The ovariectomized rat model of postmenopausal bone loss

Kalu, Dike N.

Affiliations

¹Department of Physiology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA

Abstract and keywords

An animal model of postmenopausal bone loss can be defined as a living animal in which spontaneous or induced bone loss due to ovarian hormone deficiency can be studied, and in which the characteristics of the bone loss and its sequalae resemble those found in postmenopausal women in one or more respects. Although in comparison to humans, the skeletal mass of rats remains stable for a protracted period during their lifespan, rats can be ovariectomized to make them sex-hormone deficient, and to stimulate the accelerated loss of bone that occurs in women following menopause. Ovariectomy induced bone loss in the rat and postmenopausal bone loss share many similar characteristics. These include: increased rate of bone turnover with resorption exceeding formation; an initial rapid phase of bone loss followed by a much slower phase; greater loss of cancellous than cortical bone; decreased intestinal absorption of calcium; some protection against bone loss by obesity; and similar skeletal response to therapy with estrogen, tamoxifen, bisphosphonates, parathyroid hormone, calcitonin and exercise. These wide-ranging similarities are strong evidence that the ovariectomized rat bone loss model is suitable for studying problems that are relevant to postmenopausal bone loss.

Keywords: Ovarian hormone deficiency; Bone loss; Rat model

Links

DOI: 10.1016/0169-6009(91)90124-I

PubMed: 1773131

WoS: A1991GV01200001

History

Received: 1991-01-15

Accepted: 1991-08-13

Cited Works (8)

Year	Entry
1989	Wronski TJ, Dann LM, Scott KS, Cintrón M. Long-term effects of ovariectomy and aging on the rat skeleton. Calcif Tiss Int. December 1989;45(6):360-366.
1987	Turner RT, Vandersteenhoven JJ, Bell NH. The effects of ovariectomy and 17β-estradiol on cortical bone histomorphometry in growing rats. J Bone Miner Res. 1987;2(2):115-122.
1978	Heaney RP, Recker RR, Saville PD. Menopausal changes in bone remodeling. J Lab Clin Med. December 1978;92(6):964-970.
1988	Wronski TJ, Cintron M, Doherty AL, Dann LM. Estrogen treatment prevents osteopenia and depresses bone turnover in ovariectomized rats. Endocrinology. August 1988;123(2):681-686.
1984	Baron R, Tross R, Vignery A. Evidence of sequential remodeling in rat trabecular bone: morphology, dynamic histomorphometry, and changes during skeletal maturation. Anat Rec. January 1984;208B(1):137-145.
1988	Melton LJ III, Riggs BL. Clinical spectrum. In: Riggs BL, Melton LJ III, eds. Osteoporosis: Etiology, Diagnosis, and Management. New York, NY: Raven Press; 1988:155-179.
1941	Albright F, Smith PH, Richardson AM. Postmenopausal osteoporosis: its clinical features. JAMA. May 31, 1941;116(22):2465-2474.
1988	Lindsay R. Sex steroids in the pathogenesis and prevention of osteoporosis. In: Riggs BL, Melton LJ III, eds. Osteoporosis: Etiology, Diagnosis, and Management. New York, NY: Raven Press; 1988:333-358.

Cited By (58)

