Division of Geriatrics, University of New Mexico School of Medicine, Albuquerque, NM, USA.
J Bone Miner Res. 2012 May;27(5):1215-21. doi: 10.1002/jbmr.1560.
We reported that weight loss induces bone loss which is prevented by exercise training; however, the mechanism for this observation remains unclear. Sclerostin, an inhibitor of bone formation, has been found to increase in states of unloading and may mediate the changes in bone metabolism associated with weight loss and exercise. The objective of the study was to determine the effect of lifestyle intervention in obese older adults on sclerostin levels, and on hip geometry parameters. A total of 107 obese (body mass index [BMI] ≥ 30 kg/m(2)) older (≥65 years) adults were randomly assigned to control, diet, exercise, and combined diet-exercise for 1 year. Sclerostin levels were measured by ELISA at baseline, 6 months, and 12 months, while hip geometry parameters were obtained from bone mineral density (BMD) images done by dual-energy X-ray absorptiometry using hip structure analysis at baseline and 12 months. Both the diet and diet-exercise groups had significant decreases in body weight (-9.6% and -9.4%, respectively), whereas weight was stable in the exercise and control groups. Sclerostin levels increased significantly and progressively in the diet group (6.6% ± 1.7% and 10.5% ± 1.9% at 6 and 12 months, respectively, all p < 0.05), whereas they were unchanged in the other groups; in particular, they were stable in the diet-exercise group (0.7% ± 1.6% and 0.4% ± 1.7% at 6 and 12 months, respectively, all p = 0.05). Hip geometry parameters showed significant decreases in cross-sectional area, cortical thickness, and BMD; and increases in buckling ratio at the narrow neck, intertrochanter, and femoral shaft. These negative changes on bone geometry were not observed in the diet-exercise group. Significant correlations between changes in sclerostin and changes in certain hip geometry parameters were also observed (p < 0.05). In conclusion, the increase in sclerostin levels with weight loss that was prevented by exercise may partly mediate the negative effects of weight loss on bone metabolism and the osteoprotective effect of exercise training.
我们曾报道，体重减轻会导致骨量减少，而运动训练可预防这种情况；然而，这一观察结果的机制尚不清楚。骨形成抑制剂硬骨素在失负荷状态下会增加，可能介导与体重减轻和运动相关的骨代谢变化。本研究的目的是确定生活方式干预对肥胖老年患者硬骨素水平和髋部几何参数的影响。共纳入 107 名肥胖（体重指数[BMI]≥30kg/m2）老年（≥65 岁）患者，随机分为对照组、饮食组、运动组和饮食-运动联合组，进行为期 1 年的干预。采用 ELISA 法在基线、6 个月和 12 个月时检测硬骨素水平，在基线和 12 个月时采用双能 X 线吸收法测定骨密度（BMD）图像的髋结构分析（Hip Structure Analysis，HSA）获得髋部几何参数。饮食组和饮食-运动组的体重均显著下降（分别为-9.6%和-9.4%），而运动组和对照组的体重则保持稳定。饮食组的硬骨素水平显著升高且逐渐升高（分别为 6 个月时增加 6.6%±1.7%和 12 个月时增加 10.5%±1.9%，均 p<0.05），而其他组的硬骨素水平无变化；特别是饮食-运动组的硬骨素水平保持稳定（分别为 6 个月时增加 0.7%±1.6%和 12 个月时增加 0.4%±1.7%，均 p=0.05）。髋部几何参数的变化显示，横截面积、皮质厚度和 BMD 显著降低，而在狭窄颈、转子间区和股骨干的内翻率增加。在饮食-运动组中未观察到这些与骨几何相关的负性变化。硬骨素水平变化与某些髋部几何参数变化之间也存在显著相关性（p<0.05）。总之，运动预防体重减轻引起的硬骨素水平升高，可能部分介导了体重减轻对骨代谢的负面影响以及运动训练的护骨作用。
