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Title: Pathophysiology of post-transplantation bone disease : mechanisms of bone loss after orthotopic liver transplantation
Author: Huang, C.-C.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 1997
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To enhance our understanding of the pathophysiology of bone disease associated with liver transplantation and of the mechanisms underlying bone loss in the three month period following transplantation, this prospective study was undertaken as follows: (1) bone pathophysiology was evaluated pre- and three months post-transplantation in transiliac biopsies using tetracycline-assisted histomorphometry; (2) cellular activities of bone formation and resorption pre- and post- transplantation were studied using quantitative enzyme cytochemistry in combination with histomorphometric methods; (3) cellular activities for markers of bone energy metabolism and biosynthesis and/or cell proliferation were investigated using quantitative enzyme cytochemistry; (4) plasma markers for bone metabolism were investigated at regular intervals in collaboration with other laboratories. It was concluded from this study that rapid bone loss early after transplantation is due both to increased bone turnover and a negative remodelling balance at the individual bone remodelling site. These changes were at least partially mediated by increased PTH levels secondary to a negative balance in plasma calcium. Cyclosporin A is known to increase intracellular calcium levels and inhibit calcium release from mitochondria. It also reduces glomerular filtration rate which could be sufficient to depress extracellular calcium levels and thereby cause the observed rise in PTH levels. The consequences of this for post transplant bone remodelling is a markedly enhanced risk of osteoporosis in these patients. Ensuring replete calcium and vitamin D levels pre-transplantation and supplementation of cyclosporin A treatment with vitamin D metabolites and calcium post-transplantation followed by careful monitoring of plasma calcium concentrations might offer a better overall outcome for preventing transplantation-associated osteoporosis at this early stage post transplantation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available