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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

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Abstract

Summary

This study delineates the time sequence of changes in bone tissue mineralisation in ovariectomised rats. We report that changes in bone mineral distribution arise secondary to the initial rapid bone loss but coincide with trabecular thickening. We propose that these changes compensate for elevated stresses in remaining trabeculae after bone resorption.

Introduction

Recent studies have shown that osteoporosis is not simply a disease of bone loss and microarchitectural degradation but that important changes in tissue composition also occur. Such changes may be a secondary response to early bone loss, but the time sequence of changes in bone mineral distribution is not fully understood. The objective of this study was to quantify the temporal effects of estrogen deficiency on trabecular mineral distribution in the tibia of ovariectomised (OVX) rats.

Methods

Weekly in vivo micro-CT scans and morphometric and bone mineral density distribution analyses of the proximal tibia were conducted for the first 4 weeks of estrogen deficiency and then at 8, 14 and 34 weeks.

Results

Here we report that although trabecular bone volume and architecture are significantly deteriorated within the first 4 weeks of estrogen deficiency, there is no change in the distribution of bone mineral within trabeculae during this initial period. The rate of bone loss in OVX animals dramatically reduced between week 4 and week 14, which coincided with the initiation of increases in trabecular thickness and mineralisation in the OVX group.

Conclusions

Together this study reveals for the first time that alterations in bone mineralisation and trabecular thickening arise secondary to the initial rapid bone loss. We propose that these secondary mineralisation changes act to reinforce the trabecular network in an attempt to compensate for the increased loading that ensues after severe bone loss. This study provides an insight into temporal changes in bone mineral distribution in estrogen deficiency.

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References

  1. Parfitt AM (1987) Trabecular bone architecture in the pathogenesis and prevention of fracture. Am J Med 82:68–72

    Article  CAS  Google Scholar 

  2. Compston JE, Mellish RWE, Croucher P, Newcombe R, Garrahan NJ (1989) Structural mechanisms of trabecular bone loss in man. Bone Miner 6:339–350. https://doi.org/10.1016/0169-6009(89)90039-1

    Article  CAS  PubMed  Google Scholar 

  3. Lane NE, Thompson JM, Haupt D, Kimmel DB, Modin G, Kinney JH (1998) Acute changes in trabecular bone connectivity and osteoclast activity in the ovariectomized rat in vivo. J Bone Miner Res 13:229–236. https://doi.org/10.1359/jbmr.1998.13.2.229

    Article  CAS  PubMed  Google Scholar 

  4. Laib A, Kumer JL, Majumdar S, Lane NE (2001) The temporal changes of trabecular architecture in ovariectomized rats assessed by micro-CT. Osteoporos Int 12:936–941. https://doi.org/10.1007/s001980170022

    Article  CAS  PubMed  Google Scholar 

  5. Dempster DW, Birchman R, Xu R, Lindsay R, Shen V (1995) Temporal changes in cancellous bone structure of rats immediately after ovariectomy. Bone 16:157–161. https://doi.org/10.1016/8756-3282(95)80027-N

    Article  CAS  PubMed  Google Scholar 

  6. Perilli E, Le V, Ma B et al (2010) Detecting early bone changes using in vivo micro-CT in ovariectomized, zoledronic acid-treated, and sham-operated rats. Osteoporos Int 21:1371–1382. https://doi.org/10.1007/s00198-009-1082-z

    Article  CAS  PubMed  Google Scholar 

  7. Brouwers JEM, Lambers FM, Gasser JA et al (2008) Bone degeneration and recovery after early and late bisphosphonate treatment of ovariectomized Wistar rats assessed by in vivo micro-computed tomography. Calcif Tissue Int 82:202–211. https://doi.org/10.1007/s00223-007-9084-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Waarsing JH, Day JS, Verhaar JAN, Ederveen AG, Weinans H (2006) Bone loss dynamics result in trabecular alignment in aging and ovariectomized rats. J Orthop Res 24:926–935. https://doi.org/10.1002/jor.20063

    Article  PubMed  Google Scholar 

  9. Boyd SK, Davison P, Müller R, Gasser JA (2006) Monitoring individual morphological changes over time in ovariectomized rats by in vivo micro-computed tomography. Bone 39:854–862. https://doi.org/10.1016/j.bone.2006.04.017

    Article  PubMed  Google Scholar 

  10. Busse B, Hahn M, Soltau M et al (2009) Increased calcium content and inhomogeneity of mineralization render bone toughness in osteoporosis: mineralization, morphology and biomechanics of human single trabeculae. Bone 45:1034–1043. https://doi.org/10.1016/j.bone.2009.08.002

