An in vivo experimental study on osteopenia in diabetic rats

Osteopenia is a significant problem associated with Diabetes mellitus. Osteopenia may result in an increased delay in healing of bone fractures and subsequently affect the quality of life. We evaluated the immunohistochemical localization of TRAIL and its receptor DR5 in the femoral bone of 10-week-old Sprague-Dawley male rats treated with sesame oil (control, group 1), streptozotocin (STZ), a diabetes inducer (group 2), L-NAME, a general inhibitor of NOS activity (group 3), L-arginine (group 4), (arginine acts as a NO substrate) and iNOS immunostaining in group 1 and group 4. Histological and histochemical findings showed decreased growth of metaphyseal cartilage (which was thinner), decreased osteoid surface, and reduced mineral apposition rate in STZ- and L-NAME-treated rats. These findings confirm that bone formation is impaired in diabetic osteopenia. L-arginine supplementation seems to prevent diabetes-induced bone alterations and preserve the calcification process, allowing synthesis of new bone matrix. The immunohistochemical study revealed increased immunostaining of TRAIL and DR5 in osteoblastic cells of the diaphysis (pre-metaphysis) and epiphysis treated with STZ and L-NAME, related to activation of osteoblastic apoptotic death, while the group receiving L-arginine was comparable to the control group and the higher indications of iNOS activity that may reflect its induction by L-arginine administration. The action of L-arginine suggests that increased NO synthesis and availability is potentially useful for effective prevention and treatment of diabetic osteopenia.