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High resolution peripheral quantitative computed tomography (HR-pQCT) was designed to study bone mineral density (BMD) and microarchitecture in peripheral sites at the distal radius and tibia. With the introduction of the second generation HR-pQCT scanner (XtremeCT II, Scanco Medical) that has a larger, longer gantry it is now possible to study the human knee in vivo using HR-pQCT. Previous validation of HR-pQCT measurements at the distal radius and tibia against micro-CT is not representative of the knee because the increased cross-sectional area, greater amount of soft tissue surrounding the scan region, and different imaging protocol result in potentially increased beam hardening effects and photon scatter and different signal-to-noise ratio. The objective of this study is to determine the accuracy of density and microarchitecture measurements in the human knee measured by HR-pQCT using an in vivo protocol. Twelve fresh-frozen cadaver knees were imaged using in vivo HR-pQCT (60.7 µm) protocol. Subsequentially, distal femurs were extracted and imaged using a higher resolution (30.3 µm) ex vivo protocol, replicating micro-CT imaging. Scans were registered so that agreement of density and bone microarchitecture measurements could be determined using linear regression and Bland-Altman plots. All density and microarchitecture outcomes were highly correlated between the 2 protocols (R2 > 0.89) albeit with statistically significant differences between absolute measures based on paired t tests. All parameters showed accuracy between 4.5% and 8.7%, and errors were highly systematic, particularly for trabecular BMD and trabecular thickness (R2 > 0.93). We found that BMD and microarchitecture measurements in the distal femur obtained using an in vivo HR-pQCT knee protocol contained systematic errors, and accurately represented measurements obtained using a micro-CT equivalent imaging protocol. This work establishes the validity and limitations of using HR-pQCT to study the BMD and microarchitecture of human knees in future clinical studies.

Due to difficulty assessing healing of distal radius fractures using conventional radiography, there is interest in using high resolution peripheral quantitative computed tomography (HR-pQCT) to track healing at the microarchitectural level. Unfortunately, the plaster-of-Paris and fiberglass casts used to immobilize fractures affect HR-pQCT measurements due to beam hardening, and increased noise. The challenge is compounded because casts have variable thickness, and an individual patient will often have their cast changed 2-3 times during the course of treatment. This study quantifies the effect of casts within a clinically relevant range of thicknesses on measured bone parameters at the distal radius, and establishes conversion equations to correct for systematic error in due to cast presence. Eighteen nonfractured participants were scanned by HR-pQCT in three conditions: no cast, plaster-of-Paris cast, and fiberglass cast. Measured parameters were compared between the baseline scan (no cast) and each cast scan to evaluate if systematic error exists due to cast presence. A linear regression model was used to determine an appropriate conversion for parameters that were found to have systematic error. Plaster-of-Paris casts had a greater range of thicknesses (3.2-9.5 mm) than the fiberglass casts (3.0-5.4 mm), and induced a greater magnitude of systematic error overall. Key parameters of interest were bone mineral density (total, cortical, and trabecular) and trabecular bone volume fraction, all of which were found to have systematic error due to presence of either cast type. Linear correlations between baseline and cast scans for these parameters were excellent (R2 > 0.98), and appropriate conversions could be determined within a margin of error less than a ±6% for the plaster-of-Paris cast, and ±4% for the fiberglass cast. We have demonstrated the effects of cast presence on bone microarchitecture measurements, and presented a method to correct for systematic error, in support of future use of HR-pQCT to study fracture healing.

The finite element (FE) method based on high-resolution peripheral quantitative computed tomography (HR-pQCT) use a variety of tissue constitutive properties and boundary conditions at different laboratories making comparison of mechanical properties difficult. Furthermore, the advent of a second-generation HR-pQCT poses challenges due to improved resolution and a larger region of interest (ROI). This study addresses the need to harmonize results across FE models. The aims are to establish the relationship between FE results as a function of boundary conditions and a range of tissue properties for the first-generation HR-pQCT system, and to determine appropriate model parameters for the second-generation HR-pQCT system. We implemented common boundary conditions and tissue properties on a large cohort (N = 1371), and showed the relationships were highly linear (R2 > 0.99) for yield strength and reaction force between FE models. Cadaver radii measured on both generation HR-pQCT with matched ROIs were used to back-calculate a tissue modulus that accounts for the increased resolution (61 µm versus 82 µm), resulting in a modulus of 8748 MPa for second-generation HR-pQCT to produce bone yield strength and reaction force equivalent to using 6829 MPa for first-generation HR-pQCT. Finally, in vivo scans (N = 61) conducted on both generations demonstrated that the larger ROI in the second-generation system results in stronger bone outcome measures, suggesting it is not advisable to convert FE results across HR-pQCT generations without matching ROIs. Together, these findings harmonize FE results by providing a means to compare findings with different boundary conditions and tissue properties, and across scanner generations.

Bone strength determined from finite element (FE) modelling provides an estimate of fracture healing progression following a distal radius fracture (DRF), but how these measures relate to patient-reported outcomes and functional outcomes remains unknown. We hypothesized that changes in bone stiffness and bone mineral density measured using high-resolution peripheral quantitative computed tomography (HR-pQCT) are associated with clinically available measures of functional and patient-reported outcomes. We also aimed to identify which clinical outcome measures best predict fracture stiffness and could therefore be used to inform cast removal. Participants (n = 30) with stable distal radius fractures were followed for two week intervals from the time of fracture until two months post-fracture, then at three months and six months post-fracture. At each follow-up, participants underwent clinical, radiographic, and functional assessments, as well as had their fractured wrist scanned using HR-pQCT. Recovery of bone stiffness during fracture healing was determined from micro-FE (μFE) models generated from HR-pQCT image data. During the DRF healing process, significant longitudinal changes were found in μFE-estimated stiffness, patient-reported outcomes, grip strength, range of motion (ROM), tenderness, number of cortices healed based on radiographs, and fracture line visibility (p, Highlights • Recovery of fracture stiffness may inform time required for cast immobilization. • Patient reported outcomes predict rate of fracture stiffness recovery. • Radiographic outcomes correlate weakly with fracture stiffness. • Patient reported outcomes may inform duration of cast immobilization.

The application of high resolution peripheral quantitative computed tomography (HR-pQCT) for the study of bone health has provided valuable insight into the role bone microarchitecture has in determining bone strength and fracture risk. However, conventional density and morphological parameters struggle to distinguish whether localized bone loss is present, visible as heterogeneous deterioration in the trabecular network. This is because current HR-pQCT parameters quantify a global average of properties in the cortical or trabecular compartment. This study proposes a new metric we term "void space" that segments volumes of localized deterioration in the trabecular bone network from HR-pQCT scans and quantifies void space as the void space to total volume ratio (VS/TV, %). A simple and fully automated protocol for segmenting and quantifying void space in HR-pQCT scans is presented, along with the assessment of accuracy, precision, and cross-calibration between generations of HR-pQCT systems. Finally, prevalence of void space and the association with standard HR-pQCT parameters is demonstrated using a large population-based cohort (n = 1236). Void space detection was found to be highly reproducible (accuracy95%, least significant change1.76% VS/TV) and correlation between scanner generations was strong (R