The laboratory rat as an animal model for osteoporosis research.

Osteoporosis is an important systemic disorder, affecting mainly Caucasian women, with a diverse and multifactorial etiology. A large variety of animal species, including rodents, rabbits, dogs, and primates, have been used as animal models in osteoporosis research. Among these, the laboratory rat is the preferred animal for most researchers. Its skeleton has been studied extensively, and although there are several limitations to its similarity to the human condition, these can be overcome through detailed knowledge of its specific traits or with certain techniques. The rat has been used in many experimental protocols leading to bone loss, including hormonal interventions (ovariectomy, orchidectomy, hypophysectomy, parathyroidectomy), immobilization, and dietary manipulations. The aim of the current review is not only to present the ovariectomized rat and its advantages as an appropriate model for the research of osteoporosis, but also to provide information about the most relevant age and bone site selection according to the goals of each experimental protocol. In addition, several methods of bone mass evaluation are assessed, such as biochemical markers, densitometry, histomorphometry, and bone mechanical testing, that are used for monitoring and evaluation of this animal model in preventive or therapeutic strategies for osteoporosis.

[1]  Toshitaka Nakamura,et al.  Selective cyclooxygenase-2 inhibitor prevents reduction of trabecular bone mass in collagen-induced arthritic mice in association with suppression of RANKL/OPG ratio and IL-6 mRNA expression in synovial tissues but not in bone marrow cells , 2008, Journal of Bone and Mineral Metabolism.

[2]  S. Stoch,et al.  Cathepsin K Inhibitors: A Novel Target for Osteoporosis Therapy , 2008, Clinical pharmacology and therapeutics.

[3]  R. Talmage,et al.  Calcium homeostasis: how bone solubility relates to all aspects of bone physiology. , 2007, Journal of musculoskeletal & neuronal interactions.

[4]  J. Iwamoto,et al.  Effect of vitamin K2 and growth hormone on the long bones in hypophysectomized young rats: a bone histomorphometry study , 2006, Journal of Bone and Mineral Metabolism.

[5]  Dean B. Evans,et al.  A single intravenous administration of zoledronic acid prevents the bone loss and mechanical compromise induced by aromatase inhibition in rats. , 2006, Bone.

[6]  Ralph Müller,et al.  Evaluation of Three-dimensional Image Registration Methodologies for In Vivo Micro-computed Tomography , 2006, Annals of Biomedical Engineering.

[7]  Yebin Jiang,et al.  Advanced Imaging Assessment of Bone Quality , 2006, Annals of the New York Academy of Sciences.

[8]  G Realdi,et al.  Bone microarchitecture evaluated by histomorphometry. , 2005, Micron.

[9]  J. Lotz,et al.  Basic fibroblast growth factor improves trabecular bone connectivity and bone strength in the lumbar vertebral body of osteopenic rats , 2005, Osteoporosis International.

[10]  C. Cooper,et al.  Diagnosis and epidemiology of osteoporosis , 2005, Current opinion in rheumatology.

[11]  M. Uehara,et al.  Effect of dietary magnesium supplementation on bone loss in rats fed a high phosphorus diet. , 2005, Magnesium research.

[12]  Niklas Zethraeus,et al.  Assessment of fracture risk , 2005, Osteoporosis International.

[13]  S. Fukuda,et al.  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. , 2004, The Journal of veterinary medical science.

[14]  J. Iwamoto,et al.  Differential effect of short-term etidronate treatment on three cancellous bone sites in orchidectomized adult rats. , 2004, The Keio journal of medicine.

[15]  D. Dempster Bone microarchitecture and strength , 2003, Osteoporosis International.

[16]  V. Kavuncu,et al.  A comparison of estrogen and two different doses of calcitonin in ovariectomized rats. , 2003, Yonsei medical journal.

[17]  L. Lanyon,et al.  Mechanical loading: biphasic osteocyte survival and targeting of osteoclasts for bone destruction in rat cortical bone. , 2003, American journal of physiology. Cell physiology.

[18]  R. Rizzoli,et al.  Bone strength and its determinants , 2003, Osteoporosis International.

[19]  G. Evans,et al.  Long-Term Zoledronic Acid Treatment Increases Bone Structure and Mechanical Strength of Long Bones of Ovariectomized Adult Rats , 2003, Calcified Tissue International.