    Article  CAS  PubMed  Google Scholar 

  11. Brennan M, Gleeson J, Browne M et al (2011) Site specific increase in heterogeneity of trabecular bone tissue mineral during oestrogen deficiency. Eur Cells Mater 21:396–406. https://doi.org/10.22203/eCM.v021a30

    Article  CAS  Google Scholar 

  12. Brennan O, Kuliwaba JS, Lee TC, Parkinson IH, Fazzalari NL, McNamara L, O'Brien FJ (2012) Temporal changes in bone composition, architecture, and strength following estrogen deficiency in osteoporosis. Calcif Tissue Int 91:440–449. https://doi.org/10.1007/s00223-012-9657-7

    Article  CAS  PubMed  Google Scholar 

  13. Brennan MA, Gleeson JP, O’Brien FJ, McNamara LM (2014) Effects of ageing, prolonged estrogen deficiency and zoledronate on bone tissue mineral distribution. J Mech Behav Biomed Mater 29:161–170. https://doi.org/10.1016/j.jmbbm.2013.08.029

    Article  CAS  PubMed  Google Scholar 

  14. Kneissel M, Boyde A, Gasser J (2001) Bone tissue and its mineralization in aged estrogen-depleted rats after long-term intermittent treatment with parathyroid hormone (PTH) analog SDZ PTS 893 or human PTH(1-34). Bone 28:237–250. https://doi.org/10.1016/S8756-3282(00)00448-8

    Article  CAS  PubMed  Google Scholar 

  15. Valenta A, Roschger P, Fratzl-Zelman N, Kostenuik PJ, Dunstan CR, Fratzl P, Klaushofer K (2005) Combined treatment with PTH (1–34) and OPG increases bone volume and uniformity of mineralization in aged ovariectomized rats. Bone 37:87–95. https://doi.org/10.1016/J.BONE.2005.03.013

    Article  CAS  PubMed  Google Scholar 

  16. Cheng Z, Yao W, Zimmermann EA, Busse C, Ritchie RO, Lane NE (2009) Prolonged treatments with antiresorptive agents and PTH have different effects on bone strength and the degree of mineralization in old estrogen-deficient osteoporotic rats. J Bone Miner Res 24:209–220. https://doi.org/10.1359/jbmr.81005

    Article  CAS  PubMed  Google Scholar 

  17. Verbruggen SW, Mc Garrigle MJ, Haugh MG et al (2015) Altered mechanical environment of bone cells in an animal model of short- and long-term osteoporosis. Biophys J 108:1587–1598. https://doi.org/10.1016/j.bpj.2015.02.031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Brouwers JEM, van Rietbergen B, Huiskes R (2007) No effects of in vivo micro-CT radiation on structural parameters and bone marrow cells in proximal tibia of Wistar rats detected after eight weekly scans. J Orthop Res 25:1325–1332. https://doi.org/10.1002/jor.20439

    Article  PubMed  Google Scholar 

  19. Bouxsein ML, Boyd SK, Christiansen BA et al (2010) Guidelines for assessment of bone microstructure in rodents using micro-computed tomography. J Bone Miner Res 25:1468–1486. https://doi.org/10.1002/jbmr.141

    Article  PubMed  Google Scholar 

  20. Roschger P, Paschalis EP, Fratzl P, Klaushofer K (2008) Bone mineralization density distribution in health and disease. Bone 42:456–466. https://doi.org/10.1016/j.bone.2007.10.021

    Article  CAS  PubMed  Google Scholar 

  21. Lelovas PP, Xanthos TT, Thoma SE, Lyritis GP, Dontas IA (2008) The laboratory rat as an animal model for osteoporosis research. Comp Med 58:424–430

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Kalu DN (1991) The ovariectomized rat model of postmenopausal bone loss. Bone Miner 15:175–191. https://doi.org/10.1016/0169-6009(91)90124-I

    Article  CAS  PubMed  Google Scholar 

  23. Štěpán JJ, Musilová J, Pacovský V (2009) Bone demineralization, biochemical indices of bone remodeling, and estrogen replacement therapy in adults with Turner’s syndrome. J Bone Miner Res 4:193–198. https://doi.org/10.1002/jbmr.5650040210

    Article  Google Scholar 

  24. Gallagher JC (1990) The pathogenesis of osteoporosis. Bone Miner 9:215–227. https://doi.org/10.1016/0169-6009(90)90039-I

