High-sensitivity C-reactive protein and risk of nontraumatic fractures in the Bruneck study

Arch Intern Med. 2006 Dec;166(22):2495-501. doi: 10.1001/archinte.166.22.2495.


Background: Chronic inflammatory diseases are associated with bone loss and an enhanced fracture risk. It is unknown, however, whether low-grade inflammation in healthy individuals, as estimated by the high-sensitivity C-reactive protein (hs-CRP) level, interferes with bone metabolism and affects the risk of nontraumatic fractures.

Methods: Lifetime bone fractures were carefully recorded in the cohort of the population-based Bruneck Study (n = 919) along with information on the date of occurrence and associated circumstances. The serum level of hs-CRP was measured from blood samples collected during the 1990 baseline examination and the 1995, 2000, and 2005 follow-up examinations. In addition, lifestyle and demographic characteristics, bone ultrasonographic data at the heel, and variables of bone metabolism were assessed.

Results: Between September 1, 1990, and August 31, 2005, 69 subjects experienced nontraumatic hip or vertebral fractures. The incidence of nontraumatic fractures was 1.3, 3.8, and 13.9 per 1000 person-years in the tertile groups for hs-CRP. In multivariate pooled logistic regression analysis, the adjusted relative risk (95% confidence interval) of nontraumatic fracture in the highest vs lowest tertile group for hs-CRP was 9.4 (3.6-24.8) (P < .001). The exclusion of subjects with cardiovascular disease, dementia, malignancies, and chronic inflammatory disease had little effect on the results obtained. The hs-CRP level was unrelated to ultrasonographic measures of bone density, but showed an inverse relation to laboratory markers of bone turnover, like beta-crosslaps and osteocalcin concentration (P < .001).

Conclusions: The hs-CRP level is a significant and independent risk predictor of nontraumatic fracture. This finding is consistent with the hypothesis of a tight interplay between low-grade inflammation and bone turnover.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Bone Density
  • C-Reactive Protein / analysis*
  • Female
  • Fractures, Spontaneous / blood
  • Fractures, Spontaneous / epidemiology*
  • Fractures, Spontaneous / physiopathology
  • Hip Fractures / epidemiology*
  • Hip Fractures / physiopathology
  • Humans
  • Inflammation / epidemiology
  • Life Style
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Risk Assessment
  • Spinal Fractures / epidemiology*
  • Spinal Fractures / physiopathology


  • C-Reactive Protein