands
| | - Paul Lips
- Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands
| | - Jos Wr Twisk
- Department of Clinical Epidemiology, VU University, Amsterdam, the Netherlands
| | - Martin den Heijer
- Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands.,Center of Expertise on Gender Dysphoria, VU University Medical Center, Amsterdam, the Netherlands
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Bone health and evaluation of bone mineral density in patients with premature ovarian insufficiency. MENOPAUSE REVIEW 2018; 17:112-116. [PMID: 30356979 PMCID: PMC6196778 DOI: 10.5114/pm.2018.78552] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/19/2018] [Accepted: 07/27/2018] [Indexed: 01/22/2023]
Abstract
Oestrogens exert an influence on skeletal homeostasis during growth and adulthood. Regulation of osteoclasts and osteoblasts generation and apoptosis and prolongation of the lifespan of osteocytes are some of their actions on bone metabolism. Premature ovarian insufficiency (POI) and associated loss of oestrogen action on osteoclasts leads to trabecular perforation and loss of connectivity. Lack of oestrogens acting on osteoblast progenitors also causes a decrease in critical bone mass. Postmenopausal hypoestrogenism is associated with an increase in the number of lymphocyte B-cells expressing nuclear factor κB ligand (RANKL) in the bone marrow and elevated expression of RANKL by B-cells. Increased concentration of RANKL stimulates activation of osteoclasts and leads to oestrogen deficiency-associated bone loss. It has been proven that women with POI have decreased bone mineral density (BMD) measured in lumbar spine and femoral neck. The loss of bone mass associated with oestrogen deficiency is greater in trabecular than in cortical bone, thus women with POI have a significant decrease in BMD, particularly in the lumbar spine vertebrae. Smoking cessation, weight-bearing, and muscle-strengthening exercises on most days of the week, avoidance of excessive alcohol intake, and adequate supplementation of calcium and vitamin D are the main lifestyle rules necessary to avoid decline in BMD. The most important component of decreased BMD treatment in POI patients is systemic hormonal replacement therapy (HRT). HRT should provide hormonal balance and should mimic normal ovarian function as much as possible.
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43
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Song TH, Shim JC, Jung DU, Moon JJ, Jeon DW, Kim SJ, Oh MK. Increased Bone Mineral Density after Abstinence in Male Patients with Alcohol Dependence. CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE : THE OFFICIAL SCIENTIFIC JOURNAL OF THE KOREAN COLLEGE OF NEUROPSYCHOPHARMACOLOGY 2018; 16:282-289. [PMID: 30121978 PMCID: PMC6124870 DOI: 10.9758/cpn.2018.16.3.282] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/02/2017] [Revised: 06/14/2017] [Accepted: 06/20/2017] [Indexed: 11/18/2022]
Abstract
Objective This study aimed to compare the bone mineral density of male patients with alcohol dependence with that in healthy controls and to assess changes in bone density after abstinence. Methods Forty-four inpatients with confirmed the Diagnostic and Statistical Manual of Mental Disorders, fourth edition diagnosis of alcohol abuse and 42 controls were recruited. Bone density was determined with dual-energy X-ray absorptiometry in the lumbar spine as well as in the femoral neck, trochanter, and Ward’s triangle regions of the proximal right femur. Results There were no significant differences in age and body mass index between patients with alcohol dependence and healthy controls. In the alcohol dependence group, osteopenia and osteoporosis were found in 54.5% and 34.1% of the patients, respectively, whereas in the control group, the corresponding values were 45.2% and 11.9% (p=0.001). Although the actual bone density in the femur and the corresponding T-scores were significantly lower in the alcohol dependence group, no significant differences were found in the lumbar spine. In both groups, body mass index showed a significant correlation with bone mineral density in all areas. After 3 to 4 years of abstinence, bone density significantly increased in the lumbar and femur. Conclusion We conclude that bone mineral density in patients with alcohol dependence was significantly lower than that in healthy controls, and the rates of osteopenia and osteoporosis are higher. Importantly, abstinence from alcohol increases bone density.
