Sex- and site-specific reference data for size-invariant properties using multi-stack HRpQCT.

Abstract

HRpQCT is emerging as a promising evolution to DXA for longitudinal assessment of bone properties and strength estimation beyond FN aBMD, as it provides a detailed 3D representation and separate quantification of trabecular and cortical compartments. Reference data exist for thin single stacks of 10.2 mm in second-generation HRpQCT, but these sections may not fully capture clinically relevant fracture locations and pose challenges for longitudinal monitoring due to their limited thickness. Reported parameters are mainly size-dependent properties susceptible to bias from skeletal dimensions, potentially concealing changes in bone quality at the material level. Moreover, microstructural parameters are derived from densitometric information, making them partially redundant. This study provides the first age-, sex-, and site-specific reference data for a novel multi-stack on second-generation HRpQCT at the distal radius and tibia in 381 healthy participants (144F, 237M) from a primarily Caucasian population aged 20-92 yr and identifies the size-independent parameters most sensitive to age for improved bone health assessment. Six size-independent parameters relevant for estimated mechanical properties or exhibiting short trend assessment intervals were selected as candidates for improved bone health assessment: 2 densitometric properties (total volumetric BMD, cortical volumetric BMD), 1 size-independent geometrical property (relative cortical thickness), 2 microstructural properties (trabecular degree of anisotropy, trabecular bone volume over total volume), and 1 mechanical property (apparent yield stress [^app σ _y]) estimated by homogenized finite elements. Intensive mechanical properties provided more sensitive follow-up estimations. Cortical volumetric BMD, especially in the weight-bearing tibia in women, was the most sensitive with age. Matched comparisons with single-stack counterparts demonstrated good agreement between densitometric and microstructural properties, supporting potential cross-study and cross-protocol comparisons. The present work proposes an alternative set of size-independent variables for multi-stack HRpQCT, which may offer a refined assessment of bone health and longitudinal monitoring.