Inhibitors of articular calcium crystal formation.
The coexistence of calcium phosphate and calcium pyrophosphate crystals in osteoarthritis is a well-described phenomenon. In addition to deposition in articular cartilage, the crystals induce numerous changes to biochemical parameters in the surrounding fluid. This survey discusses crystal-inhibitor interactions whereby defining the molecular structure of crystals assists in an optimal inhibitor design. Crystal growth studies in the presence and absence of a test compound can generate data on crystal face changes. Together with knowledge of the inhibitors' molecular structure, computer modeling can portray crystal-inhibitor interactions. Few inhibitors have been tested in both in vitro and in vivo phases. One exception is phosphocitrate. This compound inhibits both the development of specific calcium crystals and crystal-induced intracellular changes. Animal studies confirm a strong action on pathologic calcification. The recently described phosphocitrate in a mixed calcium and sodium salt, yet to be tested in a guinea pig osteoarthritis model, appears to be an even more powerful inhibitor.
Sallis
John D
JD
Miami VA Medical Center Research Service and Geriatrics Research, Education and Clinical Center, Miami, Florida, USA.
Cheung
Herman S
HS
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002130:Calcium Phosphates / Q000378:metabolism; D002131:Calcium Pyrophosphate / Q000378:metabolism*; D002358:Cartilage, Articular / Q000187:drug effects / Q000503:physiopathology; D002805:Chondrocalcinosis / Q000188:drug therapy* / Q000503:physiopathology*; D003460:Crystallization; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D010003:Osteoarthritis / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D011379:Prognosis; D051381:Rats; D012307:Risk Factors
D000893:Anti-Inflammatory Agents; D002130:Calcium Phosphates; C485828:alpha-tricalcium phosphate; C485830:tetracalcium phosphate; C485838:calcium phosphate, monobasic, anhydrous; C020243:calcium phosphate; C485829:calcium phosphate, dibasic, anhydrous; D002131:Calcium Pyrophosphate