Year: 2002
Type: dissertation
Abstract: Estrogen deficiency and vitamin D deficiency play key roles in the pathogenesis of\npostmenopausal osteoporosis. Aim of the studies in this thesis is to extend our knowledge on\nthe interaction between E2 and 1,25-(0H)2D3 and thereby to provide more insight into the\nsignificance of E, for 1,25-(0H)2D3 mediated processes in calcium and bone metabolism.\nFurthermore the significance of VDR genotypes for the biological response to 1,25-(0H)2D3\nand the interaction between ERa and VDR genotypes in relation to BMD and fracture risk are\nstudied.\nThe first part of the thesis focuses on the effect of E2 on 1,25-(0H)2D3 mediated processes.\nIn chapters 2 and 3 the effect of E, deficiency and E2 repletion on 1,25-(0H),D, synthesis\nand 1,25-(0H)2D3 mediated intestinal calcium absorption in a rat model for postmenopausal\nosteoporosis is described. An important bone anabolic factor is IGF-1. Both 1,25-(0H)2D3 as\nwell as Ez have been shown to regulate IGF-I expression in vitro. Chapter 4 describes the\neffect of E, deficiency and E2 repletion on IGF-I levels in bone in vivo in relation to bone\nmetabolism. The effect of E2 on bone mineralization is discussed in Chapter 5.\nThe second part of the thesis considers the significance of VDR genotypes for the biological\nresponse to 1,25-(0H)2D3 and the interaction between ERa and VDR gene polymorphisms in\nrelation to BMD and fracture risk. Chapter 6 describes a pilot study addressed to whether\ndifferences in rates of bone turnover between women with either extremely low or extremely\nhigh BMD can be ascribed to genetic variations of the VDR. Furthermore, the biochemical\nresponse to short-term substitution of 1,25-(0H)2D3 in both BMD groups was related to VDR\ngene polymorphisms. In chapter 7 functional consequences of VDR gene polymorphisms in vitro are studied. Chapter 8 discusses the association between ERa gene polymorphism and\nfracture risk in postmenopausal women. Moreover, the interaction between ERa gene and\nVDR gene polymorphisms on fracture risk is described. In chapter 9 the results are discussed\nand suggestions for future research are made. Finally, the main findings are summarized in\nChapter 10.
Author: Edgar M. Colin
Language: English
Topic: Vitamin D Research Studies
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1565719116