Dissertations and Theses

Date of Award

2023

Document Type

Thesis

Department

Biomedical Engineering

First Advisor

Mitchell B. Schaffler

Second Advisor

Susannah P. Fritton

Third Advisor

Luis Cardoso

Keywords

Bone, Fatigue Microdamage, Bisphosphonates, Nanoindentation, Material Properties

Abstract

Bisphosphonates [BPs] are the mainstay for osteoporosis treatment. They suppress bone resorption/remodeling, preventing bone loss. However, BPs also suppress the beneficial bone remodeling that replaces microscopically damaged bone that occurs from normal mechanical wear-and-tear or fatigue, leading to impaired tissue material properties and in some instances atypical femoral fractures.

In these studies, we assessed the effects of acute fatigue, fatigue induced remodeling, and fatigue microdamage with remodeling suppression using the clinical BP, alendronate [ALN], on local bone material properties. Studies were performed on cortical bone sections from rat ulnae into which fatigue damage had been introduced in vivo. Rat cortical bone does not exhibit baseline remodeling activity, so effects and interactions of BP and μcracks on material properties could be assessed directly. Nanoindentation was used to measure elastic modulus in bone around microcracks, in remodeled regions, and equivalent regions in non-fatigued, control bone. Key findings: We found that acute fatigue/microdamage caused a ~20% reduction in tissue modulus compared to control bone. The greatest degradation of modulus in these baseline fatigue bone samples was localized within approximately 5 μm of a μcrack, pointing to a zone of surrounding collateral material damage, beyond which modulus was unchanged from baseline. Tissue modulus was dramatically reduced in remodeling suppressed bone (fatigue plus 4 months ALN treatment) by ~40% versus control. Again, tissue modulus was most reduced nearest a μcrack; however, the region of impaired material properties/collateral matrix damage extended further beyond the μcracks as compared to baseline fatigue. The studies indicate that BP use in fatigue-damaged bone has a marked, negative effect on local tissue material properties–greater than acute fatigue μcracks alone. How ALN exacerbated loss of material properties remains obscure and will be the subject of future investigations.

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