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Osteoporosis is a metabolic disorder characterized by a loss of bone mass and structure and increasing the risk of fragility fractures, mostly among postmenopausal women. Sheep is a recognized large animal model for osteoporosis research. An experimental group of ewes (3-4 years old) was subjected to ovariectomy (OVX) and weekly glucocorticoid (GC) application for 24 weeks and compared with a sham control group. Blood and bone marrow parameters were analyzed before and 24 weeks after OVX and GC administration. Osteopenia was confirmed through micro-computed tomography and histomorphometric analysis of L4 vertebra in the study end. A statistically significant increase was observed in mean corpuscular volume, mean cell hemoglobin and monocytes and a decrease in red blood count and eosinophils (p<0.05). Alkaline phosphatase (ALP), gamma-glutamyl transpeptidase, magnesium and α1-globulin increased, and creatinine, albumin, sodium and estradiol decreased (p<0.05). A slight decrease of bone formation markers (bone ALP and osteocalcin) and an increase of bone resorption markers (C-terminal telopeptides of collagen type 1 and tartrate-resistant acid phosphatase) were observed, but without statistical significance. This study aims to contribute to better knowledge of sheep as a model for osteoporosis research and the consequences that a performed induction protocol may impose on organic metabolism.

Purpose of the Review: This review summarizes research on the use of sheep and goats as large animal models of human osteoporosis for preclinical and translational studies., Recent Findings: The most frequent osteoporotic sheep model used is the ovariectomized sheep with 12 months post-operatively or more and the combined treatment of ovariectomized sheep associated to calcium/vitamin D-deficient diet and glucocorticoid applications for 6 months, but other methods are also described, like pinealectomy or hypothalamic-pituitary disconnection in ovariectomized sheep. The goat model for osteoporosis research has been used in a very limited number of studies in osteoporosis research relative to sheep. These osteoporotic small ruminant models are applied for biomaterial research, bone augmentation, efficacy of implant fixation, fragility fracture-healing process improvement, or bone-defect repair studies in the osteopenic or osteoporotic bone. Sheep are a recognized large animal model for preclinical and translational studies in osteoporosis research and the goat to a lesser extent. Recently, the pathophysiological mechanism underlying induction of osteoporosis in glucocorticoid-treated ovariectomized aged sheep was clarified, being similar to what occurs in postmenopausal women with glucocorticoid-induced osteoporosis. It was also concluded that the receptor activator of NF-κB ligand was stimulated in the late progressive phase of the osteoporosis induced by steroids in sheep. The knowledge of the pathophysiological mechanisms at the cellular and molecular levels of the induction of osteoporosis in small ruminants, if identical to humans, will allow in the future, the use of these animal models with greater confidence in the preclinical and translational studies for osteoporosis research.