Year	Entry
1994	Chow JW, Chambers TJ. Indomethacin has distinct early and late actions on bone formation induced by mechanical stimulation. Am J Physiol Endocrinol Metab. August 1994;267(2):E287-E292.
1995	Dempster DW, Birchman R, Xu R, Lindsay R, Shen V. Temporal changes in cancellous bone structure of rats immediately after ovariectomy. Bone. January 1995;16(1):157-161.
1995	Newman E, Turner AS, Wark JD. The potential of sheep for the study of osteopenia: current status and comparison with other animal models. Bone. April 1, 1995;16(4)(suppl):S277-S284.
1995	Thompson DD, Simmons HA, Pirie CM, Ke HZ. FDA guidelines and animal models for osteoporosis. Bone. October 1995;17(4)(suppl):S125-S133.
1997	Bagi CM, Wilkie D, Georgelos K, Williams D, Bertolini D. Morphological and structural characteristics of the proximal femur in human and rat. Bone. September 1997;21(3):261-267.
2000	Gadeleta SJ, Boskey AL, Paschalis E, Carlson C, Menschik F, Baldini T, Peterson M, Rimnac CM. A physical, chemical, and mechanical study of lumbar vertebrae from normal, ovariectomized, and nandrolone decanoate-treated cynomolgus monkeys (macaca fascicularis). Bone. October 2000;27(4):541-550.
2002	Lee LL, Lee JSC, Waldman SD, Casper RF, Grynpas MD. Polycyclic aromatic hydrocarbons present in cigarette smoke cause bone loss in an ovariectomized rat model. Bone. June 2002;30(6):917-923.
2004	Goss PE, Qia S, Josse RG, Pritzker KP., Mendes M, Hu H, Waldman SD, Grynpas MD. The steroidal aromatase inhibitor exemestane prevents bone loss in ovariectomized rats. Bone. March 2004;34(3):384-392.
2008	Chen H, Zhou X, Washimi Y, Shoumura S. Three-dimensional microstructure of the bone in a hamster model of senile osteoporosis. Bone. September 2008;43(3):494-500.
2010	Emerton K, Hu B, Woo A, Sinofsky A, Hernandez C, Majeska R, Jepsen K, Schaffler M. Osteocyte apoptosis and control of bone resorption following ovariectomy in mice. Bone. March 2010;46(3):577-583.
2021	Androjna C, Yee CS, White CR, Waldorff EI, Ryaby JT, Zborowski M, Alliston T, Midura RJ. A comparison of alendronate to varying magnitude PEMF in mitigating bone loss and altering bone remodeling in skeletally mature osteoporotic rats. Bone. February 2021;143:115761.
2021	Jensen VFH, Mølck A-M, Dalgaard M, McGuigan FE, Akesson KE. Changes in bone mass associated with obesity and weight loss in humans: applicability of animal models. Bone. April 2021;145:115781.
2021	Li Y, Tseng W-J, de Bakker CMJ, Zhao H, Chung R, Liu XS. Peak trabecular bone microstructure predicts rate of estrogen-deficiency-induced bone loss in rats. Bone. April 2021;145:115862.
1992	Frost HM, Jee WSS. On the rat model of human osteopenias and osteoporoses. Bone Miner. September 1992;18(3):227-236.
1993	Chambers TJ, Evans M, Gardner TN, Turner-Smith A, Chow JWM. Induction of bone formation in rat tail vertebrae by mechanical loading. Bone Miner. February 1993;20(2):167-178.
1995	Chachra D, Kasra M, Vanin CM, MacLusky NJ, Casper RF, Grynpas MD. The effect of different hormone replacement therapy regimens on the mechanical properties of rat vertebrae. Calcif Tiss Int. February 1995;56(2):130-134.
2020	Komrakova M, Furtwängler J, Hoffmann DB, Lehmann W, Schilling AF, Sehmisch S. The selective androgen receptor modulator ostarine improves bone healing in ovariectomized rats. Calcif Tiss Int. February 2020;106(2):147-157.
1993	Dempster DW, Cosman F, Parisien M, Shen V, Lindsay R. Anabolic actions of parathyroid hormone on bone. Endocr Rev. December 1993;14(6):690-709.
