Broulík P D, Haluzík M, Skrha J
Third Medical Department, First Faculty of Medicine, Charles University, U nemocnice 1, 128 21 Prague 2, Czech Republic.
Physiol Res. 2003;52(6):729-34.
The pathophysiological processes underlying the development of diabetic osteopenia has not hitherto been elucidated. Induction of streptozotocin diabetes leads in our experiments to decrease of bone density, ash, mineral content and to thinner cortical width compared to control male rats. In order to investigate the pathogenetic role of bone resorption by osteoclasts in streptozotocin-induced diabetes, we determined the circulating levels of tartrate-resistant acid phosphatase (TRAP), a biochemical marker for bone resorption. Plasma TRAP values in diabetic rats did not differ from their corresponding controls. Streptozotocin diabetes by itself did not have any effect on the weight of seminal vesicles which are highly testosterone-dependent. Low doses of nitric oxide cause bone resorption, but higher doses of NO inhibit bone resorbing activity. We examined the effect of L-NAME (inhibitor of nitric oxide production) after six weeks of administration to diabetic rats. There was no further significant loss of bone mineral density, ash and mineral content or tibia weight in diabetic rats treated with L-NAME. L-NAME itself did not decrease bone metabolism. In our study no evidence of an increased bone resorption was found. Our results have indicated that a predominance of bone resorption over bone formation is not involved in the pathogenesis of diabetes-associated osteopenia. Inhibition of NO neither increased osteoclastic activity (TRAP) nor induced osteopenia in L-NAME-treated rats. This suggests a possibility that NO is not involved in the pathogenesis of diabetic osteopenia.
糖尿病性骨质减少发生的病理生理过程迄今尚未阐明。在我们的实验中，链脲佐菌素诱导的糖尿病导致骨密度、灰分、矿物质含量降低，与对照雄性大鼠相比，皮质宽度变窄。为了研究破骨细胞介导的骨吸收在链脲佐菌素诱导的糖尿病中的致病作用，我们测定了抗酒石酸酸性磷酸酶（TRAP）的循环水平，这是一种骨吸收的生化标志物。糖尿病大鼠的血浆TRAP值与相应的对照组没有差异。链脲佐菌素糖尿病本身对高度依赖睾酮的精囊重量没有任何影响。低剂量的一氧化氮会导致骨吸收，但高剂量的一氧化氮会抑制骨吸收活性。我们研究了给糖尿病大鼠连续六周注射L-NAME（一氧化氮生成抑制剂）后的效果。接受L-NAME治疗的糖尿病大鼠的骨矿物质密度、灰分、矿物质含量或胫骨重量没有进一步显著下降。L-NAME本身并没有降低骨代谢。在我们的研究中，没有发现骨吸收增加的证据。我们的结果表明，骨吸收超过骨形成并非糖尿病相关骨质减少发病机制的主要因素。在接受L-NAME治疗的大鼠中，抑制一氧化氮既没有增加破骨细胞活性（TRAP），也没有诱发骨质减少。这表明一氧化氮可能不参与糖尿病性骨质减少的发病机制。
