The ferret as a small animal model with BMU-based remodelling for skeletal research

Mackey, M. S.<sup>1</sup>; Stevens, M. L.<sup>1</sup>; Ebert, D. C.<sup>1</sup>; Tressler, D. L.<sup>1</sup>; Combs, K. S.<sup>1</sup>; Lowry, C. K.<sup>1</sup>; Smith, P. N.<sup>1</sup>; McOsker, J. E.<sup>1</sup>

Affiliations

¹Procter and Gamble Pharmaceuticals, Norwich, NY, USA

Abstract

The need exists for a small animal model with bone metabolic unit (BMU)-based remodeling to mimic the bone loss found in postmenopausal women. The purpose of this investigation was to evaluate the ferret as a potential model for skeletal research. Specifically, we determined whether the ferret: 1) exhibits evidence of BMU-remodeling, 2) has a skeletal response to parathyroid hormone (PTH) similar to other remodeling species, and 3) loses bone in response to reduced estrogen levels. Methods: Using three sets of experiments, we determined the response of female ferrets to ovariectomy/life cycle manipulation or to administration of PTH. Scanning electron microscopy, light microscopy, determination of estrogen levels and/or single-photon absorptiometry (SPA) were used for evaluation. Results: The ferret was found to exhibit BMU-based remodeling, and may therefore provide a small animal remodeling species for skeletal research. Ferrets reach skeletal maturity between four and seven months of age as evidenced by closure of the growth plate and maturation of trabecluae from thin rods to thick rods and plates. PTH treatment resulted in a marked increase in bone mass accompanied by the PTH-induced tunneling phenomenon known to occur in dogs and humans but not rats. The response to PTH supports the use of the ferret in studies of bone anabolic agents. Bone mass in the proximal tibia was significantly reduced when estrogen depletion was induced by either bilateral ovariectomy or short light/dark cycles (8 hour light, 16 hour dark). Maintenance of intact ferrets under short-light conditions mimiced ovariectomy in terms of serum estrogen levels, uterine weights, and tibial BMD. The bone loss seen following ovariectomy or short light/dark cycles suggests the ferret as a model for evaluating the effects of estrogen-depletion in a remodeling skeleton. Alteration of light-cycles may offer a reversible alternative to surgical induction of estrogen depletion. Conclusions: Based on these observations, we conclude that the ferret may offer an exciting new model for skeletal research.

Links

DOI: 10.1016/8756-3282(95)00330-G

PubMed: 8579916

WoS: A1995TE57600011

Cited By (7)

Year	Entry
1995	Sietsema WK. Animal models of cortical porosity. Bone. October 1995;17(4):S297-S305.
1999	Hirano T, Burr DB, Turner CH, Sato M, Cain RL, Hock JM. Anabolic effects of human biosynthetic parathyroid hormone fragment (1–34), LY333334, on remodeling and mechanical properties of cortical bone in rabbits. J Bone Miner Res. April 1999;14(4):536-545.
2001	Burr DB, Hirano T, Turner CH, Hotchkiss C, Brommage R, Hock JM. Intermittently administered human parathyroid hormone(1–34) treatment increases intracortical bone turnover and porosity without reducing bone strength in the humerus of ovariectomized cynomolgus monkeys. J Bone Miner Res. January 2001;16(1):157-165.
2020	Taylor EA. Validation and Implementation of Vibrational Spectroscopic Measures of Bone Composition [PhD thesis]. Ithaca, NY: Cornell University; December 2020.
2011	Wojda SJ. The Effects of Hibernation on Bone in Yellow-Bellied Marmots [Master's thesis]. Houghton, MI: Michigan Technological University; 2011.
2004	Castillo AB. The Female Ferret (Mustela Putorius Furo) as an in Vivo Model for Skeletal Research [PhD thesis]. Davis, University of California; 2004.
2022	Sales EdS. The Spatio-Temporal Behavior of Basic Multicellular Units in a PTH-Induced Cortical Bone Remodeling Rabbit Model [Master's thesis]. University of Saskatchewan; August 2022.