1995	Lane NE, Thompson JM, Strewler GJ, Kinney JH. Intermittent treatment with human parathyroid hormone (hPTH[1‐34]) increased trabecular bone volume but not connectivity in osteopenic rats. J Bone Miner Res. October 1995;10(10):1470-1477.
2001	Lanyon L, Skerry T. Postmenopausal osteoporosis as a failure of bone's adaptation to functional loading: a hypothesis. J Bone Miner Res. November 2001;16(11):1937-1947.
2009	Li X, Ominsky MS, Warmington KS, Morony S, Gong J, Cao J, Gao Y, Shalhoub V, Tipton B, Haldankar R, Chen Q, Winters A, Boone T, Geng Z, Niu Q-T, Ke HZ, Kostenuik PJ, Simonet WS, Lacey DL, Paszty C. Sclerostin antibody treatment increases bone formation, bone mass, and bone strength in a rat model of postmenopausal osteoporosis. J Bone Miner Res. April 2009;24(4):578-588.
2006	Krishnan V, Bryant HU, MacDougald OA. Regulation of bone mass by Wnt signaling. J Clin Invest. May 2006;116(5):1202-1209.
2013	Jilka RL. The relevance of mouse models for investigating age-related bone loss in humans. J Gerontol A Biol Sci Med Sci. October 2013;68(10):1209-1217.
2001	Jee WSS, Yao W. Overview: animal models of osteopenia and osteoporosis. J Musculoskel Neuron Interact. March 2001;1(3):193-207.
2023	Mackert GA, Harder M, Harhaus H, Schulte M, Trinler U, Jaeger S, Kneser U, Harhaus L, Wölf C. Validation of a novel testing machine for the investigation of the biomechanical properties of lumbar vertebrae in an osteoporotic rat model. J Orthop Surg Res. March 31, 2023;18:263.
2016	Turunen MJ, Kaspersen JD, Olsson U, Guizar-Sicairos M, Bech M, Schaff F, Tägil M, Jurvelin JS, Isaksson H. Bone mineral crystal size and organization vary across mature rat bone cortex. J Struct Biol. September 2016;195(3):337-344.
2012	Liu X, Lei W, Wu Z, Cui Y, Han B, Fu S, Jiang C. Effects of glucocorticoid on BMD, micro-architecture and biomechanics of cancellous and cortical bone mass in OVX rabbits. Med Eng Phys. January 2012;34(1):2-8.
1995	Manolagas SC, Jilka RL. Bone marrow, cytokines, and bone remodeling: emerging insights into the pathophysiology of osteoporosis. NEJM. February 2, 1995;332(5):305-311.
2002	Lill CA, Gerlach UV, Eckhardt C, Goldhahn J, Schneider E. Bone changes due to glucocorticoid application in an ovariectomized animal model for fracture treatment in osteoporosis. Osteoporos Int. May 2002;13(5):407-414.
2020	O’Sullivan LM, Allison H, Parle EE, Schiavi J, McNamara LM. Secondary alterations in bone mineralisation and trabecular thickening occur after long-term estrogen deficiency in ovariectomised rat tibiae, which do not coincide with initial rapid bone loss. Osteoporos Int. March 2020;31(3):587-599.
1994	Sims NA. The Pathogenesis of Post-Menopausal Osteopaenia Using the Oophorectomised Rat Model [PhD thesis]. Adelaide, Australia: The University of Adelaide; July 1994.
2003	Kim CH. In Vivo Trabecular Bone Response to Mechanical Loading and Parathyroid Hormone Stimulation [PhD thesis]. Columbia University; 2003.
2012	Sharma D. Effects of Estrogen Deficiency on the Osteocyte Lacunar-Canalicular Network [PhD thesis]. New York, NY: The City University of New York; 2012.
2005	Murray AW. Fracture Healing in Osteopenic Bone and the Influence of Simvastatin [MD thesis]. Edinburgh, Scotland: University of Edinburgh; 2005.
2011	Lambers FM. Functional Bone Imaging in an in Vivo Mouse Model of Bone Adaptation, Aging and Disease [PhD thesis]. Swiss Federal Institute of Technology Zürich; 2011.
2023	Micheletti C. Multimodal and Multiscale Characterization of Bone and Bone Interfaces in Health and Disease [PhD thesis]. University of Gothenburg; 2023.