    Article  CAS  PubMed  Google Scholar 

  25. Gallagher JC, Riggs BL, Eisman J, Hamstra A, Arnaud SB, DeLuca H (1979) Intestinal calcium absorption and serum vitamin D metabolites in normal subjects and osteoporotic patients. J Clin Invest 64:729–736. https://doi.org/10.1172/JCI109516

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Heaney RP, Recker RR, Omaha PDS (2009) Menopausal changes in calcium balance performance. Nutr Rev 41:86–89. https://doi.org/10.1111/j.1753-4887.1983.tb07709.x

    Article  Google Scholar 

  27. Reeve J, Meunier PJ, Parsons JA et al (1980) Anabolic effect of human parathyroid hormone fragment on trabecular bone in involutional osteoporosis: a multicentre trial. BMJ 280:1340–1344. https://doi.org/10.1136/bmj.280.6228.1340

    Article  CAS  PubMed  Google Scholar 

  28. Wronski TJ, Dann LM, Scott KS, Crooke LR (1989) Endocrine and pharmacological suppressors of bone turnover protect against osteopenia in ovariectomized rats. Endocrinology 125:810–816. https://doi.org/10.1210/endo-125-2-810

    Article  CAS  PubMed  Google Scholar 

  29. WronskiI TJ, Cintron M, Doherty AL, Dann LM (1988) Estrogen treatment prevents osteopenia and depresses bone turnover in ovariectomized rats. Endocrinology 123:681–686. https://doi.org/10.1210/endo-123-2-681

    Article  Google Scholar 

  30. Simkin A, Ayalon J, Leichter I (1987) Increased trabecular bone density due to bone-loading exercises in postmenopausal osteoporotic women. Calcif Tissue Int 40:59–63. https://doi.org/10.1007/BF02555706

    Article  CAS  PubMed  Google Scholar 

  31. Thompson DD, Simmons HA, Pirie CM, Ke HZ (1995) FDA guidelines and animal models for osteoporosis. Bone 17:S125–S133. https://doi.org/10.1016/8756-3282(95)00285-L

    Article  Google Scholar 

  32. Campbell GM, Bernhardt R, Scharnweber D, Boyd SK (2011) The bone architecture is enhanced with combined PTH and alendronate treatment compared to monotherapy while maintaining the state of surface mineralization in the OVX rat. Bone 49:225–232. https://doi.org/10.1016/j.bone.2011.04.008

    Article  CAS  PubMed  Google Scholar 

  33. Kousteni S, Bellido T, Plotkin LI, O'Brien CA, Bodenner DL, Han L, Han K, DiGregorio G, Katzenellenbogen JA, Katzenellenbogen BS, Roberson PK, Weinstein RS, Jilka RL, Manolagas SC (2001) Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors. Cell 104:719–730. https://doi.org/10.1016/S0092-8674(01)00268-9

    Article  CAS  PubMed  Google Scholar 

  34. Tomkinson A (1997) The death of osteocytes via apoptosis accompanies estrogen withdrawal in human bone. J Clin Endocrinol Metab 82:3128–3135. https://doi.org/10.1210/jc.82.9.3128

    Article  CAS  PubMed  Google Scholar 

  35. Bailey AJ, Wotton SF, Sims TJ, Thompson PW (1993) Biochemical changes in the collagen of human osteoporotic bone matrix. Connect Tissue Res 29:119–132. https://doi.org/10.3109/03008209309014239

    Article  CAS  PubMed  Google Scholar 

  36. Mansell J, Bailey A (2003) Increased metabolism of bone collagen in post-menopausal female osteoporotic femoral heads. Int J Biochem Cell Biol 35:522–529. https://doi.org/10.1016/S1357-2725(02)00312-6

    Article  CAS  PubMed  Google Scholar 

  37. Viguet-Carrin S, Garnero P, Delmas PD (2006) The role of collagen in bone strength. Osteoporos Int 17:319–336. https://doi.org/10.1007/s00198-005-2035-9

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This publication has emanated from research conducted with financial support of the Science Foundation Ireland (SFI) and is co-funded under the European Regional Development Fund under grant number 14/IA/2884.

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Authors and Affiliations

  1. Mechanobiology and Medical Devices Research Group (MMDRG), Centre for Biomechanics Research (BioMEC), Biomedical Engineering, College of Engineering and Informatics, National University of Ireland Galway, Galway, Ireland

    L. M. O’Sullivan, H. Allison, E. E. Parle, J. Schiavi & L. M. McNamara

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  1. L. M. O’Sullivan
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O’Sullivan, L.M., Allison, H., Parle, E.E. et al. 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 31, 587–599 (2020). https://doi.org/10.1007/s00198-019-05239-5

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