Inhibition of Bone Matrix Formation, Mineralization, and Resorption in Thyroparathyroidectomized Rats

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Abstract
In previous work we found that vitamin D-deficient and also calcium-deficient rats developed hypocalcemia and an impairment of bone formation and mineralization. The present study of thyroparathyroidectomized (TPTX) rats was undertaken to determine the effect of hypocalcemia without secondary hyperparathyroidism. TPTX rats fed a normal diet developed hypocalcemia and hyperphosphatemia in association with impairment of osteoblastic bone matrix formation and of mineralization of newly formed matrix. The serum calcium × phosphorus product was not decreased. The decreased formation was largely due to a reduction in matrix apposition indicating decreased synthetic activity of individual ostcoblasts. In contrast to the above results, when TPTX rats were fed a high-calcium diet to prevent hypocalcemia, no impairment of either formation or mineralization was found. From the results of these two experiments, it is reasonably certain that hypocalcemia was responsible for the inhibition of formation and mineralization. Moreover, based on the magnitude of the changes in serum calcium and bone parameters in TPTX rats, hypocalcemia could have accounted for the inhibition of formation and mineralization in calcium-deficient as well as vitamin D-deficient rats. In TPTX rats the mineralization defect was manifested by decreases in both the rate of osteoid maturation (indicating a delayed onset of mineralization) and the rate of mineralization. A strong correlation (r = 0.95, P < 0.001) was observed between these two rates suggesting a tight coupling of these two aspects of mineralization. TPTX rats also had lower bone resorption rates and higher serum phosphorus levels than sham-operated animals when the normal calcium diet was fed but not when the high-calcium diet was fed. Thus the inhibition of bone resorption in TPTX rats was at least partially prevented by correction of hyperphosphatemia. This is consistent with previous work showing an inverse relationship between serum phosphorus and bone resorption. Accordingly, the depression of bone resorption in TPTX rats was probably due to hyperphosphatemia as well as to hypoparathyroidism.