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A plasma protein-based risk score to predict hip fractures

  • Thomas R. Austin,
  • Maria Nethander,
  • Howard A. Fink,
  • Anna E. Törnqvist,
  • Diana I. Jalal,
  • Petra Buzkova,
  • Joshua I. Barzilay,
  • Laura Carbone,
  • Maiken E. Gabrielsen,
  • Louise Grahnemo,
  • Tianyuan Lu,
  • Kristian Hveem,
  • Christian Jonasson,
  • Jorge R. Kizer,
  • Arnulf Langhammer,
  • Kenneth J. Mukamal,
  • Robert E. Gerszten,
  • Bruce M. Psaty,
  • John A. Robbins,
  • Yan V. Sun,
  • Anne Heidi Skogholt,
  • John A. Kanis,
  • Helena Johansson,
  • Bjørn Olav Åsvold,
  • Rodrigo J. Valderrabano,
  • Jie Zheng,
  • J. Brent Richards,
  • Eivind Coward,
  • Claes Ohlsson

摘要

As there are effective treatments to reduce hip fractures, identification of patients at high risk of hip fracture is important to inform efficient intervention strategies. To obtain a new tool for hip fracture prediction, we developed a protein-based risk score in the Cardiovascular Health Study using an aptamer-based proteomic platform. The proteomic risk score predicted incident hip fractures and improved hip fracture discrimination in two Trøndelag Health Study validation cohorts using the same aptamer-based platform. When transferred to an antibody-based proteomic platform in a UK Biobank validation cohort, the proteomic risk score was strongly associated with hip fractures (hazard ratio per s.d. increase, 1.64; 95% confidence interval 1.53–1.77). The proteomic risk score, but not available polygenic risk scores for fractures or bone mineral density, improved the C-index beyond the fracture risk assessment tool (FRAX), which integrates information from clinical risk factors (C-index, FRAX 0.735 versus FRAX + proteomic risk score 0.776). The developed proteomic risk score constitutes a new tool for stratifying patients according to hip fracture risk; however, its improvement in hip fracture discrimination is modest and its clinical utility beyond FRAX with information on femoral neck bone mineral density remains to be determined.