Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, M3-A410, POB 19024, Seattle, WA 98109-1024, USA.
Bone. 2013 Oct;56(2):474-81. doi: 10.1016/j.bone.2013.05.018. Epub 2013 Jun 2.
The osteoprotogerin/receptor activator of NF-kappa β/receptor activator of NF-kappa β ligand (OPG/RANK/RANKL) pathway plays a critical role in bone remodeling. This study investigated associations between serum levels of OPG, soluble RANKL (sRANKL), and the ratio of OPG/sRANKL to risk of incident hip fracture.
A nested case-control study was conducted among postmenopausal, Caucasian women aged 50-79 at baseline (1993-1998), followed for hip fracture through March 2005 in the Women's Health Initiative Observational Study. 400 incident hip fracture cases were selected and individually matched to 400 controls with no prior fracture or incident hip fracture. Matching factors were baseline age, enrollment date and hormone therapy (HT) exposure. Baseline serum OPG and sRANKL levels were measured using high sensitivity ELISA. Odds ratios were computed for quartiles of each biomarker adjusting for matching factors and hip fracture risk factors.
Serum OPG was significantly associated with older age, low physical activity and poorer physical function in control women. sRANKL was inversely associated with total calcium intake in control women, but not associated with age or other fracture risk factors. The odds ratio for hip fracture comparing the highest to lowest quartiles of OPG was 2.28 (95% confidence interval (CI), 1.45-3.61) after adjusting for the matching variables (p-value for linear trend <0.001), and 1.87 (95% CI, 1.15-3.04; p for linear trend=0.02) after adjusting for self-rated health status, physical activity and physical functioning. No significant associations between sRANKL or the ratio of OPG/sRANKL and hip fracture risk were observed.
Serum OPG levels were independently associated with a nearly twofold increased risk of hip fracture in postmenopausal women.
核因子 κB 受体激活剂配体（RANKL）/核因子 κB 受体激活剂配体（OPG/RANK/RANKL）通路中的骨保护素在骨重塑中起着关键作用。本研究调查了血清骨保护素（OPG）、可溶性核因子 κB 受体激活剂配体（sRANKL）和 OPG/sRANKL 比值与髋部骨折风险之间的关系。
在妇女健康倡议观察研究中，对基线时（1993-1998 年）年龄在 50-79 岁的绝经后白种女性进行了一项巢式病例对照研究，通过 2005 年 3 月随访髋部骨折情况。选择了 400 例新发髋部骨折病例，并与无先前骨折或新发髋部骨折的 400 名对照进行了个体匹配。匹配因素包括基线年龄、入组日期和激素治疗（HT）暴露情况。使用高灵敏度 ELISA 测定基线时血清 OPG 和 sRANKL 水平。根据匹配因素和髋部骨折危险因素，对各生物标志物的四分位数进行了比值比计算。
在对照组女性中，血清 OPG 与年龄较大、体力活动较少和身体功能较差显著相关。sRANKL 与对照组女性的总钙摄入量呈负相关，但与年龄或其他骨折危险因素无关。在调整了匹配变量后，OPG 最高四分位数与最低四分位数相比，髋部骨折的比值比为 2.28（95%置信区间（CI）为 1.45-3.61）（p 值<0.001），在调整了自我报告健康状况、体力活动和身体功能后，比值比为 1.87（95%CI，1.15-3.04；p 趋势=0.02）。未观察到 sRANKL 或 OPG/sRANKL 比值与髋部骨折风险之间存在显著关联。
血清 OPG 水平与绝经后妇女髋部骨折的风险增加近两倍独立相关。
