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Published on: June 8, 2014
The selective cyclooxygenase-2 inhibitor celecoxib reduces bone resorption, but not bone formation, in ovariectomized
Yuji Kasukawa1, Naohisa Miyakoshi, Apurva K Srivastava
1Division of Orthopedic Surgery, Department of Neuro and Locomotor Science, Akita University School of Medicine, Japan. kasukawa@doc.med.akita-u.ac.jp
Abstract:
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.
Insights
Celecoxib, a COX-2 inhibitor, significantly reduced bone resorption markers in ovariectomized mice, a model for post-menopausal osteoporosis. However, it did not impact bone formation or bone mineral density, suggesting potential for preventing estrogen-deficiency-induced bone loss.
Area of Science:
- Endocrinology
- Bone Biology
- Pharmacology
Background:
- Post-menopausal osteoporosis is characterized by increased bone resorption due to estrogen deficiency.
- Selective cyclooxygenase-2 (COX-2) inhibitors, like celecoxib, have shown potential in inhibiting osteoclastogenesis in vitro.
- Evaluating celecoxib's efficacy in vivo for suppressing bone loss is crucial for osteoporosis treatment.
Purpose of the Study:
- To investigate the in vivo effects of celecoxib on elevated bone resorption in a mouse model of post-menopausal osteoporosis.
- To determine if celecoxib administration can suppress bone resorption markers caused by estrogen deficiency.
- To assess celecoxib's impact on bone formation markers and bone mineral density.
Main Methods:
- Ovariectomized (OVX) and sham-operated mice were treated with celecoxib (4 mg/kg) or vehicle for 4 weeks.
- Serum levels of C-telopeptide (bone resorption marker) and osteocalcin (bone formation marker) were measured at 2 and 4 weeks.
- Femoral bone mineral density (BMD) was assessed using peripheral quantitative computed tomography (pQCT).
Main Results:
- OVX mice exhibited significantly higher C-telopeptide levels compared to sham-operated controls.
- Celecoxib treatment significantly decreased serum C-telopeptide levels in OVX mice by 41-45% (p<0.001).
- Celecoxib did not significantly alter serum osteocalcin levels or femoral BMD in either OVX or sham-operated mice.
Conclusions:
- Celecoxib effectively suppresses elevated bone resorption in a mouse model of estrogen deficiency.
- The drug does not appear to affect bone formation markers or prevent bone mineral density loss.
- These findings suggest celecoxib may hold potential for preventing bone loss associated with estrogen deficiency.
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