Skeletal changes in the ovariectomised ewe and subsequent response to treatment with 17β oestradiol

Hornby, Simon B.; Ford, Susan L.; Mase, C.A.; Evans, G.P.

doi:10.1016/8756-3282(95)00316-6

Cited by 36 publications

(30 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Furthermore significant changes in BMD between the baseline and 6 month control animals may indicate some seasonal influence on bone status as described previously [9,16,29,42] and for this reason it is essential to include appropriate control groups to make valid comparisons [41].…”

Section: Discussionmentioning

confidence: 96%

“…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%

See 2 more Smart Citations

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

Zarrinkalam¹,

Beard²,

Schultz

et al. 2008

Eur Spine J

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Zarrinkalam¹,

Beard²,

Schultz

et al. 2008

Eur Spine J

View full text Add to dashboard Cite

show abstract

“…Yes (Ն6-mo) (120) Yes (32) Yes(1-yr) (120) Seasonal changes in BMD Possible (161,162) No No Likely Yes (163) E 2 decrease post-OX (see references in Table 2) Yes Variable: yes, no (24) Yes Yes…”

Section: ∼70-80mentioning

confidence: 99%

Review of Nonprimate, Large Animal Models for Osteoporosis Research

Reinwald

Burr

2008

Journal of Bone and Mineral Research

134

105

View full text Add to dashboard Cite

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.

show abstract

“…9 The sheep is often used as an animal model for studying different aspects of orthopedic research. [10][11][12][13][14][15][16][17][18][19] The OVX sheep has been found to be a particularly useful model for human bone turnover and remodeling activity. 11,20,21 In this study, we used an OVX sheep model to study the effects of increased bone turnover on compact bone mechanical and material properties.…”

mentioning

confidence: 99%

Effects of ovariectomy on bone turnover, porosity, and biomechanical properties in ovine compact bone 12 months postsurgery

Kennedy

Brennan

Rackard

et al. 2009

Journal Orthopaedic Research

View full text Add to dashboard Cite

Compact bone makes up approximately 80% of the human skeleton by mass; but there are little data available on the effects of increased bone turnover on compact bone mechanical and material properties. This study addresses this question by measuring intracortical remodeling, resorption cavity number, and porosity in an ovariectomized (OVX) sheep model, and measures changes in biomechanical properties. Thirty-eight sheep were divided into two groups. Group 1 were controls (n ¼ 19), and Group 2 were ovariectomized (OVX; n ¼ 19). Fluorochrome dyes were administered intravenously to both groups at five time points over 12 months post-OVX to label sites of bone turnover. At 12 months post-OVX all animals were euthanized. Samples were harvested from the left metatarsal and were analyzed for intracortical bone turnover at five time points, the number of resorption cavities, and the level of intracortical porosity. The effects of these parameters on bone biomechanical properties were then measured. Bone turnover was increased in the OVX group at 6, 9, and 12 months (p < 0.05). Resorption was also higher in the OVX group at 12 months (p < 0.05). Furthermore, porosity was significantly increased in the OVX group at 12 months (p < 0.05). Stiffness and yield strength were reduced in the OVX group compared to controls (p ¼ 0.05). Ultimate compressive strength and work to fracture did not differ between groups. These findings provide new insights into the mechanisms and effects of increased bone turnover on bone material and microstructural properties. Keywords: bone turnover; porosity; ovariectomy; ovine animal model Bone turnover is an important determinant of the structural integrity of bone. It is a crucial process of tissue renewal that normally occurs at an optimal physiological rate for maximum bone strength in a healthy individual. 1 Any change to the optimal bone turnover rate, such as the increase that occurs following ovariectomy (OVX) or menopause, has the potential to dramatically change the bone at microstructural and material levels. High bone turnover can have the effect of increasing remodeling spaces, accelerating bone loss, increasing stress concentrations, and increasing cortical porosity, each of which can undermine bone mechanical properties. A precise definition of bone quality remains elusive, however; bone turnover and microarchitecture are considered to be two important contributors to this phenomenon along with mineralization, microdamage, and collagen content. Thus, these parameters are important considerations in the pathophysiology of skeletal diseases such as osteoporosis and the mechanisms that underlie fracture. 2 Previous studies have shown that bone turnover has a direct influence on fracture risk. 3 It is thought that compact bone is affected by accelerated turnover in two ways. First, more mineralized bone is removed and replaced with younger, less mineralized bone, which reduces the material's local stiffness. Second, the presence of more resorption cavities creates stress concen...

show abstract

Skeletal changes in the ovariectomised ewe and subsequent response to treatment with 17β oestradiol

Cited by 36 publications

References 7 publications

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

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

Review of Nonprimate, Large Animal Models for Osteoporosis Research

Effects of ovariectomy on bone turnover, porosity, and biomechanical properties in ovine compact bone 12 months postsurgery

Contact Info

Product

Resources

About