GROWTH AND DEVELOPMENT OF BONE MASS IN UNTREATED ALLOXAN-DIABETIC RATS - EFFECTS OF COLLAGEN GLYCOSYLATION AND PARATHYROID ACTIVITY ON BONE TURNOVER

Body and skeletal growth and development were studied in alloxan-treated and age-matched control rats, between 3 and 23 weeks of age. For both groups the growth of the skeletal and body weights were in phase, with a maximum at 7 weeks of age. The growth data was assessed according to Parks' theory of feeding and growth. Alloxan-treated rats showed an important reduction in body and bone mass, with a greater impact on soft tissues. As expected, the asymptotic body and skeletal weights were reduced respect to controls. The time needed to attain 63% of mature food intake (Brody's 'time constant') was also reduced, indicating that maturation occurred at an earlier age than controls. The diabetic state is characterized by a reduced food conversion efficiency. Despite hyperfagia, alloxan-treated rats showed circa one-half the body and skeletal weights of age-matched controls. The following adverse effects of alloxan diabetes on bone tissue were observed: (a) a decrease in trabecular bone volume (femoral metaphyses) and cortical width (femoral diaphyses), (b) increased bone collagen glycosylation as a function of extracellular glucose concentration, (c) increased resistance of bone collagen to collagenase hydrolysis, (d) decreased rate of bone resorption except under strongly stimulated parathyroid function, (d) significantly lower ashes/bone matrix ratio in diabetic rats with more than 10 weeks of diabetes, and (e) no histological evidence of osteomalacia.