Possible role of lymphocytes in glucocorticoid-induced increase in trabecular bone mineral density

• Published in: Journal of endocrinology Vol. 224; no. 1; pp. 97 - 108
• Main Authors: Grahnemo, Louise, Jochems, Caroline, Andersson, Annica, Engdahl, Cecilia, Ohlsson, Claes, Islander, Ulrika, Carlsten, Hans
• Format: Journal Article
• Language: English
• Published: England Bioscientifica Ltd 01.01.2015
• Subjects: Animals; Bone and Bones - drug effects; Bone Density - drug effects; Dexamethasone - pharmacology; Endocrinology and Diabetes; Endokrinologi och diabetes; Female; Femur - drug effects; Glucocorticoids - pharmacology; Lymphocytes - drug effects; Lymphocytes - physiology; Mice; Mice, Inbred C57BL; Mice, SCID; Osteogenesis - drug effects; Reumatologi och inflammation; Rheumatology and Autoimmunity; Up-Regulation - drug effects; X-Ray Microtomography; immune system; glucocorticoid; estrogen; osteoporosis
• ISSN: 0022-0795; 1479-6805; 1479-6805
• DOI: 10.1530/JOE-14-0508

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.