Biomarkers of Bone Turnover Identify Subsets of Chronic Kidney Disease Patients at High Risk for Fracture

Abstract:

Background:We sought to identify biomarkers that indicated low turnover on bone histomorphometry in CKD patients, and subsequently determined if this panel identified differential risk for fractures in community-living older adults.

Methods:Among CKD patients who underwent iliac crest bone biopsies and histomorphometry, we evaluated candidate biomarkers to differentiate low turnover from other bone disease. We applied this biomarker panel to 676 participants in the Health ABC study with eGFR<60 mL/min/1.73m2who were followed for fracture. Cox proportional hazards models evaluated the association of BMD with fracture risk and determined whether biomarker-defined low bone turnover modified fracture risk at any level of BMD.

Results: In 58 CKD patients age 66±13 years, 48% female, with mean eGFR 48±10 mL/min/1.73m2who underwent bone biopsy, lower fibroblast growth factor (FGF)-23, higher ɑ-klotho, and lower parathyroid hormone (PTH) indicated low bone turnover in accordance with bone histomorphometry parameters (individual AUC=0.7, 0.7, and 0.6, respectively; sensitivity=31%, specificity=100%). In Health ABC, 676 participants with CKD were 75±3 years old, 51% female, with mean eGFR 48±10 mL/min/1.73m2. For every standard deviation lower BMD at baseline, there was a 6-fold higher fracture risk in persons with biomarker-defined low turnover (HR 5.72 [95% CI 2.67, 12.25]) vs. a 2-fold higher risk in remaining individuals (HR 2.23 [95% CI 1.67, 2.97]) (pinteraction=0.053).

Conclusions: In CKD patients who underwent bone biopsy, lower FGF-23, higher ɑ-klotho, and lower PTH together had high specificity for identifying low bone turnover. When applied to older individuals with CKD, BMD was more strongly associated with fracture risk in those with biomarker-defined low turnover.

Supplemental Table Presented Here: When the bone turnover biomarkers were evaluated individually, none of the interactions were statistically significant, yet the point estimate for fracture risk was consistently higher in the group contributing individuals to the low bone turnover subset.