Ovariectomy‐induced bone loss varies among inbred strains of mice

wbldb

Bouxsein, Mary L.^1,2; Myers, Kelly S.¹; Shultz, Kathryn L.²; Donahue, Leah R.²; Rosen, Clifford J.^2,3; Beamer, Wesley G.²

Ovariectomy‐induced bone loss varies among inbred strains of mice

J Bone Miner Res. July 2005;20(7):1085-1092

©2005 American Society for Bone and Mineral Research

Affiliations

¹Orthopedic Biomechanics Laboratory, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA

²The Jackson Laboratory, Bar Harbor, Maine, USA

³Maine Center for Osteoporosis Research, Bangor, Maine, USA
Abstract and keywords

There is a subset of women who experience particularly rapid bone loss during and after the menopause. However, the factors that lead to this enhanced bone loss remain obscure. We show that patterns of bone loss after ovariectomy vary among inbred strains of mice, providing evidence that there may be genetic regulation of bone loss induced by estrogen deficiency.

Introduction: Both low BMD and increased rate of bone loss are risk factors for fracture. Bone loss during and after the menopause is influenced by multiple hormonal factors. However, specific determinants of the rate of bone loss are poorly understood, although it has been suggested that genetic factors may play a role. We tested whether genetic factors may modulate bone loss subsequent to estrogen deficiency by comparing the skeletal response to ovariectomy in inbred strains of mice.

Materials and Methods: Four‐month‐old mice from five inbred mouse strains (C3H/HeJ, BALB/cByJ, CAST/EiJ, DBA2/J, and C57BL/6J) underwent ovariectomy (OVX) or sham‐OVX surgery (n = 6‐9/group). After 1 month, mice were killed, and μCT was used to compare cortical and trabecular bone response to OVX.

Results: The effect of OVX on trabecular bone varied with mouse strain and skeletal site. Vertebral trabecular bone volume (BV/TV) declined after OVX in all strains (−15 to −24%), except for C3H/HeJ. In contrast, at the proximal tibia, C3H/HeJ mice had a greater decline in trabecular BV/TV (−39%) than C57BL/6J (−18%), DBA2/J (−23%), and CAST/EiJ mice (−21%). OVX induced declines in cortical bone properties, but in contrast to trabecular bone, the effect of OVX did not vary by mouse strain. The extent of trabecular bone loss was greatest in those mice with highest trabecular BV/TV at baseline, whereas cortical bone loss was lowest among those with high cortical bone parameters at baseline.

Conclusions: We found that the skeletal response to OVX varies in a site‐ and compartment‐specific fashion among inbred mouse strains, providing support for the hypothesis that bone loss during and after the menopause is partly genetically regulated.

Keywords: ovariectomy; estrogen; mouse; bone architecture
Links

DOI: 10.1359/JBMR.050307

PubMed: 15940361

WoS: 000230134100002
History

Received: 2004-12-15

Revised: 2005-02-15

Accepted: 2005-03-01

Online: 2005-03-07

Cited Works (16)

