title: Possible role of lymphocytes in glucocorticoid-induced increase in trabecular bone mineral density.
abstract: Treatment with anti-inflammatory glucocorticoids is associated with osteoporosis. Many of the treated patients are postmenopausal women, who even without treatment have an increased risk of osteoporosis. Lymphocytes have been shown to play a role in postmenopausal and arthritis-induced osteoporosis, and they are targeted by glucocorticoids. The aim of this study was to investigate the mechanisms behind effects of glucocorticoids on bone during health and menopause, focusing on lymphocytes. Female C57BL/6 or SCID mice were therefore sham-operated or ovariectomized and 2 weeks later treatment with dexamethasone (dex), the nonsteroidal anti-inflammatory drug carprofen, or vehicle was started and continued for 2.5 weeks. At the termination of experiments, femurs were phenotyped using peripheral quantitative computed tomography and high-resolution micro-computed tomography, and markers of bone turnover were analyzed in serum. T and B lymphocyte populations in bone marrow and spleen were analyzed by flow cytometry. Dex-treated C57BL/6 mice had increased trabecular bone mineral density, but lower cortical content and thickness compared with vehicle-treated mice. The dex-treated mice also had lower levels of bone turnover markers and markedly decreased numbers of spleen T and B lymphocytes. In contrast, these effects could not be repeated when mice were treated with the nonsteroidal anti-inflammatory drug carprofen. In addition, dex did not increase trabecular bone in ovariectomized SCID mice lacking functional T and B lymphocytes. In contrast to most literature, the results from this study indicate that treatment with dex increased trabecular bone density, which may indicate that this effect is associated with corticosteroid-induced alterations of the lymphocyte populations.
authors.affiliation: Departments of Rheumatology and Inflammation ResearchInternal Medicine and Clinical NutritionCentre for Bone and Arthritis Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Box 480, Gothenburg 405 30, SwedenLaboratory of Tumor Immunology and BiologyCenter for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA louise.grahnemo@gu.se.
authors.forename: Louise
authors.initials: L
authors.lastname: Grahnemo
authors.affiliation: Departments of Rheumatology and Inflammation ResearchInternal Medicine and Clinical NutritionCentre for Bone and Arthritis Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Box 480, Gothenburg 405 30, SwedenLaboratory of Tumor Immunology and BiologyCenter for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA Departments of Rheumatology and Inflammation ResearchInternal Medicine and Clinical NutritionCentre for Bone and Arthritis Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Box 480, Gothenburg 405 30, SwedenLaboratory of Tumor Immunology and BiologyCenter for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Jochems
authors.affiliation: Departments of Rheumatology and Inflammation ResearchInternal Medicine and Clinical NutritionCentre for Bone and Arthritis Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Box 480, Gothenburg 405 30, SwedenLaboratory of Tumor Immunology and BiologyCenter for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Annica
authors.initials: A
authors.lastname: Andersson
authors.affiliation: Departments of Rheumatology and Inflammation ResearchInternal Medicine and Clinical NutritionCentre for Bone and Arthritis Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Box 480, Gothenburg 405 30, SwedenLaboratory of Tumor Immunology and BiologyCenter for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA Departments of Rheumatology and Inflammation ResearchInternal Medicine and Clinical NutritionCentre for Bone and Arthritis Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Box 480, Gothenburg 405 30, SwedenLaboratory of Tumor Immunology and BiologyCenter for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Engdahl
authors.affiliation: Departments of Rheumatology and Inflammation ResearchInternal Medicine and Clinical NutritionCentre for Bone and Arthritis Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Box 480, Gothenburg 405 30, SwedenLaboratory of Tumor Immunology and BiologyCenter for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Claes
authors.initials: C
authors.lastname: Ohlsson
authors.affiliation: Departments of Rheumatology and Inflammation ResearchInternal Medicine and Clinical NutritionCentre for Bone and Arthritis Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Box 480, Gothenburg 405 30, SwedenLaboratory of Tumor Immunology and BiologyCenter for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Ulrika
authors.initials: U
authors.lastname: Islander
authors.affiliation: Departments of Rheumatology and Inflammation ResearchInternal Medicine and Clinical NutritionCentre for Bone and Arthritis Research, Institute of Medicine, The Sahlgrenska Academy, University of Gothenburg, Box 480, Gothenburg 405 30, SwedenLaboratory of Tumor Immunology and BiologyCenter for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Hans
authors.initials: H
authors.lastname: Carlsten
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005269:Femur / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D010012:Osteogenesis / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D055114:X-Ray Microtomography
chemical_list: D005938:Glucocorticoids; D003907:Dexamethasone
keywords: estrogen; glucocorticoid; immune system; osteoporosis