The effect of bone remodeling inhibition by zoledronic acid in an animal model of cartilage matrix damage.
OBJECTIVE
The purpose of this work was to test the effect of inhibition of bone remodeling, through the use of the bisphosphonate, zoledronic acid, on cartilage matrix damage in an animal model of cartilage matrix damage.


METHODS
New Zealand white rabbits were divided into four groups for treatment purposes: (1) untreated controls; (2) injected into one knee joint with the cartilage matrix degradation enzyme, chymopapain; (3) injected into one knee joint with chymopapain and also given subcutaneous injections of the bisphosphonate, zoledronic acid, three times per week until sacrifice at either day 28 or 56 post-chymopapain-injection; (4) received only the zoledronic acid injections. At sacrifice, the knee joints were examined grossly and histologically, and biochemically for proteoglycan content. Urine samples were analysed, at intervals, for levels of collagen cross-links which are biochemical markers of cartilage and bone.


RESULTS
Animals receiving both intraarticular chymopapain injections and subcutaneous zoledronic acid injections displayed a significantly lower degree of grossly and histologically detectable cartilage degeneration on the tibial articular surfaces (the articular surface displaying the greatest degree of degeneration) than did animals only receiving the chymopapain injections. In addition, urinary levels of collagen cross-links for bone and cartilage were significantly higher in those animals only receiving chymopapain injections.


CONCLUSIONS
The bone resorption observed after chymopapain injection into the rabbit knee joint can be inhibited through the use of the bisphosphonate, zoledronic acid. Furthermore, zoledronic acid does not increase the level of cartilage degeneration and appears to provide some level of chondroprotection in this model.
Muehleman
C
C
Department of Anatomy, Rush Medical College, Chicago, Illinois 60612, USA. cmehleman@rushu.rush.edu
Green
J
J
Williams
J M
JM
Kuettner
K E
KE
Thonar
E J-M A
EJ
Sumner
D R
DR
D000818:Animals; D015415:Biomarkers / Q000652:urine; D016723:Bone Remodeling / Q000187:drug effects*; D002357:Cartilage Diseases / Q000139:chemically induced*; D002358:Cartilage, Articular / Q000378:metabolism; D002917:Chymopapain / Q000009:adverse effects; D003094:Collagen / Q000652:urine; D004164:Diphosphonates / Q000009:adverse effects*; D006614:Hindlimb; D007093:Imidazoles / Q000009:adverse effects*; D007596:Joints; D008297:Male; D023421:Models, Animal; D010003:Osteoarthritis / Q000139:chemically induced; D011509:Proteoglycans / Q000737:chemistry; D011817:Rabbits; D000077211:Zoledronic Acid
D015415:Biomarkers; D004164:Diphosphonates; D007093:Imidazoles; D011509:Proteoglycans; D000077211:Zoledronic Acid; D003094:Collagen; D002917:Chymopapain