Year	Entry
1986	Riggs BL, Wahner HW, Melton LJ III, Richelson LS, Judd HL, Offord KP. Rates of bone loss in the appendicular and axial skeletons of women: evidence of substantial vertebral bone loss before menopause. J Clin Invest. May 1986;77(5):1487-1491.
1996	Garnero P, Hausherr E, Chapuy M, Marcelli C, Grandjean H, Muller C, Cormier C, Bréart G, Meunier PJ, Delmas PD. Markers of bone resorption predict hip fracture in elderly women: the EPIDOS prospective study. J Bone Miner Res. October 1996;11(10):1531-1538.
2000	Turner CH, Hsieh Y, Müller R, Bouxsein ML, Baylink DJ, Rosen CJ, Grynpas MD, Donahue LR, Beamer WG. Genetic regulation of cortical and trabecular bone strength and microstructure in inbred strains of mice. J Bone Miner Res. June 2000;15(6):1126-1131.
2003	Amblard D, Lafage-Proust M-H, Laib A, Thomas T, Rüegsegger P, Alexandre C, Vico L. Tail suspension induces bone loss in skeletally mature mice in the C57BL/6J strain but not in the C3H/HeJ strain. J Bone Miner Res. March 2003;18(3):561-569.
1998	Akhter MP, Cullen DM, Pedersen EA, Kimmel DB, Recker RR. Bone response to in vivo mechanical loading in two breeds of mice. Calcif Tiss Int. November 1998;63(5):442-449.
2002	Riggs BL, Khosla S, Melton LJ III. Sex steroids and the construction and conservation of the adult skeleton. Endocr Rev. June 2002;23(3):279-302.
1996	Beamer WG, Donahue LR, Rosen CJ, Baylink DJ. Genetic variability in adult bone density among inbred strains of mice. Bone. May 1996;18(5):397-403.
1997	Hildebrand T, Rüegsegger P. Quantification of bone microarchitecture with the structure model index. Comput Methods Prog Biomed. 1997;1(1):15-23.
2004	Judex S, Garman R, Squire M, Donahue L, Rubin C. Genetically based influences on the site‐specific regulation of trabecular and cortical bone morphology. J Bone Miner Res. April 2004;19(4):600-606.
2003	Jepsen KJ, Akkus OJ, Majeska RJ, Nadeau JH. Hierarchical relationship between bone traits and mechanical properties in inbred mice. Mamm Genome. February 2003;14(2):97-104.
1999	Kodama Y, Dimai HP, Wergedal J, Sheng M, Malpe R, Kutilek S, Beamer W, Donahue LR, Rosen C, Baylink DJ, Farley J. Cortical tibial bone volume in two strains of mice: effects of sciatic neurectomy and genetic regulation of bone response to mechanical loading. Bone. August 1999;25(2):183-190.
1997	Hildebrand T, Rüegsegger P. A new method for the model-independent assessment of thickness in three-dimensional images. J Microsc (Oxford). 1997;185(1):67-75.
1998	Klein RF, Mitchell SR, Phillips TJ, Belknap JK, Orwoll ES. Quantitative trait loci affecting peak bone mineral density in mice. J Bone Miner Res. November 1998;13(11):1648-1656.
2000	Kodama Y, Umemura Y, Nagasawa S, Beamer WG, Donahue LR, Rosen CR, Baylink DJ, Farley JR. Exercise and mechanical loading increase periosteal bone formation and whole bone strength in C57BL/6J mice but not in C3H/Hej mice. Calcif Tiss Int. April 2000;66(4):298-306.
2004	Judex S, Garman R, Squire M, Busa B, Donahue L-R, Rubin C. Genetically linked site-specificity of disuse osteoporosis. J Bone Miner Res. April 2004;19(4):607-613.
2002	Robling AG, Turner CH. Mechanotransduction in bone: genetic effects on mechanosensitivity in mice. Bone. November 2002;31(5):562-569.

Cited By (36)

