TETRACYCLINE PREVENTS CANCELLOUS BONE LOSS AND MAINTAINS NEAR-NORMAL RATES OF BONE-FORMATION IN STREPTOZOTOCIN-DIABETIC RATS

The skeletal consequences of streptozotocin-induced (STZ) diabetes in the rat are characterized by decreased bone formation and, consequentl y, reductions in bone mass, Given the ability of tetracyclines to inhi bit the breakdown of connective tissue collagen in experimental diabet es (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 analy zed and compared between vehicle-treated control and diabetic rats and control and diabetic rats treated orally with 20 mg/day of minocyclin e, 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 perio d, diabetic CD) and minocycline-treated diabetic (MTD) rats were polyu ric with reduced body weights and significantly elevated blood and uri nary glucose levels (p < 0.01), Compared to control (C) and minocyclin e-treated control (MTC) animals, the periosteal and cancellous bone fo rmation in the D rats had virtually ceased (p < 0.001), and the cancel lous bone mass in the tibial metaphysis was reduced 47% (p < 0.01), In contrast, bone formation rates in the MTD animals were increased comp ared 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 MT C 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. (C) 1997 by Elsevier Sci ence Inc. All rights reserved.