Baek Ki Hyun, Oh Ki Won, Lee Won Young, Tae Hyun Jung, Rhee Eun Jung, Han Je Ho, Cha Bong Yun, Kim Yoo Jin, Lee Kwang Woo, Son Ho Young, Kang Sung Koo, Kim Chun Choo, Kang Moo Il
Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Mary's Hospital, The Catholic University of Korea, # 62 Yoido-dong Youngdeungpo-Gu, Seoul 150-713, Republic of Korea.
Bone. 2006 Dec;39(6):1352-60. doi: 10.1016/j.bone.2006.06.011. Epub 2006 Aug 14.
This study prospectively investigated the changes of the serum levels of the sex steroids, IL-7, soluble receptor activator of nuclear factor kappaB ligand (sRANKL) and osteoprotegerin (OPG) in bone marrow transplantation (BMT) recipients. This study also examined whether the changes of these cytokine levels and sex steroids actually influence bone turnover and post-BMT bone loss by correlation analysis. Data were analyzed from 39 patients (33.6+/-6.4 years, 19 men and 20 women) who had DXA performed before BMT and at 1 year after BMT. The bone turnover markers, sex steroids and the cytokine levels were measured before BMT and serially after BMT. The mean bone loss in the lumbar spine and the total proximal femur was 5.9% (P < 0.01) and 11.3% (P < 0.01), respectively. During the immediate post-BMT period, bone formation decreased, whereas the bone resorption increased. For the female recipients, the estradiol levels declined at 1 week after BMT, and they did not recover to the basal levels. For the male recipients, the testosterone levels decreased at 1 week and then it increased to its baseline level. The IL-7 levels reached their maximum at 1 week and then declined to baseline level by 3 months. The serum sRANKL, OPG levels and the sRANKL/OPG ratio showed their peak at post-BMT 3 weeks. The mean daily dose of steroid was associated with suppressed bone formation, enhanced bone resorption and increased sRANKL levels. The IL-7 levels were also noted to be either positively correlated with the levels of ICTP or they were negatively correlated with the levels of osteocalcin at 1 and 3 weeks after BMT. Bone loss at the lumbar spine and the proximal femur was influenced by the decreased sex steroids and increased IL-7 levels. During the observation period, the IL-7 levels showed positive correlations with the sRANKL levels and the sRANKL/OPG ratio. For the female patients, the serum IL-7 levels were negatively associated with the estradiol levels at 1 and 3 weeks after BMT. All these findings suggest that IL-7 plays an important role for post-BMT bone loss, and this possibly happens via the RANKL pathway. These data also suggest that the up-regulation of IL-7 during the early post-BMT period may result from a deficiency of estrogen.
本研究前瞻性调查了骨髓移植（BMT）受者血清中性类固醇、白细胞介素-7（IL-7）、核因子κB受体活化因子配体可溶性受体（sRANKL）和骨保护素（OPG）水平的变化。本研究还通过相关性分析检查了这些细胞因子水平和性类固醇的变化是否真的会影响骨转换和BMT后的骨质流失。对39例患者（年龄33.6±6.4岁，19例男性和20例女性）的数据进行了分析，这些患者在BMT前和BMT后1年进行了双能X线吸收法（DXA）检查。在BMT前及BMT后连续测量骨转换标志物、性类固醇和细胞因子水平。腰椎和股骨近端的平均骨质流失分别为5.9%（P<0.01）和11.3%（P<0.01）。在BMT后的即刻期，骨形成减少，而骨吸收增加。对于女性受者，BMT后1周雌二醇水平下降，且未恢复至基础水平。对于男性受者，睾酮水平在1周时下降，然后升至基线水平。IL-7水平在1周时达到最高，然后在3个月时降至基线水平。血清sRANKL、OPG水平及sRANKL/OPG比值在BMT后3周达到峰值。类固醇的平均每日剂量与骨形成受抑制、骨吸收增强及sRANKL水平升高有关。还发现BMT后1周和3周时，IL-7水平与I型胶原羧基末端肽（ICTP）水平呈正相关，与骨钙素水平呈负相关。腰椎和股骨近端的骨质流失受性类固醇减少和IL-7水平升高的影响。在观察期内，IL-7水平与sRANKL水平及sRANKL/OPG比值呈正相关。对于女性患者，BMT后1周和3周时血清IL-7水平与雌二醇水平呈负相关。所有这些发现表明，IL-7在BMT后的骨质流失中起重要作用，这可能是通过RANKL途径发生的。这些数据还表明，BMT后早期IL-7的上调可能是由于雌激素缺乏所致。
