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Original research article
Cardiovascular biomarkers predict fragility fractures in older adults
  1. Madeleine Johansson1,
  2. Fabrizio Ricci1,2,
  3. Giuseppe Di Martino3,
  4. Cecilia Rogmark1,4,
  5. Richard Sutton5,
  6. Viktor Hamrefors1,6,
  7. Olle Melander1,6,
  8. Artur Fedorowski1,7
  1. 1 Department of Clinical Sciences, Faculty of Medicine, Clinical Research Center, Lund University, Malmö, Sweden
  2. 2 Department of Neuroscience, Imaging and Clinical Sciences, Institute for Advanced Biomedical Technologies, ’G d’Annunzio' University, Chieti, Italy
  3. 3 Department of Medicine and Ageing Sciences, School of Hygiene and Preventive Medicine, ’G d’Annunzio' University, Chieti, Italy
  4. 4 Department of Orthopedics, Skåne University Hospital, Malmö, Sweden
  5. 5 National Heart and Lung Institute, Imperial College London, London, UK
  6. 6 Department of Internal Medicine, Skåne University Hospital, Malmö, Sweden
  7. 7 Department of Cardiology, Skåne University Hospital, Malmö, Sweden
  1. Correspondence to Dr Artur Fedorowski, Department of Cardiology, Skåne University Hospital, Malmö 214 28, Sweden; artur.fedorowski{at}


Objective To assess the role of four biomarkers of neuroendocrine activation and endothelial dysfunction in the longitudinal prediction of fragility fractures.

Methods We analysed a population-based prospective cohort of 5415 community-dwelling individuals (mean age, 68.9±6.2 years) enrolled in the Malmö Preventive Project followed during 8.1±2.9 years, and investigated the longitudinal association between C-terminal pro-arginine vasopressin (CT-proAVP), C-terminal endothelin-1 precursor fragment (CT-proET-1), the mid-regional fragments of pro-adrenomedullin (MR-proADM) and pro-atrial natriuretic peptide (MR-proANP), and incident vertebral, pelvic and extremity fractures.

Results Overall, 1030 (19.0%) individuals suffered vertebral, pelvic or extremity fracture. They were older (70.7±5.8 vs 68.4±6.3 years), more likely women (46.9% vs 26.3%), had lower body mass index and diastolic blood pressure, were more often on antihypertensive treatment (44.1% vs 38.4%) and had more frequently history of fracture (16.3% vs 8.1%). Higher levels of MR-proADM (adjusted HR (aHR) per 1 SD: 1.51, 95% CI 1.01 to 2.28, p<0.001) and MR-proANP (aHR: 1.23, 95% CI 1.05 to 1.45, p<0.001) were independently associated with increased risk of any fracture. The fracture risk increased linearly across MR-proANP quartiles. Individuals who were in the top quartile of all four biomarkers had a significant higher risk of fracture at any site (aHR: 2.32, 95% CI 1.86 to 2.91), vertebral fracture (aHR: 3.16, 95% CI 1.97 to 5.07) and femoral fracture (aHR: 2.35, 95% CI 1.64 to 3.36).

Conclusions Elevated levels of MR-proADM and MR-proANP independently predict fragility fractures in older adults. In subjects with top quartile levels of all four biomarkers there is a twofold to threefold increase in risk of vertebral and femoral fractures.

  • fractures
  • biomarkers
  • vasopressin
  • adrenomedullin
  • endothelin-1
  • atrial natriuretic peptide
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  • Funding This work was supported by grants from the Swedish Medical Research Council, the Swedish Heart and Lung Foundation, the Medical Faculty of Lund University, Malmö University Hospital, the Albert Påhlsson Research Foundation, the Crafoord Foundation, the Ernhold Lundströms Research Foundation, the Region Skane, the Hulda and Conrad Mossfelt Foundation, the King Gustaf V and Queen Victoria Foundation, The Wallenberg Foundation and the Lennart Hanssons Memorial Fund.

  • Competing interests AF reports personal fees from Cardiome and a patent Thermo Fisher pending outside the submitted work. RS reports personal fees and other from Medtronic, Abbott Laboratories outside the submitted work; performs consultancy for Medtronic; is a member of the speakers' bureau of Abbott Laboratories; and is a shareholder in Boston Scientific, Edwards Lifesciences and AstraZeneca.

  • Patient consent Not required.

  • Ethics approval Regional Ethical Review Board of Lund University, Sweden.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement No additional data are available.

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