Multisite longitudinal calibration of HR-pQCT scanners and precision in osteogenesis imperfecta

wbldb

Mikolajewicz, Nicholas^1,2; Zimmermann, Elizabeth A.^1,2,3; Rummler, Maximilian^1,2; Hosseinitabatabaei, Seyedmahdi^1,2,4; Julien, Catherine^1,2; Glorieux, Francis H.¹; Rauch, Frank¹; Willie, Bettina M.^1,2,4

Multisite longitudinal calibration of HR-pQCT scanners and precision in osteogenesis imperfecta

Bone. June 2021;147:115880

©2021 Elsevier Inc. All rights reserved.

Affiliations

¹Research Centre, Shriners Hospital for Children-Canada, Montreal, Canada

²Department of Pediatric Surgery, McGill University, Montreal, Canada

³Faculty of Dentistry, McGill University, Montreal, Canada

⁴Department of Biomedical Engineering, McGill University, Montreal, Canada
Abstract and keywords

Background: For high-resolution peripheral quantitative computed tomography (HR-pQCT) to be used in longitudinal multi-center studies to assess disease and treatment effects, data must be aggregated across multiple timepoints and scanners. This requires an understanding of the factors contributing to scanner precision, and multi-scanner cross-calibration procedures, especially for clinical populations with severe phenotypes, like osteogenesis imperfecta (OI).

Methods: To address this, we first evaluated single- and multi-center short- and long-term precision errors of standard HR-pQCT parameters. Two imaging phantoms were circulated among 13 sites (7 XtremeCT and 6 XtremeCT2) and scanned in triplicate at 3 timepoints/site. Additionally, duplicate in vivo radial and tibial scans were acquired in 29 individuals with OI. Secondly, we investigated subject- and scanner-related factors that contribute to precision errors using regression analysis. Thirdly, we proposed a reference site selection criterion for multisite cross-calibration and demonstrated the external validity of phantom-based calibrations.

Results: Our results show excellent short-term single-site precision in both phantoms (CV % < 0.5%) and in density, microarchitecture and finite element parameters of OI participants (CV % = 0.75 to 1.2%). In vivo reproducibility significantly improved with (i) cross sectional area image registration versus no registration and (ii) scans with no motion artifacts. While reproducibility was similar across OI subtypes and anatomical sites, XtremeCT2 scanners achieved ~2.5% better precision than XtremeCT for trabecular parameters. Finally, we demonstrate that multisite longitudinal precision errors resulting from inconsistencies between scanners can be partially corrected through scanner cross-calibration.

Conclusions: This study is the first to assess long-term reproducibility and cross-calibration in a study using first and second generation HR-pQCT scanners. The results presented in this context provide timely guidelines for future use of this powerful clinical imaging modality in multi-center longitudinal clinical trials.

Keywords: Statistical methods; HR-pQCT; Osteogenesis imperfecta; Precision; Multisite; Cross-calibration
Links

DOI: 10.1016/j.bone.2021.115880

PubMed: 33561589

WoS: 000643707100012
History

Received: 2020-09-27

Revised: 2021-02-3

Accepted: 2021-02-3

Online: 2021-02-6

Cited Works (24)

