Animal models for the study of bone loss after cessation of ovarian function

Rodgers, Janet B.; Monier‐Faugere, Marie‐Claude; Malluche, Hartmut H.

doi:10.1016/8756-3282(93)90166-8

Cited by 65 publications

(34 citation statements)

References 22 publications

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“…Many factors must be considered when discussing possible models for osteoporosis, and these are well defined by Rodgers et al (1993) as "convenience, relevance (comparability to the human condition), and appropriateness: a complex of other factors that make a given species the best for studying a particular phenomenon". An appropriate animal model for any research should be based on the following considerations: "1) appropriateness as an analog, 2) transferability of information, 3) genetic uniformity of organisms where applicable, 4) background knowledge of biological properties, 5) cost and availability, 6) generalizability of the results, 7) ease and adaptability to experimental manipulation, 8) ecological considerations, and 9) ethical and societal implications" (Davidson et al, 1987).…”

Section: Requirements For An Ideal Animal Modelmentioning

confidence: 99%

Animal models of osteoporosis - necessity and limitations

2001

eCM

240

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There is a great need to further characterise the available animal models for postmenopausal osteoporosis, for the understanding of the pathogenesis of the disease, investigation of new therapies (e.g. selective estrogen receptor modulators (SERMs)) and evaluation of prosthetic devices in osteoporotic bone. Animal models that have been used in the past include non-human primates, dogs, cats, rodents, rabbits, guinea pigs and minipigs, all of which have advantages and disadvantages. Sheep are a promising model for various reasons: they are docile, easy to handle and house, relatively inexpensive, available in large numbers, spontaneously ovulate, and the sheep's bones are large enough to evaluate orthopaedic implants. Most animal models have used females and osteoporosis in the male has been largely ignored. Recently, interest in development of appropriate prosthetic devices which would stimulate osseointegration into osteoporotic, appendicular, axial and mandibular bone has intensified. Augmentation of osteopenic lumbar vertebrae with bioactive ceramics (vertebroplasty) is another area that will require testing in the appropriate animal model. Using experimental animal models for the study of these different facets of osteoporosis minimizes some of the difficulties associated with studying the disease in humans, namely time and behavioral variability among test subjects. New experimental drug therapies and orthopaedic implants can potentially be tested on large numbers of animals subjected to a level of experimental control impossible in human clinical research.

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Section: Requirements For An Ideal Animal Modelmentioning

confidence: 99%

Animal models of osteoporosis - necessity and limitations

2001

eCM

240

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“…There are several hypotheses attempting to explain its action on bone resorption (3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Among the different animal models (13)(14)(15)(16) and methods (17) applied in studies inducing osteoporosis, the model most frequently used is the ovariectomized rat (18)(19)(20)(21). This model allows us to study the bone loss and to evaluate the effects of drugs commonly used to treat osteoporosis.…”

Section: Introductionmentioning

confidence: 99%

Effect of 17ß-estradiol or alendronate on the bone densitometry, bone histomorphometry and bone metabolism of ovariectomized rats

Paz

Falco

Teng

et al. 2001

Braz J Med Biol Res

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The objective of the present study was to evaluate the effect of 17ß-estradiol or alendronate in preventing bone loss in 3-month-old ovariectomized Wistar rats. One group underwent sham ovariectomy (control, N = 10), and the remaining three underwent double ovariectomy. One ovariectomized group did not receive any treatment (OVX, N = 12). A second received subcutaneous 17ß-estradiol at a dose of 30 µg/ kg for 6 weeks (OVX-E, N = 11) and a third, subcutaneous alendronate at a dose of 0.1 mg/kg for 6 weeks (OVX-A, N = 8). Histomorphometry, densitometry, osteocalcin and deoxypyridinoline measurements were applied to all groups. After 6 weeks there was a significant decrease in bone mineral density (BMD) at the trabecular site (distal femur) in OVX rats. Both alendronate and 17ß-estradiol increased the BMD of ovariectomized rats, with the BMD of the OVX-A group being higher than that of the OVX-E group. Histomorphometry of the distal femur showed a decrease in trabecular volume in the untreated group (OVX), and an increase in the two treated groups, principally in the alendronate group. In OVX-A there was a greater increase in trabecular number. An increase in trabecular thickness, however, was seen only in the OVX-E group. There was also a decrease in bone turnover in both OVX-E and OVX-A. The osteocalcin and deoxypyridinoline levels were decreased in both treated groups, mainly in OVX-A. Although both drugs were effective in inhibiting bone loss, alendronate proved to be more effective than estradiol at the doses used in increasing bone mass.

