The in Vivo Inhibition of Bone Formation by Alizarin Red S

Harris, W.H.; Travis, D.F.; Friberg, U.; Radin, E.

Journal of Bone and Joint Surgery. American Volume 46: 493-508

1964


ISSN/ISBN: 0021-9355
PMID: 14131428
Document Number: 3189
Ectopic-bone formation is a common and often disabling complication of severe trauma to the elbow, dislocations and fracture-dislocations of the hip, reconstructions of the hip, and paraplegia. Surgical treatment of such deposits is often unsatisfactory. A method to prevent or to inhibit this abnormal bone formation by a chemical or drug is needed. Moreover, the ability to reduce bone accretion and to decrease the skeletal uptake of certain ions, such as calcium, strontium, and radium, is a current need in the study of the prevention of skeletal incorporation of radioactive isotopes and also as a tool in the study of skeletal metabolism. On a broader scale, the general biological process of bone production lies at the heart of the majority of the therapeutic efforts of orthopaedists. We depend upon bone formation to heal the fractures which we align and immobilize. It must restore continuity after osteotomy and fill in defects after bone resection. One of the main avenues of approach to the study of biological processes, such as bone formation, is the investigation of factors which block, prevent, or retard the normal process. This report concerns studies of the inhibition of bone formation by alizarin red S in dogs. Significant inhibition of bone formation in dogs was observed in areas of intense skeletal uptake of alizarin red S. Electron microscopy revealed that the organic matrix in these areas was severely disturbed. The areas which contained no recognizable collagen had the least mineral. In vitro alizarin red S reacted strongly with hydroxyapatite and reconstituted guineα-pig-skin collagen. The collagen reaction is divalent cation dependent. The evidence suggests that alizarin red S interferes with collagen synthesis or aggregation in vivo. The inhibition could also be related to a disturbance of the nucleation of hydroxyapatite and to retardation of crystal growth. Other possible mechanisms are also considered.

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The in Vivo Inhibition of Bone Formation by Alizarin Red S