Oral salmon calcitonin reduces cartilage and bone pathology in an osteoarthritis rat model with increased subchondral bone turnover.
OBJECTIVE
Traumatic osteoarthritis (OA) is possibly augmented by effects from loss of sex hormones. Salmon calcitonin is shown to reduce OA pathogenesis and bone resorption. We investigated the effects of oral salmon calcitonin treatment and ovariectomy on cartilage and bone pathology in a traumatic OA model.


METHODS
Six groups with 10 7-month-old female Sprague Dawley rats each were subjected to bilateral meniscectomy (MNX), ovariectomy (OVX) or Sham surgery and treated for 8 weeks with oral salmon calcitonin (CT) or vehicle (V) in the following way: (1) Sham+V; (2) MNX+V; (3) MNX+CT; (4) OVX+V; (5) MNX/OVX+V; (6) MNX/OVX+CT. Weights were recorded weekly and CTX-II was measured in serum. At termination 56 days post-surgery, the right tibia was analyzed for changes in articular cartilage thickness, extent of cartilage damage and subchondral bone changes in predefined zones, as recommended in the novel OARSI histopathology score.


RESULTS
The combined MNX/OVX model produced a significantly reduced cartilage thickness (P=0.033) in the outer zone (Z1) of the tibial plateau and increased calcified cartilage damage (P=0.0004) and serum CTX-II (P=0.003). Addition of OVX to MNX significantly increased the width of matrix damage at the surface (P=0.025) and 50% cartilage depth (P=0.004). Treatment with oral salmon calcitonin counteracted the loss of cartilage thickness (P=0.055), significantly reduced subchondral bone damage score (P=0.019) and reduced the type II collagen degradation (P=0.009).


CONCLUSIONS
Addition of ovariectomy augmented site-specific traumatic OA pathology, which was reduced by oral salmon calcitonin treatment. Treatments for OA might ideally affect both bone and cartilage.
Nordic Bioscience A/S, Herlev Hovedgade 207, DK-2730 Herlev, Denmark. rhn@nordicbioscience.com
R H
RH
Nielsen
A-C
AC
Bay-Jensen
I
I
Byrjalsen
M A
MA
Karsdal
D000284:Administration, Oral; D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D002116:Calcitonin / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D010003:Osteoarthritis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000473:pathology*
D050071:Bone Density Conservation Agents; C028815:salmon calcitonin; D002116:Calcitonin