Complete understanding of the regulation of bone resorption by hormones and drugs could provide a rational basis for the treatment of metabolic bone diseases involving increased bone resorption (e.g. osteoporosis and Paget's disease) and of inflammatory bone lysis (e.g. periodontal disease and rheumatoid arthritis). Such information would also be useful for the control of hypercalcemia of malignancy and for the problem of unpredictable bone graft resorption. New experimental models are needed to demonstrate the origin, differentiation, and regulation of bone resorbing cells. Implantation of devitalized bone particles (BP) in subcutaneous sites elicits rapid resorption of the BP by cells with many characteristics of in osso bone-resorbing cells. In preliminary experiments we have shown that this process is quantifiable and can be modulated by bone-active hormones and drugs. Because the cells in this model, monocytes, macrophages, epitheliod cells, osteoclasts, and mast cells are similar to cells involved in normal and pathological bone resorption, the model provides a convenient system to evaluate the mechanism by which substanaces exert effects on resorption. Because no osteoblasts are present in these experimental tissues, resorption can be investigated separate from bone formation. We propose to evaluate the effects of excess and deficient parathyroid hormone and calcitonin, as well as the drugs, dichloromethane diphosphonate, heparin, glucocorticoids and protamine. Our hypothesis is that the latter acts to inhibit mast-cell heparin, a cofactor in resorption. The techniques used to evaluate these processes include histomorphometry, electron microscopy and morphometry, enzymology, and in vivo endocrine manipulations in rats.
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| DeFranco, D J; Glowacki, J; Cox, K A et al. (1991) Normal bone particles are preferentially resorbed in the presence of osteocalcin-deficient bone particles in vivo. Calcif Tissue Int 49:43-50 |
