Morphological analysis of articular cartilage biopsies from a randomized, clinical study comparing the effects of 500-730 kDa sodium hyaluronate (Hyalgan) and methylprednisolone acetate on primary osteoarthritis of the knee.
OBJECTIVE
Histomorphometric study on cartilage samples taken from osteoarthritic human knees before and 6 months after intraarticular injections of a specific fraction (500-730 kDa) of hyaluronan. The results obtained with hyaluronan were compared with the results of methylprednisolone acetate treatment.


METHODS
Twenty-four subjects with primary osteoarthritis (OA) of the knee were considered. Eleven patients were treated with Hyaluronan (Hyalgan), 20 mg/2 ml once a week for 5 weeks) and 13 with methylprednisolone (Depo-Medrol, 40 mg/1 ml once a week for 3 weeks). At the time of baseline and after 6 months from the start of treatment, biopsies of cartilage were taken and processed for electron microscopy. Articular surface morphology, territorial matrix, chondrocyte number and ultrastructure were characterized by a set of morphometric parameters. Samples from 19 informed patients showing no arthroscopic sign of OA were also used for comparison.


RESULTS
Six months after hyaluronan treatment a significant reconstitution of the superficial layer were observed together with an improvement in chondrocyte density and territorial matrix appearance. Furthermore, chondrocytes appeared significantly improved in their metabolism, as indicated by the increased extension of the synthetic structures and mitochondria with respect to the organelles having catabolic or storage functions. Hyaluronan treatment produced results that were significantly superior to those delivered with Methylprednisolone in almost all the morphometric estimators.


CONCLUSIONS
These results cannot be explained simply by temporary restoration of the synovial fluid viscoelasticity, and provide further evidence that the specific fraction of hyaluronan used in this study is a useful tool in OA treatment, with a potential structure-modifying activity.
Guidolin
D D
DD
FIDIA Research Laboratories, Abano Terme, Italy. dguidolin@fidiapharma.it
Ronchetti
I P
IP
Lini
E
E
Guerra
D
D
Frizziero
L
L
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001706:Biopsy / Q000379:methods; D002358:Cartilage, Articular / Q000378:metabolism / Q000648:ultrastructure; D019902:Chondrocytes / Q000378:metabolism* / Q000648:ultrastructure; D003692:Delayed-Action Preparations; D004359:Drug Therapy, Combination; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage*; D008775:Methylprednisolone / Q000009:adverse effects* / Q000031:analogs & derivatives*; D000077555:Methylprednisolone Acetate; D008854:Microscopy, Electron; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000188:drug therapy* / Q000473:pathology
D000276:Adjuvants, Immunologic; D003692:Delayed-Action Preparations; D000077555:Methylprednisolone Acetate; D006820:Hyaluronic Acid; D008775:Methylprednisolone