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Affiliation(s)
- Tae-Hong Song
- Departments of Psychiatry, Inje University Busan Paik Hospital, Busan, Korea
| | | | - Do-Un Jung
- Departments of Psychiatry, Inje University Busan Paik Hospital, Busan, Korea
| | - Jung-Joon Moon
- Departments of Psychiatry, Inje University Busan Paik Hospital, Busan, Korea
| | - Dong-Wook Jeon
- Departments of Psychiatry, Inje University Busan Paik Hospital, Busan, Korea
| | - Sung-Jin Kim
- Departments of Psychiatry, Inje University Busan Paik Hospital, Busan, Korea
| | - Min-Kyung Oh
- Departments of Pharmacology, Inje University Busan Paik Hospital, Busan, Korea
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44
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Dhindsa S, Ghanim H, Batra M, Dandona P. Hypogonadotropic Hypogonadism in Men With Diabesity. Diabetes Care 2018; 41:1516-1525. [PMID: 29934480 PMCID: PMC6014549 DOI: 10.2337/dc17-2510] [Citation(s) in RCA: 86] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2017] [Accepted: 04/02/2018] [Indexed: 02/03/2023]
Abstract
One-third of men with obesity or type 2 diabetes have subnormal free testosterone concentrations. The lower free testosterone concentrations are observed in obese men at all ages, including adolescents at completion of puberty. The gonadotropin concentrations in these males are inappropriately normal; thus, these patients have hypogonadotropic hypogonadism (HH). The causative mechanism of diabesity-induced HH is yet to be defined but is likely multifactorial. Decreased insulin and leptin signaling in the central nervous system are probably significant contributors. Contrary to popular belief, estrogen concentrations are lower in men with HH. Men with diabesity and HH have more fat mass and are more insulin resistant than eugonadal men. In addition, they have a high prevalence of anemia and higher mortality rates than eugonadal men. Testosterone replacement therapy results in a loss of fat mass, gain in lean mass, and increase in insulin sensitivity in men with diabesity and HH. This is accompanied by an increase in insulin-signaling genes in adipose tissue and a reduction in inflammatory mediators that interfere with insulin signaling. There is also an improvement in sexual symptoms, anemia, LDL cholesterol, and lipoprotein (a). However, testosterone therapy does not consistently affect HbA1c in men with diabetes. The effect of testosterone replacement on cardiovascular events or mortality in men with diabesity is not known and remains to be studied in prospective trials.
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Affiliation(s)
- Sandeep Dhindsa
- Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, and Kaleida Health, Buffalo, NY.,Division of Endocrinology, Diabetes and Metabolism, Saint Louis University, St. Louis, MO
| | - Husam Ghanim
- Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, and Kaleida Health, Buffalo, NY
| | - Manav Batra
- Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, and Kaleida Health, Buffalo, NY
| | - Paresh Dandona
- Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, and Kaleida Health, Buffalo, NY
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45
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Ng Tang Fui M, Hoermann R, Nolan B, Clarke M, Zajac JD, Grossmann M. Effect of testosterone treatment on bone remodelling markers and mineral density in obese dieting men in a randomized clinical trial. Sci Rep 2018; 8:9099. [PMID: 29904126 PMCID: PMC6002535 DOI: 10.1038/s41598-018-27481-3] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Accepted: 06/04/2018] [Indexed: 11/09/2022] Open
Abstract
To assess the effect of testosterone treatment on bone remodelling and density in dieting obese men, 100 obese men aged 53 years (interquartile range 47-60) with a total testosterone level <12 nmol/L receiving 10 weeks of a very low energy diet (VLED) followed by 46 weeks of weight maintenance were randomly assigned at baseline to 56 weeks of intramuscular testosterone undecanoate (n = 49, cases) or matching placebo (n = 51, controls). Pre-specified outcomes were between-group differences (mean adjusted difference, MAD) in serum c-telopeptide (CTx), N-terminal propeptide of type 1 procollagen (P1NP) and bone mineral density (BMD). At trial end, CTx was significantly reduced in men receiving testosterone compared to placebo, MAD -66 ng/L (95% CI -113, -18), p = 0.018, and this was apparent already after the 10 week VLED phase, MAD -63 ng/L (95% CI -108, -18), p = 0.018. P1NP was marginally increased after VLED, MAD +4.2 ug/L (95% CI -0.01, +8.4), p = 0.05 but lower at study end, MAD -5.6 ug/L (95% CI -10.1, -1.1), p = 0.03. No significant changes in sclerostin, lumbar spine BMD or femoral BMD were seen. We conclude that in obese men with low testosterone levels undergoing weight loss, bone remodelling markers are modulated in a way that may have favourable effects on bone mass.
