Bone effects of glitazones and other anti-diabetic drugs.
Several lines of evidence suggest that diabetes causes harmful effects on bone. This may be due to the diabetic disease per se i.e., high as well as low insulin and glucose levels may cause direct effects on bone metabolism. Moreover, diabetes associated co-morbidity, including impaired vision and neuropathy may affect physical activity and postural stability with effects on bone mineral density (BMD) and fracture risk. In type 1 diabetes, a 7-fold increase in risk of fracture has been reported but there is controversy about whether risk of fracture can be reduced by tight glycaemic control. However, the increased fracture risk seems at least in part to be associated with complications of diabetes, and therefore good metabolic control may reduce the risk of fracture in the long term. Risk of fracture is also increased in type 2 diabetes, but there are no good-quality studies comparing effects on bone of insulin with oral anti-diabetic agents. However, there are differences between bone effects of different oral anti-diabetic drugs. From a bone perspective, metformin and sulphonylureas should be chosen rather than glitazones, as randomised trials have shown that glitazones decrease BMD and increase fracture risk. The mechanism of action is probably through decreased bone formation. Conversely, metformin and sulphonylureas may counter the harmful bone effects of diabetes, as risk of fracture in patients treated with these drugs seems to be reduced compared with the general population. Studies are needed to elucidate mechanisms of action by which metformin and sulphonylureas may affect bone.
Rejnmark
Lars
L
Department of Endocrinology and Metabolism C, Aarhus Sygehus, Aarhus University Hospital, Aarhus, Denmark. rejnmark@post6.tele.dk
D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D002986:Clinical Trials as Topic; D050723:Fractures, Bone / Q000139:chemically induced*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000009:adverse effects* / Q000627:therapeutic use
D007004:Hypoglycemic Agents; D045162:Thiazolidinediones