Oral salmon calcitonin reduces Lequesne's algofunctional index scores and decreases urinary and serum levels of biomarkers of joint metabolism in knee osteoarthritis.
OBJECTIVE
To evaluate the effects of oral salmon calcitonin (sCT) on Lequesne's algofunctional index scores and on biomarkers of joint metabolism in knee osteoarthritis.


METHODS
In this randomized, double-blind trial, patients received either placebo (n = 18), 0.5 mg of sCT (n = 17), or 1 mg of sCT (n = 18) daily for 84 days. Biomarkers included C-telopeptide of type II collagen (CTX-II), type II collagen neoepitope C2C, collagenases (matrix metalloproteinase 1 [MMP-1], MMP-8, and MMP-13), stromelysin (MMP-3), tissue inhibitors of metalloproteinases 1 and 2, and hyaluronan. Statistical analysis included nonparametric tests.


RESULTS
A total of 41 patients completed the study (13 in the group receiving 0.5 mg of sCT and 14 in each of the other 2 other groups). Although, on day 84, patients in both the placebo group and the group receiving 1 mg of sCT exhibited a similar significant decrease in pain scores, a significant reduction in the function score was observed only in the 2 sCT groups. On day 84, there was no significant decrease in biomarker levels in the placebo group, whereas significant reductions in the levels of both MMP-3 and hyaluronan were observed in the 2 sCT groups. The group of patients receiving 1 mg of sCT exhibited significant decreases in the levels of CTX-II, C2C, and MMP-13.


CONCLUSIONS
By improving functional disability and by reducing levels of biomarkers that are thought to be predictive of joint space narrowing (and thus cartilage loss), oral sCT at a dose of 1 mg might be a useful pharmacologic agent in human knee OA.
Manicourt
Daniel-Henri
DH
St. Luc University Hospital and Christian de Duve Institute of Cellular Pathology, Université Catholique de Louvain, Brussels, Belgium. manicourt@bchm.ucl.ac.be
Azria
Moïse
M
Mindeholm
Linda
L
Thonar
Eugene J-M
EJ
Devogelaer
Jean-Pierre
JP
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D002116:Calcitonin / Q000009:adverse effects / Q000494:pharmacology*; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006820:Hyaluronic Acid / Q000235:genetics / Q000378:metabolism; D007719:Knee Joint / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism* / Q000652:urine; D010146:Pain / Q000209:etiology; D012720:Severity of Illness Index; D016896:Treatment Outcome
D015415:Biomarkers; D024043:Collagen Type II; C028815:salmon calcitonin; D006820:Hyaluronic Acid; D002116:Calcitonin; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3