Mount Sinai Bone Program, Mount Sinai School of Medicine, New York, New York 10029 , USA.
Endocr Pract. 2010 Sep-Oct;16(5):874-81. doi: 10.4158/EP10118.RA.
To review new discoveries that revisit our current thinking on the genesis of osteoporosis using hypogonadal and thyrotoxic bone loss as examples.
We focus on cell biologic, mouse genetic, and human studies that have established a direct action of the interior pituitary hormones follicle-stimulating hormone and thyrotropin on the skeleton and discuss emerging clinical evidence for a novel pituitary-bone axis in humans that bypasses master endocrine organs, namely the ovaries and thyroid gland.
The cataloguing of human mutations, the use of genetically modified mice that recapitulate human disease, and the rapid growth of genomic sciences have together had a profound impact on how basic research is translated into clinical practice. The skeleton has become a paradigm for the application of such advances to an extent that hitherto unrecognized physiologic and pathophysiologic findings have emerged. We propose that hypogonadal and thyrotoxic bone loss are not solely due to changes in the level of master hormones, but instead also arise from the direct action of anterior pituitary hormones on the skeleton.
We predict a pituitary-bone axis in which pituitary hormones bypass traditional endocrine targets to affect the skeleton directly with remarkable sensitivity. New therapeutic targets thus become a likely possibility.
以性腺功能减退和甲状腺毒症性骨丢失为例，回顾重新审视骨质疏松症发病机制的新发现，更新我们目前的认识。
我们重点关注细胞生物学、小鼠遗传学和人类研究，这些研究已经证实了脑垂体内部激素卵泡刺激素和促甲状腺素对骨骼的直接作用，并讨论了新兴的人类垂体-骨骼轴的临床证据，该轴绕过了主要的内分泌器官，即卵巢和甲状腺。
人类基因突变的编目、模拟人类疾病的基因修饰小鼠的应用以及基因组科学的快速发展，共同深刻地影响了基础研究向临床实践的转化。骨骼已经成为应用这些进展的范例，以至于出现了以前未被认识的生理和病理生理发现。我们提出，性腺功能减退和甲状腺毒症性骨丢失不仅是由于主要激素水平的变化，而且还源于脑垂体激素对骨骼的直接作用。
我们预测，垂体激素将绕过传统的内分泌靶标，以惊人的敏感性直接作用于骨骼，形成一个垂体-骨骼轴。因此，新的治疗靶点成为可能。
