Osteoarthritis (OA) is a degenerative
joint disease characterized by progressive degeneration of articular cartilage. Due to its high prevalence and limited treatment options, OA has become one of the most disabling diseases in developed countries. In recent years, OA has been recognized as a heterogenic disease with various phenotypes.
Calcium crystal-related endotypes, which are defined by either a distinct functional or pathobiological mechanism, are present in approximately 60% of all OA patients. Two different
calcium crystals can accumulate in the joint and thereby calcify the cartilage matrix, which are basic
calcium phosphate (BCP) and
calcium pyrophosphate (
CPP) crystals. The formation of these crystals depends mainly on the balance of
phosphate and
pyrophosphate, which is regulated by specific
proteins controlling the
pyrophosphate metabolism. Dysregulation of these molecules subsequently leads to preferential formation of either BCP or
CPP crystals. BCP crystals, on the one hand, are directly associated with OA severity and cartilage degradation. They are mostly located in the deeper cartilage layers and are associated with chondrocyte
hypertrophy.
CPP crystal deposition, on the other hand, is a hallmark of
chondrocalcinosis and is associated with aging and chondrocyte senescence. Therefore, BCP and
CPP crystals are associated with different chondrocyte phenotypes. However, BCP and
CPP crystals are not mutually exclusive and can coexist in OA, creating a mixed endotype of OA. Both crystals clearly play a role in the pathogenesis of OA. However, the exact impact of each crystal type on either driving the
disease progression or being a result of chondrocyte differentiation is still to be elucidated.