Protective effect of an aldose reductase inhibitor against bone loss in galactose-fed rats: Possible involvement of the polyol pathway in bone metabolism

Many patients with diabetes mellitus show a moderate reduction in bone mass . Our recent in vitro studies showed that sustained exposure of osteoblast- like MG-63 cells to high glucose by itself impairs their functions partly v ia the polyol pathway. To investigate the role of hyperglycemia in the etio logy of diabetic osteopenia in vivo separately from insulin deficiency, we determined whether epalrestat, an aldose reductase (AR) inhibitor (ARI), le ssens the abnormalities in calcium (Ca) metabolism in galactose-fed rats. W eight gain was impaired in the rats, which was not altered by epalrestat. G alactose feeding temporarily enhanced bone resorption as reflected by incre ased biochemical markers for bone resorption (urinary excretion of pyridino line [PYR] and deoxypyridinoline [DPYR]) at 1 to 3 months, which were signi ficantly decreased by epalrestat. Epalrestat also restored the positive cor relation between a bone-formation marker (serum osteocalcin [OC]) and a bon e-resorption marker (urinary DPYR excretion) at 6.5 months. Histomorphometr ic analysis of bone performed 6.5 months after galactose feeding showed tha t both the bone volume and osteoblast numbers in the tibia, which were sign ificantly suppressed by galactose feeding, were partly restored to a signif icant extent by the simultaneous administration of epalrestat. In summary, epalrestat partially protected against the development of osteoblast dysfun ction and reduced the temporary increase in biochemical markers for bone re sorption induced by galactose feeding, with a resultant increase in bone vo lume, suggesting that the polyol pathway may be intimately involved in the development of abnormal bone metabolism in galactose-fed rats. Copyright (C ) 1999 by W.B. Saunders Company.