Multi-site phantomless bone mineral density from clinical quantitative computed tomography in males

Volumetric bone mineral density (vBMD) is commonly assessed using QCT. Although standard vBMD calculation methods require phantom rods that may not be available, internal-reference phantomless (IPL) and direct measurements of Hounsfield units (HU) can be used to calculate vBMD in their absence. Yet, neither approach has been systemically assessed across skeletal sites, and HU need further validation as a vBMD proxy. This study evaluated the accuracy of phantomless methods, including IPL and regression-based phantomless (RPL) calibration using HU to calculate vBMD, compared to phantom-based (PB) methods. vBMD from QCT scans of 100 male post-mortem human subjects (PMHS) was calculated using site-specific PB calibration at multiple skeletal sites throughout the body. A development sample of 50/100 PMHS was used to determine site-specific reference material density for IPL calibration and RPL equations. Reference densities and equations from the development sample were used to calculate IPL and RPL vBMD on the remaining 50/100 PMHS for method validation. PB and IPL/RPL vBMD were not significantly different (p > .05). Univariate regressions between PB and IPL/RPL vBMD were universally significant (p < 0.05), except for IPL Rad-30 (p = 0.078), with a percent difference across all sites of 6.97% ± 5.95% and 5.22% ± 4.59% between PB and IPL/RPL vBMD, respectively. As vBMD increased, there were weaker relationships and larger differences between PB vBMD and IPL/RPL vBMD. IPL and RPL vBMD had strong relationships with PB vBMD across sites (R² = 97.99, R² = 99.17%, respectively), but larger residual differences were found for IPL vBMD. As the accuracy of IPL/RPL vBMD varied between sites, phantomless methods should be site-specific to provide values more comparable to PB vBMD. Overall, this study suggests that RPL calibration may better represent PB vBMD compared to IPL calibration, increases the utility of opportunistic QCT, and provides insight into bone quality and fracture risk.