Temporal changes in cancellous bone structure of rats immediately after ovariectomy

Dempster, D. W.; Birchman, R.; Xu, R.; Lindsay, R.; Shen, V.

Affiliations

¹Regional Bone Center, Helen Hayes Hospital, West Haverstraw, NY, USA

²Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, NY, USA

³Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY, USA

Abstract and keywords

To understand the structural changes accompanying estrogen deficiency-induced bone loss, we examined the temporal changes in cancellous bone structure in an animal model of postmenopausal osteoporosis. Matured rats were subjected to bilateral ovariectomy, and groups of eight animals were sacrificed at 5-day intervals. Histomorphometric and trabecular strut analyses of the excised proximal tibia, and bone mineral density measurement of the distal femur, were used to investigate cancellous bone loss as a result of estrogen deficiency. There was an immediate increase in bone turnover after ovariectomy, as evidenced by rapid increases in osteoclast surface (400%) and bone formation rate (270%). The resultant time-dependent decrease in cancellous bone volume was highly related to a decrease in trabecular plate number and connectivity parameters, but was not related to the thickness of the remaining cancellous plates. Our results suggest that cancellous bone loss due to estrogen deficiency is the result of decreased connectivity, likely due to osteoclast perforation of trabecular plates, followed by complete removal of the plate without prior generalized thinning.

Keywords: Ovariectomy; Histomorphometry; Osteopenia; Cancellous bone; Strut analysis

Links

DOI: 10.1016/8756-3282(95)80027-N

PubMed: 7742075

WoS: A1995RB63100024

History

Received: 194-06-29

Revised: 1994-07-25

Accepted: 1994-09-16

Cited Works (18)

Year	Entry
1986	Wronski TJ, Walsh CC, Ignaszewski LA. Histologic evidence for osteopenia and increased bone turnover in ovariectomized rats. Bone. 1986;7(2):119-123.
1987	Garrahan NJ, Mellish RWE, Vedi S, Compston JE. Measurement of mean trabecular plate thickness by a new computerized method. Bone. 1987;8(4):227-230.
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.
1969	Wakamatsu E, Sissons HA. The cancellous bone of the iliac crest. Calcif Tiss Res. December 1969;4(1):147-161.
1988	Parfitt AM. Bone remodeling: relationship to the amount and structure of bone, and the pathogenesis and prevention of fractures. In: Riggs BL, Melton LJ III, eds. Osteoporosis: Etiology, Diagnosis, and Management. New York, NY: Raven Press; 1988:45-93.
1991	Kalu DN. The ovariectomized rat model of postmenopausal bone loss. Bone Miner. December 1991;15(3):175-191.
1989	Mellish RWE, Garraha NJ, Compston JE. Age-related changes in trabecular width and spacing in human iliac crest biopsies. Bone Miner. July 1989;6(3):331-338.
1983	Parfitt AM, Mathews CH, Villanueva AR, Kleerekoper M, Frame B, Rao DS. Relationships between surface, volume, and thickness of iliac trabecular bone in aging and in osteoporosis: implications for the microanatomic and cellular mechanisms of bone loss. J Clin Invest. October 1983;72(4):1396-1409.
1986	Riggs BL, Melton LJ III. Involutional osteoporosis. NEJM. June 26, 1986;314(26):1676-1686.
1988	Wronski TJ, Cintrón M, Dann LM. Temporal relationship between bone loss and increased bone turnover in ovariectomized rats. Calcif Tiss Int. September 1988;43(3):179-183.
1988	Mosekilde L. Age-related changes in vertebral trabecular bone architecture—assessed by a new method. Bone. 1988;9(4):247-250.
1987	Aaron JE, Makins NB, Sagreiya K. The microanatomy of trabecular bone loss in normal aging men and women. Clin Orthop Relat Res. February 1987;215:260-271.
1989	Compston JE, Mellish RWE, Croucher P, Newcombe R, Garrahan NJ. Structural mechanisms of trabecular bone loss in man. Bone Miner. July 1989;6(3):339-350.
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.
1987	Weinstein RS, Hutson MS. Decreased trabecular width and increased trabecular spacing contribute to bone loss with aging. Bone. 1987;8(3):137-142.
1992	Frost HM, Jee WSS. On the rat model of human osteopenias and osteoporoses. Bone Miner. September 1992;18(3):227-236.
1986	Dempster DW, Shane E, Horbert W, Lindsay R. A simple method for correlative light and scanning electron microscopy of human iliac crest bone biopsies: qualitative observations in normal and osteoporotic subjects. J Bone Miner Res. February 1986;1(1):15-21.
1991	Mellish RWE, Ferguson‐Pell MW, Cochran GVB, Lindsay R, Dempster DW. A new manual method for assessing two‐dimensional cancellous bone structure: comparison between iliac crest and lumbar vertebra. J Bone Miner Res. July 1991;6(7):689-696.

Cited By (15)

Year	Entry
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.
1998	Lane NE, Thompson JM, Haupt D, Kimmel DB, Modin G, Kinney JH. Acute changes in trabecular bone connectivity and osteoclast activity in the ovariectomized rat in vivo. J Bone Miner Res. February 1998;13(2):229-236.
1998	Kinney JH, Ladd AJC. The relationship between three-dimensional connectivity and the elastic properties of trabecular bone. J Bone Miner Res. May 1998;13(5):839-845.
2004	Riggs BL, Melton LJ III, Robb RA, Camp JJ, Atkinson EJ, Peterson JM, Rouleau PA, McCollough CH, Bouxsein ML, Khosla S. Population-based study of age and sex differences in bone volumetricdensity, size, geometry, and structure at different skeletal sites. J Bone Miner Res. December 2004;19(12):1945-1954.
2001	Laib A, Kumer JL, Majumdar S, Lane NE. The temporal changes of trabecular architecture in ovariectomized rats assessed by MicroCT. Osteoporos Int. November 2001;12(11):936-941.
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.
1997	Westerlind KC, Wronski TJ, Ritman EL, Luo Z-P, An K-N, Bell NH, Turner RT. Estrogen regulates the rate of bone turnover but bone balance in ovariectomized rats is modulated by prevailing mechanical strain. Proc Natl Acad Sci USA. April 15, 1997;94(8):4199-4204.
2005	Murray AW. Fracture Healing in Osteopenic Bone and the Influence of Simvastatin [MD thesis]. Edinburgh, Scotland: University of Edinburgh; 2005.
2020	O’Sullivan LM. Time-Sequence of Biomechanical Adaption in Trabecular Tissue During Estrogen Deficiency [PhD thesis]. National University of Ireland Galway; March 2020.
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.
2018	Samvelyan H. The Effect of Timing of Feeding on Bone's Adaptive Response to Mechanical Loading [PhD thesis]. University of Sheffield; March 2018.
2005	Ruimerman R. Modeling and Remodeling in Bone Tissue [PhD thesis]. Eindhoven, The Netherlands: Technische Universiteit Eindhoven; 2005.
2001	Boyd SK. Microstructural Bone Adaptation in an Experimental Model of Osteoarthritis [PhD thesis]. Calgary, AB: University of Calgary; January 2001.
2020	Hiebert B. The Development of a Cortical Bone Turnover Model: Parathyroid Hormone Effects in the Rabbit [Master's thesis]. University of Saskatchewan; July 2020.
2021	Harrison KD. A Novel in Vivo Synchrotron Radiation Micro-CT Imaging Platform for the Direct Tracking of Remodeling Events in Cortical Bone [PhD thesis]. University of Saskatchewan; December 2021.