High-sensitivity C-reactive protein and risk of nontraumatic fractures in the Bruneck study.
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.
Schett
Georg
G
Department of Internal Medicine III and Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany. Georg.Schett@med3.imed.uni-erlangen.de
Kiechl
Stefan
S
Weger
Siegfried
S
Pederiva
Angelo
A
Mayr
Agnes
A
Petrangeli
Manuele
M
Oberhollenzer
Friedrich
F
Lorenzini
Rolando
R
Redlich
Kurt
K
Axmann
Roland
R
Zwerina
Jochen
J
Willeit
Johann
J
D000328:Adult; D000368:Aged; D015519:Bone Density; D002097:C-Reactive Protein / Q000032:analysis*; D005260:Female; D005598:Fractures, Spontaneous / Q000097:blood / Q000453:epidemiology* / Q000503:physiopathology; D006620:Hip Fractures / Q000453:epidemiology* / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000453:epidemiology; D008019:Life Style; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018570:Risk Assessment; D016103:Spinal Fractures / Q000453:epidemiology* / Q000503:physiopathology
D002097:C-Reactive Protein