Jump Christopher M, Duke Kathryn, Malik Rayaz A, Charalambous Charalambos P
Department of Orthopaedics, Blackpool Victoria Hospital, Blackpool, United Kingdom.
Weill Cornell Medicine-Qatar, Ar-Rayyan, Qatar.
JBJS Rev. 2021 Jan 26;9(1):e19.00153. doi: 10.2106/JBJS.RVW.19.00153.
Frozen shoulder is a common, poorly understood condition affecting the shoulder joint, with poor long-term outcomes in some in relation to pain and mobility. Understanding the pathophysiology of frozen shoulder at a cellular level and a molecular level may help in the development of novel treatments. The aim of this study was to perform a systematic review of studies examining the cellular, molecular, and metabolic findings in frozen shoulder.
A literature search was conducted using Embase, CINAHL (Cumulative Index of Nursing and Allied Health Literature), and PubMed using relevant terms. Studies were included if they assessed cellular, molecular, or metabolic alterations in tissue or blood samples of patients with frozen shoulder.
Of 4,794 studies identified, 25 were included for analysis. Histological findings included nonspecific chronic inflammation and the proliferation of fibroblasts, adipocytes, and blood vessels. Molecular studies showed increased pro-inflammatory mediators, reduced matrix metalloproteinases (MMPs), and increased activity of factors promoting fibroblast activation and nerve growth. Metabolic alterations included an increase in blood lipids.
Frozen shoulder is thought to occur after a primary insult to the shoulder triggers a complex cascade and upregulation of growth factors and cytokines with an increased turnover of the extracellular matrix, activation of myofibroblasts with deposition of collagen, and reduced matrix degradation. The presence of a background pro-inflammatory state (e.g., patients with diabetes or hyperlipidemia) may exacerbate these abnormalities. Further work assessing patients in early stages of the disease and comparing the inflammatory or fibrogenic characteristics of the shoulder capsule with those of the other joints may help to determine the initiating factors and to explain the predisposition of the shoulder to stiffness.
Our findings may form the basis for identifying new targets for the clinical management of frozen shoulder.
肩周炎是一种常见但了解不足的影响肩关节的病症，在疼痛和活动度方面，部分患者的长期预后较差。在细胞水平和分子水平了解肩周炎的病理生理学可能有助于开发新的治疗方法。本研究的目的是对研究肩周炎细胞、分子和代谢结果的研究进行系统综述。
使用Embase、CINAHL（护理及相关健康文献累积索引）和PubMed，通过相关术语进行文献检索。如果研究评估了肩周炎患者组织或血液样本中的细胞、分子或代谢改变，则纳入研究。
在检索到的4794项研究中，25项被纳入分析。组织学结果包括非特异性慢性炎症以及成纤维细胞、脂肪细胞和血管的增殖。分子研究显示促炎介质增加、基质金属蛋白酶（MMPs）减少，以及促进成纤维细胞活化和神经生长的因子活性增加。代谢改变包括血脂升高。
肩周炎被认为是在肩部受到原发性损伤后引发复杂的级联反应，生长因子和细胞因子上调，细胞外基质更新增加，肌成纤维细胞活化并伴有胶原蛋白沉积，基质降解减少。存在背景性促炎状态（如糖尿病或高脂血症患者）可能会加剧这些异常。进一步评估疾病早期患者并比较肩袖与其他关节的炎症或纤维化特征的工作，可能有助于确定起始因素并解释肩部易于僵硬的倾向。
我们的研究结果可能为确定肩周炎临床管理的新靶点奠定基础。
