Recent advances in the noninvasive diagnosis of renal osteodystrophy

Abstract

Chronic kidney disease-mineral and bone disorder (CKD-MBD) is the term used to describe a constellation of biochemical abnormalities, bone disturbances that may lead to fractures, and extraskeletal calcification in soft tissues and arteries seen in CKD. This review focuses on the noninvasive diagnosis of renal osteodystrophy, the term used exclusively to define the bone pathology associated with CKD. Transiliac bone biopsy and histomorphometry with double-labeled tetracycline or its derivatives remains the gold standard for diagnosis of renal osteodystrophy. However, histomorphometry provides a 'window' into bone only at a single point in time, and is not clinically practical for studying continuous changes in bone morphology. Furthermore, the etiology of fractures in CKD is multifactorial and not fully explained by histomorphometry findings alone. The propensity of a bone to fracture is determined by bone strength, which is affected by bone mass and bone quality; the latter is a term used to describe the structure and composition of bone. Bone quantity is traditionally assessed by dual X-ray absorptiometry (DXA) and CT-based methods. Bone quality is more difficult to assess noninvasively, but newer techniques are emerging and are described in this review. Ultimately, the optimal diagnostic strategy for renal osteodystrophy may be a combination of multiple imaging techniques and biomarkers that are specific to each gender and race in CKD, with a goal of predicting fracture risk and optimizing therapy.

Figure 1. Determinants of Bone Strength

Legend: Bone strength is comprised of both bone density and quality. Bone quality refers to bone turnover, microarchitecture, micro-fractures, mineralization as well as the composition of mineral matrix. Trabecular microarchitecture includes trabecular thickness, the ratio of plates and rods, their connectivity and spacing. Cortical microarchitecture includes cortical thickness, porosity and bone size. Composition of mineral matrix includes changes in the cross-linking of type 1 collagen and alterations in the size and structure of bone mineral. Bones accumulate microfractures over time even with normal physical activity. The ability to repair these affects bone quality.

Figure 2

The figure is a graphical example of how the TMV system provides more information than the present, commonly used classification scheme. Each axis represents one of the descriptors in the TMV classification: turnover (from low to high), mineralization (from normal to abnormal), and bone volume (from low to high). Individual patient parameters could be plotted on the graph, or means and ranges of grouped data could be shown. For example, many patients with renal osteodystrophy cluster in areas shown by the bars. The red bar (OM, osteomalacia) is currently described as low-turnover bone with abnormal mineralization. The bone volume may be low to medium, depending on the severity and duration of the process and other factors that affect bone. The green bar (AD, adynamic bone disease) is currently described as low-turnover bone with normal mineralization, and the bone volume in this example is at the lower end of the spectrum, but other patients with normal mineralization and low turnover will have normal bone volume. The yellow bar (mild HPT, mild hyperparathyroid-related bone disease) and purple bar (OF, osteitis fibrosa or advanced hyperparathyroid-related bone disease) are currently used distinct categories, but in actuality represent a range of abnormalities along a continuum of medium to high turnover, and any bone volume depending on the duration of the disease process. Finally, the blue bar (MUO, mixed uremic osteodystrophy) is variably defined internationally. In the present graph, it is depicted as high-turnover, normal bone volume, with abnormal mineralization. In summary, the TMV classification system more precisely describes the range of pathologic abnormalities that can occur in patients with CKD. From Moe S, Drueke T, Cunningham J, et al. Definition, evaluation, and classification of renal osteodystrophy: A position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2006; 69(11):1945–53.