Association between sclerostin and bone density in chronic spinal cord injury.
Association between sclerostin and bone density in chronic spinal cord injury.
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DOI：
10.1002/jbmr.546
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发表时间：
2012-02
影响因子：
6.2
通讯作者：
Battaglino, Ricardo A.
中科院分区：
文献类型：
--
作者：
Morse, Leslie R.;Sudhakar, Supreetha;Danilack, Valery;Tun, Carlos;Lazzari, Antonio;Gagnon, David R.;Garshick, Eric;Battaglino, Ricardo A.
脊髓损伤（SCI）由于肌肉麻痹和不能行走而导致严重的骨丢失。硬化素是骨细胞产生的Wnt信号通路拮抗剂，是骨形成的有效抑制剂。在啮齿动物模型中的短期研究已经证明了增加的硬化素响应于机械卸载，其被重新加载逆转。这些研究表明，完全性脊髓损伤，一种导致瘫痪下肢机械卸载的状况，将与高硬化素水平相关。我们评估了39名慢性SCI患者和10名非SCI患者的循环硬化素和骨密度之间的关系。我们发现，更大的总肢体骨矿物质含量与更高的硬化素循环水平显着相关。与经常行走的SCI患者相比，使用轮椅的SCI患者的硬化蛋白水平降低，而不是升高。同样，与经常行走的无SCI患者相比，使用轮椅的SCI患者的sclerostin水平较低。这些发现表明，循环硬化蛋白是骨质疏松症严重程度的生物标志物，而不是长期慢性截瘫中持续骨丢失的介导物。这与在机械卸载的动物模型中证实的急性硬化蛋白介导的骨丢失形成对比，其中高硬化蛋白水平抑制骨形成。由于这些数据表明，与短期啮齿动物模型相比，慢性SCI中机械卸载、硬化蛋白和骨之间的关系存在重要差异，因此硬化蛋白可能不是治疗慢性SCI诱导的骨质疏松症的良好治疗靶点。
Spinal cord injury (SCI) results in profound bone loss due to muscle paralysis and the inability to ambulate. Sclerostin, a Wnt signaling pathway antagonist produced by osteocytes, is a potent inhibitor of bone formation. Short-term studies in rodent models have demonstrated increased sclerostin in response to mechanical unloading that is reversed with reloading. These studies suggest that complete spinal cord injury, a condition resulting in mechanical unloading of the paralyzed lower extremities, will be associated with high sclerostin levels. We assessed the relationship between circulating sclerostin and bone density in 39 subjects with chronic SCI and 10 without SCI. We found that greater total limb bone mineral content was significantly associated with greater circulating levels of sclerostin. Sclerostin levels were reduced, not elevated, in subjects with SCI who use a wheelchair compared to those with SCI who walk regularly. Similarly, sclerostin levels were lower in subjects with SCI who use a wheelchair compared to persons without SCI who walk regularly. These findings suggest that circulating sclerostin is a biomarker of osteoporosis severity, not a mediator of ongoing bone loss, in long-term, chronic paraplegia. This is in contrast to the acute sclerostin-mediated bone loss demonstrated in animal models of mechanical unloading where high sclerostin levels suppress bone formation. As these data indicate important differences in the relationship between mechanical unloading, sclerostin, and bone in chronic SCI compared to short-term rodent models, it is likely that sclerostin is not a good therapeutic target to treat chronic SCI-induced osteoporosis.
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影响因子：
4
作者：
Morse, L. R.;Battaglino, R. A.;Garshick, E.
通讯作者：
Garshick, E.
影响因子：
2.8
作者：
GARLAND, DE;STEWART, CA;WEINSTEIN, DA
通讯作者：
WEINSTEIN, DA
影响因子：
6.2
作者：
Li, Xiaodong;Ominsky, Michael S.;Paszty, Chris
通讯作者：
Paszty, Chris
影响因子：
2.1
作者：
Morse, Leslie R.;Giangregorio, Lora;Garshick, Eric
通讯作者：
Garshick, Eric
DOI：
10.1016/j.apmr.2005.02.006
发表时间：
2005-08-01
影响因子：
4.3
作者：
Grandas, NF;Jain, NB;Garshick, E
通讯作者：
Garshick, E