title: Dissecting the relationship between high-sensitivity serum C-reactive protein and increased fracture risk: the Rotterdam Study.
abstract: Serum high-sensitivity C-reactive protein (CRP) is an inflammatory biomarker. We investigated the relationship between CRP and bone health in the Rotterdam Study. Serum high-sensitivity CRP was associated with fracture risk and lower femoral neck bending strength. Mendelian randomization analyses did not yield evidence for this relationship being causal.
  
  
  BACKGROUND
  Inflammatory diseases are associated with bone pathology, reflected in a higher fracture risk. Serum high-sensitivity CRP is an inflammatory biomarker. We investigated the relationship between CRP and bone mineral density (BMD), hip bone geometry, and incident fractures in the Rotterdam Study, a prospective population-based cohort.
  
  
  METHODS
  At baseline, serum high-sensitivity CRP was measured. A weighted genetic risk score was compiled for CRP based on published studies (29 polymorphisms; Illumina HumanHap550 Beadchip genotyping and HapMap imputation). Regression models were reported per standard deviation increase in CRP adjusted for sex, age, and BMI. Complete data was available for 6,386 participants, of whom 1,561 persons sustained a fracture (mean follow-up, 11.6 years).
  
  
  RESULTS
  CRP was associated with a risk for any type of fracture [hazard ratio (HR) = 1.06; 95 % confidence interval (CI), 1.02-1.11], hip fractures (HR = 1.09; 1.02-1.17) and vertebral fractures [odds ratio (OR) = 1.34; 1.14-1.58]. An inverse relationship between CRP levels and section modulus (-0.011 cm(3); -0.020 to -0.003 cm(3)) was observed. The combined genetic risk score of CRP single nucleotide polymorphisms (SNPs) was associated with serum CRP levels (p = 9 × 10(-56)), but not with fracture risk (HR = 1.00; 0.99-1.00; p = 0.23).
  
  
  CONCLUSIONS
  Serum high-sensitivity CRP is associated with fracture risk and lower bending strength. Mendelian randomization analyses did not yield evidence for this relationship being causal. Future studies might reveal what factors truly underlie the relationship between CRP and fracture risk.
authors: Department of Internal Medicine, Erasmus MC, P.O. Box 2040 ee5-79, 3000 CA, Rotterdam, The Netherlands.
authors: L
authors: L
authors: Oei
authors: N
authors: N
authors: Campos-Obando
authors: A
authors: A
authors: Dehghan
authors: E H G
authors: EH
authors: Oei
authors: L
authors: L
authors: Stolk
authors: J B J
authors: JB
authors: van Meurs
authors: A
authors: A
authors: Hofman
authors: A G
authors: AG
authors: Uitterlinden
authors: O H
authors: OH
authors: Franco
authors: M C
authors: MC
authors: Zillikens
authors: F
authors: F
authors: Rivadeneira
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D015519:Bone Density / Q000502:physiology; D002097:C-Reactive Protein / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D005260:Female; D005272:Femur Neck / Q000503:physiopathology; D005838:Genotype; D006801:Humans; D015994:Incidence; D008159:Lumbar Vertebrae / Q000503:physiopathology; D008297:Male; D057182:Mendelian Randomization Analysis; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D058866:Osteoporotic Fractures / Q000097:blood* / Q000453:epidemiology* / Q000235:genetics / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D018570:Risk Assessment / Q000379:methods
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein