Changes in Skeletal Mass and Fragility With Castration in the Rat: A Model of Osteoporosis*

Saville, Paul D.

doi:10.1111/j.1532-5415.1969.tb03169.x

Cited by 153 publications

(52 citation statements)

References 9 publications

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“…The increase curve of body weight in females was different from that of males; the body weight in males increased until 12 months and then reached a plateau (about 400 g), whereas that in females continued to increase to about 300 g (Fig. 1), but our data showed that the BMD values in females were also higher than those in males, as observed in Charles River CD rats aged 23~150 days after birth by Saville [28]. Wronski et al [35] have reported that bone loss is induced regardless of the increase in body weight after ovariectomy, although the tendency to slightly increase bone volume is observed partly in the metaphyses of long bones.…”

Section: Discussioncontrasting

confidence: 50%

Age-Related Changes in Bone Mineral Density, Cross-Sectional Area and the Strength of Long Bones in the Hind Limbs and First Lumbar Vertebra in Female Wistar Rats

Fukuda¹,

Iida²

2004

J. Vet. Med. Sci.

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ABSTRACT. Age-related changes in bone mineral density (BMD) and cross-sectional area and bone strength index (SSI) of the femur, tibia, humerus, and first lumbar vertebra in female Wistar (WM/MsNrs) rats were examined by a quantitative computed tomography (pQCT) method. One hundred and sixteen virgin female Wistar (WM/MsNrs) rats aged 2-33 months were used. The data indicate that the to tal BMD values of metaphyses and diaphyses of long bones increased until 12 months, then decreased to a varying degree depending on the bone after 15-24 months, but the values of cortical and trabecular BMD with age were not always similar to the total BMD value. Nevetheless, the values for cross-sectional area and SSI in the long bones increased regardless of the total BMD decrease with a ge, indicating that this increase might have been due to a characteristic of the modeling pattern in rats. The total and cortical BMD values in the first lumbar vertebra decreased after 18 months, and SSI did after 15 months. The data obtained in this study were compared with those obtained from males in a previous study. In conclusion, it was indicated that in this strain the rats over 12 months with the highest total BMD values in the femur and tibia, and before the onset of various tumors, are useful as a model animal for osteoporosis experiments and observation of senile bone change. KEY WORDS: bone mineral density, cross-sectional area, female Wistar rat (WM/MsNrs), pQCT, strength strain index.J. Vet. Med. Sci. 66 (7): [755][756][757][758][759][760] 2004 We have previously reported the age-related changes in bone mineral density (BMD), cross-sectional area, and strength strain index (SSI), an indicator of bone fragility, in male rats [17], as rats are widely used for experiments regarding bone disease and for pharmacological tests. Female rats are more frequently used than males, for example, as a model of postmenopausal osteoporosis after ovariectomy treatment. Nevertheless, the differences between rats and humans in bone metabolic and morphologic characteristics have been contested [2,7,8,18,25,34]. Furthermore, although many studies on bones in the rat have carried out, the data have varied because of differences in the bones observed and the measurement methods [3,9,11,13,16,22,27,32,33].We consider it important to clarify the age-related changes in bones throughout the life span of rats to determine whether it is worthwhile to use rats in studies related to bones. Our report regarding the life span and incidence of tumors in this strain is available to aid in our understanding of the changes in bones with age in rats as laboratory animals [10].The measurement of BMD, cross-sectional area, and SSI in the present study was done by the QCT method because this method has merits with regard to simultaneously measuring BMD and morphologic features by separating trabecular and cortical bones, and because it can be carried out in live rats, the same as in clinical use for humans, as described previously [17].The purpose of the present stud...

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Section: Discussioncontrasting

confidence: 50%

Age-Related Changes in Bone Mineral Density, Cross-Sectional Area and the Strength of Long Bones in the Hind Limbs and First Lumbar Vertebra in Female Wistar Rats

Fukuda¹,

Iida²

2004

J. Vet. Med. Sci.

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“…It is well known that rats develop osteopenia after ovariectomy (OVX),' and the OVX rat has been used as a model for postmenopausal osteoporosis (1)(2)(3). Our studies have shown that bone density in rats is reduced 6 mo post-OVX, and that the ratio of femoral cortical thickness to midshaft diameter was significantly lower than normal (x-ray femoral score; Table I).…”

Section: Introductionmentioning

confidence: 72%

Bone deficit in ovariectomized rats. Functional contribution of the marrow stromal cell population and the effect of oral dihydrotachysterol treatment.

