Virtual bone biopsy: time-lapse high-resolution peripheral quantitative computed tomography provides noninvasive comprehensive skeletal assessment

PURPOSE OF REVIEW: Skeletal complications are a pressing concern across prevalent chronic endocrine and cardiovascular conditions. Patient-specific skeletal assessment encompassing bone remodeling dynamics, density, geometry, microarchitecture, and strength are essential for elucidating underlying pathogenesis and informing treatment strategies. High-resolution peripheral quantitative computed tomography (HR-pQCT) accurately assesses three-dimensional bone density, geometry, microarchitecture, and strength in vivo. Time-lapse analysis enables noninvasive investigations into dynamic bone remodeling processes by longitudinally tracking voxel-level bone gain and loss. Integrating time-lapse analysis with HR-pQCT ('time-lapse HR-pQCT') provides a comprehensive skeletal assessment - virtual bone biopsy - that is accessible, noninvasive, and reliable. RECENT FINDINGS: Time-lapse analysis was validated for in vivo skeletal assessment in microCT-based preclinical studies two decades ago. Recently, clinical time-lapse HR-pQCT research has demonstrated its feasibility in assessing bone turnover in patients with chronic kidney disease, and in characterizing spatial mapping of long-term bone gain/loss in response to bone-targeted drugs, mechanical loading, and disease/injury. Nevertheless, future challenges remain, including validation against bone biopsy with quantitative histomorphometry, comparisons to established circulating bone turnover biomarkers, and adaptation for pediatric populations. SUMMARY: Time-lapse HR-pQCT is a skeletal assessment capable of evaluating and longitudinally monitoring changes in bone remodeling dynamics, density, geometry, microarchitecture, and biomechanics. We advocate for its broader implementation, provided that rigorous validation and ongoing methodological optimization are ensured.