Oral salmon calcitonin reduces cartilage and bone pathology in an osteoarthritis rat model with increased subchondral bone turnover

被引:90
作者
Nielsen, R. H. [1 ]
Bay-Jensen, A. -C. [1 ]
Byrjalsen, I. [1 ]
Karsdal, M. A. [1 ]
机构
[1] Nord Biosci AS, DK-2730 Herlev, Denmark
关键词
Osteoarthritis; Oral salmon calcitonin; OARSI score; Meniscectomy; Ovariectomy; Rat model; Cartilage pathology; CRUCIATE LIGAMENT TRANSECTION; ESTROGEN REPLACEMENT THERAPY; II COLLAGEN DEGRADATION; ARTICULAR CHONDROCYTES; KNEE OSTEOARTHRITIS; CYNOMOLGUS MONKEYS; SEVERITY; SEX; OSTEOCLASTS; WOMEN;
D O I
10.1016/j.joca.2011.01.008
中图分类号
R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学(修复外科学)];
学科分类号
100224 [整形外科学];
摘要
Objectives: 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. (C) 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:466 / 473
页数:8
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