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“…However, although the pig is an excellent model for human bone study, it grows to an excessively large adult body weight of approximately 150 kg. In contrast, miniature pig rarely exceeds 60 kg at maturity, requires less housing space, and does not require special handling equipment [28,37]. Consequently, in the future, more investigators may turn to the miniature pig as model for bone research, but at present virtually nothing is known of bone change with age in this animal.…”

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confidence: 99%

“…The pig is an excellent model of the human because it is omnivore and diurnal animal, and has a 21-day reproductive cycle that is similar to the human menstrual cycle [28,37]. Previous study has presented that pig has trabecular bone with a lamellar structure and a remodeling sequence similar to that of human bone [26].…”

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Age-Related Changes of Bone Mineral Density and Microarchitecture in Miniature Pigs

Inui

Itamoto

Takuma³

et al. 2004

J. Vet. Med. Sci.

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ABSTRACT. Bone mineral density (BMD), distribution of its density and bone histomorphometric parameters were evaluated in lumbar vertebra of normally growing miniature pigs. The fourth lumbar vertebra (L4) of the Göttingen miniature pig were used in this cross-sectional study in vitro. The BMD of the miniature pig was similar to that of humans in tendency of gender differences and some growth patterns during puberty. In these regards this animal appears useful as a model for human bone study. However, the trabecular and cortical BMDs of lumbar spine were extremely high value (399.43 ± 26.36 mg/cm 3 in female trabeculae; 973.06 ± 69.55 mg/cm 3 in female cortical bone; 419.04 ± 34.84 mg/cm 3 in male trabeculae; 1038.81 ± 125.72 mg/cm 3 in male cortical bone in pigs 30 months or more). Furthermore, histomorphometric analysis yielded values that were remarkably different from those found in humans. From these results, it was revealed that miniature pig had a higher bone mass and denser trabecular network than human, indicating that its bone is probably stronger. Therefore, care should be taken in choosing the miniature pig as a bone study model. KEY WORDS: bone mineral density, histomorphometric analyses, lumbar spine, miniature pig.J. Vet. Med. Sci. 66(6): 599-609, 2004 Metabolic bone diseases such as osteoporosis are becoming more important because of an aging society in human medicine. These diseases increase the risk of fragility fracture as bone mineral levels decrease, and also reduces their quality of life. Previous studies have reported that bone strength and fracture risk are closely related to bone mineral density (BMD) [6,9,27]. In contrast, several studies have suggested that changes in bone architecture increase fracture risk [29,31,33,34,43]. Therefore, it is necessary to study the changes in both BMD and architecture for more sensitive investigation of the bone disease.Quantitative computed tomography (QCT) has been widely investigated and applied in recent years as a means of non-invasive quantification of BMD. It has been reported that QCT might be most sensitive to changes in bone density caused by rapid bone turnover, such as in menopausal immobilization or hyperthyroidism [9]. QCT can selectively measure both trabecular and cortical bone [9,13,22,38], and the BMD is expressed in milligrams per cubic centimeter (volumetric density) [9]. Ebbesen et al. showed highly correlation between BMD by QCT and compressive strength in the lumbar vertebrae [9].Several studies have reported that bone disorders such as osteoporosis lead to trabecular and cortical bone alterations in humans. These alterations are characterized not only by a reduction of bone mass but also by structural changes in microarchitecture which is measured by histomorphometry of bone [29,31,33]. Therefore, it has been considered that histomorphometric analysis have an important role as contributor to bone strength, in addition to BMD.Recently, miniature pig has been noticed as for experimental animal of bone study. The pig is an excel...

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Animal models for the study of bone loss after cessation of ovarian function

Cited by 65 publications

References 22 publications

Animal models of osteoporosis - necessity and limitations

Animal models of osteoporosis - necessity and limitations

Effect of 17ß-estradiol or alendronate on the bone densitometry, bone histomorphometry and bone metabolism of ovariectomized rats

Age-Related Changes of Bone Mineral Density and Microarchitecture in Miniature Pigs

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