[20]  A. Fotovati,et al.  Animal Models of Osteoporosis , 2002 .

[21]  C. Cooper,et al.  Recent developments in the epidemiology of osteoporosis , 2002, Current opinion in rheumatology.

[22]  Turner As Animal models of osteoporosis--necessity and limitations. , 2001 .

[23]  W. Jee,et al.  Overview: animal models of osteopenia and osteoporosis. , 2001, Journal of musculoskeletal & neuronal interactions.

[24]  K. Aoki,et al.  Trabecular bone turnover, bone marrow cell development, and gene expression of bone matrix proteins after low calcium feeding in rats. , 1999, Bone.

[25]  Y. Tamura,et al.  Histomorphometric Evaluation of the Effects of Ovariectomy on Bone Turnover in Rat Caudal Vertebrae , 1999, Calcified Tissue International.

[26]  J. Waterton,et al.  Stimulation and inhibition of bone formation: use of peripheral quantitative computed tomography in the mouse in vivo , 1998, Laboratory animals.

[27]  P. Aljama,et al.  The PTH-Calcium Relationship During a Range of Infused PTH Doses in the Parathyroidectomized Rat , 1998, Calcified Tissue International.

[28]  R. Lindsay,et al.  Prednisolone alone, or in combination with estrogen or dietary calcium deficiency or immobilization, inhibits bone formation but does not induce bone loss in mature rats. , 1997, Bone.

[29]  H. W. Sampson,et al.  Alcohol consumption inhibits bone growth and development in young actively growing rats. , 1996, Alcoholism, clinical and experimental research.

[30]  T. Wronski,et al.  Time course of femoral neck osteopenia in ovariectomized rats. , 1996, Bone.

[31]  R. Erben,et al.  Trabecular and endocortical bone surfaces in the rat: Modeling or remodeling? , 1996, The Anatomical record.

[32]  T. Wronski,et al.  Comparative study of skeletal response to estrogen depletion at red and yellow marrow sites in rats , 1996, The Anatomical record.

[33]  Y. Ma,et al.  Time responses of cancellous and cortical bones to sciatic neurectomy in growing female rats. , 1996, Bone.

[34]  J. Gasser Assessing bone quantity by pQCT. , 1995, Bone.

[35]  W. Jee,et al.  Bone histomorphometric changes in the femoral neck of aging and ovariectomized rats , 1995, The Anatomical record.

[36]  Y. Ma,et al.  Adaptation of non-growing former epiphysis and metaphyseal trabecular bones to aging and immobilization in rat. , 1995, Bone.

[37]  M. Holick,et al.  Differentiating between orchiectomized rats and controls using measurements of trabecular bone density: A comparison among DXA, Histomorphometry, and peripheral quantitative computerized tomography , 1995, Calcified Tissue International.

[38]  J. Kanis,et al.  Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: Synopsis of a WHO report , 1994, Osteoporosis International.

[39]  L. Mosekilde,et al.  The positive effect of parathyroid hormone on femoral neck bone strength in ovariectomized rats is more pronounced than that of estrogen or bisphosphonates. , 1994, Endocrinology.

[40]  J. Tobias,et al.  The estrogen antagonist ICI 182,780 reduces cancellous bone volume in female rats. , 1993, Endocrinology.

[41]  S. Miller,et al.  Comparative morphometric changes in rat cortical bone following ovariectomy and/or immobilization. , 1993, Bone.

[42]  W. Jee,et al.  Prostaglandin E2 increased rat cortical bone mass when administered immediately following ovariectomy. , 1993, Bone and mineral.

[43]  H. Frost,et al.  On the rat model of human osteopenias and osteoporoses. , 1992, Bone and mineral.

[44]  W. Jee,et al.  Adaptation of diaphyseal structure to aging and decreased mechanical loading in the adult rat: A densitometric and histomorphometric study , 1991, The Anatomical record.

[45]  D. Woodbury,et al.  Adaptation of cancellous bone to aging and immobilization in the rat: A single photon absorptiometry and histomorphometry study , 1990, The Anatomical record.

[46]  D. Kimmel,et al.  Nondestructive measurement of bone mineral in femurs from ovariectomized rats , 1990, Calcified Tissue International.

[47]  T. Wronski,et al.  Long-term effects of ovariectomy and aging on the rat skeleton , 1989, Calcified Tissue International.