2008	Xu Q. Evaluation of Bone Quality Using Novel Image Analyses and Mechanical Testing Methods [PhD thesis]. Louisville, KY: University of Louisville; August 2008.
2017	Mathavan N. The Anabolic - Anti-Catabolic Paradigm of Augmenting Skeletal Regeneration: A Bone Quality Perspective [PhD thesis]. Lund, Sweden: Lund University; 2017.
2013	Verbruggen SW. Mechanobiological Origins of Osteoporosis [PhD thesis]. National University of Ireland Galway; September 2013.
2020	O’Sullivan LM. Time-Sequence of Biomechanical Adaption in Trabecular Tissue During Estrogen Deficiency [PhD thesis]. National University of Ireland Galway; March 2020.
2023	Ning B. In Vivo Experimental Platform Evaluating Synchronously 3D Bone Growth, (re)modeling, Microdamage and Mechanical Properties [PhD thesis]. École polytechnique de Montréal; August 2023.
2013	Schumacher Y. Comparison of Two Loading Surface Preparation Methods on Rat Vertebral Bodies for Compression Testing [Master's thesis]. Queen's University; September 2013.
2013	Irish JM. Peri-Implant Bone Turnover in a Rat Model [Master's thesis]. Rush University; 2013.
2017	Owen R. Tissue Engineering an in Vitro Model of Osteoporosis [PhD thesis]. Sheffield, UK: University of Sheffield; October 2017.
2010	Trinward A. Osteoporosis Drugs Prevent Bone Loss, Normalize Metabolic Parameters and Negatively Correlate Bone and Fat [Master's thesis]. Stony Brook, NY: Stony Brook University; 2010.
2012	Acerbo AS. Local Chemical and Nanostructural Properties of Rat Cortical Bone Are Altered by Osteoporosis and Pharmaceutical Treatments [PhD thesis]. Stony Brook, NY: Stony Brook University; August 2012.
2012	Kwaczala AT. Alendronate and PTH Differentially Modulate Bone Quality and Reduce Adiposity in an OVX Rat Model [PhD thesis]. Stony Brook, NY: Stony Brook University; December 2012.
2008	Kennedy OD. The Effect of Bone Turnover on Bone Quality and Material Properties [PhD thesis]. Trinity College Dublin; 2008.
1996	Bober MB. The Regulation of Gene Expression by Mechanical Stimulation and Parathyroid Hormone in Bone in Vivo [PhD thesis]. Tulane University; 1996.
2007	Klinck RJ. Establishing in Vivo Micro-CT for Use in Mouse Models of Osteoprosis [Master's thesis]. Calgary, AB: University of Calgary; December 2007.
2004	Castillo AB. The Female Ferret (Mustela Putorius Furo) as an in Vivo Model for Skeletal Research [PhD thesis]. Davis, University of California; 2004.
2010	Melhus G. Molecular Studies on Bone With Focus on Fracture Healing in Experimental Osteoporosis [PhD thesis]. Oslo, Norway: University of Oslo; 2010.
1993	McCubbrey DA. The Macroscopic Architectural Properties of Vertebral Trabecular Bone and Their Relation to Whole Vertebral Failure Loads [PhD thesis]. University of Michigan; 1993.
2021	Li Y. Adaptation of Maternal Skeletal Mechano-Responsiveness, Osteocyte Microenvironment, and Bone Marrow Adipocytes in Response to Reproduction and Lactation [PhD thesis]. Philadelphia, PA: University of Pennsylvania; 2021.
2013	Bernick JH. A Preclinical Assessment of Lithium to Enhance Fracture Healing [Master's thesis]. University of Toronto; 2013.
2013	Liu CC. Effects of a New Conjugate Drug in a Rat Model of Postmenopausal Osteoporosis [Master's thesis]. University of Toronto; 2013.
2016	Vachhani KJ. A Pre-Clinical Assessment of Lithium to Enhance Fracture Healing in Healthy and Impaired Bone Rat Model [Master's thesis]. University of Toronto; 2016.
1996	Sheng MH. The Role of Boron Alone or in Combination With Estrogen or PTH in the Treatment of Postmenopausal Osteoporosis in Ovariectomized Rats [PhD thesis]. Virginia Polytechnic Institute and State University; December 1996.