Pathophysiological Studies of Diabetic Osteopenia

(2008’s JSNFS Award for Excellence in Research)

Abstract

To clarify the pathogenesis of altered bone and mineral metabolism in diabetes, biological markers for osteoblastic and osteoclastic function were measured in patients with type 2 diabetes. A significant reduction of serum osteoblastic markers was found in the diabetic group, whereas circulating and urinary levels of osteoclastic markers in the diabetics were significantly higher than in the controls. Unexpectedly, serum levels of osteoprotegerin (OPG), a known osteoblast-derived bone coupling factor that inhibits osteoclastgenesis, tended to be higher in the diabetic group, and these values exhibited a significantly positive correlation with those of osteoclastic, but not osteoblastic, markers. In addition, there was a significantly negative correlation between serum OPG and bone mineral density. It seems probable that OPG exerts a suppressive and protective role against increased bone resorption to prevent further loss of skeletal bone mass under conditions of reduced osteoblastic function in type 2 diabetes. The increase in osteoclastic function would be at least partly due to acceleration of the polyol pathway, possibly leading to enhanced endogenous oxidative stress under hyperglycemic conditions. Elucidation of the precise mechanisms responsible for altered bone and mineral metabolism in the diabetic state will be very important for prevention and treatment of bone mass loss to preserve the quality of life of diabetic patients, in view of the increasing number of aged diabetics in Japan, who would be expected to develop diabetic osteopenia, and thus have a high risk of bone fracture.