[48]  A. Goulding,et al.  A new way to induce oestrogen-deficiency osteopaenia in the rat: comparison of the effects of surgical ovariectomy and administration of the LHRH agonist buserelin on bone resorption and composition. , 1989, The Journal of endocrinology.

[49]  T. Wronski,et al.  Temporal relationship between bone loss and increased bone turnover in ovariectomized rats , 1988, Calcified Tissue International.

[50]  G. Rodan,et al.  Indomethacin inhibition of tenotomy‐induced bone resorption in rats , 1988, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[51]  R. Turner,et al.  Chronic alcohol treatment results in disturbed vitamin D metabolism and skeletal abnormalities in rats. , 1988, Alcoholism, clinical and experimental research.

[52]  R T Turner,et al.  The effects of ovariectomy and 17β‐estradiol on cortical bone histomorphometry in growing rats , 1987, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[53]  J. Trueta,et al.  Effects of activity on bone growth and development in the rat. , 1981, Clinical orthopaedics and related research.

[54]  E. Morey,et al.  Spaceflight and Bone Turnover: Correlation with a New Rat Model of Weightlessness , 1979 .

[55]  Harry K. Genant,et al.  Application of micro-ct assessment of 3-d bone microstructure in preclinical and clinical studies , 2009, Journal of Bone and Mineral Metabolism.

[56]  A. M. Parfitt,et al.  The cellular basis of bone remodeling: The quantum concept reexamined in light of recent advances in the cell biology of bone , 2006, Calcified Tissue International.

[57]  T. Hefferan,et al.  Animal Models For Osteoporosis , 2004, Reviews in Endocrine and Metabolic Disorders.

[58]  L. Mosekilde,et al.  Cortical bone mass, composition, and mechanical properties in female rats in relation to age, long-term ovariectomy, and estrogen substitution , 2004, Calcified Tissue International.

[59]  M. Uehara,et al.  Effect of dietary calcium: Phosphorus ratio on bone mineralization and intestinal calcium absorption in ovariectomized rats , 2004, BioFactors.

[60]  R. Jilka,et al.  Sex steroids and bone. , 2002, Recent progress in hormone research.

[61]  M. Seibel,et al.  Molecular Markers of Bone Turnover: Biochemical, Technical and Analytical Aspects , 2000, Osteoporosis International.

[62]  Kay Dickersin,et al.  Osteoporosis prevention, diagnosis, and therapy. , 2000, NIH consensus statement.

[63]  H. Nakamuta,et al.  Glucocorticoid-induced secondary osteopenia in female rats: a time course study as compared with ovariectomy-induced osteopenia and response to salmon calcitonin. , 1999, Japanese journal of pharmacology.

[64]  D. Hans,et al.  Do Markers of Bone Resorption Add to Bone Mineral Density and Ultrasonographic Heel Measurement for the Prediction of Hip Fracture in Elderly Women? The EPIDOS Prospective Study , 1998, Osteoporosis International.

[65]  D. Williams,et al.  Raloxifene (LY139481 HCI) prevents bone loss and reduces serum cholesterol without causing uterine hypertrophy in ovariectomized rats. , 1994, The Journal of clinical investigation.

[66]  Y. Ma,et al.  Prostaglandin E2 adds bone to a cancellous bone site with a closed growth plate and low bone turnover in ovariectomized rats. , 1994, Bone.

[67]  S. Miller,et al.  Calcium absorption and osseous organ-, tissue-, and envelope-specific changes following ovariectomy in rats. , 1991, Bone.

[68]  T. Wronski,et al.  Time course of vertebral osteopenia in ovariectomized rats. , 1989, Bone.

[69]  T. Yamamuro,et al.  Effect of 1 alpha-hydroxyvitamin D3 on osteoporosis induced by immobilization combined with ovariectomy in rats. , 1987, Bone.

[70]  T. Einhorn,et al.  Production of a standard closed fracture in laboratory animal bone , 1984, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[71]  H. Frost The regional acceleratory phenomenon: a review. , 1983, Henry Ford Hospital medical journal.

[72]  R. Turner,et al.  Printed in U.S.A. Copyright © 1997 by The Endocrine Society The Effects of Orbital Spaceflight on Bone Histomorphometry and Messenger Ribonucleic Acid Levels for Bone Matrix Proteins and Skeletal Signaling Peptides in Ovariectomized Growing Rats* , 2022 .