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Affiliation(s)
- Mark Ng Tang Fui
- Department of Medicine Austin Health, University of Melbourne, Heidelberg, Australia.,Department of Endocrinology, Austin Health, Heidelberg, Australia
| | - Rudolf Hoermann
- Department of Medicine Austin Health, University of Melbourne, Heidelberg, Australia
| | - Brendan Nolan
- Department of Endocrinology, Austin Health, Heidelberg, Australia
| | - Michelle Clarke
- Department of Medicine Austin Health, University of Melbourne, Heidelberg, Australia
| | - Jeffrey D Zajac
- Department of Medicine Austin Health, University of Melbourne, Heidelberg, Australia.,Department of Endocrinology, Austin Health, Heidelberg, Australia
| | - Mathis Grossmann
- Department of Medicine Austin Health, University of Melbourne, Heidelberg, Australia. .,Department of Endocrinology, Austin Health, Heidelberg, Australia.
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Abstract
UNLABELLED This meta-analysis pooled results from 23 qualifying individual cohort studies and found that depression was significantly associated with an increased risk of fractures and bone loss. INTRODUCTION The association between depression and risk of fracture remains controversial. We conducted a comprehensive meta-analysis to examine the effect of depression on the risk of osteoporotic fractures and bone loss. METHODS We searched databases and reviewed citations in relevant articles for eligible cohort studies. Two investigators independently conducted study selection, appraisal, and data abstraction through the use of a standardized protocol. Random effect models were used for meta-analysis. Cochrane Q and I2 statistics were used to assess heterogeneity. Funnel plots and rank correlation tests were used to evaluate publication bias. RESULTS Twenty-three studies were included for meta-analysis. In studies that reported hazard ratio (HR) as the outcome (nine studies [n = 309,862]), depression was associated with 26% increase in fracture risk (HR = 1.26, 95% CI, 1.10-1.43, p < 0.001). Studies that reported risk ratio (RR) as the outcome (seven studies [n = 64,975]) suggested that depression was associated with 39% increase in fracture risk (RR = 1.39, 95% CI, 1.19-1.62, p < 0.001). Among studies that reported hip bone mineral density (BMD) as an outcome (eight studies [n = 15,442]), depression was associated with a reduced mean annual bone loss rate of 0.35% (0.18-0.53%, p < 0.001). The increased risk of fracture and bone loss associated with depression was consistent in all meta-analysis having modified inclusion criteria and in different subgroup analyses as well. Significant heterogeneity was observed in the meta-analysis; however, no significant publication bias was detected. CONCLUSION Depression is associated with a significant increased risk in fracture and bone loss. Effective prevention may decrease such risk.
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Affiliation(s)
- Q Wu
- Nevada Institute of Personalized Medicine, Department of Environmental & Occupational Health School of Community Health Sciences, University of Nevada, Las Vegas, NV, 89154, USA.
| | - B Liu
- Nevada Institute of Personalized Medicine, Department of Environmental & Occupational Health School of Community Health Sciences, University of Nevada, Las Vegas, NV, 89154, USA
- Department of Mathematical Science, University of Nevada, Las Vegas, NV, USA
| | - S Tonmoy
- Department of Mathematical Science, University of Nevada, Las Vegas, NV, USA
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Sharifi MD, Mohebbi M, Farrokhfar M, Farzaneh R, Disfani HF, Hashemian AM. Analysis of correlation between estradiol and fracture of femur neck. Eur J Transl Myol 2018; 28:7379. [PMID: 29991984 PMCID: PMC6036315 DOI: 10.4081/ejtm.2018.7379] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2018] [Revised: 04/29/2018] [Accepted: 04/29/2018] [Indexed: 01/24/2023] Open
Abstract
Osteoporosis is a major public health challenge all over the world. Estrogen hormone was cited amongst other hormones to be an efficient hormone for the production and maintenance of bone density. This study was designed with the purpose of evaluating and analyzing the estradiol effect on fractures of femur neck in the Iranian society. This study evaluated men over 50 years of age suffering with mild trauma (falling off the same level height or lower) and with a fracture on their femur neck. Also, their serum level of estradiol was measured with an ELISA method. Using this procedure, the patients were assigned into groups with either normal estradiol serum level (10pg/ml and higher) or with lower than normal level (lower than 10 pg/ml). A control group including 50-year-old and older men without hip fracture, or its history, was chosen to access their estradiol serum level. Data collected from these two groups were statistically compared. A total of 120 patients were evaluated (60 in the control and 60 in the test group). The mean age of patients in the control and test groups were 67.9±10.22 and 69.5±8.84 years, respectively (p=0.376). Smoker patients’ percentages in the control and test groups were 35% and 31.7%, respectively (p=0.699). On the basis of the serum estradiol level, patients’ percentages with low estradiol level in control and test groups were 10% and 16.7%, respectively (p=0.283). The only significant factor in predicting serum estradiol level was smoking. In conclusion, in this study it was observed that fractures of the femoral neck following a mild trauma were not correlated to low level of serum estradiol.
