A need for normalization of bone histomorphometry parameters in chronic kidney disease

Bone histomorphometry remains the only method capable of providing a direct, tissue-level assessment of bone remodeling, mineralization, and bone volume in patients with chronic kidney disease (CKD). The introduction of the TMV (turnover, mineralization, volume) classification represented a major conceptual advance by offering a unified framework to describe the heterogeneous skeletal abnormalities of renal osteodystrophy. However, nearly two decades after its introduction, the clinical and research application of the TMV system remains inconsistent. This limitation reflects not conceptual shortcomings of the framework, but the persistent lack of robust and standardized normative reference values for human bone tissue.

Recent consensus statements and analytical studies have highlighted substantial inter-center variability in the use of the TMV classification. Differences in reference standards, reporting practices, and cut-off definitions significantly affect the diagnosis and categorization of renal osteodystrophy. Emerging initiatives have proposed ethically acceptable strategies to generate contemporary normative datasets, including the use of bone biopsies from living kidney donors. In parallel, increasing attention has been drawn to the biological importance of cortical bone histomorphometry, which remains underrepresented and methodologically inconsistent across studies.

Normalization of histomorphometric parameters - encompassing both trabecular and cortical compartments - remains the principal unresolved challenge. Addressing this issue is essential to enhance the clinical and scientific impact of bone histomorphometry in CKD and to support its integration with biomarkers, imaging techniques, and data-driven approaches.