minocycline and Bone-Diseases--Metabolic

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.

Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Blood Glucose; Body Weight; Bone Density; Bone Diseases, Metabolic; Diabetes Mellitus, Experimental; Disease Models, Animal; Glycosuria; Growth Plate; Male; Minocycline; Rats; Rats, Sprague-Dawley; Streptozocin; Tibia