骨质疏松及其骨折的局部药物治疗

Local drug therapy for osteoporosis and osteoporotic fractures

骨质疏松虽然是一种系统性代谢性骨骼疾病,但其最大的危害却是局部脆性骨折。目前骨质疏松的治疗仍主要依赖于系统用药,但系统用药存在周期长、费用高、治疗依从性差、全身性副作用较大等缺陷。骨质疏松骨折好发部位非常集中,多集中在胸腰段和双髋,随着现代微创介入外科的迅速发展,使得局部治疗骨质疏松成为可能。局部药物治疗可以实现局部促进骨形成或者抑制骨吸收,从而在重点部位起到预防骨折、加速骨折愈合以及增强植入物稳定性的作用,弥补了系统用药的副作用及起效慢等缺点。局部治疗可通过局部注射药物或内植物表面涂层的药物释放以发挥作用,目前有多种呈递系统能够有效搭载并缓释具有生物活性的药物。双膦酸盐、甲状旁腺激素(parathyroid hormone,PTH)、骨形成蛋白(bone morphogenetic protein,BMP)、他汀类药物等都是常见的临床前研究药物。此外,靶向核因子κB受体活化因子(receptor activator of nuclear factor kappa-B,RANK)和Wnt通路等生物靶向药也处在研究之中。总之,骨质疏松的局部治疗或能提供新的辅助治疗策略,联合应用系统用药和局部用药,取长补短,是未来治疗骨质疏松的研究及应用方向。

Although osteoporosis is a systemic metabolic bone disease, its severest outcome is local fragility fracture.Current treatment of osteoporosis is still largely dependent on systemic administration of drugs.However, systemic medications have certain drawbacks such as long treatment duration, high cost, poor compliance and large systemic side effects.The predilection sites for osteoporotic fractures are mostly concentrated in the thoracolumbar vertebra bodies and hips.The rapid development of modern minimally invasive surgery makes it possible for the local treatment of osteoporosis.By local stimulation of bone formation or inhibition of bone resorption, local drug therapy can prevent fractures, accelerate fracture healing and strengthen the stability of implants in destination spots, and thus compensate for the side effects and slow onset of systemic medications.Local treatment works by local injection of drugs or implant surface coatings.At present, a variety of delivery systems are available for efficient loading and sustained release of biologically active drugs.Other than common preclinical drugs such as bisphosphonates, parathyroid hormone （PTH）, bone morphogenetic protein （BMP） and statins, those targeting receptor activator of nuclear factor kappa-B （RANK） and the wingless-related integration site （Wnt） signaling pathways are also under study.In brief, local treatment of osteoporosis may provide a new adjuvant treatment strategy.Combined application of systemic and local treatment is the trend of osteoporosis research and treatment.