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Effects of administration of hormone therapy or raloxifene on the immune system and on biochemical markers of bone remodeling

Pineda, Begoña PhD1; Hermenegildo, Carlos PhD2; Tarín, Juan J. PhD3; Cano, Antonio MD4; García-Pérez, Miguel Ángel PhD1,5

Menopause: The Journal of The North American Menopause Society: March 2012 - Volume 19 - Issue 3 - p 319–327
doi: 10.1097/gme.0b013e3182310a98
Original Articles

Objective Over the last few years, conclusive evidence of the involvement of the immune system in the regulation of bone metabolism has been identified. Consequently, one question that should be formulated concerns the possible effects of antiresorptive therapies on the immune system. Therefore, the purpose of the present work was to evaluate both the functionality of the immune system and bone turnover in women receiving antiresorptive therapies, such as hormone therapy (HT; n = 33) and raloxifene (RLX; n = 66), acting through estrogen receptors.

Methods To that end, this study analyzed bone turnover markers in a population of postmenopausal women before and after beginning therapy and compared these with data of women not treated (NT; n = 102). In a subgroup of participants (NT = 33, RLX = 24, and HT = 26), we analyzed the effects of treatments on immune system parameters such as serum levels of interleukin (IL)-6, tumor necrosis factor α, and IL-1β; lymphocyte subpopulations; cell proliferation by peripheral blood mononuclear cells (PBMCs); in vitro production of IL-1β by PBMCs; and the expression of receptor activator of nuclear factor-κB ligand, transforming growth factor β, and IL-4 genes by PBMCs.

Results The results showed that bone resorption was inhibited strongly in women in the RLX and HT groups when compared with women in the NT group. Interestingly, the administration of RLX inhibited the production of the Wnt/β-catenin signaling pathway inhibitor Dickkopf Homolog-1 (P < 0.05) and tended to increase the levels of the osteoclastogenesis inhibitor osteoprotegerin at month 6 (P = 0.059). With regard to the immune system, the different treatments did not markedly perturb the parameters analyzed, with the exception of the increase in serum IL-1β detected in the HT group at month 6 (P < 0.05).

Conclusions The main conclusions of the present work were that HT or RLX do not disturb the immune system and that both treatments have a similar antiresorptive power.

The implication of the immune system in postmenopausal bone loss raises the question of whether antiresorptive drugs acting through estrogen receptors affect immune mechanisms. This study suggests that neither raloxifene nor hormone therapy affects the immune system and that both treatments exhibit similar antiresorptive power.

From the 1Research Foundation, Hospital Clínico Universitario, INCLIVA, Valencia, Spain; and Departments of 2Physiology, 3Functional Biology and Physical Anthropology, 4Pediatrics, Obstetrics, and Gynecology, and 5Genetics, University of Valencia, Valencia, Spain.

Received April 19, 2011; revised and accepted July 28, 2011.

Funding/support: This work was supported by grants GV05/141 from Conselleria d’Empresa, Universitat i Ciència (Generalitat Valenciana), EVES 045-2007, and PS09/00184 and PS09/01687 from Instituto Carlos III (Ministerio de Ciencia e Innovación, Madrid, Spain).

Financial disclosure/conflicts of interest: Dr. Cano reports having received lecture fees from Eli Lilly. Dr. García-Pérez was a recipient of a research contract from Fondo de Investigación Sanitaria–Consellería de Sanitat (Generalitat Valenciana) during the performance of this work. All the other authors have nothing to declare.

Address correspondence to: Miguel Ángel García-Pérez, PhD, Department of Genetics, University of Valencia, C/ Dr. Moliner, 50, 46100-Burjassot, Valencia, Spain. E-mail:

©2012The North American Menopause Society