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Affiliation(s)
- Mohammad Davood Sharifi
- Department of Emergency Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.,Equally first authors
| | - Masoud Mohebbi
- Metabolic Syndrome Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahmood Farrokhfar
- Department of Emergency Medicine, Emergency Medicine Specialist, Hasheminejad Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.,Equally first authors
| | - Roohie Farzaneh
- Department of Emergency Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hamideh Feiz Disfani
- Department of Emergency Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir Masoud Hashemian
- Department of Emergency Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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Pernow Y, Shahror R, Acharya S, Jahnson L, Vumma R, Venizelos N. Aberrant tryptophan transport in cultured fibroblast from patients with Male Idiopathic Osteoporosis: An in vitro study. Bone Rep 2018; 8:25-28. [PMID: 29379847 PMCID: PMC5787622 DOI: 10.1016/j.bonr.2018.01.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2017] [Revised: 12/21/2017] [Accepted: 01/02/2018] [Indexed: 11/28/2022] Open
Abstract
It has been demonstrated, that long-term chronic tryptophan deficiency, results in decreased serotonin synthesis, which may lead to low bone mass and low bone formation. Findings from studies in male patients with idiopathic osteoporosis suggested a decreased transport of tryptophan in erythrocytes of osteoporotic patients, indicating that serotonin system defects may be involved in the etiology of low bone mass. Tryptophan is the precursor of serotonin, and a disturbed transport of tryptophan is implicated in altered serotonin synthesis. However, no study has investigated the tryptophan transport kinetics in MIO patients. The aim of this study is to investigate the kinetic parameters of tryptophan transport in fibroblasts derived from MIO patients compared to age and sex matched controls. Fibroblast cells were cultured from skin biopsies obtained from 14 patients diagnosed with Male Idiopathic Osteoporosis and from 13 healthy age-sex matched controls, without a diagnosis of osteoporosis. Transport of the amino acid tryptophan across the cell membrane was measured by the cluster tray method. The kinetic parameters, maximal transport capacity (Vmax) and affinity constant (Km) were determined by using the Lineweaver-Burke plot equation. The results of this study have shown a significantly lower mean value for Vmax (p = 0.0138) and lower Km mean value (p = 0.0009) of tryptophan transport in fibroblasts of MIO patients compared to the control group. A lower Vmax implied a decreased tryptophan transport availability in MIO patients. In conclusion, reduced cellular tryptophan availability in MIO patients might result in reduced brain serotonin synthesis and its endogenous levels in peripheral tissues, and this may contribute to low bone mass/formation. The findings of the present study could contribute to the etiology of idiopathic osteoporosis and for the development of novel approaches for diagnosis, treatment and management strategies of MIO.
