Genetics and Mechanisms of Crystal Deposition in Calcium Pyrophosphate Deposition Disease

Calcium pyrophosphate deposition (CPPD) disease (common in older adults) can be asymptomatic, associated with osteoarthritis, or can present as acute/chronic inflammatory arthritis. Due to the phenotypic complexity of CPPD, the European League Against Rheumatism (EULAR) recently made recommendations on terminology, diagnosis, and management based on available research evidence and expert consensus. There are no disease-modifying treatments for CPPD disease, and therapy remains nonspecific with the use of anti-inflammatory and analgesic drugs. For years, it has been known that inorganic phosphate and pyrophosphate regulate the formation of CPP or hydroxyapatite crystals. The discovery of ANKH (human homologue of progressive ankylosis) mutations in familial CPPD disease confirmed the importance of phosphate/pyrophosphate homeostasis in CPPD, with ANKH being a regulator of inorganic pyrophosphate transport. Despite progress in our understanding of the function of ANKH, much remains to be investigated. This review summarizes the genetic basis of this disease and focuses on the challenges of research in this area.