The Ovariectomized Sheep as a Model for Human Bone Loss

Newton, B.I.; Cooper, R.C.; Gilbert, John E.; Johnson, Roger B.; Zardiackas, Lyle D.

doi:10.1016/j.jcpa.2003.12.007

Cited by 52 publications

(53 citation statements)

References 18 publications

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“…However, the time required to establish an accurate osteoporosis model remains inconsistent between studies. A number of previous studies (20)(21)(22)(23) have found that bone formation in sheep continues to decline between 10 weeks and 6 months after an ovariectomy, with certain studies reporting that the BMD significantly decreases 6 months after an ovariectomy (24); however, other studies have not observed these results (25).…”

Section: Discussionmentioning

confidence: 99%

Long-term effects of ovariectomy on the properties of bone in goats

Wang

Tang

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. Large animal models of osteoporosis are essential for osteoporosis research. However, the time required to establish an accurate osteoporosis model is unknown. Therefore, the aim of the present study was to establish a large animal model of osteoporosis in goats. In total, 14 Chinese goats were divided into an ovariectomized (OVX, n=7) or sham-operated (SHAM, n=7) group. Vertebral bodies were used to measure the bone mineral density (BMD) prior to the ovariectomy and at 24 months after the ovariectomy. In addition, the BMD of the femoral neck, femoral diaphysis and tibial diaphysis were measured 24 months postoperatively. Bone samples from the vertebral body, femoral head and femoral neck were scanned by micro-computed tomography (CT) to visualize the trabecular and cortical microstructure. Furthermore, the vertebral body, femoral head, femoral neck and tibial diaphysis were analyzed for mechanical strength. The BMD of vertebral body of the OVX group decreased significantly (P<0.01) at 24 months after the ovariectomy when compared with the baseline measurements. Micro-CT scans of the vertebral body revealed that the bone volume fraction, trabecular number, trabecular thickness and the degree of anisotropy decreased by 37.1, 36.7, 10.5 and 16.5%, respectively (P<0.01) in the OVX group when compared with the SHAM group. Additionally, the specific bone surface and trabecular spacing significantly increased by 37.7 and 62%, respectively in the OVX group (P<0.001). Cortical bone porosity in the vertebral body and femoral neck was greater in the OVX group when compared with the SHAM group (P<0.05). In addition, mechanical testing revealed a statistically significant difference between the vertebral bodies of the OVX group and the SHAM group. In conclusion, the present study demonstrated that an ovariectomy was able to induce significant osteoporosis and deterioration of mechanical properties in the bones of goats.

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Section: Discussionmentioning

confidence: 99%

Long-term effects of ovariectomy on the properties of bone in goats

Wang

Tang

et al. 2015

Experimental and Therapeutic Medicine

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“…Bone loss at both anatomical sites was in excess of 25% (after 5 months of treatment) which is sufficient to categorise these animals as osteoporotic [24] supporting the stated hypothesis and suggests that the mechanism of bone loss could differ temporally as well as anatomically. Bone loss has been reported previously at various skeletal sites in sheep following ovariectomy [5,16,27,28,42], chronic steroid therapy [7,10] or dietary manipulation [9], but in none of these studies, could these animals be classified as osteoporotic by standard definitions. Other studies have implemented combination treatments to induce osteoporosis in sheep [13, 14, 19-21, 29, 32, 33] and although such treatments have resulted in further bone loss compared to the single treatments, lumbar spine BMD was either not reduced significantly [13,29,32,33] or it did not achieve the minimum of 25% bone loss [20,21] required to classify them as osteoporotic.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown that sheep develop osteopaenia at various sites to different extents following ovariectomy [16,27,28,42], chronic steroid therapy [7,10] or dietary manipulation [9] or combinations of these treatments [13, 14, 19-21, 29, 32, 33, 42] but invariably either the BMD of the lumbar spine was not investigated as these studies were focussed more on developing models for repair of long bone fractures or if the spine was investigated the reduction of BMD fell substantially short of the generally accepted definition of osteoporosis in humans, which is BMD B 25% of the young normal value [24].…”

Section: Introductionmentioning

confidence: 99%

Validation of the sheep as a large animal model for the study of vertebral osteoporosis

Zarrinkalam¹,

Beard²,

Schultz

et al. 2008

Eur Spine J

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Rats have long been the animal of choice for research in the field of osteoporosis. In the search for a complementary large animal model the sheep appears useful but hitherto the extent of bone loss from the spine has failed to reach a level that is generally accepted as osteoporotic in humans. Osteoporosis was induced in ten sheep using ovariectomy, low calcium diet and steroid injection for 6 months. Bone samples of iliac crest (IC), lumbar spine (LS), and proximal femur (PF) from the osteoporotic sheep were compared with those from four normal sheep using densitometry, histomorphometry, biochemistry and basic mechanical testing. The differences were examined using an analysis of variance with Tukey-Kramer test. Overall, the bone mineral density at LS and PF decreased more than 25% after treatment. Trabecular bone volume decreased by 29.2, 33.4 and 42.6% in IC, LS and PF, respectively. The failure load of the LS in axial compression was reduced to 2,003 from 6,140 N. The extent of bone loss was sufficient to categorise these sheep as osteoporotic although the pattern of bone loss varied between sites. Reduced mechanical competence in LS confirmed the suitability of this model for evaluation of potential treatments for osteoporosis.

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“…The sheep model seems to be the best one, due to its appropriate rate of metabolism of bone tissue together with the size and anatomy of its skeleton (Newton et al 2004, Oheim et al 2012. Osteoporosis, as defined above, does not directly affect animals, therefore one of the first stages of examination performed in vivo on animal models is to provide conditions which are clinically similar to osteoporosis.…”

Section: Introductionmentioning

confidence: 99%

The experimental osteoporosis in sheep – clinical approach

Kiełbowicz¹,

Piątek²,

Bieżyński³

et al. 2015

Polish Journal of Veterinary Sciences

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The implementation of new methods of oseoporotic therapy requires tests on an animal model. One of the best is the sheep, whose numerous advantages over other models are described in the literature. The aim of this study was induction of osteoporosis using steroids and ovariorectomy methods in sheep and description of the change in parameters with regard to healthy sheep. The study was performed on female "merino" breed sheep divided into three groups: Negative control (NC) healthy animals, positive control (PC) ovariorectomised animals and steroid group (SC) where methylprednisolone was implemented. Blood tests, diagnostic arthroscopy, quantitative computed tomography and X-Ray micro-tomography of bone were carried out. Blood tests revealed a decreased level of estrogens, progesterone and increased parathormone and cortisol levels in the SC group. A decrease in bone turnover markers and an increase in bone resorption markers in all groups were also noted. Diagnostic arthroscopy revealed osteoarthrosis in PC and SC groups. Radiological density tests showed a slight decrease in PC and NC groups whereas there was more than a triple decrease in SC. Results obtained from microCT showed quickly developing osteoporosis in the SC group, which is reflected in numerous parameters analysed in this study. The best effects for osteoporosis induction were obtained using ovariorectomised sheep with methylprednisolone injections.

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The Ovariectomized Sheep as a Model for Human Bone Loss

Cited by 52 publications

References 18 publications

Long-term effects of ovariectomy on the properties of bone in goats

Long-term effects of ovariectomy on the properties of bone in goats

Validation of the sheep as a large animal model for the study of vertebral osteoporosis

The experimental osteoporosis in sheep – clinical approach

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