Immunodeficiency Provides Partial Protection from Bone Loss Induced by Castration and Ovariectomy

Problem Statement: The interaction of osteoblasts and osteoclasts with cells of the immune system has been suggested as a contributing factor in the development of osteoporoses. Evidence from studies in rodents suggests that T cells play a significant role in bone loss following estrogen deficiency. The goal of this study was to investigate whether the lack of functional T cells in nude rats prevents bone loss induced by Castration (Ctx) or Ovariectomy (Ovx). Approach: A pilot study was done to establish the immune phenotype of immunodeficient (NU) and immuno-competent CD rats using flow cytometry analysis of lymphocyte subsets. The main study included the following age-matched study groups: Males: CD Sham, CD Ctx, NU Sham and NU Ctx and Females: CD Sham, CD Ovx, NU Sham and NU Ovx. Bone mass, structure and BMD were assessed on long bones by microCT and strength by 3-point bending method. Results: Flow cytometry data showed that normal CD rats have significantly higher values for NKT, T, CD8⁺, CD4⁺ and CD25⁺ cells relative to nudes, but also emphasize existing heterogeneity in lymphocyte subpopulation between different strains of immunodeficient rats. Deprivation of sex steroids caused only moderate loss of cancellous bone in NU rats relative to normal controls. Conclusion: Even though immunodeficiency does not provide complete protection from bone loss, regulation of bone metabolism by immune system prevents excessive deterioration of bone mass and structure seen in normal rats after Ctx and Ovx. This work supports concept that modulators of immune system could be welcomed addition to standard antiresorptive and anabolic therapies to treat osteoporoses of various etiologies.