Treatment with calcitonin suppresses the responses of bone, cartilage, and synovium in the early stages of canine experimental osteoarthritis and significantly reduces the severity of the cartilage lesions.
OBJECTIVE
To relate the rate of bone resorption to serum levels of both hyaluronan (HA) and antigenic keratan sulfate (KS) in canine experimental osteoarthritis (OA) and to evaluate the effects of calcitonin on these parameters and the OA lesions of the unstable knee.


METHODS
Twenty-two dogs underwent anterior cruciate ligament transection (ACLT) and 6 dogs underwent sham operation. Urinary pyridinium crosslinks were quantified by high-performance liquid chromatography. Immunoassays quantified hyaluronan (HA) and antigenic KS. Macroscopic and histologic OA lesions were scored. Calcitonin treatment was started on day 14 postsurgery and stopped on either day 49 or day 104 postsurgery. Control dogs and all treated dogs were killed on day 105.


RESULTS
All ACLT joints developed OA. In contrast to sham-operated animals, all operated dogs exhibited an early and sustained rise in the levels of their urinary and serum markers. Calcitonin markedly reduced the levels of these markers and the severity of OA lesions. Furthermore, the longer the period of calcitonin therapy, the lower the score of the OA lesions.


CONCLUSIONS
Bone, synovium, and articular cartilage all appear to be involved in the state of hypermetabolism that develops in unstable joints. Furthermore, the rate of bone resorption increases markedly in the early stages of this OA model and is likely to contribute to cartilage breakdown. Since calcitonin reduced the severity of OA changes, this form of therapy may have benefits for humans who have recently experienced a traumatic knee injury.
Manicourt
D H
DH
Université de Louvain, International Institute of Cellular and Molecular Pathology, and Saint-Luc University Hospital, Brussels, Belgium.
Altman
R D
RD
Williams
J M
JM
Devogelaer
J P
JP
Druetz-Van Egeren
A
A
Lenz
M E
ME
Pietryla
D
D
Thonar
E J
EJ
D000596:Amino Acids / Q000652:urine; D000818:Animals; D016118:Anterior Cruciate Ligament / Q000601:surgery; D015415:Biomarkers / Q000652:urine; D001862:Bone Resorption / Q000188:drug therapy; D001842:Bone and Bones / Q000187:drug effects*; D002116:Calcitonin / Q000627:therapeutic use*; D002358:Cartilage, Articular / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004285:Dogs; D006820:Hyaluronic Acid / Q000097:blood*; D007632:Keratan Sulfate / Q000097:blood*; D010003:Osteoarthritis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000652:urine; D013583:Synovial Membrane / Q000187:drug effects* / Q000473:pathology
D000596:Amino Acids; D015415:Biomarkers; C015484:pyridinoline; C036020:deoxypyridinoline; D006820:Hyaluronic Acid; D002116:Calcitonin; D007632:Keratan Sulfate