Osteoporosis treatment: recent developments and ongoing challenges.
Osteoporosis treatment: recent developments and ongoing challenges.
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DOI：
10.1016/s2213-8587(17)30188-2
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发表时间：
2017-11
期刊：
影响因子：
--
通讯作者：
Hofbauer LC
中科院分区：
文献类型：
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作者：
Khosla S;Hofbauer LC
骨质疏松症是一个巨大的和日益增长的公共卫生问题。它曾经被认为是老龄化的必然后果，现在显然是可以预防和治疗的。具有讽刺意味的是，尽管有巨大的治疗进展，但对于高骨折风险患者的治疗差距越来越大。在这篇系列论文中，我们追溯了骨质疏松症药物治疗的演变，始于20世纪40年代，当时Fuller Albright证明雌激素治疗可以逆转绝经或卵巢切除术后妇女的负钙平衡。我们注意到2000年左右骨质疏松症药物发现的一个分水岭，当时开发新疗法的方法从动物研究和临床观察的发现转向（如雌激素、降钙素和特立帕肽）或现有化合物的机会性再利用（例如，双膦酸盐）到基础骨生物学进展驱动的一种（例如，地舒单抗）加上罕见骨病患者的线索（例如，romosozumab，odanacatib）。尽管取得了这些显著的进展，但人们对抗骨吸收药物（特别是双膦酸盐）的罕见副作用的担忧，以及缺乏支持其长期疗效的明确证据，导致许多可能从药物治疗中获益的患者不服用这些药物。因此，仍然存在重要的临床需求，以开发提高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对骨具有延长的合成代谢作用的新药。这种变化可能导致真正扭转这种潜在的破坏性疾病的老龄化。
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.