Bain S, Ramamurthy N S, Impeduglia T, Scolman S, Golub L M, Rubin C
SkeleTech Inc., Seattle, WA, USA.
Bone. 1997 Aug;21(2):147-53. doi: 10.1016/s8756-3282(97)00104-x.
The skeletal consequences of streptozotocin-induced (STZ) diabetes in the rat are characterized by decreased bone formation and, consequently, reductions in bone mass. Given the ability of tetracyclines to inhibit the breakdown of connective tissue collagen in experimental diabetes (and in other diseases), we examined the potential of this drug to prevent the osteopenia associated with STZ diabetes. To evaluate drug efficacy, the cortical and trabecular bone histomorphometry were analyzed and compared between vehicle-treated control and diabetic rats and control and diabetic rats treated orally with 20 mg/day of minocycline, a semisynthetic tetracycline. In addition, blood and urine glucose, body weight change, tibia lengths, cortical bone densities, and bone ash content were compared. At the end of the 26 day experimental period, diabetic (D) and minocycline-treated diabetic (MTD) rats were polyuric with reduced body weights and significantly elevated blood and urinary glucose levels (p < 0.01). Compared to control (C) and minocycline-treated control (MTC) animals, the periosteal and cancellous bone formation in the D rats had virtually ceased (p < 0.001), and the cancellous bone mass in the tibial metaphysis was reduced 47% (p < 0.01). In contrast, bone formation rates in the MTD animals were increased compared to the D rats (p < 0.001), while cancellous bone areas in the MTD animals were essentially equivalent to those observed in the C and MTC groups. Moreover, growth plate thickness, reduced 43% in the D rats, was preserved in the diabetic animals treated with minocycline. These results demonstrate that minocycline treatment of the streptozotocin diabetic rat maintains normal bone formation, normalizes growth plate thickness, and prevents cancellous bone loss.
链脲佐菌素诱导的（STZ）大鼠糖尿病的骨骼后果表现为骨形成减少，进而导致骨量降低。鉴于四环素能够抑制实验性糖尿病（以及其他疾病）中结缔组织胶原蛋白的分解，我们研究了该药物预防与STZ糖尿病相关的骨质减少的潜力。为评估药物疗效，对接受载体处理的对照大鼠与糖尿病大鼠，以及口服20毫克/天米诺环素（一种半合成四环素）的对照大鼠与糖尿病大鼠的皮质骨和小梁骨组织形态计量学进行了分析和比较。此外，还比较了血糖和尿糖、体重变化、胫骨长度、皮质骨密度和骨灰含量。在26天实验期结束时，糖尿病（D）大鼠和米诺环素治疗的糖尿病（MTD）大鼠出现多尿，体重减轻，血糖和尿糖水平显著升高（p<0.01）。与对照（C）大鼠和米诺环素治疗的对照（MTC）动物相比，D大鼠的骨膜和松质骨形成几乎停止（p<0.001），胫骨近端干骺端的松质骨量减少了47%（p<0.01）。相比之下，MTD动物的骨形成率高于D大鼠（p<0.001），而MTD动物的松质骨面积与C组和MTC组基本相当。此外，D大鼠生长板厚度减少了43%，而用米诺环素治疗的糖尿病动物的生长板厚度得以保留。这些结果表明，用米诺环素治疗链脲佐菌素诱导的糖尿病大鼠可维持正常的骨形成，使生长板厚度正常化，并防止松质骨丢失。
