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Osteoporosis treatment: recent developments and ongoing challenges
The Lancet Diabetes & Endocrinology ( IF 44.5 ) Pub Date : 2017-07-06 , DOI: 10.1016/s2213-8587(17)30188-2
Sundeep Khosla , Lorenz C Hofbauer

Osteoporosis is an enormous and growing public health problem. Once considered an inevitable consequence of ageing, it is now eminently preventable and treatable. Ironically, despite tremendous therapeutic advances, there is an increasing treatment gap for patients at high fracture risk. In this Series paper, we trace the evolution of drug therapy for osteoporosis, which began in the 1940s with the demonstration by Fuller Albright that treatment with oestrogen could reverse the negative calcium balance that developed in women after menopause or oophorectomy. We note a watershed in osteoporosis drug discovery around the year 2000, when the approach to developing novel therapeutics shifted from one driven by discoveries in animal studies and clinical observations (eg, oestrogen, calcitonin, and teriparatide) or opportunistic repurposing of existing compounds (eg, bisphosphonates) to one driven by advances in fundamental bone biology (eg, denosumab) coupled with clues from patients with rare bone diseases (eg, romosozumab, odanacatib). Despite these remarkable advances, concerns about rare side-effects of anti-resorptive drugs, particularly bisphosphonates, and the absence of clear evidence in support of their long-term efficacy is leading many patients who could benefit from drug therapy to not take these drugs. As such, there remains an important clinical need to develop ways to enhance patient acceptance and compliance with these effective drugs, and to continue to develop new drugs that do not cause these side-effects and have prolonged anabolic effects on bone. Such changes could lead to a true reversal of this potentially devastating disease of ageing.



中文翻译:

骨质疏松症治疗:最新发展和持续挑战

骨质疏松症是一个巨大且日益严重的公共卫生问题。一旦被认为是衰老的必然结果,现在就可以预防和治疗了。具有讽刺意味的是,尽管取得了巨大的治疗进展,但高骨折风险患者的治疗缺口仍在增加。在本系列论文中,我们追踪了骨质疏松症药物治疗的演变,该发展始于1940年代,富勒·奥尔布赖特(Fuller Albright)证明,雌激素治疗可以逆转更年期或卵巢切除术后女性体内的钙负平衡。我们注意到,大约在2000年左右,骨质疏松症药物的开发出现了一个分水岭,当时开发新疗法的方法已经从动物研究和临床观察结果(例如,雌激素,降钙素,或特立帕肽(teriparatide))或将现有化合物(例如双膦酸盐)改组为一种药物,该药物是由基本骨骼生物学(例如denosumab)的发展以及骨骼疾病罕见的患者(例如romosozumab,odanacatib)提供的线索驱动的。尽管取得了这些令人瞩目的进步,但人们仍然担心抗吸收药物(尤其是双膦酸盐)的罕见副作用,并且缺乏支持其长期疗效的明确证据,这导致许多可能从药物治疗中受益的患者不服用这些药物。因此,仍然存在重要的临床需要,以开发增强患者对这些有效药物的接受度和依从性的方法,并继续开发不会引起这些副作用并且对骨骼具有长期合成代谢作用的新药物。

更新日期:2017-11-10
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