Phosphocitrate blocks calcification-induced articular joint degeneration in a guinea pig model.
OBJECTIVE
Calcium deposition occurs frequently in osteoarthritic (OA) joints. However, evidence for a causal role of calcification in cartilage degeneration is inferential. The present study was undertaken to examine the role of calcification in OA disease progression and to evaluate a formulation of phosphocitrate (PC) as a potential therapeutic agent.


METHODS
We have identified a guinea pig OA model in which meniscal calcification appears to correlate with aging and disease progression. We synthesized a new formulation of PC, [CaNa(PC)2(H2O)](n) (CaNaPC), which is a potent antimineralization agent and a specific inhibitor of crystal-induced biologic effects. After weekly treatment of guinea pigs with experimental OA with CaNaPC for 3 months, we examined calcification in menisci and cartilage degeneration. As a control, we examined whether similar CaNaPC treatment had any therapeutic effect in a hemi-meniscectomy model in which there is no known crystal involvement.


RESULTS
Meniscal calcification correlated with cartilage degeneration in this animal model. PC treatment led to significant reduction of calcium deposits and arrested OA disease progression. Similar treatment had no effect in the hemi-meniscectomy model.


CONCLUSIONS
CaNaPC diminishes mineralization in a cutaneous calcergy model and a model of OA in which intraarticular mineralization is a prominent feature. In the OA guinea pig model, inhibition of calcification is accompanied by diminished cartilage degeneration. CaNaPC has no therapeutic effect in the hemi-meniscectomy model. We conclude that pathologic calcification may initiate or amplify processes leading to cartilage degeneration and that CaNaPC may interrupt such a pathway.
Cheung
Herman S
HS
VA Medical Center, Miami, Florida 33125, USA. hcheung@med.miami.edu
Sallis
John D
JD
Demadis
Konstantino D
KD
Wierzbicki
Andrzej
A
D000818:Animals; D002114:Calcinosis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002951:Citrates / Q000737:chemistry / Q000627:therapeutic use*; D003460:Crystallization; D018360:Crystallography, X-Ray; D004195:Disease Models, Animal; D018450:Disease Progression; D006168:Guinea Pigs; D007596:Joints / Q000187:drug effects* / Q000473:pathology / Q000601:surgery; D008297:Male; D008592:Menisci, Tibial / Q000737:chemistry / Q000601:surgery; D020370:Osteoarthritis, Knee / Q000188:drug therapy* / Q000473:pathology; D011817:Rabbits; D013264:Stifle / Q000601:surgery
D002951:Citrates; C014148:phosphocitrate; D002118:Calcium