Non-invasive Diagnostic Tests for Renal Osteodystrophy

Chronic Kidney Disease – Mineral Bone Disorder (CKD-MBD) is a common complication of advanced chronic kidney disease (CKD). Bone abnormalities of CKD-MBD are known as renal osteodystrophy (ROD) and are characterised by abnormal bone turnover and mineralization. ROD results in bone microstructural and mechanical changes which increases bone fragility. Thus, fracture risk is increased and subsequent mortality is high in these patients. Correct diagnosis of ROD is required before potential treatment to reduce fracture risk can be commenced. This can only be done with bone biopsy which is the gold standard test but this is an invasive and painful procedure. We conducted a cross sectional study with the primary aim of testing new non-invasive tests to diagnose and classify ROD as shown on bone biopsy. Sixty-nine advanced CKD stages 4-5D and their age and gender-matched healthy controls were recruited. All participants had blood samples collected for bone turnover markers (BTMs) analysis and had bone scan using high resolution peripheral quantitative computed tomography (HR-pQCT). Forty-three CKD patients had trans-iliac bone biopsy samples evaluable for histomorphometry. We also used a new technique using HR-pQCT to simultaneously assess bone and vascular calcification (VC) relationship in CKD. We found that advanced CKD patients have worse bone microstructure compared to controls. Importantly, BTMs such as bone alkaline phosphatase (bALP), intact procollagen type 1 N-terminal propeptide (intact PINP) and tartrate-resistant acid phosphatase 5b (TRAP5b), and bone imaging of radius using HR-pQCT were able to discriminate low bone turnover in advanced CKD patients. These non-invasive tests are robust diagnostic tools and have the potential to be translated into clinical practice. We also found that ankle arteries VC was associated with worse bone microstructure of cortical bone at the tibia. These non-invasive tests could be instrumental in further research into treatment to reduce fracture risk in advanced CKD.