Review: Unmet Needs and the Path Forward in Joint Disease Associated With Calcium Pyrophosphate Crystal Deposition

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.