Comprehensive Validations of HR-pQCT Based Morphological and Biomechanical Measures of

Human Distal Radius and Tibia

Bin Zhou1, Ji Wang, M.S1, Y. Eric Yu1, Zhendong Zhang1, Ruoyu Sheng1, Alexander Wang1, Kyle Nishiyama,

PhD2, Elizabeth Shane2, X. Edward Guo1. 1Columbia University, New York, NY, USA, 2Columbia University Medical Center, New York, NY, USA.

Disclosures: B. Zhou: None. J. Wang: None. Y. Yu: None. Z. Zhang: None. R. Sheng: None. A. Wang:

None. K. Nishiyama: None. E. Shane: None. X. Guo: None.

Introduction: High-resolution peripheral quantitative computed tomography (HR-pQCT) is an in vivo

imaging modality to assess the three-dimensional (3D) microstructure of cortical and trabecular bone at

distal radius and tibia. HR-pQCT has demonstrated its capability in detecting diseases and treatment-

related bone microstructural changes, as well as providing additional fracture risk determinants

compared to dual energy x-ray absorptiometry (DXA) [1-2]. Typically, a standard 9.02 mm segment of

the distal radius or tibia is imaged and processed for microstructural and biomechanical analyses. In

addition, advanced individual trabecula segmentation (ITS), which decomposes trabecular bone

microstructure into individual trabecular plates and rods, has been also used on the HR-pQCT images to

provide additional trabecular morphological assessments in clinical studies. However, all these

techniques, originated from high-resolution micro CT (µCT), have not been rigorously and

comprehensively validated in human radii and tibiae. For example, the clinical standard morphological

and advanced ITS morphological analyses have not been validated for HR-pQCT of both tibia and radius

segments. The biomechanical analyses of these standardized HR-pQCT segments have not been

compared with the gold standard experimental biomechanical measurements. Furthermore, it remains

to be determined whether the current selection of the HR-pQCT segment is representative of the entire

radius and tibia, both morphologically and biomechanically. Therefore, in this study we 1) performed

HR-pQCT standard, ITS morphological and biomechanical analyses and compare the HR-pQCT measures

to those by gold standard µCT and directly mechanical testing on both radii and tibiae from the same

cadaveric human subjects; 2) applied HR-pQCT analyses on three adjacent regions along distal radius

and tibia to examine the variations of bone geometry and morphology in different regions (Fig. 1), and

determined their associations with the experimentally determined whole bone stiffness.

Methods: 26 paired whole tibiae and radii bone were first scanned by HR-pQCT at 82 µm and µCT at 37

µm. The radius and tibia segment corresponding to the clinical HR-pQCT region was prepared and

scanned again by HR-pQCT. Standard HR-pQCT evaluation was applied on the segment for

microstructural evaluation. Based on the threshold image of HR-pQCT segments, standard µCT

evaluations (direct) were applied to calculate model-independent trabecular microstructural

parameters. The µCT image was registered to the HR-pQCT segment and standard µCT evaluation was

performed on the µCT trabecular compartment. ITS analyses were then applied to examine the

trabecular plate and rod related microstructural parameters. The whole radius and tibia HR-pQCT image

were registered with the clinical segment image and two adjacent regions were determined and applied

to HR-pQCT evaluations: 1) the most distal region, the section between the distal radial or tibial end

surface and the start of the standard region; 2) the proximal region, the section starting from the end of

standard region and contain a 24.6 mm section toward proximal direction. Before the segment was cut,

the entire radius and tibia were embedded with PMMA and nondestructively tested mechanically to

measure the whole bone stiffness. After the segment was cut, uniaxial mechanical testing was

performed to measure the segment stiffness. Finite element analyses were performed based on the

clinical segment HR-QCT images and the accuracy was examined through comparison with µCT image

based FEA predications and mechanical testing results. Spearman correlation coefficient was used to

characterize the correlations between the HR-pQCT measurements and whole bone stiffness. Paired

Student’s t-tests were applied to examine the difference between HR-pQCT and µCT measurements.

Results: All of the standard HR-pQCT microstructural measurements were significantly different from

those of µCT at both radius and tibia (Table 1). The HR-pQCT standard evaluation parameters (BV/TVd,

Tb.N*, Tb.Th and Tb.Sp) and direct measurement parameters (BV/TV, Tb.N*, Tb.Th* and Tb.Sp*)

correlate significantly and most of them strongly with the corresponding gold-standard µCT

measurements (r=0.56~0.96) at the radius and tibia. Significant correlations were also found for BS/BV,

Conn.D and SMI between direct and µCT measurements (r=0.72~0.92), at the radius and tibia. ITS

measures based on HR-pQCT images were significantly different from those based on registered gold-

standard µCT images. HR-pQCT measures of pBV/TV, aBV/TV, pBV/BV, rBV/TV, pTb.N, pTb.Th and rTb.Th

were found strongly to moderately correlated with those of µCT measures at the radius and tibia

(r=0.65~0.92). However, there were no correlations for rTb.N, R-R Junc.D and P-R Junc.D at the radius

and rTb.ℓ, P-R Junc.D and R-R Junc.D at the tibia between HR-pQCT and µCT image. The HR-pQCT based

FEA predications were found to be excellently correlated with those of the µCT predications and

mechanical testing results (r=0.96~0.98) at radius and tibia. HR-pQCT measurements of the standard

region only moderately correlated with whole bone stiffness at both radius and tibia (Table 2). The

correlations between the HR-pQCT measurements and whole bone stiffness were found to be the

highest at the distal section for both radius and tibia. Among the HR-pQCT parameters at distal section,

average BMD and trabecular BMD were most highly correlated with whole bone stiffness at the tibia

(r=0.93). Similarly, trabecular BMD had the highest correlation with whole bone stiffness at the radius

(r=0.9).

Discussion: The accuracy of HR-pQCT and HR-pQCT based ITS morphological analysis of the standard

clinical interest region was fully examined by comparing with gold-standard high resolution µCT and

direct mechanical testing measures at both the radius and tibia. Although differed, the HR-pQCT and HR-

pQCT based ITS morphological measurements were strongly correlated with those of µCT

measurements. pBV/TV and aBV/TV, two parameters that significantly contribute to bone strength,

correlate the highest with gold-standard µCT measures. The applications of these two parameters would

provide important additional insights in current clinical HR-pQCT studies. The moderate correlations

between the HR-pQCT measurements from standard clinical region and whole bone stiffness suggested

that the morphological parameters of the HR-pQCT scan region were not representative of the whole

bone mechanical properties. The significantly higher correlations between the HR-pQCT measures and

whole bone stiffness at the most distal section indicated that the clinical HR-pQCT scanning region

should consider moving toward distal direction to better represent the whole bone mechanics.

Significance: HR-pQCT and HR-pQCT based ITS morphological evaluation has the potential to be the

clinical standard for microstructural evaluations. The standard HR-pQCT scans should include more from

distal end to better represent whole bone quality.

ORS 2015 Annual Meeting

Poster No: 1504