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Using Time-Lapse HR-pQCT for Bone Turnover Classification in CKD-MBD Patients

Abstract

Patients with chronic kidney disease – mineral and bone disorder, a disease that results in a high risk for bone fractures, can be classified based on the rate of total bone turnover. Currently, bone turnover rates are determined from iliac crest bone biopsies followed by quantitative histomorphometry. However, this method is painful, invasive, and performed in an area not typically prone to fractures. In this ongoing prospective study, we explore the use of time-lapse high resolution peripheral quantitative computed tomography (HR-pQCT) imaging as a non-invasive method to determine bone turnover in patients. Fifteen participants are expected to participate in this study. To date, six participants were recruited to undergo HR-pQCT scans at four different timepoints with two-month intervals. Three scans will be performed at the first timepoint and one scan will be performed at the three following timepoints. The three repeat baseline scans and each of the follow-up scans underwent time-lapse analysis to determine total bone turnover. For this thesis project, the objective was to establish methodology for this study, including determine the time-lapse threshold needed to detect <0.5% reproducibility differences, determine the more robust image processing pipeline between two processing techniques, determine the least significant change (LSC) from baseline repeat scans, and determine if there are detectable time-lapse changes in total bone turnover at two-months. The preliminary results determined that using a Laplace-Hamming image processing pipeline performed better than the standard analysis protocol, determined that a threshold of 525 mgHA/ccm led to <0.5% reproducibility differences, demonstrated a LSC of 0.088 and 0.040 for the radius and tibia respectively, and showed that after two months, time-lapse HR-pQCT could measure in vivo total bone turnover in patients but not greater than the LSC values. Since determining the optimal time to scan was an objective of this study, the continuation of the study and scanning at longer timeframes will uncover the period with which we can measure bone turnover greater than the LSC. The continuation of this study will also elucidate the relationship between time-lapse HR-pQCT results and the gold standard of bone biopsies and verify our initial conclusions.

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