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Affiliation(s)
- Ylva Pernow
- Department of Molecular Medicine and Surgery, Endocrine and Diabetes Unit, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
| | - Rami Shahror
- NGBI, Neuropsychiatric Research Laboratory, Faculty of Medicine and Health, School of Medical Sciences, Örebro University, SE 701 82 Örebro, Sweden
| | - Shikha Acharya
- NGBI, Neuropsychiatric Research Laboratory, Faculty of Medicine and Health, School of Medical Sciences, Örebro University, SE 701 82 Örebro, Sweden
| | - Lena Jahnson
- Department of Internal Medicine, Örebro University Hospital, SE 701 85 Örebro, Sweden
| | - Ravi Vumma
- Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences, Linnaeus University, SE-391 82 Kalmar, Sweden
| | - Nikolaos Venizelos
- NGBI, Neuropsychiatric Research Laboratory, Faculty of Medicine and Health, School of Medical Sciences, Örebro University, SE 701 82 Örebro, Sweden
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Ozaki E, Yamada S, Kuriyama N, Matsui D, Watanabe I, Koyama T, Imanishi Y, Inaba M, Watanabe Y. Association of BAP with urinary albumin excretion in postmenopausal, but not premenopausal, non-CKD Japanese women. Sci Rep 2018; 8:82. [PMID: 29311711 PMCID: PMC5758794 DOI: 10.1038/s41598-017-18473-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2017] [Accepted: 12/11/2017] [Indexed: 12/15/2022] Open
Abstract
We investigated whether the phosphate (Pi) load in the circulation causes renal damage in non-CKD women. This cross-sectional study included 1,094 non-CKD Japanese women. Fibroblast growth factor (FGF)-23 as a parameter for the Pi load, bone alkaline phosphatase (BAP) as a bone metabolic marker, and the urinary albumin-to-creatinine ratio (UACR) as an early marker for renal damage were measured. Postmenopausal women exhibited significantly higher levels of serum Pi, FGF-23, BAP, and UACR and significantly lower eGFR than premenopausal women. In postmenopausal women, a multiple regression analysis confirmed a correlation between serum BAP and log UACR. In premenopausal women, although serum FGF-23 did not correlate with log UACR, a multiple regression analysis revealed that FGF-23 correlated with log UACR. Based on the i ncrease observed in BAP and its close relationship with log UACR in postmenopausal women, the release of Pi from bone may be linked to the systemic circulation of Pi, which has the potential to induce renal and vascular damage. Therefore, serum FGF-23 may be a useful marker for renal and vascular damage in premenopausal women; however, it currently remains unclear whether FGF-23 by itself or as a surrogate marker for the Pi load induces damage in the kidney and/or vasculature.
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Affiliation(s)
- Etsuko Ozaki
- Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine Graduate School of Medical Science, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Shinsuke Yamada
- Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.
| | - Nagato Kuriyama
- Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine Graduate School of Medical Science, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Daisuke Matsui
- Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine Graduate School of Medical Science, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Isao Watanabe
- Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine Graduate School of Medical Science, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Teruhide Koyama
- Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine Graduate School of Medical Science, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
| | - Yasuo Imanishi
- Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan
| | - Masaaki Inaba
- Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan
| | - Yoshiyuki Watanabe
- Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine Graduate School of Medical Science, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan
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Khosla S, Monroe DG. Regulation of Bone Metabolism by Sex Steroids. Cold Spring Harb Perspect Med 2018; 8:cshperspect.a031211. [PMID: 28710257 DOI: 10.1101/cshperspect.a031211] [Citation(s) in RCA: 178] [Impact Index Per Article: 25.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Osteoporosis is a significant public health problem, and a major cause of the disease is estrogen deficiency following menopause in women. In addition, considerable evidence now shows that estrogen is also a major regulator of bone metabolism in men. Since the original description of the effects of estrogen deficiency on bone by Fuller Albright more than 70 years ago, there has been enormous progress in understanding the mechanisms of estrogen and testosterone action on bone using human and mouse models. Although we understand more about the effects of estrogen on bone as compared with testosterone, both sex steroids do play important roles, perhaps in a somewhat compartment-specific (i.e., cancellous vs. cortical bone) manner. This review summarizes our current knowledge of sex steroid action on bone based on human and mouse studies, identifies both agreements and potential discrepancies between these studies, and suggests directions for future research in this important area.
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Affiliation(s)
- Sundeep Khosla
- Robert and Arlene Kogod Center on Aging and Endocrine Research Unit, Mayo Clinic College of Medicine, Rochester, Minnesota 55905
| | - David G Monroe
- Robert and Arlene Kogod Center on Aging and Endocrine Research Unit, Mayo Clinic College of Medicine, Rochester, Minnesota 55905
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