Year	Entry
2007	McDonnell P, McHugh PE, O’Mahoney D. Vertebral osteoporosis and trabecular bone quality. Ann Biomed Eng. February 2007;35(2):170-189.
2006	Boyd SK, Davison P, Müller R, Gasser JA. Monitoring individual morphological changes over time in ovariectomized rats by in vivo micro-computed tomography. Bone. October 2006;39(4):854-862.
2009	Fajardo RJ, Cory E, Patel ND, Nazarian A, Laib A, Manoharan RK, Schmitz JE, DeSilva JM, MacLatchy LM, Snyder BD, Bouxsein ML. Specimen size and porosity can introduce error into μCT-based tissue mineral density measurements. Bone. 2009;44(1):176-184.
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.
2014	Taiani JT, Buie HR, Campbell GM, Manske SL, Krawetz RJ, Rancourt DE, Boyd SK, Matyas JR. Embryonic stem cell therapy improves bone quality in a model of impaired fracture healing in the mouse; tracked temporally using in vivo micro-CT. Bone. July 2014;64:263-272.
2021	Akhter MP, Recker RR. High resolution imaging in bone tissue research-review. Bone. February 2021;143:115620.
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.
2023	Mountain RV, Langlais AL, Hu D, Baron R, Lary CW, Motyl KJ. Social isolation through single housing negatively affects trabecular and cortical bone in adult male, but not female, C57BL/6J mice. Bone. July 2023;172:116762.
2010	Manolagas SC. From estrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of osteoporosis. Endocr Rev. June 2010;31(3):266-300.
2007	Glatt V, Canalis E, Stadmeyer L, Bouxsein ML. Age‐related changes in trabecular architecture differ in female and male C57BL/6J mice. J Bone Miner Res. August 2007;22(8):1197-1207.
2008	Fritton JC, Myers ER, Wright TM, van der Meulen MCH. Bone mass is preserved and cancellous architecture altered due to cyclic loading of the mouse tibia after orchidectomy. J Bone Miner Res. May 2008;23(5):663-671.
2008	Buie HR, Moore CP, Boyd SK. Postpubertal architectural developmental patterns differ between the l3 vertebra and proximal tibia in three inbred strains of mice. J Bone Miner Res. 2008;23(12):2048-2059.
2010	Bouxsein ML, Boyd SK, Christiansen BA, Guldberg RE, Jepsen KJ, Müller R. Guidelines for assessment of bone microstructure in rodents using micro-computed tomography. J Bone Miner Res. July 2010;25(7):1468-1486.
2022	Spasic M, Duffy MP, Jacobs CR. Fenoldopam sensitizes primary cilia-mediated mechanosensing to promote osteogenic intercellular signaling and whole bone adaptation. J Bone Miner Res. May 2022;37(5):972-982.
2023	Sharma A, Michels LV, Pitsillides AA, Greeves J, Plotkin LI, Cardo V, Sims NA, Clarkin CE. Sexing bones: improving transparency of sex reporting to address bias within preclinical studies. J Bone Miner Res. January 2023;38(1):5-13.
2008	Klinck RJ, Campbell GM, Boyd SK. Radiation effects on bone architecture in mice and rats resulting from in vivo micro-computed tomography scanning. Med Eng Phys. September 2008;30(7):888-895.
2012	Hayward LNM. Investigations Into the Quantitative Relationship Between the Mechanical Environment and Skeletal Healing [PhD thesis]. Boston University; 2012.
2008	Bandstra ER. The Spaceflight Environment and the Skeletal System [PhD thesis]. Clemson, SC: Clemson University; August 2008.
2018	Spasic M. Targeting Primary Cilia-Mediated Mechanotransduction to Promote Whole Bone Formation [PhD thesis]. Columbia University; 2018.
2010	Lynch ME. Cancellous Bone Adaptation to Non-Invasive Mechanical Loading in the Murine Tibia [PhD thesis]. Ithaca, NY: Cornell University; August 2010.
2014	Melville KM. Estrogen Receptor Alpha in Osteoblasts Mediates Bone Mass and Bone's Response to in Vivo Loading [PhD thesis]. Ithaca, NY: Cornell University; August 2014.
2020	Rooney A. Interactions Among Estrogen Receptor-Alpha, Parathyroid Hormone, and Mechanical Loading in Skeletal Health [PhD thesis]. Ithaca, NY: Cornell University; December 2020.
2007	Schneider P. Ultrastructural Phenotyping of Murine Bone Using Synchrotron Micro- and Nano-Computed Tomography [PhD thesis]. Swiss Federal Institute of Technology Zürich; 2007.
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.
2012	Mulholland B. The Role of Post-Menopausal Osteoporosis in Bone Metastatic Breast Cancer and the Effect of Monocyte Chemoattractant Protein-1 [PhD thesis]. Brisbane, Australia: Griffith University; April 2012.
2013	Morton JJ. An Investigation of Rat Vertebra Failure Behaviour Under Uniaxial Compression Through Time-Lapsed Micro-CT Imaging [Master's thesis]. Queen's University; 2013.
2019	Beltejar M-JG. Understanding the Genetic Basis for Bone-Matrix Quality [PhD thesis]. University of Rochester; 2019.
2020	Doolittle ML. Dissecting the Genetic Influences on Osteoporosis Reveals Zbtb40* as a Novel Regulator of Osteoblast Function* [PhD thesis]. University of Rochester; 2020.
2009	Ozcivici E. Recovery of Trabecular Bone from Disuse Induced Deterioration in Cellular, Morphological and Biomechanical Properties [PhD thesis]. Stony Brook, NY: Stony Brook University; May 2009.
2008	Mulvihill BMC. Computational Investigation Into the Mechanoregulation of Osteoporosis [PhD thesis]. Trinity College Dublin; December 2008.
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.
2007	Ackert-Bicknell CL. The Effects of Allelic Variation in Pparg* on Skeletal Metabolism* [PhD thesis]. Orono, ME: University of Maine; December 2007.
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.
2010	Magalhaes JKRS. The Role of Rac1 and Rac2 in Determining Bone Quality in Aged and Osteoporotic Female Mouse Models [Master's thesis]. University of Toronto; 2010.
2018	Zhang L. Effects of Osteoblast-Specific Gα_S Overexpression on Skeletal Development and Response to Catabolic and Anabolic Stimuli Using a Transgenic Mouse Model [PhD thesis]. University of Toronto; 2018.
2007	McDonald MM. The Role of the Osteoclast During Endochondral Ossification in a Rat Fracture Model [PhD thesis]. University of Technology Sydney (UTS); May 2007.