Effects of combined treatment of insulin and human parathyroid hormone(1–34) on cancellous bone mass and structure in streptozotocin-induced diabetic rats

Abstract

The purpose of this study was to test the hypothesis that combined treatment with insulin and human parathyroid hormone (hPTH) is more effective than treatment with insulin or hPTH alone in improving cancellous bone mass, connectivity, and strength in insulin-dependent diabetic rats. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ) in 7-month-old female Wistar rats. The diabetic rats received insulin, hPTH, insulin and hPTH, or hPTH vehicle for 4 weeks, starting 8 weeks after STZ injection. They were compared with baseline controls and normal controls that received STZ alone and STZ vehicle alone, respectively. The rats’ proximal right tibias were processed to serve as undecalcified Villanueva-stained bone sections for histomorphometry. Changes in trabecular connectivity were determined through node-strut analysis. The decreased cancellous bone volume (BV/TV) and bone formation in diabetic rats improved in all the drug-treated groups compared with baseline controls. Furthermore, recovery of BV/TV was greater in rats that received the combination of insulin and hPTH than in those that received insulin or hPTH alone. In node-strut analysis, the node-related parameter (N.Nd/TV) significantly increased in rats that received the combination of insulin and hPTH, but did not increase in those that received insulin or hPTH alone. In addition to these results, the combination treatment significantly increased bone mineral density of the femur and bone strength in the femoral metaphysis compared with treatment with insulin or hPTH alone. These results indicate that the doses of insulin and hPTH employed in the combination treatment were more effective in improving not only bone mass but also trabecular connectivity and bone strength than treatment with insulin or hPTH alone in insulin-dependent diabetic rats.