Hepatic Osteodystrophy: The Mechanism of Bone Loss in Hepatocellular Disease and the Effects of Pamidronate Treatment
Keywords:Hepatic Osteodystrophy, Osteoporosis, Mice, Bone Remodeling, Ccirrhosis
AbstractOBJECTIVES: The present study was designed to evaluate the bone phenotypes and mechanisms involved in bone disorders associated with hepatic osteodystrophy. Hepatocellular disease was induced by carbon tetrachloride (CCl4). In addition, the effects of disodium pamidronate on bone tissue were evaluated. METHODS: The study included 4 groups of 15 mice: a) C = mice subjected to vehicle injections; b) C+P = mice subjected to vehicle and pamidronate injections; c) CCl4+V = mice subjected to CCl4 and vehicle injections; and d) CCl4+P = mice subjected to CCl4 and pamidronate injections. CCl4 or vehicle was administered for 8 weeks, while pamidronate or vehicle was injected at the end of the fourth week. Bone histomorphometry and biomechanical analysis were performed in tibiae, while femora were used for micro-computed tomography and gene expression. RESULTS: CCl4 mice exhibited decreased bone volume/trabecular volume and trabecular numbers, as well as increased trabecular separation, as determined by bone histomorphometry and micro-computed tomography, but these changes were not detected in the group treated with pamidronate. CCl4 mice showed increased numbers of osteoclasts and resorption surface. High serum levels of receptor activator of nuclear factor-κB ligand and the increased expression of tartrate-resistant acid phosphatase in the bones of CCl4 mice supported the enhancement of bone resorption in these mice. CONCLUSION: Taken together, these results suggest that bone resorption is the main mechanism of bone loss in chronic hepatocellular disease in mice.
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Spirlandeli, A. L., Dick-de-Paula, I., Zamarioli, A., Jorgetti, V., Ramalho, L. N., Nogueira-Barbosa, M. H., Volpon, J. B., Jordão, A. A., Cunha, F. Q., Fukada, S. Y., & de Paula, F. J. (2017). Hepatic Osteodystrophy: The Mechanism of Bone Loss in Hepatocellular Disease and the Effects of Pamidronate Treatment. Clinics, 72(4), 231-237. https://doi.org/10.6061/clinics/2017(04)07