A Short Treatment With an Antibody to Sclerostin Can Inhibit Bone Loss in an Ongoing Model of Colitis
A Short Treatment With an Antibody to Sclerostin Can Inhibit Bone Loss in an Ongoing Model of Colitis
复制标题
DOI：
10.1359/jbmr.090403
复制
发表时间：
2009-10-01
影响因子：
6.2
通讯作者：
Robinson, Martyn K.
中科院分区：
文献类型：
--
作者：
Eddleston, Alison;Marenzana, Massimo;Robinson, Martyn K.
慢性炎症导致骨丢失，并且在许多人类慢性炎症性病症中已经报道了骨折率增加。本文报道的研究调查了在慢性结肠炎小鼠模型中给予骨调节蛋白sclerostin的中和抗体对骨骼的影响。当给药时，sclerostin抗体（Scl-AbI）并没有减少与结肠炎相关的体重减轻或组织学变化，但确实预防了炎症诱导的骨丢失。在实验结束时，Scl-AbI处理的动物具有比对照抗体（Cntrl-Ab）处理的动物显著更高的股骨BMD（+27%，p < 0.05）。在第二个实验中，Scl-AbI的治疗被推迟到结肠炎发展，此时结肠炎动物股骨的机械性能明显比健康年龄匹配的对照小鼠差（最大载荷，-26%，p < 0.05;能量，-37%，p < 0.05;极限强度，-33%，p < 0.05;弹性模量，-17%，p < 0.05）。Scl-AbI短期治疗可阻止骨丢失，逆转股骨内在和外在机械性能的下降，因此，治疗19天后，Scl-AbI治疗动物的骨机械性能与非结肠炎年龄匹配的对照组无显著差异。骨形成和骨吸收的血清标志物表明，sclerostin抗体刺激成骨细胞活性，抑制破骨细胞介导的骨吸收。骨矿研究杂志2009;24：1662-1671。在线发表于2009年4月27日; doi：10.1359/JBMR.090403
Chronic inflammation leads to bone loss, and increased fracture rates have been reported in a number of human chronic inflammatory conditions. The study reported here investigates the skeletal effects of dosing a neutralizing antibody to the bone regulatory protein sclerostin in a mouse model of chronic colitis. When dosed prophylactically, an antibody to sclerostin (Scl-AbI) did not reduce the weight loss or histological changes associated with colitis but did prevent inflammation-induced bone loss. At the end of the experiment, Scl-AbI-treated animals had a significantly higher femoral BMD (+27%, p < 0.05) than control antibody (Cntrl-Ab)-treated animals. In a second experiment, treatment with Scl-AbI was delayed until colitis had developed, by which time the mechanical properties of femurs in colitic animals were significantly worse than those of healthy age-matched control mice (maximum load, -26%, p < 0.05; energy, -37%, p < 0.05; ultimate strength, -33%, p < 0.05; elastic modulus, -17%, p < 0.05). A short treatment with Scl-AbI halted bone loss and reversed the decline of both intrinsic and extrinsic mechanical properties of the femur such that, after 19 days of treatment, the bone mechanical properties in the Scl-AbI-treated animals were not significantly different from those of noncolitic age-matched controls. Serum markers of bone formation and resorption suggested that the antibody to sclerostin stimulated osteoblast activity and inhibited osteoclast-mediated bone resorption. J Bone Miner Res 2009;24:1662-1671. Published online on April 27, 2009; doi: 10.1359/JBMR.090403