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

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.