The Selective Cyclooxygenase-2 Inhibitor Celecoxib Reduces Bone Resorption, but not Bone Formation, in Ovariectomized Mice in Vivo

The Selective Cyclooxygenase-2 Inhibitor Celecoxib Reduces Bone Resorption, but not Bone Formation, in Ovariectomized Mice in Vivo

YUJI KASUKAWA,¹ NAOHISA MIYAKOSHI,¹ APURVA K. SRIVASTAVA,^2,3 KOJI NOZAKA,¹ SHIGETO MAEKAWA,¹ DAVID J. BAYLINK,^2,3 SUBBURAMAN MOHAN^2,3 and EIJI ITOI¹

¹Division of Orthopedic Surgery, Department of Neuro and Locomotor Science, Akita University School of Medicine, Akita, Japan
²Musculoskeletal Disease Center, Jerry L. Pettis VA Medical Center, Loma Linda, CA, USA
³Department of Medicine, Loma Linda University, Loma Linda, CA, USA

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.

keywords —— celecoxib; cyclooxygenase-2 (COX-2) inhibitor; ovariectomized mice; bone formation; bone resorption

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Tohoku J. Exp. Med., 2007, 211, 275-283

Correspondence: Yuji Kasukawa, M.D., Department of Orthopedic Surgery, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.

e-mail: kasukawa@doc.med.akita-u.ac.jp