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

Abstract

A B S T R A C T In previous work we found that vitamin D-deficiernt 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 X phosphorus product was not decreased. The decreased formation was largely due to a reduction in matrix apposition indicating decreased synthetic activity of individual osteoblasts. 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 ani-A preliminary report of this work was published in ab-.

Bone mineralization and metabolism of3H-25-hydroxyvitamin D3 in thyroparathyroidectomized rats treated with parathyroid extract

“…In contrast, in normocalcemic TPTX rats (diet: 1.2% calcium, 0.55% phosphorus), osteoid maturation rate and the rate of initial mineralization are not significantly different from those of intact animals fed the same diet [4]. However, observations that osteoid width and mineralizing front width remain significantly higher in the normocalcemic TPTX rats than corresponding values in intact rats fed the same diet [4] from 0-20% of maximum concentration in the mineralizing front [7]. The method used here to determine this parameter is based on measurement of the distance which tetracycline diffuses into bone of low mineral content and gives results comparable to those obtained from measurements of the actual rates of calcium and phosphorus deposition made by means of the electron microprobe [16].…”

“…NS, not significant at 0.05 probability level osteoid width, as well as decreases in osteoid maturation rate and the rate of initial mineralization [4]. In contrast, in normocalcemic TPTX rats (diet: 1.2% calcium, 0.55% phosphorus), osteoid maturation rate and the rate of initial mineralization are not significantly different from those of intact animals fed the same diet [4]. However, observations that osteoid width and mineralizing front width remain significantly higher in the normocalcemic TPTX rats than corresponding values in intact rats fed the same diet [4] from 0-20% of maximum concentration in the mineralizing front [7].…”

“…These changes include increases in Mean • SD h Probability estimated by t test. NS, not significant at 0.05 probability level osteoid width, as well as decreases in osteoid maturation rate and the rate of initial mineralization [4]. In contrast, in normocalcemic TPTX rats (diet: 1.2% calcium, 0.55% phosphorus), osteoid maturation rate and the rate of initial mineralization are not significantly different from those of intact animals fed the same diet [4].…”

“…Only those animals whose serum cal-0167-967X/79/0029-0021 $01.20 cium was less than 8 mg/dl at this time were considered successfully TPTX. The rats were randomly divided into three groups and placed on a diet containing 1.2% calcium, 0.55% phosphorus [4] for the remainder of the study. The rats were housed singly in suspended wire cages and allowed food and water ad lib.…”

“…For example, when weanling rats are parathyroidectomized and maintained on a diet containing 0.6% calcium, 0.6% phosphorus, the animals become hypocalcemic and hyperphosphatemic [4]. Rates of bone matrix formation, osteoid maturation, and bone mineralization are decreased in such rats when compared to corresponding values in intact rats on the same diet [4].…”