Year	Entry
2012	Pialat JB, Burghardt AJ, Sode M, Link TM, Majumdar S. Visual grading of motion induced image degradation in high resolution peripheral computed tomography: impact of image quality on measures of bone density and micro-architecture. Bone. January 2012;50(1):111-118.
2004	Rauch F, Glorieux FH. Osteogenesis imperfecta. Lancet. April 24, 2004;363(9418):1377-1385.
2018	Whittier DE, Manske SL, Kiel DP, Bouxsein M, Boyd SK. Harmonizing finite element modelling for non-invasive strength estimation by high-resolution peripheral quantitative computed tomography. J Biomech. October 26, 2018;80:63-71.
2010	Burghardt AJ, Kazakia GJ, Sode M, de Papp AE, Link TM, Majumdar S. A longitudinal HR-pQCT study of alendronate treatment in postmenopausal women with low bone density: relations among density, cortical and trabecular microarchitecture, biomechanics, and bone turnover. J Bone Miner Res. December 2010;25(12):2558-2571.
2015	Manske SL, Zhu Y, Sandino C, Boyd SK. Human trabecular bone microarchitecture can be assessed independently of density with second generation HR-pQCT. Bone. October 2015;79:213-221.
1998	Laib A, Häuselmann HJ, Rüegsegger P. In vivo high resolution 3D-QCT of the human forearm. Technol Health Care. 1998;6(5-6):329-337.
2020	Mikolajewicz N, Bishop N, Burghardt AJ, Folkestad L, Hall A, Kozloff KM, Lukey PT, Molloy‐Bland M, Morin SN, Offiah AC, Shapiro J, van Rietbergen B, Wager K, Willie BM, Komarova SV, Glorieux FH. HR‐pQCT measures of bone microarchitecture predict fracture: systematic review and meta‐analysis. J Bone Miner Res. March 2020;35(3):446-459.
2020	Kemp TD, de Bakker CMJ, Gabel L, Hanley DA, Billington EO, Burt LA, Boyd SK. Longitudinal bone microarchitectural changes are best detected using image registration. Osteoporos Int. October 2020;31(10):1995-2005.
2005	Boutroy S, Bouxsein ML, Munoz F, Delmas PD. In vivo assessment of trabecular bone microarchitecture by high-resolution peripheral quantitative computed tomography. J Clin Endocrinol Metab. December 2005;90(12):6508-6515.
1995	Glüer C-C, Blake G, Lu Y, Blunt BA, Jergas M, Genant HK. Accurate assessment of precision errors: how to measure the reproducibility of bone densitometry techniques. Osteoporos Int. July 1995;5(4):262-270.
2015	Tsai JN, Uihlein AV, Burnett-Bowie S-AM, Neer RM, Zhu Y, Derrico N, Lee H, Bouxsein ML, Leder BZ. Comparative effects of teriparatide, denosumab, and combination therapy on peripheral compartmental bone density, microarchitecture, and estimated strength: the DATA-HRpQCT study. J Bone Miner Res. January 2015;30(1):39-45.
2010	Burghardt AJ, Buie HR, Laib A, Majumdar S, Boyd SK. Reproducibility of direct quantitative measures of cortical bone microarchitecture of the distal radius and tibia by HR-pQCT. Bone. September 2010;47(3):519-528.
2014	Ellouz R, Chapurlat R, van Rietbergen B, Christen P, Pialat J-B, Boutroy S. Challenges in longitudinal measurements with HR-pQCT: evaluation of a 3D registration method to improve bone microarchitecture and strength measurement reproducibility. Bone. June 2014;63:147-157.
2018	Rolvien T, Stürznickel J, Schmidt FN, Butscheidt S, Schmidt T, Busse B, Mundlos S, Schinke T, Kornak U, Amling M, Oheim R. Comparison of bone microarchitecture between adult osteogenesis imperfecta and early-onset osteoporosis. Calcif Tiss Int. November 2018;103(5):512-521.
2020	Whittier DE, Boyd SK, Burghardt AJ, Paccou J, Ghasem-Zadeh A, Chapurlat R, Engelke K, Bouxsein ML. Guidelines for the assessment of bone density and microarchitecture in vivo using high-resolution peripheral quantitative computed tomography. Osteoporos Int. September 2020;31(9):1607-1627.
2017	Bonaretti S, Majumdar S, Lang TF, Khosla S, Burghardt AJ. The comparability of HR-pQCT bone measurements is improved by scanning anatomically standardized regions. Osteoporos Int. July 2017;28(7):2115-2128.
2017	Ghasem-Zadeh A, Burghardt A, Wang X-F, Iuliano S, Bonaretti S, Bui M, Zebaze R, Seeman E. Quantifying sex, race, and age specific differences in bone microstructure requires measurement of anatomically equivalent regions. Bone. August 2017;101:206-213.
2017	Manske SL, Davison EM, Burt LA, Raymond DA, Boyd SK. The estimation of second-generation HR-pQCT from first-generation -pQCT using in vivo cross-calibration. J Bone Miner Res. July 2017;32(7):1514-1524.
2008	MacNeil JA, Boyd SK. Improved reproducibility of high-resolution peripheral quantitative computed tomography for measurement of bone quality. Med Eng Phys. July 2008;30(6):792-799.
2012	Engelke K, Stampa B, Timm W, Dardzinski B, de Papp AE, Genant HK, Fuerst T. Short-term in vivo precision of BMD and parameters of trabecular architecture at the distal forearm and tibia. Osteoporos Int. August 2012;23(8):2151-2158.
2018	Chiba K, Okazaki N, Kurogi A, Isobe Y, Yonekura A, Tomita M, Osaki M. Precision of second-generation high-resolution peripheral quantitative computed tomography: intra- and intertester reproducibilities and factors involved in the reproducibility of cortical porosity. J Clin Densitom. April–June 2018;21(2):295-302.
1999	Hildebrand T, Laib A, Müller R, Dequeker J, Rüegsegger P. Direct three-dimensional morphometric analysis of human cancellous bone: microstructural data from spine, femur, iliac crest, and calcaneus. J Bone Miner Res. July 1999;14(7):1167-1174.
2007	Buie HR, Campbell GM, Klinck RJ, MacNeil JA, Boyd SK. Automatic segmentation of cortical and trabecular compartments based on a dual threshold technique for in vivo micro-CT bone analysis. Bone. October 2007;41(4):505-515.
2019	Burt LA, Billington EO, Rose MS, Raymond DA, Hanley DA, Boyd SK. Effect of high-dose vitamin D supplementation on volumetric bone density and bone strength: a randomized clinical trial. JAMA. August 27, 2019;322(8):736-745.

Cited By (1)

Year	Entry
2022	Hosseinitabatabaei S, Mikolajewicz N, Zimmermann EA, Rummler M, Steyn B, Julien C, Rauch F, Willie BM. 3D image registration marginally improves the precision of HR-pQCT measurements compared to cross-sectional-area registration in adults with osteogenesis imperfecta. J Bone Miner Res. May 2022;37(5):908-924.