CKD Stages, Bone Metabolism Markers, and Cortical Porosity Index: Associations and Mediation Effects Analysis

Chronic kidney disease (CKD) has a significant negative impact on bone health. However, the mechanisms of cortical bone deterioration and cortical porosity enlargement caused by CKD have not been fully described. We therefore examined the association of CKD stages with cortical porosity index (PI), and explored potential mediators of this association. Double-echo ultrashort echo-time magnetic resonance imaging (UTE MRI) provides the possibility of quantifying cortical porosity in vivo. A total of 95 patients with CKD stages 2-5 underwent 3D double-echo UTE-Cones MRI (3.0T) of the midshaft tibia to obtain the PI. PI was defined as the ratio of the image signal intensity of a sufficiently long echo time (TE) to the shortest achievable TE. Parathyroid hormone (PTH), β-CrossLaps (β-CTX), total procollagen type I amino-terminal propeptide (T-P1NP), osteocalcin (OC), 25-hydroxyvitamin D (25OHD), and lumbar bone mineral density (BMD) were measured within one week of the MRI. Partial correlation analysis was performed to address associations between PI, eGFR and potential mediators (PTH, β-CTX, T-P1NP, OC, 25OHD, BMD, and T-score). Multiple linear regression models were used to assess the association between CKD stages and PI value. Then, a separate exploratory mediation analysis was carried out to explore the impact of CKD stages and mediators on the PI value. The increasing CKD stages were associated with a higher PI value (P(trend) < 0.001). The association of CKD stages and PI mediated 34.4% and 30.8% of the total effect by increased PTH and β-CTX, respectively. Our study provides a new idea to monitor bone health in patients with CKD, and reveals the internal mechanism of bone deterioration caused by CKD to some extent.