Long-term effect of sodium hyaluronate (Hyalgan) on osteoarthritis progression in a rabbit model.
BACKGROUND
Intra-articular (IA) hyaluronan (HA) injections are approved for the treatment of knee osteoarthritis (OA) pain. One of the currently available products is approved for repeat treatment courses. While HA is classed as a symptom-modifying agent, there is substantial evidence that this therapeutic modality also possesses disease-modifying activity.


OBJECTIVE
A rabbit model of OA, anterior cruciate ligament transection (ACLT), was used to investigate the long-term effects of single and sequential courses of HA therapy on OA progression.


METHODS
One or two courses of five weekly IA injections of sodium hyaluronate (Hyalgan) average molecular weight, MW, of 500-730 kDa, or vehicle were administered to rabbits (N=10 per group), initiated 4 and 13 weeks (for groups that received a second course) after ACLT. Gross morphological and histomorphometric evaluations were performed on harvested knee joints following sacrifice at 26 weeks after surgery.


RESULTS
All the rabbits exhibited the characteristic pathologic changes of OA. Rabbits that received one or two courses of HA injections showed less disease progression than rabbits treated with ACLT alone or with 10 vehicle injections. However, rabbits that received five vehicle injections also showed improved morphology compared with those given no injections. Rabbits that received 10 HA injections showed significantly less surface roughness of the femoral cartilage compared with rabbits treated with ACLT, 5 HA injections, or 10 vehicle injections, and showed significantly less surface roughness of the tibial plateau compared with all other treatment groups (P<0.05).


CONCLUSIONS
Repeat courses of HA injections reduced the degree of articular degeneration in a rabbit ACLT model of OA. Sequential courses of HA therapy may be advantageous in the long-term management of OA.
Amiel
D
D
Department of Orthopaedics, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093-0630, USA. damiel@ucsd.edu
Toyoguchi
T
T
Kobayashi
K
K
Bowden
K
K
Amiel
M E
ME
Healey
R M
RM
D000818:Animals; D016118:Anterior Cruciate Ligament; D002358:Cartilage, Articular / Q000473:pathology; D004247:DNA / Q000032:analysis; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006820:Hyaluronic Acid / Q000627:therapeutic use*; D007270:Injections, Intra-Articular; D008297:Male; D008592:Menisci, Tibial / Q000473:pathology; D010003:Osteoarthritis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D011817:Rabbits; D013583:Synovial Membrane / Q000737:chemistry
D006820:Hyaluronic Acid; D004247:DNA