AO Research Institute Davos, Clavadelerstrasse 8, 7270 Davos Platz, Switzerland.
AO Research Institute Davos, Clavadelerstrasse 8, 7270 Davos Platz, Switzerland.
Acta Biomater. 2015 Jan;11:412-34. doi: 10.1016/j.actbio.2014.09.006. Epub 2014 Sep 16.
Fragility fractures can cause significant morbidity and mortality in patients with osteoporosis and inflict a considerable medical and socioeconomic burden. Moreover, treatment of an osteoporotic fracture is challenging due to the decreased strength of the surrounding bone and suboptimal healing capacity, predisposing both to fixation failure and non-union. Whereas a systemic osteoporosis treatment acts slowly, local release of osteogenic agents in osteoporotic fracture would act rapidly to increase bone strength and quality, as well as to reduce the bone healing period and prevent development of a problematic non-union. The identification of agents with potential to stimulate bone formation and improve implant fixation strength in osteoporotic bone has raised hope for the fast augmentation of osteoporotic fractures. Stimulation of bone formation by local delivery of growth factors is an approach already in clinical use for the treatment of non-unions, and could be utilized for osteoporotic fractures as well. Small molecules have also gained ground as stable and inexpensive compounds to enhance bone formation and tackle osteoporosis. The aim of this paper is to present the state of the art on local drug delivery in osteoporotic fractures. Advantages, disadvantages and underlying molecular mechanisms of different active species for local bone healing in osteoporotic bone are discussed. This review also identifies promising new candidate molecules and innovative approaches for the local drug delivery in osteoporotic bone.
脆性骨折可导致骨质疏松症患者出现严重的发病率和死亡率，并造成相当大的医疗和社会经济负担。此外，由于周围骨骼强度降低和愈合能力欠佳，骨质疏松性骨折的治疗极具挑战性，这两者都容易导致固定失败和不愈合。虽然全身性骨质疏松症治疗起效缓慢，但在骨质疏松性骨折部位局部释放成骨剂可以迅速增加骨强度和质量，缩短骨愈合期，并预防出现有问题的不愈合。具有刺激骨形成和提高骨质疏松性骨骼中植入物固定强度潜力的药物的鉴定为快速增强骨质疏松性骨折带来了希望。通过局部递送生长因子刺激骨形成已经用于治疗骨不连的临床应用，也可以用于骨质疏松性骨折。小分子也已成为增强骨形成和治疗骨质疏松症的稳定且廉价的化合物。本文旨在介绍骨质疏松性骨折局部药物递送的最新技术。讨论了不同活性物质在骨质疏松性骨局部骨愈合中的优缺点和潜在的分子机制。本综述还确定了骨质疏松性骨局部药物递送有前途的新候选分子和创新方法。
