The Role of Cortical and Cancellous Bone Quality on Vertebral Fragility

A serious health concern of aging populations is the increased risk of non-traumatic fracture caused by age-related changes in bone's structure and morphology. Thinning bone caused by asymmetric bone resorption, diagnosed as osteoporosis, is commonly the focal point for age-related fracture risk. Although the majority of orthopedic research is conducted on decreased bone quantity, changes in bone's quality are as equally impactful on the fracture mechanics of bone and are largely overlooked. One of the most prevalent modifications in aging bone is the accumulation of advanced glycation end-products (AGEs) caused by nonenzymatic glycation (NEG). AGE content in bone increases with age and has a deleterious effect on bone's material properties.

Vertebral fractures account for more than half of all osteoporotic fractures and correlate to increased mortality and morbidity. In order to define an objective fracture risk indicator, interactions between cortical and cancellous constituents of vertebrae have been widely studied. Notwithstanding, some disparity remains over the exact fracture modality within the vertebrae. Despite known limitations, bone mineral density (BMD) remains the standard for assessing vertebral fragility. As alterations in bone's organic matrix have a marked impact on the tissue's material properties, it is imperative to elucidate the effects of nonenzymatic glycation on load bearing ability of the vertebrae's constituent parts.

Therefore, the objective of this doctoral research is to combine biochemical, mechanical, and computational methods to: a) better characterize the load sharing role of cortical and cancellous bone within the vertebrae, b) determine the effect of AGE accumulation on load sharing within the vertebrae, and c) validate the feasibility of reversing the effects of NEG-mediated AGE crosslinking using n-Phenacylthiazolium Bromide.

The results presented herein provide a better understanding of load sharing and fracture within the vertebrae. They also reinforce the degenerative nature of age-related changes within bone's organic matrix, stressing the importance of considering quality as well as quantity of bone when defining fracture risk. To reverse the effects of NEG, a novel compound is proposed and verified as a possible therapy for the accumulation of AGEs within bone's structure. Finally, a computational model encompassing a damaged-plasticity material definition is vetted as a predictive tool for assigning fracture risk. When combined, this work may provide a baseline for the development of much-needed fracture risk assessment tools to diagnose and prescribe necessary treatments for the aging skeleton.

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Year

Entry

1990

Beaupré GS, Orr TE, Carter DR. An approach for time‐dependent bone modeling and remodeling: theoretical development. J Orthop Res. September 1990;8(5):651-661.

1970

Merz WA, Schenk RK. A quantitative histological study on bone formation in human cancellous bone. Acta Anat. 1970;76(1):1-15.

2002

Currey JD. Bones: Structure and Mechanics. Princeton, NJ: Princeton University Press; 2002.

2010

Gourion-Arsiquaud S, Allen MR, Burr DB, Vashishth D, Tang SY, Boskey AL. Bisphosphonate treatment modifies canine bone mineral and matrix properties and their heterogeneity. Bone. March 2010;46(3):666-672.

1970

Abendschein W, Hyatt GW. Ultrasonics and selected physical properties of bone. Clin Orthop Relat Res. March–April 1970;69:294-301.