Year of Publication

2014

Degree Name

Doctor of Philosophy (PhD)

Document Type

Doctoral Dissertation

College

Engineering

Department

Biomedical Engineering

First Advisor

Dr. David Pienkowski

Abstract

Bone’s ability to resist fracture is often ignored until a low-energy fracture occurs. Patients with Chronic Kidney Disease (CKD) or osteoporosis are at an increased risk of low-energy fracture. Generally, fracture risk is evaluated by using a bone mineral density (BMD) test. BMD values; however, do not fully predict bone’s ability to resist fracture. This suggests that other parameters may be involved. Bone quality is the term used to describe these parameters, which are categorized into three groups: structural, material, and microdamage. The aim of this dissertation research was to examine whether bone quality was altered in patients who: 1) had abnormal bone turnover (high or low) due to CKD, 2) suffered a low-energy fracture despite normal BMD, or 3) had osteoporosis and were treated with bisphosphonates. These studies used iliac crest bone specimens from Caucasian females aged 21 to 87 years. Bone’s material parameters were measured by Fourier transform infrared spectroscopy. The key finding from the turnover study was that high and low turnover was associated with altered bone quality. Specifically, bone with high turnover had a lower mineral-to-matrix ratio compared to normal and low turnover (p<0.05), while low turnover had a lower cancellous bone volume and trabecular thickness compared to normal or high turnover (p<0.05). The key finding from the fracture study was that patients with normal BMD and low-energy fractures had altered bone quality (greater collagen crosslinking ratio) compared to patients who had low-BMD with low-energy fractures and healthy subjects (controls) (p<0.05). Lastly, the key findings from the bisphosphonate studies were that osteoporosis patients treated with these drugs had altered bone quality (specifically, greater (p<0.05) mineral-to-matrix ratio) compared to untreated turnover-matched osteoporotic patients, and that were several positive linear correlations with the nanoindentation derived Young’s modulus and hardness of cortical and trabecular bone and the duration of bisphosphonate treatment (p<0.05). The findings presented provide further evidence that bone quantity is not the sole factor in determining bone’s ability to resist fractures and that bone quality is an essential factor.

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