title: Bone loss in surgically ovariectomized premenopausal women is associated with T lymphocyte activation and thymic hypertrophy.
abstract: Postmenopausal 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 postmenopausal osteoporosis. We recruited premenopausal women who underwent ovariectomy for benign gynecologic conditions or for prophylaxis against ovarian cancer and a group of matched control women without ovariectomy (OVX). Subjects provided blood samples to characterize T-lymphocyte phenotype by flow cytometry 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 2 years, and volumetric measurements by computed tomography (CT) of the thymus were obtained during the first 6 months. We enrolled 6 patients who underwent 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 owing to the small sample size. The T-lymphocyte phenotype in the OVX subjects demonstrated increased T-lymphocyte activation by flow cytometry compared to the control subjects. Our 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.
authors.affiliation: From the *Division of Endocrinology, Metabolism and Lipids, Department of Medicine, †Department of Surgery, and ‡Department of Radiology, Emory University School of Medicine, Atlanta; and §Atlanta VA Medical Center, Decatur, GA.
authors.forename: Saira
authors.initials: S
authors.lastname: Adeel
authors.forename: Karnail
authors.initials: K
authors.lastname: Singh
authors.forename: Kay H
authors.initials: KH
authors.lastname: Vydareny
authors.forename: Meena
authors.initials: M
authors.lastname: Kumari
authors.forename: Era
authors.initials: E
authors.lastname: Shah
authors.forename: Mervyn Neale
authors.initials: MN
authors.lastname: Weitzmann
authors.forename: Vin
authors.initials: V
authors.lastname: Tangpricha
mesh_terms: D000328:Adult; D015519:Bone Density / Q000502:physiology*; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D008213:Lymphocyte Activation / Q000502:physiology*; D008875:Middle Aged; D010052:Ovariectomy / Q000009:adverse effects* / Q000639:trends; D017697:Premenopause / Q000097:blood*; D011446:Prospective Studies; D013601:T-Lymphocytes / Q000378:metabolism*; D013952:Thymus Hyperplasia / Q000097:blood* / Q000175:diagnosis / Q000209:etiology