Kasukawa Yuji, Miyakoshi Naohisa, Srivastava Apurva K, Nozaka Koji, Maekawa Shigeto, Baylink David J, Mohan Subburaman, Itoi Eiji
Division of Orthopedic Surgery, Department of Neuro and Locomotor Science, Akita University School of Medicine, Japan.
Tohoku J Exp Med. 2007 Mar;211(3):275-83. doi: 10.1620/tjem.211.275.
Suppression of increased bone resorption is an important issue in treatment of post-menopausal osteoporosis. Celecoxib is a highly selective inhibitor of cyclooxygenase-2 (COX-2), and inhibits osteoclastogenesis in vitro. In the present study, to test whether celecoxib can suppress elevated bone resorption caused by estrogen deficiency in vivo, celecoxib (4 mg/kg) or its vehicle was administered to sham-operated or ovariectomized (OVX) mice (model of post-menopausal osteoporosis). The treatment with celecoxib or vehicle was started immediately after the sham operation or ovariectomy, and lasted for 4 weeks. At 2 and 4 weeks after surgery, OVX mice administered vehicle had significantly higher levels of C-telopeptide, a marker of bone resorption in serum, than sham-operated mice administered vehicle (37% and 60% higher, respectively; p<0.01). At 2 and 4 weeks after surgery, celecoxib treatment significantly decreased serum C-telopeptide levels in OVX mice, but not in sham-operated mice (45% and 41%, respectively; p<0.001). In contrast, in both sham-operated and OVX mice, celecoxib did not significantly affect serum osteocalcin levels (a marker of bone formation) or bone mineral density (BMD) of the femur, which was evaluated by peripheral quantitative computed tomography (pQCT). In conclusion, treating OVX mice with celecoxib significantly suppressed the increase in serum levels of the bone resorption marker, but did not affect levels of the bone formation marker. Also, celecoxib did not prevent the decrease of femoral BMD in OVX mice. The present study suggests the possibility that celecoxib may be used to prevent bone loss caused by estrogen deficiency.
抑制骨吸收增加是绝经后骨质疏松症治疗中的一个重要问题。塞来昔布是一种高度选择性的环氧化酶-2（COX-2）抑制剂，在体外可抑制破骨细胞生成。在本研究中，为了测试塞来昔布是否能在体内抑制雌激素缺乏引起的骨吸收升高，将塞来昔布（4mg/kg）或其溶媒给予假手术或去卵巢（OVX）小鼠（绝经后骨质疏松症模型）。塞来昔布或溶媒治疗在假手术或去卵巢后立即开始，持续4周。在手术后2周和4周，给予溶媒的OVX小鼠血清中骨吸收标志物C-末端肽水平显著高于给予溶媒的假手术小鼠（分别高37%和60%；p<0.01）。在手术后2周和4周，塞来昔布治疗显著降低了OVX小鼠血清C-末端肽水平，但对假手术小鼠无此作用（分别降低45%和41%；p<0.001）。相反，在假手术和OVX小鼠中，塞来昔布对血清骨钙素水平（骨形成标志物）或通过外周定量计算机断层扫描（pQCT）评估的股骨骨密度（BMD）均无显著影响。总之，用塞来昔布治疗OVX小鼠可显著抑制骨吸收标志物血清水平的升高，但不影响骨形成标志物水平。此外，塞来昔布不能预防OVX小鼠股骨BMD的降低。本研究提示塞来昔布可能用于预防雌激素缺乏引起的骨质流失。
