Type 2 Diabetes, Thiazolidinediones: Bad to the Bone?

Extract

“… Any reduction of bone mass in diabetics that is revealed by sophisticated analysis is of no medical or economic importance… Further extensive studies of bone metabolism in diabetics are unlikely to yield results of practical importance… ” (1).

Despite this pronouncement from 1980, there have been further studies and they do have practical importance. It now seems clear that patients with type 1 diabetes have increased risk of fracture compared with people without diabetes, due in large part to reduced bone mineral density (BMD). Patients with type 2 diabetes appear to have increased BMD, possibly due in part to an anabolic effect of hyperinsulinemia and in part because of obesity. Obesity may also be associated with reduced fracture risk by providing some cushioning in the event of a fall. In addition, patients with type 2 diabetes have reduced bone turnover and may have reduced levels of PTH. All this should protect patients with type 2 diabetes from fracture. However, counter-forces are also at work. Bone loss appears to be more rapid in patients with type 2 diabetes (2). Insulin resistance might counter the beneficial effects of hyperinsulinemia. Hyperglycemia may cause hypercalciuria, hypomagnesemia, and lower levels of 25-hydroxyvitamin D that could have negative effects on bone. IGF-I, which is anabolic for bone, may be reduced. Advanced glycosylation products might adversely affect bone collagen. Microangiopathy and inflammation could have negative effects on bone. Renal disease in diabetes potentially reduces bone strength. Visual impairment, foot problems, cognitive dysfunction, peripheral neuropathy, and hypoglycemia in patients with type 2 diabetes increase the risk of falling and injury. So how does all this add up?