PubMed · 1456210
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J M Dibbets. 1992. Comment on TMJ case report.. https://doi.org/10.1016/s0889-5406(05)80678-x
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Zoledronic acid (ZOL) is a nitrogen-containing bisphosphonate and its use in reducing osteoporosis and cancer-induced osteolysis is increasing. Recent findings indicated that ZOL has a direct effect on cancer cells. In this study, the effect of ZOL was examined on the aggressive MDA-MB-231 breast cancer cell line. ZOL induces an important inhibition of cell invasion at low concentrations (1 microM). This is not explained by modifications of proteases involved in cell invasiveness (matrix metalloproteinases and urokinase-type plasminogen activator), but by a disorganisation of actin cytoskeleton due to RhoA inhibition related to its defective prenylation as it was reversed by geranylgeraniol (GGOH) and mimicked by the Rho selective inhibitor C3 exoenzyme. In addition, ZOL inhibits the chemotactic effect induced by stromal cell-derived factor 1(SDF-1), a chemokine greatly involved in cancer metastasis to bone. This effect is related to both reduction of cell motility induced by RhoA inhibition and to a decreased expression of CXCR-4, the SDF-1 receptor. Finally, ZOL reduces Cox-2 expression and, consequently, the secretion of prostaglandins E2 (PGE2) in a RhoA-independent manner. This inhibition could contribute to bone protection in breast cancers because PGE2 stimulates osteoclast-mediated bone resorption. In summary, new insights in the mechanism of ZOL action on aggressive breast cancer cells are demonstrated and could explain its beneficial action in both the reduction of osteolysis and prevention of metastasis.
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STUDY DESIGN: Computational analysis using the finite-element method was used to examine a possible etiology of idiopathic scoliosis. OBJECTIVES: To compare changes in the coronal and the transverse planes of idiopathic thoracic scoliosis with changes produced in a finite-element buckling model, and to investigate the influence of bone modeling on the buckling spine. SUMMARY OF BACKGROUND DATA: Although it is now widely accepted that growth is related strongly to the onset and progression of scoliosis, the pathomechanism or etiology of idiopathic scoliosis still is not clear. A previous study showed that a buckling phenomenon caused by anterior spinal overgrowth can produce scoliosis, and that the fourth buckling mode matched the clinical characteristics associated with the thoracic type of idiopathic scoliosis. The fourth buckling mode occurs when the first, second, and third buckling modes are prevented. METHODS: The spinal finite-element model used in this study consisted of 68,582 elements and 84,603 nodes. The transverse changes seen in the computed tomography images of 41 patients with idiopathic thoracic scoliosis (apex, T8; average Cobb angle, 52.5 degrees) were compared with those produced in the fourth buckling mode. Bone modeling (bone formation and resorption) was simulated as heat deformation caused by changes in temperature. The bone formation and resorption were simulated, respectively, by positive and negative volume changes in proportion to the stress that occurred in the buckling spine. RESULTS: Computed tomography images of scoliosis show that as the scoliosis becomes more severe, the thoracic cage decreases on the convex side of the curve and increases on the concave side. The opposite thoracic cage deformation was obtained in the fourth buckling mode. In patients with scoliosis, the sternum essentially remains in its original position with respect to the vertebrae, but in the linear buckling model, it shifted in the direction of vertebral body rotation. In contrast to clinical data, the incremental deformation resulting from bone formation corrected the original curve, and the thoracic cage distorted. On the other hand, incremental deformation resulting from bone resorption worsened the original curve, and the thoracic cage distorted in a manner similar to that described by the clinical data. CONCLUSIONS: This computational investigation suggests that scoliotic changes in the spinal column triggered by the buckling phenomenon are counteracted by bone formation, but worsened by bone resorption. The authors hypothesized that scoliosis progressed with resorption of loaded bone. However, it is unclear whether this hypothesis applies to a living body in practice because of the effects from additional factors.