Reduction of the severity of canine osteoarthritis by prophylactic treatment with oral doxycycline.
OBJECTIVE
In vitro studies have indicated that levels of neutral metalloproteinases in osteoarthritic (OA) cartilage are elevated and that doxycycline (doxy) inhibits collagenolytic and gelatinolytic activity in extracts of OA cartilage. The purpose of the present study was to test the effect of oral doxy administration on the severity of cartilage degeneration in OA.


METHODS
OA was induced in 12 adult mongrel dogs by transection of the anterior cruciate ligament (ACL) 2 weeks after dorsal root ganglionectomy. Six dogs received doxy orally from the day after ACL transection until they were killed 8 weeks later; the other 6 served as untreated OA controls.


RESULTS
The unstable knee of each untreated dog exhibited extensive full-thickness cartilage ulceration of the medial femoral condyle. In sharp contrast, cartilage on the distal aspect of the femoral condyle of the unstable knee was grossly normal in 2 doxy-treated dogs, and exhibited only thinning and/or surface irregularity in the others. Degenerative cartilage lesions on the medial trochlear ridge, superficial fibrillation of the medial tibial plateau, and osteophytosis were, however, unaffected by doxy treatment. Collagenolytic activity and gelatinolytic activity in cartilage extracts from OA knees of untreated dogs were 5-fold and 4-fold greater, respectively, than in extracts from dogs given doxy.


CONCLUSIONS
Prophylactic administration of doxy markedly reduced the severity of OA in weight-bearing regions of the medial femoral condyle. It remains to be determined whether administration of doxy after OA changes have developed is also effective.
Yu
L P
LP
Rheumatology Division, Indiana University School of Medicine, Indianapolis 46202-5103.
Smith
G N
GN
Brandt
K D
KD
Myers
S L
SL
O'Connor
B L
BL
Brandt
D A
DA
D000284:Administration, Oral; D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D046508:Culture Techniques; D004285:Dogs; D004318:Doxycycline / Q000008:administration & dosage / Q000627:therapeutic use*; D005684:Gait; D018093:Gelatinases; D006025:Glycosaminoglycans / Q000096:biosynthesis; D061965:Matrix Metalloproteinase Inhibitors; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D010434:Pepsin A / Q000037:antagonists & inhibitors; D013582:Synovial Fluid / Q000378:metabolism; D014574:Uronic Acids / Q000378:metabolism
D006025:Glycosaminoglycans; D061965:Matrix Metalloproteinase Inhibitors; D014574:Uronic Acids; D010434:Pepsin A; D018093:Gelatinases; D004318:Doxycycline