Ovariectomized rat model of osteoporosis: a practical guide

Abstract

Osteoporosis affects about 200 million people worldwide and is a silent disease until a fracture occurs. Management of osteoporosis is still a challenge that warrants further studies for establishing new prevention strategies and more effective treatment modalities. For this purpose, animal models of osteoporosis are appropriate tools, of which the ovariectomized rat model is the most commonly used. The aim of this study is to provide a 4-step guideline for inducing a rat model of osteoporosis by ovariectomy (OVX): (1) selection of the rat strain, (2) choosing the appropriate age of rats at the time of OVX, (3) selection of an appropriate surgical method and verification of OVX, and (4) evaluation of OVX-induced osteoporosis. This review of literature shows that (i) Sprague-Dawley and Wistar rats are the most common strains used, both responding similarly to OVX; (ii) six months of age appears to be the best time for inducing OVX; (iii) dorsolateral skin incision is an appropriate choice for initiating OVX; and (iv) the success of OVX can be verified 1-3 weeks after surgery, following cessation of the regular estrus cycles, decreased estradiol, progesterone, and uterine weight as well as increased LH and FSH levels. Current data shows that the responses of trabecular bones of proximal tibia, lumbar vertebrae and femur to OVX are similar to those in humans; however, for short-term studies, proximal tibia is recommended. Osteoporosis in rats is verified by lower bone mineral density and lower trabecular number and thickness as well as higher trabecular separation, changes that are observed at 14, 30, and 60 days post-OVX in proximal tibia, lumbar vertebrae and femur, respectively.

Keywords: animal model; bone; osteoporosis; ovariectomy; rat.

Table 1. Advantages and disadvantages of OVX at different ages in rats (Kalu, 1991; Grynpas et al., 2000; Jee and Yao, 2001; Laib et al., 2001; Johnston and Ward, 2015; Liu et al., 2015; Jiang et al., 2018)

Table 2. Potential limitations and proposed solutions for using the ovariectomized rat model of osteoporosis

Figure 1. Step-by-step guideline for inducing osteoporosis using an ovariectomized rat model. OVX, ovariectomy; LH, luteinizing hormone; FSH, follicle stimulating hormone; BMD, bone mineral density; Tb.N, trabecular number; Tb.Sp, trabecular separation; Tb.Th, trabecular thickness; P1NP, amino-terminal propeptides of procollagen type I; CTX, carboxy-terminal cross-linking telopeptide of type I collagen.

Figure 2. Effect of ovariectomy (OVX) on trabecular bone volume of proximal tibia, lumbar vertebrae and femur in rat

Figure 3. Effect of ovariectomy (OVX) on bone mineral density (BMD) of proximal tibia, lumbar vertebrae and femur in rat

Figure 4. Effect of ovariectomy (OVX) on trabecular number (Tb.N) (A), trabecular separation (Tb.Sp) (B), and trabecular thickness (Tb.Th) (C) of proximal tibia, lumbar vertebrae and femur in rat