Stanford University, Stanford, CA, USA.
Osteoporos Int. 2011 Aug;22(8):2241-8. doi: 10.1007/s00198-011-1598-x. Epub 2011 Mar 31.
The ability of parathyroid glandular extracts to stimulate bone acquisition in rodents was established in the 1920s, but interest in this action lay dormant for almost 50 years until application of contemporary laboratory methods permitted the large-scale production of an amino-terminal fragment of PTH, (1-34) hPTH (teriparatide), which was capable of carrying out all known actions of the full-length (1-84) PTH molecule. In the 1970s, largely stimulated by the efforts of a British pharmacologist, Dr. John Parsons, the scientific community began to revisit these anabolic actions and showed that single daily injections of teriparatide dramatically increased bone mass in several mammalian species and restored bone in oöphorectomized rats. Shortly thereafter, human studies confirmed a striking increase in trabecular bone mass and showed also that an important part of teriparatide's action is to increase cortical bone. Eli Lilly and Company conducted a formal registration trial in postmenopausal women with osteoporosis. The unexpected occurrence of osteosarcomas in Fisher 344 rats treated long-term with teriparatide provoked an abrupt cessation of that trial, but ambiguity concerning the relevance of this rat finding to human disease, combined with significant anti-fracture efficacy, led to FDA approval of teriparatide for men and postmenopausal women with osteoporosis "at high risk for fracture" in 2002. Subsequently, teriparatide has been approved also for treatment of patients with glucocorticoid-associated osteoporosis, and papers indicating utility of this agent for dental and orthopedic applications have begun to appear.
甲状旁腺提取物刺激啮齿动物骨骼形成的能力在 20 世纪 20 年代就已确立，但人们对这种作用的兴趣在近 50 年里一直处于休眠状态，直到应用当代实验室方法能够大规模生产 PTH 的氨基端片段（1-34）hPTH（特立帕肽），这种片段能够发挥全长（1-84）PTH 分子的所有已知作用。20 世纪 70 年代，在英国药理学家约翰·帕森斯博士的努力的主要推动下，科学界开始重新研究这些合成代谢作用，并表明特立帕肽的每日单次注射可显著增加几种哺乳动物的骨量，并恢复去卵巢大鼠的骨量。此后不久，人体研究证实了小梁骨量的显著增加，并表明特立帕肽的一个重要作用部分是增加皮质骨。礼来公司在绝经后骨质疏松症妇女中进行了特立帕肽的正式注册试验。在长期接受特立帕肽治疗的 Fisher 344 大鼠中意外发生骨肉瘤，促使该试验突然停止，但关于这种大鼠发现与人类疾病的相关性的不确定性，加上显著的抗骨折疗效，导致 FDA 在 2002 年批准特立帕肽用于骨质疏松症 "骨折风险高" 的男性和绝经后妇女。随后，特立帕肽也被批准用于治疗糖皮质激素相关骨质疏松症患者，并且表明该药物在牙科和骨科应用的有效性的论文开始出现。
