Cancellous Bone Volume Is an Indicator for Trabecular Bone Connectivity in Dialysis Patients

Background and objectives: A new assessment system for bone histology, termed the turnover-mineralization-volume system, is advocated for patients with chronic kidney disease-related mineral and bone disorder. The system measures cancellous bone volume (BV/TV) as a third major evaluation axis; however, the physiologic significance of BV/TV remains unclear.Design, setting, participants, & measurements: Conventional bone histomorphometry was performed in 75 iliac bone samples obtained from dialysis patients. In 47 of the 75 samples, the remaining samples were subjected to direct microfocus x-ray computed tomographic observation. Quantitative morphologic examinations, including micro-bone mineral densitometry, and marrow space star volume, Euler number, and node-strut analyses, were performed in the virtual three-dimensional space reconstructed from the microfocus x-ray computed tomographic images.Results: The levels of BV/TV were comparable in each of the conventional bone histomorphometric criteria. No significant correlations were found between BV/TV and other parameters. Two- and three-dimensional BV/TVs were significantly correlated with cancellous bone mass but not with cortical bone thickness or cortical bone mass. Two- and three-dimensional BV/TVs were significantly correlated with trabecular bone connectivity as determined by marrow space star volume, Euler number, and node-strut analyses.Conclusions: In dialysis patients, BV/TV is not dependent on bone turnover or bone mineralization. BV/TV is unlikely to indicate the balance between bone formation and bone resorption. Instead, it reflects trabecular bone connectivity, and improved trabecular bone connectivity is physiologically beneficial in terms of bone quality. The turnover-mineralization-volume system offers an advantage over the conventional system for the assessment of bone quality.Chronic kidney disease (CKD) is associated with various forms of metabolic bone disorders (1), which are accompanied by mineral and parathyroid metabolic abnormalities. These abnormalities are considered to be symptoms of a systemic syndrome called CKD-related mineral and bone disorder (CKD-MBD) (2).The current gold standard for assessing bone status in CKD-MBD is bone histology (3). Bone histology is conventionally classified into five categories on the basis of tetracycline labeling-dependent bone histomorphometric findings. In this conventional classification, the histologic findings are classified according to two major assessment criteria: bone turnover and bone mineralization (4). However, the Kidney Disease: Improving Global Outcomes recently advocated the addition of cancellous bone volume (BV/TV) as a third major evaluation criterion for bone histology in CKD-MBD patients. The concept of this system, called turnover-mineralization-volume (TMV) classification (2,5), has become widely recognized.The Kidney Disease: Improving Global Outcomes considers BV/TV to be the result of a balance between bone formation and bone resorption. However, the target for bone histomorphometric analysis is currently confined to cancellous bone area in most cases. Therefore, BV/TV actually indicates the balance between cancellous bone formation and cancellous bone resorption, which may not be identical to the balance between bone formation and bone resorption. The significance of knowing the balance between cancellous bone formation and cancellous bone resorption remains unknown.Thus, the justification of the use of BV/TV in the TMV system has not yet been demonstrated. First, it has not been confirmed whether BV/TV is independent of bone turnover and bone mineralization. If significant associations were found between these factors, the significance of BV/TV as an evaluation criterion would be limited.Moreover, the reason why BV/TV should be included in this classification has not been fully explained. It must be clarified whether BV/TV can theoretically enhance the balance between bone formation and bone resorption. It is unknown whether BV/TV reflects cortical bone mass, which is the major determinant of bone strength. Other factors that affect bone strength are referred to as bone quality (6), which includes the chemical and structural properties. In terms of chemical properties, bone turnover and bone mineralization can be assessed by conventional bone histomorphometry. However, it is unknown whether BV/TV is associated with the structural properties of bone quality. The validation of the TMV system in terms of these aspects has not yet been performed.On the basis of this background, we performed three-dimensional quantitative morphologic analyses of biopsied iliac bone samples obtained from CKD stage 5D (CKD5D) patients. We performed microfocus computed tomography (MCT) and novel three-dimensional image analysis (7–9). The aims of this study were (1) to confirm whether BV/TV, a new assessment criterion applied to the TMV system, is independent of bone turnover and bone mineralization, and (2) to determine whether and/or how BV/TV could be used to predict bone strength.