Table 2.

Author suggestions for pathways to address unmet needs in CPPD pathogenesis, detection and diagnosis: Advance understanding of factors that increase PPi generation and release, modify PPi degradation, and modulate CPP crystal deposition in articular connective tissues: Development and validation of chondrocyte and cartilage culture systems, and transgenic animal modelling of CPPD, to advance identification and testing of potential new therapy targets Better define environmental, diet and lifestyle, and iatrogenic factors influencing CPPD at population levels, ideally using international consortia Genomics and “multi-omics” studies of primary CPPD with clinically manifest disease, including different races and ethnicities Generate a better, unifying disease model (or models) for primary CPPD with and without clinically manifest disease: Model 1: (?) Systemic disorder of calcification expressed only in articular and periarticular tissues predisposed to generate and/or alternatively transport more PPi (and possibly also ATP) in aging Model 2: (?) Systemic disorder of abnormal calcification expressed in articular tissues, various soft tissues and arteries, and with metabolic bone disease

CPP crystal detection and diagnosis Uniform, internationally standardized nomenclature and classification criteria for CPPD, emphasizing clearer lines between the asymptomatic CPPD disorder, OA with CPPD, and unique symptomatic disease phenotypes Prospective, randomized, blinded clinical trials of new diagnostic approaches, with comparison to reference standards (compensated polarized light microscopy, plain radiography) Inclusion of studies in real-world clinical practice scenarios, where patients are referred for clinical diagnosis Development of point-of care crystal identification approaches, adapting highly specific analytic modalities for portability and cost-effectiveness (eg, Raman spectroscopy, lens-free polarized microscopy with wide field of view, high-resolution holographic imaging of birefringent objects) Further advanced imaging studies for CPPD, with development of internationally accepted protocols and standards