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骨关节炎中骨与软骨转换的偶联:骨再吸收抑制剂和合成代谢剂作为潜在治疗方法的机会?

The coupling of bone and cartilage turnover in osteoarthritis: opportunities for bone antiresorptives and anabolics as potential treatments?

机构信息

Nordic Bioscience, , Herlev, Denmark.

出版信息

Ann Rheum Dis. 2014 Feb;73(2):336-48. doi: 10.1136/annrheumdis-2013-204111. Epub 2013 Nov 27.

DOI:10.1136/annrheumdis-2013-204111
PMID:24285494
Abstract

Osteoarthritis (OA) is the most common form of arthritic disease, and a major cause of disability and impaired quality of life in the elderly. OA is a complex disease of the entire joint, affecting bone, cartilage and synovium that thereby presents multiple targets for treatment. This manuscript will summarise emerging observations from cell biology, preclinical and preliminary clinical trials that elucidate interactions between the bone and cartilage components in particular. Bone and cartilage health are tightly associated. Ample evidence has been found for bone changes during progression of OA including, but not limited to, increased turnover in the subchondral bone, undermineralisation of the trabecular structure, osteophyte formation, bone marrow lesions and sclerosis of the subchondral plate. Meanwhile, a range of investigations has shown positive effects on cartilage health when bone resorption is suppressed, or deterioration of the cartilage when resorption is increased. Known bone therapies, namely oestrogens, selective oestrogen receptor modifiers (SERMs), bisphosphonates, strontium ranelate, calcitonin and parathyroid hormone, might prove useful for treating two critical tissue components of the OA joint, the bone and the cartilage. An optimal treatment for OA likely targets at least these two tissue components. The patient subgroups for whom these therapies are most appropriate have yet to be fully defined but would likely include, at a minimum, those with high bone turnover.

摘要

骨关节炎(OA)是最常见的关节炎疾病,也是导致老年人残疾和生活质量下降的主要原因。OA 是一种累及整个关节的复杂疾病,影响骨骼、软骨和滑膜,因此有多种治疗靶点。本文将总结细胞生物学、临床前和初步临床试验中的新发现,特别是阐明骨与软骨成分之间的相互作用。骨骼和软骨健康密切相关。有充分的证据表明,OA 进展过程中会发生骨骼变化,包括但不限于软骨下骨的周转率增加、小梁结构脱矿、骨赘形成、骨髓病变和软骨下板硬化。同时,一系列研究表明,抑制骨吸收或增加骨吸收时,对软骨健康有积极影响。已知的骨治疗药物,如雌激素、选择性雌激素受体调节剂(SERMs)、双磷酸盐、雷奈酸锶、降钙素和甲状旁腺激素,可能对治疗 OA 关节的两个关键组织成分——骨骼和软骨有用。OA 的最佳治疗方法可能至少针对这两个组织成分。这些治疗方法最适合的患者亚组尚未完全确定,但可能至少包括那些高骨转换的患者。

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