Altered Bone Metabolism in db/db Mice.

Abstract

Bone and calcium metabolism was investigated in genetically obese, diabetic db/db mice and compared with that in a new hypoglycemic agent (AS-6) treated db/db mice and in their lean litter mates as controls. The 5-week-old db/db mice (serum Ca 9.88 +/- 0.22 mg/dl, glucose 258.6 +/- 13.3 mg/dl) were randomly divided into two groups. One group, together with their lean litter mates, was fed a commercial diet (CE-2). The other db/db group was fed CE-2 diet containing 0.1% of AS-6. Both groups were fed for 20 weeks. The serum glucose and calcium levels in db/db control groups (serum Ca 12.3 +/- 0.1 mg/dl, glucose 650.2 +/- 23.9 mg/dl) were higher than those in lean control groups (Ca 9.8 +/- 0.2 mg/dl, glucose 180.7 +/- 10.1 mg/dl). The wet, dry and ashed weights of the femur in db/db control were significantly lower and the length of femur in db/db control was significantly shorter than those of lean controls. These data suggest that retarded bone growth in db/db mice is related to progression of diabetes. Although, there was no change in Ca/P, Ca/ash and total perimeter in femurs, the cortical area in the femurs of db/db control mice (0.65 +/- 0.02 mm2) was significantly smaller than that of the femurs of lean control mice (0.74 +/- 0.02 mm2). The cortical bone thinning observed in the db/db control could have been caused by increased bone resorption. Treatment with AS-6 for 20 weeks resulted in a 48.6% decrease of serum glucose and 5.2% decrease of calcium as compared with db/db controls.(ABSTRACT TRUNCATED AT 250 WORDS)