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.

Calcium metabolism of rats with varying degrees of insulinopenia.

This paper reports an investigation designed to determine the influence of varying degrees of insulinopenia upon the calcium metabolism of actively growing, alloxan-treated rats fed diets with three levels of calcium. A significant reduction in the skeletal mass (in absolute terms) was observed one month after alloxan administration in rats fed diets with normal or high calcium contents. The impact of insulin deficiency was greater on bone collagen than on the mineral mass, as shown by the increased calcium/hydroxyproline ratio. Alloxan-treated rats showed rather increased levels of PTH which was at variance with respect to control animals and unrelated to the calcium content of the diet. In spite of the high PTH levels, diabetic rats showed significantly diminished rates of bone Ca accretion and resorption. In addition, the animals fed the diet with the normal Ca content, showed significantly reduced areas of osteocytes lacunae and hypocalcemia after 24 h of fasting. The overall information obtained indicates that, in the rat, insulin deficiency more pronouncedly affects organic matrix than mineral turnover. The diabetic state is characterized by an impaired response of bone tissue to physiological stimuli, which is attributed to defective cellular activity caused by insulin deficit. Diminished bone resorption is considered to be an adaptative response to preserve bone mass.