Related Experiment Videos
FDA Guidelines and animal models for osteoporosis
D D Thompson1, H A Simmons, C M Pirie
1Department of Metabolic Diseases, Pfizer Inc., Groton, CT 06340, USA.
Bone
|October 1, 1995
Summary
The ovariectomized (OVX) rat model effectively mimics postmenopausal bone loss in short-term studies for osteoporosis drug evaluation. However, long-term studies show altered bone turnover, complicating efficacy assessments for new osteoporosis therapies.
Area of Science:
- Pharmacology
- Orthopedics
- Endocrinology
Background:
- FDA guidelines recommend specific animal models for osteoporosis drug evaluation.
- The ovariectomized (OVX) rat model is a key component for assessing efficacy and safety.
- The suitability of the OVX rat model for long-term studies requires further investigation.
Purpose of the Study:
- To evaluate the adequacy of the OVX rat model for osteoporosis drug assessment.
- To determine if the recommended endpoints and study design are appropriate.
- To assess the model's utility for both prevention and treatment of osteoporosis.
Main Methods:
- Utilized ovariectomized (OVX) rat models.
- Examined cancellous bone loss and turnover over time.
- Compared OVX rats to sham controls.
- Evaluated bone parameters in proximal tibia, distal femur, and lumbar vertebrae.
Main Results:
- The OVX rat model accurately reflects postmenopausal cancellous bone loss in shorter durations.
- Estrogen effectively prevents OVX-induced bone turnover and loss.
- Over 12 months, bone turnover indices in OVX rats normalize, but bone volume remains reduced.
- This normalization complicates the assessment of therapeutic agents' effects on bone turnover.
Conclusions:
- The OVX rat model is suitable for short-term evaluation of osteoporosis prevention agents.
- Extended study durations (12 months) in OVX rats present challenges for assessing bone turnover.
- Further refinement of study design may be needed for long-term osteoporosis drug efficacy studies.