Predictive Power of Bone Turnover Biomarkers to Estimate Bone Mineral Density after Kidney Transplantation with or without Denosumab: A post hoc Analysis of the POSTOP Study

Kidney Blood Press Res. 2020;45(5):758-767. doi: 10.1159/000510565. Epub 2020 Sep 30.

Abstract

Background: Low bone mineral density (BMD) represents a major risk factor for bone fractures in patients with chronic kidney disease (CKD) as well as after kidney transplantation. However, modalities to solidly predict patients at fracture risk are yet to be defined. Better understanding of bone turnover biomarkers (BTMs) may close this diagnostic gap. This study strives to correlate BTMs to BMD in kidney transplant recipients.

Methods: Changes in BTMs - procollagen type I N-terminal propeptide (P1NP), bone-specific alkaline phosphatase (BSAP), β-isomer of the C-terminal telopeptide of type I collagen, and urine deoxypyridinoline/Cr - at the time of transplant and 3 months were correlated to changes in BMD measured by dual-energy X-ray absorptiometry at the time of transplant, 6, and 12 months, respectively. Half of the collective was treated with denosumab twice yearly in addition to the standard treatment with calcium and vitamin D.

Results: Changes in bone formation markers BSAP and P1NP within 3 months showed a significant negative correlation to changes in BMD at the hip within 6 months in denosumab-naïve patients. This correlation was abrogated by denosumab treatment.

Conclusions: Changes in BSAP and P1NP showed promise in short-term prediction of BMD. We suggest further trials expanding on the knowledge of these BTMs with assessment of fracture risk, sequential measurements of BTMs within the first 6 months, and the additional use of computed tomography to assess BMD.

Keywords: Biomarkers of bone turnover; Bone mineral metabolism; Denosumab; Kidney transplantation.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Alkaline Phosphatase / analysis
  • Biomarkers / analysis
  • Bone Density / drug effects*
  • Bone Density Conservation Agents / therapeutic use*
  • Bone Remodeling / drug effects*
  • Collagen Type I / analysis
  • Denosumab / therapeutic use*
  • Female
  • Humans
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Peptide Fragments / analysis
  • Procollagen / analysis

Substances

  • Biomarkers
  • Bone Density Conservation Agents
  • Collagen Type I
  • Peptide Fragments
  • Procollagen
  • procollagen Type I N-terminal peptide
  • Denosumab
  • ALPL protein, human
  • Alkaline Phosphatase