Kidney Week

Abstract: TH-OR026

A Serum Biomarker Panel of Low Bone Turnover Identifies Higher Fracture Risk in Community Dwelling Individuals with CKD

Session Information

• CKD-MBD: Phosphorus, FGF-23, and Trials
  October 25, 2018 | Location: 33C, San Diego Convention Center
  Abstract Time: 05:30 PM - 05:42 PM

Category: Bone and Mineral Metabolism

• 402 Bone and Mineral Metabolism: Clinical

Authors

• Hughes-Austin, Jan M., University of California, San Diego, La Jolla, California, United States

Jan M. Hughes-Austin, PhD

• Katz, Ronit, University of Washington, Seattle, Washington, United States

Ronit Katz,

• Semba, Richard, Johns Hopkins University, Baltimore, Maryland, United States

Richard Semba,

• Bauer, Doug, UCSF, San Francisco, California, United States

Doug Bauer,

• Sarnak, Mark J., Tufts Medical Center, Boston, Massachusetts, United States

Mark J. Sarnak,

• Shlipak, Michael, San Francisco VA Medical Center, San Francisco, California, United States

Michael Shlipak,

• Lima, Florence, University of Kentucky, Lexington, Kentucky, United States

Florence Lima,

• Malluche, Hartmut H., University of Kentucky, Lexington, Kentucky, United States

Hartmut H. Malluche,

• Ix, Joachim H., UCSD , San Diego, California, United States

Joachim H. Ix,

Background

Individuals with chronic kidney disease (CKD) can have low or high turnover bone disease, either of which could lead to low bone mineral density (BMD). We identified a panel of biomarkers on biopsy that marked low turnover bone disease. Then, in a community-dwelling cohort of persons with CKD, we determined if this panel identified a subset at high risk for fracture.

Methods

Among 58 patients with CKD stage 2-5 who had undergone bone biopsies, we used CART analysis to define a panel of serum biomarkers that could differentiate low turnover from non-low turnover bone disease. We then applied this panel of biomarkers to 676 participants in the Health ABC study who had eGFR < 60 mL/min/1.73m²and had BMD measurements at baseline. We used Cox proportional hazards models to evaluate the association of BMD with fracture risk and to determine whether biomarker defined low- vs non-low bone turnover modified the risk of fracture.

Results

CART analysis in 58 CKD patients defined cut-off points for differentiation of low bone turnover: PTH below the median, soluble a-klotho above the median, and FGF-23 below the median (AUC = 0.6, 0.7, and 0.7, respectively). Among the 676 participants with CKD in Health ABC, mean age was 75±3 years, and were 51% female and 36% African-American. Average eGFR was 48±10 mL/min/1.73m². For every standard deviation (SD=0.16 g/cm²) lower hip BMD at baseline there was higher risk for hip (HR 2.5 (1.9, 3.2)) and spine fractures (HR 1.6 (1.3, 2.1 )) during follow-up. This risk differed in individuals with biomarker defined low vs non-low bone turnover (p_interactionhip= 0.05; spine= 0.07), where individuals characterized as having low bone turnover had higher risk of fracture (Table)

Conclusion

In individuals with CKD, a biomarker panel of PTH, a-klotho, and FGF-23 can be used to identify individuals more likely to have low bone turnover. In such individuals, the relationship of low BMD with risk for incident hip and spine fractures is much higher than in others.

Funding

• Other NIH Support