Synthetic analogue of bone mineral formation.
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Biomedical subjects
Publications and source records attributed to A L Boskey.
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The epiphyseal (cartilage) and diaphyseal (bone) regions of the long bones of vitamin D-deficient, phosphate-deficient, immature rats have been shown to contain Ca-PL-PO4 complexes in amounts comparable to that found in normal rat bones. This suggests that these calcium acidic phospholipid complexes are formed prior to mineralization. The metaphysis (bone and calcified cartilage) of the experimental animals contained less Ca-PL-PO4 than control bone, which suggests that Ca-PL-PO4 content is elevated as mineralizing activity increases. Overall bone lipid composition was dependent on the vitamin D status of the animals. Total lipid, cholesterol, and cholesterol ester content was higher in experimental animals than in controls. In contrast, free fatty acid and lysophosphatide were lower in experimental than in control animal's bones. The total phospholipid content (based on organic phosphate analyses) was unaltered by the vitamin D status. These lipid changes, reminiscent of changes seen in the intestinal brush border membrane of rachitic animals, suggest that vitamin D effects on lipid metabolism in bone may be similar to those in the intestine.
High dietary strontium induces rickets in both calcium-replete and calcium-deficient animals. To test the hypothesis that strontium directly perturbs complexed acidic phospholipid (CPLX) metabolism and thus, mineralization, the effect of strontium treatment on CPLX formation was studied in solution, in culture, and in growing rats. Synthetic CPLX containing calcium or strontium were found to be similar in composition. Strontium, however, appeared to incorporate into CPLX less avidly than calcium. Mineralizing chick limb bud mesenchymal cell cultures treated with strontium demonstrated a significantly increased CPLX content and decreased 45Ca uptake compared to calcium-treated cultures. Long bones from young growing rats fed a diet supplemented with strontium demonstrated defective mineralization based on radiologic and histologic analyses. Metaphyseal bone of strontium-fed rats contained significantly greater amounts of CPLX and had significantly lower ash weights compared with control bone. Thus, treatment of mineralizing tissues with strontium both in vitro and in vivo resulted in defective mineralization and an accumulation of CPLX. Strontium appears to perturb mineralization, in part, by a direct effect on the cells of mineralizing tissues.
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The lipids associated with osteonecrotic bone have a higher cholesterol content than those associated with normal (nondiseased) or osteoarthritic bone. A study of 18 osteonecrotic femoral heads showed elevated total lipids in the affected superolateral regions of the osteonecrotic bone as compared with both the unaffected inferomedial regions and the superolateral regions of nondiseased femoral heads. Cholesterol content was elevated in both the affected and unaffected regions of the osteonecrotic bones when contrasted with the cholesterol contents of control bones. Greatest elevations were noted for those persons with histories of combined steroid use and alcohol abuse. Seven controls and four osteoarthritic femoral heads had lower total lipid and cholesterol contents. The bone cholesterol content was correlated (r = 0.82) with the proportion of the tissue that was necrotic. The elevated cholesterol content in the necrotic tissues may contribute to cell death by altering membrane metabolism.