PNAS：卵泡刺激素多克隆抗体治愈骨质疏松症

一项新的研究表明相比现有的预防或治疗骨质疏松症方法，阻断卵泡刺激素（FSH）的多克隆抗体对卵巢摘除小鼠可能会​​是一种更有效的治疗手段这项研究使用更年期的小鼠模型注射多克隆抗肽抗体发现在减缓骨质的破坏同时也能促进骨的再生。此外，西奈山医学院的研究人员证实单克隆抗体可能是更安全的，因为它能从血液中清除，并不残留在骨中。

研究结果发表在8月20日的PNAS杂志上。Zaidi研究团队开发的FSH多克隆抗肽抗体，测试它对卵巢摘除小鼠的作用。Zaidi说：几年前我们发现FSH（卵泡刺激素）直接绕过雌激素轴来调节骨。在更年期早起FSH升高，能负向调节骨的形成。通过阻断卵泡刺激素FSH-多克隆抗体，我们能够阻止破骨细胞的骨吸收和刺激成骨细胞来促进骨的形成。

Zaidi总结该研究小组的目标：我们的目标是找到一个方法以防止骨质疏松症，而不是简单地测试疾病目前使用的已经有很好耐受性的药物。我们相信一个未来的人源化FSH单克隆抗体可能比现有的治疗方法更安全，因为它不会残留在骨中。

西奈山骨的研究人员在了解骨重建和开发新的骨质疏松症治疗方法上已经取得了突破性的发现，这项新的研究发现估计会影响全球50多万名妇女。西奈山骨计划成立于1999年，博士Zaidi为其创始董事。它是公认的国内和国际上尖端的骨质疏松症和其他骨疾病包括罕见的遗传性疾病如Gaucher疾病的研究项目。它是由美国国立卫生研究院支持。

编译自：Dual Action Polyclonal Antibody May Offer More Effective, Safer Protection Against Osteoporosis

doi:10.1073/pnas.1212806109
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Blocking antibody to the β-subunit of FSH prevents bone loss by inhibiting bone resorption and stimulating bone synthesis

Ling-Ling Zhu, Harry Blair, Jay Cao, Tony Yuen, Rauf Latif, Lida Guo, Irina L. Tourkova, Jianhua Li, Terry F. Davies, Li Sun, Zhuan Bian, Clifford Rosen, Alberta Zallone, Maria I. New, and Mone Zaidi.

Low estrogen levels undoubtedly underlie menopausal bone thinning. However, rapid and profuse bone loss begins 3 y before the last menstrual period, when serum estrogen is relatively normal. We have shown that the pituitary hormone FSH, the levels of which are high during late perimenopause, directly stimulates bone resorption by osteoclasts. Here, we generated and characterized a polyclonal antibody to a 13-amino-acid-long peptide sequence within the receptor-binding domain of the FSH β-subunit. We show that the FSH antibody binds FSH specifically and blocks its action on osteoclast formation in vitro. When injected into ovariectomized mice, the FSH antibody attenuates bone loss significantly not only by inhibiting bone resorption, but also by stimulating bone formation, a yet uncharacterized action of FSH that we report herein. Mesenchymal cells isolated from mice treated with the FSH antibody show greater osteoblast precursor colony counts, similarly to mesenchymal cells isolated from FSH receptor (FSHR)?/? mice. This suggests that FSH negatively regulates osteoblast number. We confirm that this action is mediated by signaling-efficient FSHRs present on mesenchymal stem cells. Overall, the data prompt the future development of an FSH-blocking agent as a means of uncoupling bone formation and bone resorption to a therapeutic advantage in humans.