Tabuchi¹,

Simmons²,

Fausto³

et al. 1986

J. Clin. Invest.

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This study investigates the proliferative and osteogenic role of marrow stromal/osteoprogenitor cells in the development of the cortical bone deficit in ovariectomized (OVX) female rats. In vitro, clonal growth of marrow stromal cells from OVX rats was significantly impaired (vs. sham-operated controls). Yet in vivo, cells from sham-operated and OVX rats had equal osteogenic potential in several in vivo experimental situations, such as in intraperitoneally implanted millipore diffusion chambers and in intramuscular implants of marrow plus osteoinductive bone matrix (composite grafts). Long-term (6 mo) dihydrotachysterol (DHT) treatment of OVX rats enhanced their in vitro proliferative potential and clonal growth, as well as their osteogenic expression in composite grafts. The observation that the in vivo osteogenic performance of OVX rat marrow stromal cells was normal at extraosseous sites suggests that the mechanisms leading to osteopenia may involve an abnormality in cell-matrix interactions.

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“…Ovariectomy (Ovx)' induces osteoporosis in rats ( 12,13) by increasing bone turnover ( 14,15) and the rat has been successfully used as an animal model for postmenopausal osteoporosis (16,17). Estrogen prevents bone loss in this animal model by reducing bone turnover (18)(19)(20)(21)(22) while PTH, given intermittently, acts as an anabolic agent for bone formation (23)(24)(25)(26)(27)(28)(29).…”

Section: Introductionmentioning

confidence: 99%

Loss of cancellous bone mass and connectivity in ovariectomized rats can be restored by combined treatment with parathyroid hormone and estradiol.

Shen¹,

Dempster²,

Birchman³

et al. 1993

J. Clin. Invest.

172

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To evaluate the potential use of a combination of antiresorption and bone formation-promoting agents as a treatment for postmenopausal osteoporosis, we examined the effects of combined and separate administration of estrogen ( 17,8-estradiol, 30 ;Lg/ kg per d, s.c.) and parathyroid hormone (rPTH 40 ;&g/ kg per d, s.c.) on the proximal tibia of ovariectomized (Ovx) rats. The treatments lasted for 4 wk and were initiated 1, 3, and 5 wk after surgery. Ovx resulted in rapid loss of cancellous bone volume (Cn-BV/TV) as well as trabecular connectivity, as determined by two dimensional strut analysis. When administered in a preventive mode, treatment beginning I wk postOvx, estrogen or PTH treatment alone preserved Cn-BV/TV and trabecular connectivity, and combined estrogen and PTH treatment caused a 40% increment in Cn-BV/TV while maintaining comparable trabecular connectivity with that seen in the Sham-operated animals. When administered in a curative mode to rats with established osteoporosis, treatments beginning 3 or 5 wk post-Ovx, estrogen or PTH treatment alone prevented further loss of connectivity and Cn-BV/TV, whereas the combined treatment resulted in as much as a 300% improvement in one of the parameters of trabecular connectivity, node to node strut length, and a 106% increase in Cn-BV/TV, with respect to the bone status at the initiation of treatment. The beneficial effects of this combined treatment derive from estrogen's ability to prevent accelerated bone resorption and, simultaneously, PTH's promotion of bone formation. These data demonstrate, in an animal model, that therapies can be devised to cure the skeletal defects associated with established osteoporosis. (J.

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Changes in Skeletal Mass and Fragility With Castration in the Rat: A Model of Osteoporosis*

Cited by 153 publications

References 9 publications

Age-Related Changes in Bone Mineral Density, Cross-Sectional Area and the Strength of Long Bones in the Hind Limbs and First Lumbar Vertebra in Female Wistar Rats

Age-Related Changes in Bone Mineral Density, Cross-Sectional Area and the Strength of Long Bones in the Hind Limbs and First Lumbar Vertebra in Female Wistar Rats

Bone deficit in ovariectomized rats. Functional contribution of the marrow stromal cell population and the effect of oral dihydrotachysterol treatment.

Loss of cancellous bone mass and connectivity in ovariectomized rats can be restored by combined treatment with parathyroid hormone and estradiol.

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