University of Nottingham, UK City Hospital, Nottingham, UK.
Boston University School of Medicine, Boston, Massachusetts.
Arthritis Rheumatol. 2018 Aug;70(8):1182-1191. doi: 10.1002/art.40517. Epub 2018 Jun 14.
Calcium pyrophosphate (CPP) crystal deposition (CPPD) is prevalent and can be associated with synovitis and joint damage. The population of elderly persons predominantly affected by CPPD is growing rapidly. Since shortfalls exist in many aspects of CPPD, we conducted an anonymous survey of CPPD unmet needs, prioritized by experts from the Gout, Hyperuricemia and Crystal-Associated Disease Network. We provide our perspectives on the survey results, and we propose several CPPD basic and clinical translational research pathways. Chondrocyte and cartilage culture systems for generating CPP crystals in vitro and transgenic small animal CPPD models are needed to better define CPPD mechanism paradigms and help guide new therapies. CPPD recognition, clinical research, and care would be improved by international consensus on CPPD nomenclature and disease phenotype classification, better exploitation of advanced imaging, and pragmatic new point-of-care crystal analytic approaches for detecting CPP crystals. Clinical impacts of CPP crystals in osteoarthritis and in asymptomatic joints in elderly persons remain major unanswered questions that are rendered more difficult by current inability to therapeutically limit or dissolve the crystal deposits and assess the consequent clinical outcome. Going forward, CPPD clinical research studies should define clinical settings in which articular CPPD does substantial harm and should include analyses of diverse clinical phenotypes and populations. Clinical trials should identify the best therapeutic targets to limit CPP crystal deposition and associated inflammation and should include assessment of intraarticular agents. Our perspective is that such advances in basic and clinical science in CPPD are now within reach and can lead to better treatments for this disorder.
焦磷酸钙（CPP）晶体沉积（CPPD）很常见，可引起滑膜炎和关节损伤。受 CPPD 影响的老年人群体正在迅速增长。由于 CPPD 在许多方面都存在不足，我们对 CPPD 未满足的需求进行了一项匿名调查，由痛风、高尿酸血症和晶体相关疾病网络的专家进行优先级排序。我们提供了对调查结果的看法，并提出了几种 CPPD 基础和临床转化研究途径。需要建立软骨细胞和软骨培养系统，以在体外生成 CPP 晶体，并建立转基因小型 CPPD 模型，从而更好地定义 CPPD 机制范例，并帮助指导新的治疗方法。通过 CPPD 命名和疾病表型分类的国际共识、更好地利用先进的成像技术以及实用的新即时晶体分析方法来检测 CPP 晶体，可改善 CPPD 的识别、临床研究和护理。CPP 晶体在骨关节炎和老年人无症状关节中的临床影响仍然是尚未解决的主要问题，由于目前无法治疗性地限制或溶解晶体沉积并评估随之而来的临床结果，这些问题变得更加复杂。展望未来，CPPD 临床研究应确定 CPPD 造成实质性损害的临床环境，并应包括对不同临床表型和人群的分析。临床试验应确定限制 CPP 晶体沉积和相关炎症的最佳治疗靶点，并应包括对关节内药物的评估。我们的观点是，CPPD 在基础和临床科学方面的这些进展现在已经触手可及，并可以为这种疾病提供更好的治疗方法。
