title: Effects of administration of hormone therapy or raloxifene on the immune system and on biochemical markers of bone remodeling.
abstract: 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.
authors: Research Foundation, Hospital Clínico Universitario, INCLIVA, Valencia, Spain.
authors: Begoña
authors: B
authors: Pineda
authors: Carlos
authors: C
authors: Hermenegildo
authors: Juan J
authors: JJ
authors: Tarín
authors: Antonio
authors: A
authors: Cano
authors: Miguel Ángel
authors: MÁ
authors: García-Pérez
mesh_terms: D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D016723:Bone Remodeling / Q000187:drug effects* / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D053244:Osteoprotegerin / Q000097:blood; D020849:Raloxifene Hydrochloride / Q000627:therapeutic use*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000096:biosynthesis / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000276:immunology
chemical_list: D050071:Bone Density Conservation Agents; C501126:DKK1 protein, human; C508585:IL1B protein, human; C508598:IL4 protein, human; C508600:IL6 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D053583:Interleukin-1beta; D015850:Interleukin-6; D053244:Osteoprotegerin; D053246:Receptor Activator of Nuclear Factor-kappa B; C506030:TNFRSF11B protein, human; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D020849:Raloxifene Hydrochloride