On the rat model of human osteopenias and osteoporoses

Frost, Harold M.; Jee, Webster S. S.

doi:10.1016/0169-6009(92)90809-r

Cited by 410 publications

(269 citation statements)

References 60 publications

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“…The cortical bone of the rat lacked the primary and secondary osteons that were present in both the human and the sheep. These findings are supported by the observations of other investigators (Frost and Jee, 1992;Newman et al, 1995;Bentolila et al, 1998), who found that the rat normally lacks Haversian remodeling, except in extreme mechanical loading situations and in the occasional older rat. This is the first investigation to compare the percent ash of calcified fibrocartilage from tendon insertions between different species.…”

Section: Discussionsupporting

confidence: 89%

“…This was accomplished by determining whether the tendon insertions of the greater trochanter of the human, rat, and sheep differ in terms of morphology, mineral content of the calcified fibrocartilage, and mineral content of the underlying cortical bone. The rat and sheep were chosen because both are common animal models used in orthopedic and soft-tissue insertion research (Frost and Jee, 1992;Newman et al, 1995;Aerssens et al, 1998;Clark and Stechschulte, 1998).…”

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confidence: 99%

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Experimental confirmation of the sheep model for studying the role of calcified fibrocartilage in hip fractures and tendon attachments

Shea¹,

Hallows²,

Bloebaum³

2002

Anat. Rec.

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Research has shown that there is a dramatic increase in the fractional area of calcified fibrocartilage from tendon and capsular insertions on the human femoral neck Shea et al., 2001b). Additional information regarding the properties of the proximal femur's cortical shell, gained from the use of an animal model, may result in a better understanding of elderly hip fracture since the cortical shell is a significant contributor to the strength of the proximal femur. The objective of the present study was to determine if the greater trochanter's tendon insertions of the human, rat, and sheep differ in terms of morphology and mineralization. The tendons of the greater trochanter of the human, rat, and sheep were observed to insert via a fibrocartilage insertion. The mineral content of the human and sheep calcified fibrocartilage was significantly higher than that of the rat calcified fibrocartilage (P Ͻ 0.01). Additionally, the mineral content of the rat cortical bone was significantly higher than that of the human cortical bone (P Ͻ 0.01). The mineral content of the calcified fibrocartilage and bone of the human and sheep were not statistically different from each other. There were also more similarities between the bone structure and lacunae density of the human and sheep than between the human and the rat. This suggests that the tendon insertions of the sheep are a better model than the tendon insertions of the rat for the investigation of calcified fibrocartilage in elderly hip fractures.

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Section: Discussionsupporting

confidence: 89%

mentioning

confidence: 99%

Experimental confirmation of the sheep model for studying the role of calcified fibrocartilage in hip fractures and tendon attachments

Shea¹,

Hallows²,

Bloebaum³

2002

Anat. Rec.

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“…Of all laboratory animals mice and rats are considered to have skeletons and bone biologies that are least similar to humans since their skeletons are modelling-driven due to permanently open growth plates at the epiphyses of long bones, a lack of the Haversian system and low cancellous bone content at the epiphyses of the long bones [100,[130][131][132][133][134][135][136]. However, studies in rodents are very informative and cost effective.…”

Section: Rodentsmentioning

confidence: 99%

The rational use of animal models in the evaluation of novel bone regenerative therapies

Perić¹,

Dumić-Čule²,

Grčević³

et al. 2015

Bone

130

116

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“…Ovariectomy (OVX) in rats produces estrogen deficiency and increases bone turnover leading to trabecular bone loss similar to that observed in postmenopausal women (37)(38)(39)(40). OVX in female rats causes significant bone loss in the lumbar vertebrae, proximal tibial, and distal femoral metaphyses 4 weeks post-surgery (41,43).…”

Section: Effect Of Las On Bone In the Ovariectomized (Ovx) Rat Modelmentioning

confidence: 83%

Lasofoxifene (CP-336,156), a novel selective estrogen receptor modulator, in preclinical studies

Brown

Thompson

2002

AGE

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Estrogen replacement therapy is reported to reduce the incidence of vertebral fractures in postmenopausal women, however, its compliance is limited because of side effects and safety concerns. Estrogen's side effects on breast and uterine tissues leading to the potential increased risk of uterine and breast cancer limit widespread estrogen usage. Thus, there is a significant medical need for a therapy that protects against postmenopausal bone loss but is free of estrogen's negative effects on reproductive tissues. Selective estrogen receptor modulators (SERMs) have been investigated as an alternative to hormone replacement therapy. One such compound, raloxifene, has been approved for the prevention and treatment of osteoporosis.Lasofoxifene (LAS), a new, nonsteroidal, and potent SERM, is an estrogen antagonist or agonist depending on the target tissue. LAS selectively binds with high affinity to human estrogen receptors. In ovariectomized (OVX) rat studies, LAS prevented the decrease in femoral bone mineral density, tibial and lumbar vertebral trabecular bone mass at an EDlo o of about 60 ~g/kg/day. LAS inhibited the activation of trabecular and endocortical bone resorption and bone turnover in tibial metaphyses and diaphyses, and lumbar vertebral body in OVX rats. In addition, LAS decreased total serum cholesterol, inhibited body weight gain and increased soleus muscle weight in OVX rats. Similarly, LAS prevented bone loss induced by orchidectomy or aging in male rats by decreasing bone resorption and bone turnover while it had no effect in the prostate. Further, LAS decreased total serum cholesterol in intact aged male rats or in orchidectomized male rats. Synergestic skeletal effects were found with LAS in combination with bone anabolic agents such as prostaglandin E 2 (PGE2), parathyroid hormone (PTH) or a growth hormone secretagoue (GHS) in OVX rats. In combination with estrogen, LAS inhibited the uterine stimulating effects of estrogen but did not block the bone protective effects of estrogen. In immature and aged female rats, LAS did not affect the uterine weight and uterine histology. In OVX adult female rats, LAS slightly but significantly increased uterine weight. These results demonstrated that LAS produced effects on the skeleton indistinguishable from estrogen in female and male rats. However, unlike estrogen, I_AS had little effect on uterine weight and cellular proliferation of uterus in female rats. In preclinical anti-tumor studies, LAS inhibited human breast cancer growth in mice bearing MCF7 tumors, prevented NMU-induced mammary carcinomas and possessed chemotherapeutic effects in NMU-induced carcinomas in rats.Therefore, we conclude that LAS possesses the antiestrogenic effects in breast tissue and estrogenic effects in bone and serum cholesterol, but lacks estrogen's side effects on uterine tissue. These data support the therapeutic potential of I_AS for the prevention and treatment of postmenopausal bone loss and mammary carcinomas in humans.

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On the rat model of human osteopenias and osteoporoses

Cited by 410 publications

References 60 publications

Experimental confirmation of the sheep model for studying the role of calcified fibrocartilage in hip fractures and tendon attachments

Experimental confirmation of the sheep model for studying the role of calcified fibrocartilage in hip fractures and tendon attachments

The rational use of animal models in the evaluation of novel bone regenerative therapies

Lasofoxifene (CP-336,156), a novel selective estrogen receptor modulator, in preclinical studies

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