Review of Nonprimate, Large Animal Models for Osteoporosis Research

Abstract

Large animal models are required for preclinical prevention and intervention studies related to osteoporosis research. The challenging aspect of this requirement is that no single animal model exactly mimics the progression of this human-specific chronic condition. There are pros and cons associated with the skeletal, hormonal, and metabolic conditions of each species that influence their relevance and applicability to human physiology. Of all larger mammalian species, nonhuman primates (NHPs) are preeminent in terms of replicating important aspects of human physiology. However, NHPs are very expensive, putting them out of reach of the vast majority of researchers. Practical, cost-effective alternatives to NHPs are sought after among ungulate (porcine, caprine, and ovine) and canine species that are the focus of this review. The overriding caveat to using large lower-order species is to take the time in advance to understand and appreciate the limitations and strengths of each animal model. Under these circumstances, experiments can be strategically designed to optimize the potential of an animal to develop the cardinal features of postmenopausal bone loss and/or yield information of relevance to treatment.

Wnt3a Reestablishes Osteogenic Capacity to Bone Grafts from Aged Animals

“…The robust bone-inducing capacity of L-Wnt3a prompted us to extend our studies into a large animal, long-bone model 59 . As in humans, aged rabbits experience fatty degeneration of their marrow 60,61 .…”

Longitudinal Assessment of In Vivo Bone Dynamics in a Mouse Tail Model of Postmenopausal Osteoporosis

“…Preclinical studies using animal models that approximate the progression of (postmenopausal) osteoporosis in humans are essential for the development of safer and more effective prevention and treatment of osteoporosis [2]. Removal of the ovaries (ovariectomy) in rats is a well-established model in postmenopausal osteoporosis research [3,4].…”

“…In order to have a valid postmenopausal osteoporosis model, several main requirements have to be fulfilled [2,3]. First, there should be a large amount of bone loss as women can lose up to 20% of their bone mass in the first 5-7 years that follow menopause [22].…”

Animal models to explore the effects of glucocorticoids on skeletal growth and structure

“…Whilst larger animals such as primates and dogs may have the most similar reproductive, anatomical and physiological characteristics, there are ethical issues to consider as well as difficulties with their maintenance and costs (Reinwald & Burr 2008). Sheep, rabbits, and pigs have also been developed as large animal models of GIO in previous studies (Scholz-Ahrens et al 2007, Baofeng et al 2010, Ding et al 2010) but these too have limitations.…”

“…Of these, two of the potentially most serious and challenging to manage are glucocorticoid-induced osteoporosis (GIO) and growth retardation. Osteoporosis is characterized by a reduction in bone mass and loss of bone microarchitecture, leading to impaired bone strength and increased fracture risk (Reinwald & Burr 2008). GIO is the most prevalent type of secondary osteoporosis and accounts for about 25% of cases (Eastell et al 1998).…”