Bone Loss in Surgically Ovariectomized Pre-Menopausal Women is Associated with T Lymphocyte Activation and Thymic Hypertrophy

• Type of Material: Article
• Authors: Saira Adeel, Emory University; Karnail Singh, Emory University; Kay Vydareny, Emory University; Meena Kumari, Emory University; Era Shah, Emory University; M Neale Weitzmann, Emory University; Vin Tangpricha, Emory University
• Language: English
• Date: 2013-12-01
• Publisher: Lippincott, Williams & Wilkins
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 American Federation for Medical Research, Published by the BMJ Publishing Group Limited.
• Final Published Version (URL): https://jim.bmj.com/content/61/8/1178.long
• Title of Journal or Parent Work: Journal of Investigative Medicine
• ISSN: 1081-5589
• Volume: 61
• Issue: 8
• Start Page: 1178
• End Page: 1183
• Grant/Funding Information: Supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR000454 and NIH Grants #K23AR054334 (VT) and #5T32DK007298 (ES, MK).
• Keywords: pro-osteoclastic cytokines; deficiency; activated T-lymphocyte phenotype; osteoporosis; estrogen; post-menopause; bone loss; ovariectomy
• Research Categories: Health Sciences, Obstetrics and Gynecology

Abstract

Post-menopausal osteoporosis is associated with estrogen deficiency and rapid bone loss. The mechanism by which estrogen deficiency results in bone loss has not been fully explained. Studies in mice rendered acutely estrogen deficient by ovariectomy have suggested that estrogen deficiency results in an activated T-lymphocyte phenotype and increased production of pro-osteoclastic cytokines. The aim of this study was to translate these findings from mouse models that suggest that the T-lymphocyte plays an important role in the etiology of post-menopausal osteoporosis. We recruited pre-menopausal women who underwent ovariectomy (OVX) for benign gynecologic conditions or for prophylaxis against ovarian cancer and a group of matched control women without OVX. Subjects provided blood samples to characterize T-lymphocyte phenotype by Fluorescence-activated cell sorting (FACS) and for T-lymphocyte culture and collection of conditioned media. Bone mineral density at the lumbar spine and left femoral neck was performed annually for two years and volumetric measurements by computed tomography (CT) of the thymus were obtained during the first 6 months. We enrolled 6 OVX and 13 control women. The OVX subjects had a significant loss of bone mineral density at the lumbar spine and left femoral neck. The volumetric thymus measurements suggested an increase in thymus size in the OVX subjects but did not reach statistical significance due to the small sample size. The T-lymphocyte phenotype in the OVX subjects demonstrated increased T-lymphocyte activation by FACS compared to the control subjects. Our preliminary findings support the hypothesis that estrogen deficiency leads to an activated T-lymphocyte phenotype which may contribute to the bone loss seen in estrogen deficiency. Larger clinical studies are necessary to confirm these findings.