자료유형  

 학위논문

Control Number  

0016932761

International Standard Book Number  

9798379850128

Dewey Decimal Classification Number  

616

Main Entry-Personal Name  

Damrath, John George, IV.

Publication, Distribution, etc. (Imprint  

[S.l.] : Purdue University., 2022

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2022

Physical Description  

1 online resource(99 p.)

General Note  

Source: Dissertations Abstracts International, Volume: 85-01, Section: B.

General Note  

Advisor: Wallace, Joseph M.

Dissertation Note  

Thesis (Ph.D.)--Purdue University, 2022.

Restrictions on Access Note  

This item must not be sold to any third party vendors.

Summary, Etc.  

요약Chronic kidney disease (CKD) affects 15% of Americans and dramatically increases their risk of skeletal fractures and fracture-related mortality. The progression of CKD is marked by abnormal biochemistries including disrupted mineral homeostasis and elevated parathyroid hormone (PTH). High PTH is linked to the bone alterations seen in CKD including cortical porosity and altered turnover. To mitigate the effects of sustained elevations in PTH, dialysis patients are commonly given calcimimetics which act by sensitizing the calcium-sensing receptor on parathyroid chief cells, lowering PTH synthesis and secretion. While calcimimetics are suggested to reduce fracture risk in dialysis patients, little is known about how these drugs impact bone tissue properties or whether they can be implemented in early CKD to prevent CKD-induced bone deterioration. Therefore, understanding how calcimimetics alter bone quality may reveal new strategies to prevent fractures in patients with CKD. While CKD represents a major global health crisis, nearly half of all CKD patients also have diabetes. Diabetes disrupts numerous physiologic systems and independently increases fracture risk by lowering bone mass and quality. Therefore, we have two major objectives in this work. Firstly, we developed a method for analyzing bone composition and material properties in a spatially resolved manner and found that calcimimetics increase mineral crystallinity and stiffness in newly formed periosteal bone while increasing relative mineralization, stiffness, and hardness in perilacunar bone. Further, we found that these properties depended on distance from the osteocyte lacunar wall. Secondly, we developed a novel combined murine model of type 1 diabetes and CKD which revealed a unique combination of detriments in structural and tissue-level bone microarchitecture, mechanical properties, and fracture toughness. Taken together, this work represents a thorough investigation of how diabetes and CKD alter bone quality on multiple scales and how calcimimetics improve bone quality in localized regions in early CKD.

Subject Added Entry-Topical Term  

Hemodialysis.

Subject Added Entry-Topical Term  

Diabetes.

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Vitamin D.

Subject Added Entry-Topical Term  

Mortality.

Subject Added Entry-Topical Term  

Crack initiation.

Subject Added Entry-Topical Term  

Urine.

Subject Added Entry-Topical Term  

Insulin.

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Mechanics.

Subject Added Entry-Topical Term  

Bone density.

Subject Added Entry-Topical Term  

Nitrogen.

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Oxidative stress.

Subject Added Entry-Topical Term  

Hemoglobin.

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Electrolytes.

Subject Added Entry-Topical Term  

Collagen.

Subject Added Entry-Topical Term  

Spectrum analysis.

Subject Added Entry-Topical Term  

Pancreas.

Subject Added Entry-Topical Term  

Glucose.

Subject Added Entry-Topical Term  

Fractures.

Subject Added Entry-Topical Term  

Diabetic neuropathy.

Subject Added Entry-Topical Term  

Hospital costs.

Subject Added Entry-Topical Term  

Endocrine system.

Subject Added Entry-Topical Term  

Bone diseases.

Subject Added Entry-Topical Term  

Analytical chemistry.

Subject Added Entry-Topical Term  

Chemistry.

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Medicine.

Subject Added Entry-Topical Term  

Optics.

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Pharmaceutical sciences.

Subject Added Entry-Topical Term  

Public health.

Added Entry-Corporate Name  

Purdue University.

Host Item Entry  

Dissertations Abstracts International. 85-01B.

Host Item Entry  

Dissertation Abstract International

Electronic Location and Access  

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Control Number  

joongbu:643801