The effect of streptozotocin-induced chronic diabetes mellitus on bone and mineral homeostasis in the rat

Diabetes mellitus was induced in Lewis rats by streptozotocin, and these animals and control rats fed ad lib were studied after 7 weeks. At the time of sacrifice, nondecalcified, histological sections of bone were prepared and subsequently quantitated by micromorphometric techniques. In addition, tibial alkaline phosphatase and mineral ash content were determined. The bones obtained from the diabetic animals are characterized by significant decrements in the quantities of osteoid and osteoclasts and by failure to acquire a tetracycline label. These histological features are attended by reduced quantities of urinary hydroxyproline and tibial alkaline phosphatase. As compared with control animals fed ad lib, diabetes rats are hyperphosphatemic and markedly hypercalciuric. Circulating alkaline phosphatase is also elevated and associated with a parallel increase in intestinal content of this enzyme. Although serum corticosterone levels are increased, diabetes is associated with decrements in both circulating immunoreactive parathyroid hormone and 1,25(OH) ₂D. We conclude that prolonged streptozotocin-induced diabetes mellitus in the rat results in reduced bone turnover. The relative roles that functional caloric deprivation, low circulating levels of 1,25(OH) ₂D, hypercalciuria, hypercortisolemia, and decreased blood parathyroid hormone levels play in the genesis of these skeletal abnormalities remain to be determined.