The effect of oral calcitonin on cartilage turnover and surface erosion in an ovariectomized rat model.
OBJECTIVE
To investigate whether oral calcitonin treatment influences the increases in type II collagen (CII) degradation and related surface erosions of articular cartilage in ovariectomized rats.


METHODS
Fifty rats were randomly allocated into 1 of the 5 following intervention groups: sham-operated, ovariectomy, ovariectomy plus subcutaneously implanted 17beta-estradiol pellet, ovariectomy plus 2 mg/kg salmon calcitonin plus 50 mg/kg 5CNAC (carrier), or ovariectomy plus 50 mg/kg 5CNAC. Each treatment was administered for 9 weeks after the ovariectomy. Blood samples for biochemical marker analysis were collected from fasting animals at baseline, on day 3, and after 1, 2, 4, 6, and 9 weeks. CII degradation was quantified by specific immunoassay, and the changes in severity scores of articular cartilage erosions were visualized and scored in histologic sections of the knees.


RESULTS
Ovariectomy resulted in a marked increase in serum levels of C-telopeptide of type II collagen (CTX-II) (P < 0.001), which could be effectively reversed by 17beta-estradiol supplementation. Oral administration of calcitonin elicited similar decreases in serum levels of CTX-II (P < 0.001). Histologic scoring of cartilage erosion showed significantly less cartilage erosion in calcitonin-treated ovariectomized rats versus control ovariectomized rats that were untreated or treated with 5CNAC alone. (P < 0.01).


CONCLUSIONS
The in vivo effects of calcitonin in rats suggest that calcitonin is able to counteract CII degradation and the accompanying structural disintegration of articular cartilage promoted by estrogen deficiency. Clinical assessment of the chondroprotective potential of calcitonin in postmenopausal women seems warranted.
Sondergaard
Bodil-Cecilie
BC
Nordic Bioscience Diagnostics, Herlev Hovedgade 207, DK-2730 Herlev, Denmark.
Oestergaard
Svetlana
S
Christiansen
Claus
C
Tankó
Laszló B
LB
Karsdal
Morten Asser
MA
D000284:Administration, Oral; D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D002116:Calcitonin / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D024042:Collagen Type I / Q000097:blood; D024043:Collagen Type II / Q000378:metabolism*; D004195:Disease Models, Animal; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D010052:Ovariectomy; D010455:Peptides / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D013264:Stifle / Q000187:drug effects / Q000473:pathology
D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D024043:Collagen Type II; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D004958:Estradiol; C028815:salmon calcitonin; D002116:Calcitonin