Nardone Valeria, D'Asta Federica, Brandi Maria Luisa
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Clinics (Sao Paulo). 2014 Jun;69(6):438-46. doi: 10.6061/clinics/2014(06)12.
Osteogenesis and bone remodeling are complex biological processes that are essential for the formation of new bone tissue and its correct functioning. When the balance between bone resorption and formation is disrupted, bone diseases and disorders such as Paget's disease, fibrous dysplasia, osteoporosis and fragility fractures may result. Recent advances in bone cell biology have revealed new specific targets for the treatment of bone loss that are based on the inhibition of bone resorption by osteoclasts or the stimulation of bone formation by osteoblasts. Bisphosphonates, antiresorptive agents that reduce bone resorption, are usually recommended as first-line therapy in women with postmenopausal osteoporosis. Numerous studies have shown that bisphosphonates are able to significantly reduce the risk of femoral and vertebral fractures. Other antiresorptive agents indicated for the treatment of osteoporosis include selective estrogen receptor modulators, such as raloxifene. Denosumab, a human monoclonal antibody, is another antiresorptive agent that has been approved in Europe and the USA. This agent blocks the RANK/RANKL/OPG system, which is responsible for osteoclastic activation, thus reducing bone resorption. Other approved agents include bone anabolic agents, such as teriparatide, a recombinant parathyroid hormone that improves bone microarchitecture and strength, and strontium ranelate, considered to be a dual-action drug that acts by both osteoclastic inhibition and osteoblastic stimulation. Currently, anti-catabolic drugs that act through the Wnt-β catenin signaling pathway, serving as Dickkopf-related protein 1 inhibitors and sclerostin antagonists, are also in development. This concise review provides an overview of the drugs most commonly used for the control of osteogenesis in bone diseases.
骨生成和骨重塑是复杂的生物学过程,对于新骨组织的形成及其正常功能至关重要。当骨吸收与形成之间的平衡被打破时,可能会导致骨疾病和紊乱,如佩吉特病、骨纤维发育不良、骨质疏松症和脆性骨折。骨细胞生物学的最新进展揭示了治疗骨质流失的新的特定靶点,这些靶点基于抑制破骨细胞的骨吸收或刺激成骨细胞的骨形成。双膦酸盐是一种减少骨吸收的抗吸收剂,通常被推荐作为绝经后骨质疏松症女性的一线治疗药物。大量研究表明,双膦酸盐能够显著降低股骨和椎骨骨折的风险。其他用于治疗骨质疏松症的抗吸收剂包括选择性雌激素受体调节剂,如雷洛昔芬。地诺单抗是一种人单克隆抗体,是另一种已在欧洲和美国获批的抗吸收剂。该药物阻断负责破骨细胞激活的RANK/RANKL/OPG系统,从而减少骨吸收。其他获批药物包括骨合成代谢剂,如特立帕肽,一种重组甲状旁腺激素,可改善骨微结构和强度,以及雷奈酸锶,被认为是一种通过抑制破骨细胞和成骨细胞刺激起作用的双重作用药物。目前,通过Wnt-β连环蛋白信号通路起作用的抗分解代谢药物,作为Dickkopf相关蛋白1抑制剂和硬化蛋白拮抗剂,也在研发中。本简要综述概述了骨疾病中最常用于控制骨生成的药物。