Formation, mineralization, and resorption of bone in vitamin D—deficient rats

Abstract

A B S T R A C T Quantitative histologic methods have been devised to measure several processes dealing with formation and mineralization of matrix and bone resorption. In vitamin D-deficient rats, the total osteoblastic matrix formation rate was 20% less and the total osteoclastic bone resorption rate was 80% more than in pair-fed control rats. These changes were found to be primarily because of changes in the rates of matrix formation and of bone resorption per unit area of forming or resorbing surfaces rather than to changes in the areas of these surfaces. The rate of maturation of osteoid and the rate of initial mineralization both were reduced to half of normal in the vitamin D-deficient rats. These variables related to matrix formation and mineralization were significantly correlated with the concentration of calcium but not with the concentration of phosphate in serum. The occurrence of hypocalcemia is interpreted as the consequence, both of reduced calcium absorption and of inadequate resorptive response of bone cells to homeostatic stimuli, such that, although bone resorption was greater than normal, it did not adequately compensate for the reduced intestinal absorption.

25-hydroxycholecalciferol-enhanced bone maturation in the parathyroprivic state.

“…The results are consistent with those of Paterson and Fourman (28) and others (29)(30)(31)(32), wherein vitamin D and/ or its active metabolites were reported to enhance bone collagen synthesis and to stimulate lysyl oxidase activity when administered to hypocalcemic and/or vitamin D-deficient animals. Unlike the vitamin D-deficient animal, however, the serum calciums of the PTX-calcium supplemented animals, although lower than normal, were never at the hypocalcemic levels which have been shown to decrease bone maturation (33). Rather, the 8.3 mg/100 ml serum calcium, which was maintained in this study (Table I), was comparable to the serum calcium concentration which Au and Raisz (34) found sufficient to maintain skeletal responsiveness in PTX rats.…”

Tissue and cellular basis for impaired bone formation in aluminum-related osteomalacia in the pig.

“…3, the corrected rates of mineralized bone apposition in Al fall below those determined in C by a minimum of 1 Despite the similarity between the current experimental data and the skeletal findings in early vitamin D deficiency, it is unlikely that the histologic and dynamic response of bone to aluminum loading represents resistance to the actions of vitamin D at the tissue level. Hypocalcemia almost invariably occurs in vitamin D deficiency, and this disturbance is a major determinant of the defect in the calcification of osteoid in this disorder (31)(32)(33)(34). In contrast, the lesion of aluminum-related osteomalacia develops in the presence of normal or increased levels ofcalcium in serum (35 (37).…”

Lithium inhibition of bone mineralization and osteoid formation.

“…The discrepancies in the reported bone mineralization rates in rats (22)(23)(24)(25) are most likely a result of differences in the experimental conditions, the weights and ages of the animals, and the bones studied. Both the rat tibia and f'emur are complicated by structural asymmetry and cortical drift (25)(26).…”