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

Modificações no periodonto de ratos diabéticos após a movimentação ortodôntica Periodontal ligament changes after induced dental movement in diabetic rats

OBJETIVOS: o objetivo deste trabalho foi avaliar as modificações do ligamento periodontal de incisivos de ratos diabéticos submetidos a forças ortodônticas. MÉTODOS: vinte ratos machos Wistar (Rattus norvegicus) com 105 dias de idade foram empregados. Os ratos foram divididos em quatro grupos: C - animais normoglicêmicos não submetidos à movimentação dentária; CAO - animais normoglicêmicos submetidos à movimentação dentária; D - animais diabéticos não submetidos à movimentação dentária; DAO - animais diabéticos submetidos à movimentação dentária. Os animais permaneceram com o dispositivo de movimentação dentária por 5 dias. Foram avaliados o número de vasos sangüíneos e a espessura do ligamento periodontal nos terços cervical, médio e apical dos cortes histológicos. RESULTADOS E CONCLUSÕES: no lado de tensão, a movimentação dentária nos animais do grupo CAO resultou em um ligamento periodontal mais espesso (17,64% no terço apical, 39,28% no terço médio e 51,35% na região cervical), quando comparado ao grupo C (p < 0,05 para os terços médio e cervical). No grupo DAO, o aumento da espessura do ligamento periodontal foi 50,55% (terço apical), 48,14% (terço médio) e 50% (terço cervical) maior que nos animais do grupo D (p < 0,05). O número de vasos sanguíneos encontrados no ligamento periodontal não apresentou diferenças estatisticamente significantes quando todos os grupos foram comparados (p > 0,05). Ainda no lado de tensão, foram observadas lacunas de reabsorção nos animais dos grupos CAO, D e DAO. O lado de pressão não foi examinado nesta fase do estudo.<br>AIM: The aim of this study was to evaluate the periodontal ligament changes after induced dental movement of the upper incisor in diabetic rats. METHODS: Twenty Wistar rats (Rattus norvegicus) with 105 days of age were used. The rats were divided in four groups: C - normoglicemic animals not submitted to dental movement; CAO - normoglicemic animals submitted to dental movement; D - diabetic animals not submitted the dental movement; DAO - diabetic animals submitted to dental movement. The animals had remained with dental movement devices during 5 days. The number of sanguine vessels and the thickness of the periodontal ligament were evaluated at cervical, medium and apical histological cut regions. RESULTS AND CONCLUSION: At tension side, the dental movement in the animals of group CAO resulted in a thicker periodontal ligament (17.64% apical, 39.28% medium, 51.35% cervical) when compared to C group (p < 0.05 for medium and cervical area). Group DAO exhibited an increase of periodontal ligament thickness of 50.55% (apical), 48.14% (average) and 50% (cervical) when compared to group D (p < 0.05). The periodontal ligament sanguine vessels number did not differed significantly for all groups (p < 0.05). At tension side, bone reabsorption lacunae were observed in CAO, D and DAO groups. The pressure side was not examined in this study phase

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