Streptozotocin, Type I Diabetes Severity and Bone

As many as 50% of adults with type I (T1) diabetes exhibit bone loss and are at increased risk for fractures. Therapeutic development to prevent bone loss and/or restore lost bone in T1 diabetic patients requires knowledge of the molecular mechanisms accounting for the bone pathology. Because cell culture models alone cannot fully address the systemic/metabolic complexity of T1 diabetes, animal models are critical. A variety of models exist including spontaneous and pharmacologically induced T1 diabetic rodents. In this paper, we discuss the streptozotocin (STZ)-induced T1 diabetic mouse model and examine dose-dependent effects on disease severity and bone. Five daily injections of either 40 or 60 mg/kg STZ induce bone pathologies similar to spontaneously diabetic mouse and rat models and to human T1 diabetic bone pathology. Specifically, bone volume, mineral apposition rate, and osteocalcin serum and tibia messenger RNA levels are decreased. In contrast, bone marrow adiposity and aP2 expression are increased with either dose. However, high-dose STZ caused a more rapid elevation of blood glucose levels and a greater magnitude of change in body mass, fat pad mass, and bone gene expression (osteocalcin, aP2). An increase in cathepsin K and in the ratio of RANKL/OPG was noted in high-dose STZ mice, suggesting the possibility that severe diabetes could increase osteoclast activity, something not seen with lower doses. This may contribute to some of the disparity between existing studies regarding the role of osteoclasts in diabetic bone pathology. Examination of kidney and liver toxicity indicate that the high STZ dose causes some liver inflammation. In summary, the multiple low-dose STZ mouse model exhibits a similar bone phenotype to spontaneous models, has low toxicity, and serves as a useful tool for examining mechanisms of T1 diabetic bone loss

An update on diabetes related skeletal fragility

There are several mechanisms by which diabetes could affect bone mass and strength. These mechanisms include insulin deficiency; hyperglycemia; the accumulation of advanced glycation end products that may influence collagen characteristics; marrow adiposity and bone inflammation. Furthermore, associated diabetic complications and treatment with thaizolidinediones may also increase risk of fracturing. The following article provides its readers with an update on the latest information pertaining to diabetes related bone skeletal fragility. In the authors’ opinion, future studies are needed in order to clarify the impact of different aspects of diabetes metabolism, glycemic control, and specific treatments for diabetes on bone. Given that dual energy x-ray absorptiometry is a poor predictor of bone morbidity in this group of patients, there is a need to explore novel approaches for assessing bone quality. It is important that we develop a better understanding of how diabetes affects bone in order to improve our ability to protect bone health and prevent fractures in the growing population of adults with diabetes