Animal Models of Osteoporosis

Hayashi, Kazuo; Fotovati, Abbas

doi:10.1201/b14228-7

Cited by 4 publications

(3 citation statements)

References 129 publications

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“…NONRODENT ANIMALS Several large animals might be used as models of osteoporosis, but the most suitable are the dog, the pig, the sheep, and the nonhuman primates (Hayashi and Fotovati 2003;Kalu 1999;Rodgers, Monier-Faugere, and Malluche 1993). The dog offers several advantages: dogs possess Haversian systems, and the intracortical remodeling activity in dogs is similar to that found in the human skeleton; their epiphyses fuse following maturity; they lose bone with aging; and repeat biopsies may be taken from the ilium.…”

Section: Animal Models For Postmenopausal Osteoporosismentioning

confidence: 99%

“…While the ovariectomized rat has an established status as a powerful and acceptable model of postmenopausal osteoporosis, and other large animals can be used in its place, equally reliable models of senile osteoporosis are not available, although aged animals have been used for this research (Hayashi and Fotovati 2003). As a result, special types of animals have been developed.…”

Section: Animal Models For Senile Osteoporosismentioning

confidence: 99%

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Osteoporosis—Bone Remodeling and Animal Models

Bonucci

Ballanti

2013

Toxicol Pathol

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Osteoporosis is a very common skeletal disorder characterized by reduced bone mass and altered trabecular microarchitecture that leads to bone fragility and fractures. Such disease is due to alterations of the remodeling process that occurs in the basic multicellular units that are transitory cellular complexes including an osteoclastic phase (osteoclast activation and resorption of microscopic portions of bone), a reversion phase (osteoclast replacement by so-called postosteoclastic cells), and an osteoblastic phase (osteoblastic reconstruction of the resorbed bone matrix till the initial volume is regained). Bone remodeling is regulated by a number of systemic and local factors; among the former, besides physical activity and mechanical stresses, a primary role is played by hormones such as parathyroid hormone, vitamin D metabolites, estrogens, calcitonin, and glucocorticoids; among the latter, several growth factors (macrophage colony-stimulating factor, transforming growth factor b, platelet-derived growth factor, fibroblast growth factor 1, bone morphogenetic protein, and insulin-like growth factor 1), as well as the osteoprotegerin-receptor activator of nuclear factor-B ligand system and the sclerostin, play a primary function. The remodeling phases can be evaluated by static and dynamic histomorphometry. Their abnormalities may lead to several osteopathies, the most common of which is osteoporosis (above all senile and postmenopausal), a rather elusive disease chiefly due to its slow development. The use of animal models in its study is emphasized.

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Section: Animal Models For Postmenopausal Osteoporosismentioning

confidence: 99%

Section: Animal Models For Senile Osteoporosismentioning

confidence: 99%

Osteoporosis—Bone Remodeling and Animal Models

Bonucci

Ballanti

2013

Toxicol Pathol

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“…The effect of an EP4 receptor agonist on bone‐implant fixation for smooth‐surfaced HA‐coated or noncoated implants in an osteopenic condition has been previously examined,5 where it enhanced the bone‐implant fixation of HA‐coated, but not the noncoated implants, especially. In a previous study, we also suggested that the stability of rough‐surfaced implants, especially in HA‐free implants, might benefit from EP4 receptor agonist‐induced osteogenesis 25, 26. Thus, the aim of this study was to develop a new approach for the acquisition of superior early fixation between the bone and the implant, which is effective even in osteopenic conditions.…”

Section: Introductionmentioning

confidence: 94%

Effect of a prostaglandin EP4 receptor agonist on early fixation of hydroxyapatite/titanium composite‐ and titanium‐coated rough‐surfaced implants in ovariectomized rats

Hayashi

Fotovati

Ali

et al. 2009

J Biomedical Materials Res

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The agonist of the prostaglandin EP4 receptor can increase bone density in osteoporosis. Using ovariectomized (OVX) and sham-operated (SO) rats, the effects of the EP4 receptor agonist, ONO-4819, and hydroxyapatite (HA) on implant-bone fixation in implants with a rough surface were investigated. Female Wistar rats (12 weeks old) were divided into either SO or bilateral OVX groups. Twenty four weeks later, either hydroxyapatite/titanium (HA/Ti) composite-coated or Ti-coated implants were implanted into the femora, and the animals were treated with either ONO-4819 or saline for 4 weeks. The fixation strength of the HA/Ti-coated implants was higher than that of the Ti-coated implants in the saline-treated OVX rats. In the OVX rats, ONO-4819 enhanced fixation of the rough Ti-coated implants to levels similar to that of HA/Ti-coated implants. These data suggest that a combination of treatment with an EP4 receptor agonist and a rough-surfaced implant might be useful in increasing the early fixation of cement-less arthroplasty, particularly in elderly patients with osteoporosis.

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Effects of increased hypothalamic leptin gene expression on ovariectomy-induced bone loss in rats

et al. 2011

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Estrogen deficiency results in accelerated bone turnover with a net increase in bone resorption. Subcutaneous administration of leptin attenuates bone loss in ovariectomized (ovx) rats by reducing bone resorption. However, in addition to its direct beneficial effects, leptin has been reported to have indirect (central nervous system-mediated) antiosteogenic effects on bone, which may limit the efficacy of elevated serum leptin to prevent estrogen deficiency-associated bone loss. The present study evaluated the long-term effects of increased hypothalamic leptin transgene expression, using recombinant adeno-associated virus-leptin (rAAV-Lep) gene therapy, on bone mass, architecture, and cellular endpoints in sexually mature ovx Sprague-Dawley rats. Ovx rats were implanted with cannulae in the 3rd ventricle of the hypothalamus and injected with either rAAV-Lep or rAAV-GFP (control vector encoding green fluorescent protein) and maintained for 10 weeks. Additional controls consisted of ovary-intact rats and ovx rats pair-fed to rAAV-Lep rats. Lumbar vertebrae were analyzed by micro-computed tomography and tibiae by histomorphometry. Cancellous bone volume was lower and osteoclast perimeter, osteoblast perimeter, and bone marrow adipocyte density were greater in ovx rats compared to ovary-intact controls. In contrast, differences among ovx groups were not detected for any endpoint evaluated. In conclusion, whereas estrogen deficiency resulted in marked cancellous osteopenia, increased bone turnover and marrow adiposity, increasing hypothalamic leptin transgene expression in ovx rats had neither detrimental nor beneficial effects on bone mass, architecture, or cellular endpoints. These findings demonstrate that the antiresorptive effects of subcutaneous leptin administration in ovx rats are mediated through leptin targets in the periphery.

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Animal Models of Osteoporosis

Cited by 4 publications

References 129 publications

Osteoporosis—Bone Remodeling and Animal Models

Osteoporosis—Bone Remodeling and Animal Models

Effect of a prostaglandin EP4 receptor agonist on early fixation of hydroxyapatite/titanium composite‐ and titanium‐coated rough‐surfaced implants in ovariectomized rats

Effects of increased hypothalamic leptin gene expression on ovariectomy-induced bone loss in rats

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