Soluble RANKL and risk of nontraumatic fracture.
BACKGROUND
The receptor activator of nuclear factor kappaB ligand (RANKL) is essential for osteoclast and, possibly, osteoblast activation and may represent a key link between bone formation and resorption.


OBJECTIVE
To determine the relationship between serum level of RANKL and the risk of nontraumatic fracture.


METHODS
As part of a prospective population-based study conducted in Bruneck, Italy, we recorded all fractures that occurred between 1990 and 2000 in 906 participants and classified them as traumatic (n = 115) or nontraumatic (n = 31). Serum levels of RANKL and osteoprotegerin and characteristics of bone metabolism and lifestyle were assessed in 1990 and at follow-up in 1995 and 2000.


METHODS
Incident nontraumatic fracture by levels of RANKL.


RESULTS
Levels of RANKL did not differ between sexes and were not related to age, menopausal status, lifestyle characteristics, or data from bone ultrasound at the heel. However, RANKL emerged as a significant predictor of nontraumatic fracture. In pooled logistic regression analysis, the relative risks of nontraumatic fracture in the lowest and middle vs highest tertile for RANKL were 10.0 (95% confidence interval [CI], 2.3-43.1) and 3.9 (95% CI, 0.8-19.0) (P<.001 for trend), respectively. Patients in the highest-tertile group had a low risk of fracture even in the presence of other predisposing factors, whereas women aged 60 years or older in the lowest tertile had a 5-year rate of nontraumatic fracture greater than 7%.


CONCLUSIONS
A low level of RANKL is an independent predictor of nontraumatic fracture. This finding is consistent with the hypothesis of an important role of RANKL in human bone turnover and if confirmed in future investigations may gain relevance for assessment of fracture risk.
Department of Internal Medicine III, Division of Rheumatology, University of Vienna, Vienna, Austria. georg.schett@akh-wien.ac.at
Georg
G
Schett
Stefan
S
Kiechl
Kurt
K
Redlich
Friedrich
F
Oberhollenzer
Siegfried
S
Weger
Georg
G
Egger
Agnes
A
Mayr
Josef
J
Jocher
Qingbo
Q
Xu
Peter
P
Pietschmann
Steven
S
Teitelbaum
Josef
J
Smolen
Johann
J
Willeit
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001842:Bone and Bones / Q000378:metabolism; D005260:Female; D005598:Fractures, Spontaneous / Q000097:blood* / Q000453:epidemiology; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D015994:Incidence; D008019:Life Style; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D053244:Osteoprotegerin; D011379:Prognosis; D011446:Prospective Studies; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood*; D018124:Receptors, Tumor Necrosis Factor; D012307:Risk Factors; D012959:Socioeconomic Factors
D015415:Biomarkers; D006023:Glycoproteins; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506030:TNFRSF11B protein, human