THE ROLE OF THE T-LYMPHOCYTE IN ESTROGEN DEFICIENCY OSTEOPENIA

Our laboratory has previously demonstrated that the T-lymphocyte is cr itical in the development of cyclosporin A-induced osteopenia in the r at model, A similar state of osteopenia is induced by estrogen depleti on in the ovariectomized (OVX) rat, which is the animal model of postm enopausal bone loss, However, the role of the immune system, and parti cularly the T-lymphocyte, in estrogen deplete osteopenia has not been elucidated, We used the Rowett athymic nude rat as our model of T-lymp hocyte deficiency, In this study, the experimental rats were divided i nto four groups as follows: (1) sham-operated Rowett heterozygous (rnu /+) euthymic rats (control group); (2) OVX Rowett heterozygous (rnu/+) euthymic rats; (3) sham-operated Rowett homozygous (rnu/rnu) athymic nude rats, which are T-lymphocyte deficient; and (4) ovariectomized Ro wett homozygous (rnu/rnu) rats, Rats were weighed, and venous blood wa s taken in weeks 2, 4, and 6 for determination of serum osteocalcin, S erum 1,25-dihydroxyvitamin D (1,25(OH)(2)D) was determined on the day of sacrifice, Following sacrifice, histomorphometry was performed on d ouble-labeled proximal tibial metaphyses, Flow cytometric analysis of splenic mononuclear cell isolates stained for OX19-positive (CD5) T-ly mphocytes was performed, T-lymphocyte analysis revealed significant re ductions in both athymic nude groups, while OVX euthymic rats demonstr ated a diminished number of T-cells relative to their sham-operated co unterparts, Histomorphometric data indicated that both OVX groups exhi bited a significant loss of trabecular volume, with associated increas es in indices for bone formation and resorption, with resorption likel y outstripping formation, resulting in osteopenia. Serum osteocalcin w as significantly elevated in the ovariectomized euthymic group through out the experimental period compared with the control group (p < 0.01) ; it was elevated in the ovariectomized athymic group on week 4 only ( p < 0.01 vs. control), It appears that the T-lymphocyte may not be an essential component in the pathogenesis of estrogen deficiency osteope nia, The contribution of circulating T-lymphocytes as well as other T- lymphocyte-rich organs needs to be explored further.