Schett Georg, Kiechl Stefan, Redlich Kurt, Oberhollenzer Friedrich, Weger Siegfried, Egger Georg, Mayr Agnes, Jocher Josef, Xu Qingbo, Pietschmann Peter, Teitelbaum Steven, Smolen Josef, Willeit Johann
Department of Internal Medicine III, Division of Rheumatology, University of Vienna, Vienna, Austria.
JAMA. 2004 Mar 3;291(9):1108-13. doi: 10.1001/jama.291.9.1108.
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.
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.
Incident nontraumatic fracture by levels of RANKL.
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%.
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.
核因子κB受体活化因子配体（RANKL）对破骨细胞以及可能对成骨细胞的活化至关重要，可能是骨形成与骨吸收之间的关键联系。
确定血清RANKL水平与非创伤性骨折风险之间的关系。
设计、地点和参与者：作为在意大利布鲁内克进行的一项基于人群的前瞻性研究的一部分，我们记录了1990年至2000年期间906名参与者发生的所有骨折，并将其分为创伤性骨折（n = 115）或非创伤性骨折（n = 31）。在1990年以及1995年和2000年的随访中评估了血清RANKL和骨保护素水平以及骨代谢和生活方式特征。
按RANKL水平划分的非创伤性骨折发生率。
RANKL水平在性别之间无差异，且与年龄、绝经状态、生活方式特征或足跟骨超声数据无关。然而，RANKL是显著的非创伤性骨折预测指标。在汇总逻辑回归分析中，RANKL处于最低和中间三分位数组与最高三分位数组相比，非创伤性骨折的相对风险分别为10.0（95%置信区间[CI]，2.3 - 43.1）和3.9（95%CI，0.8 - 19.0）（趋势P<.001）。即使存在其他易感因素，最高三分位数组的患者骨折风险也较低，而最低三分位数组中60岁及以上的女性5年非创伤性骨折发生率超过7%。
低水平的RANKL是独立的非创伤性骨折预测指标。这一发现与RANKL在人体骨转换中起重要作用的假设一致，如果在未来研究中得到证实，可能对骨折风险评估具有重要意义。
