An Ovariectomy-Induced Rabbit Osteoporotic Model: A New Perspective

Wanderman, Nathan Robert; Mallet, Cindy; Giambini, Hugo; Bao, Nirong; Zhao, Chunfeng; An, Kai Nan; Freedman, Brett A; Nassr, Ahmad

Abstract

STUDY DESIGN: Experimental Animal Model. PURPOSE: The aim of our study was to validate a pure bilateral ovariectomy (OVX) female New Zealand white rabbit model of postmenopausal osteoporosis utilizing animal-sparing in vivo techniques for evaluating bone mineral density (BMD). We also sought to demonstrate that bilateral OVX in female New Zealand white rabbits can produce diminished BMD in the spinal column and simulate osteoporosis, without the need for adjuvant chemotherapeutic agents (i.e., no additional glucocorticosteroids or other drugs were used for stimulating accelerated BMD loss), which can be assessed by in vivo BMD testing. OVERVIEW OF LITERATURE: Multiple animal models of postmenopausal osteoporosis have been described. Rat ovariectomy models have been successful, but are limited by rats' inability to achieve true skeletal maturity and a slight morphology that limits surgical instrumentation. Rabbit models have been described which do not have these limitations, but previous models have relied on adjunctive steroid therapy to achieve osteoporosis and have required animal sacrifice for bone mineral density assessment.
METHODS
Thirty-six skeletally mature female rabbits underwent bilateral OVX. BMD was measured using dual-energy X-ray absorptiometry on the metaphysis of the proximal tibia and distal femur, at baseline and 17 weeks postoperatively.
RESULTS
Mean BMD values were significantly reduced by 21.9% (p < 0.05) in the proximal tibia and 11.9% (p < 0.001) in the distal femur at 17 weeks.
CONCLUSIONS
This study is the first to demonstrate a significant bone loss within four months of pure OVX in rabbits using animal-sparing validation techniques. We believe that this OVX model is safe, reproducible, and can be employed to longitudinally evaluate the effect of anti-osteoporosis therapeutics and surgical interventions.