TY - JOUR
T1 - Soluble RANKL and Risk of Nontraumatic Fracture
AU - Schett, Georg
AU - Kiechl, Stefan
AU - Redlich, Kurt
AU - Oberhollenzer, Friedrich
AU - Weger, Siegfried
AU - Egger, Georg
AU - Mayr, Agnes
AU - Jocher, Josef
AU - Xu, Qingbo
AU - Pietschmann, Peter
AU - Teitelbaum, Steven
AU - Smolen, Josef
AU - Willeit, Johann
PY - 2004/3/3
Y1 - 2004/3/3
N2 - Context: The receptor activator of nuclear factor κB 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. Design, Setting, and Participants: 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. Main Outcome Measure: 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% Cl, 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.
AB - Context: The receptor activator of nuclear factor κB 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. Design, Setting, and Participants: 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. Main Outcome Measure: 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% Cl, 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.
UR - http://www.scopus.com/inward/record.url?scp=10744223478&partnerID=8YFLogxK
U2 - 10.1001/jama.291.9.1108
DO - 10.1001/jama.291.9.1108
M3 - Article
C2 - 14996780
AN - SCOPUS:10744223478
SN - 0098-7484
VL - 291
SP - 1108
EP - 1113
JO - JAMA
JF - JAMA
IS - 9
ER -