Markers of Bone Remodeling and Bone Structure at Different Life Stages in Wistar Rats

Main Article Content

Estefania M. Zeni Coronel
https://orcid.org/0000-0002-3436-7535
Marina S. Bonanno
Hernán Mascias
Morena Longo
Susana Zeni
Mariana Seijo
https://orcid.org/0000-0002-9398-0196

Abstract

Introduction: bone mass undergoes dynamic changes throughout growth. The objective was to evaluate variations in bone remodeling markers, trabecular microarchitecture, and densitometric and biomechanical properties of the femur in female Wistar rats.


Materials and methods: six age groups were studied (newborn, 21, 45, 90, 105, and 180 days; n=6/group). Serum levels of calcium (Ca), phosphorus (Pi), osteocalcin (OCN), and C-terminal telopeptide of type I collagen (CTX) were determined. Bone structure was evaluated by histomorphometry (BV/TV), density (BMDft), and femoral bone mineral content (BMOft) by densitometry (DXA), and biomechanics (CSMI, stiffness, fracture strength, Young's modulus) by three-point bending test.


Results: the results showed that Ca was highest at 21 and 180 days, and the lowest Pi value was observed at 90 days (p<0.05). OCN decreased and CTX increased from 21 to 180 days of age. BV/TV increased significantly from birth to 45 days. DMOft and CMOft increased up to 180 days. Biomechanical properties reached their maximum values in early adulthood.


Discussion: taken together, these findings describe the physiological sequence of bone maturation, where bone turnover initially predominates, followed by a phase of structural gain and, finally, mechanical consolidation of the bone.


Conclusions: these data may serve as a reference for experimental studies evaluating interventions on bone health during growth.

Article Details

How to Cite
1.
Zeni Coronel EM, Bonanno MS, Mascias H, Longo M, Zeni S, Seijo M. Markers of Bone Remodeling and Bone Structure at Different Life Stages in Wistar Rats. Actual. Osteol. [Internet]. 2026 Apr. 2 [cited 2026 Apr. 2];21(2):138-49. Available from: https://ojs.osteologia.org.ar/ojs33010/index.php/osteologia/article/view/724
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References

Akhiiarova K, Khusainova R, Minniakhmetov I, Mokrysheva N, Tyurin A. Peak Bone Mass Formation: Modern View of the Problem. Biomedicines 2023; 11 (11): 2982. https://doi.org/10.3390/biomedicines11112982.

Walker MD, Shane E. Postmenopausal Osteoporosis. N Engl J Med 2023; 389(21):1979-91. https://doi.org/10.1056/NEJMcp2307353.

Bolamperti S, Villa I, Rubinacci A. Bone Remodeling: An Operational Process Ensuring Survival and Bone Mechanical Competence. Bone Res 2022; 10(1): 48. https://doi.org/10.1038/s41413-022-00219-8.

Schini M, Vilaca T, Gossiel F, Salam S, Eastell R. Bone Turnover Markers: Basic Biology to Clinical Applications. Endocr Rev 2022; 44 (3): 417-73. https://doi.org/10.1210/endrev/bnac031.

Vasikaran SD, Miura M, Pikner R, BhattoaHP, Cavalier E; IOF-IFCC Joint Committee on Bone Metabolism (C-BM). Practical Considerations for the Clinical Application of Bone Turnover Markers in Osteoporosis. Calcif Tissue Int 2023; 112 P(2):148-57. https://doi.org/10.1007/s00223-021-00930-4.

Szulc, P Bauer DC, Eastell R. Chapter 65 - Biochemical Markers of Bone Turnover in Osteoporosis. In: Dempster DW, Cauley JA, Bouxsein ML, Cosman F (eds). Marcus and Feldman’s Osteoporosis 5thEdition (Chapter 65). Cambridge, MA: Academic Press; 2021. pp. 1545-588. https://doi.org/10.1016/B978-0-12-813073-5.00065-4.

National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals. Guide for the Care and Use of Laboratory Animals. 8th ed. The National Academies Collection: Reports funded by National Institutes of Health; National Academies Press (US): Washington (DC), 2011.

Leary S, Pharmaceuticals F, Underwood W, et al. AVMA Guidelines for the Euthanasia of Animals: 2020 Edition. 2020.

Shepherd JA. Positions of The International Society for Clinical Densitometry and Their Etiology: A Scoping Review. J ClinDensitomOffJ Int Soc Clin Densitom 2023;26 M(3): 101369. https://doi.org/10.1016/j.jocd.2023.101369.

Seijo, Bryk G, Zeni Coronel M, et al. Effect of Adding a Galacto-Oligosaccharides/Fructo-Oligosaccharides (GOS/FOS®) Mixture to a Normal and Low Calcium Diet, on Calcium Absorption and Bone Health in Ovariectomy-Induced Osteopenic Rats. Calcif Tissue Int 2019; 104(3):30112. https://doi.org/10.1007/s00223-018-0490-5.

Brun LR, Brance ML, Lombarte M, Maher MC, Di Loreto VE, Rigalli A. Effects of Yerba Mate (IIex Paraguariensis) on Histomorphometry, Biomechanics, and Densitometry on Bones in the Rat. Calcif Tissue Int 2015; 97(5): 527-34. https://doi.org/10.1007/s00223-015-0043-0.

Seeman E. Bone Modeling and Remodeling. Crit Rev Eukaryot Gene Expr 2009; 19(3):219-33. https://doi.org/10.1615/critreveukargeneexpr.v19.i3.40.

Parfitt AM, Drezner MK, Glorieux FH, et al. Bone Histomorphometry: Standardization of Nomenclature, Symbols, and Units. Report of the ASBMR Histomorphometry Nomenclature Committee. J Bone Miner Res Off J Am Soc Bone Miner Res 1987; 2(6):595-610. https://doi.org/10.1002/jbmr.5650020617.

Chavassieux P, Chapurlat R. Interest of Bone Histomorphometry in Bone Pathophysiology Investigation: Foundation, Present, and Future. Front Endocrinol 2022; 13:907914. https://doi.org/10.3389/fendo.2022.907914.

Zeni Coronel EM, Bryk G, Bonanno MS, Seijo M, Zeni SN, Remodelamiento óseo: cambios en los marcadores de formación y resorción ósea en función de la edad y asociados a la caída en los niveles de estrógenos en ratas hembras. In Vet Investig Vet 2025; 27: 1-11. https://doi.org/10.62168/invet.v27i1.47.

Allen MR, Burr DB, Bone Growth, Modeling, and Remodeling. In: Basic and Applied Bone Biology; Cambridge, MA: Academic Press, 2019. pp. 85-100. https://doi.org/10.1016/B978-0-12-813259-3.00005-1.

Turner CH, Burr DB. Basic Biomechanical Measurements of Bone: A Tutorial. Bone 1993; 14(4):595-608. https://doi.org/10.1016/8756-3282(93)90081-k.

Langdahl B, Ferrari S, Dempster DW. Bone Modeling and Remodeling: Potential as Therapeutic Targets for the Treatment of Osteoporosis. Ther Adv Musculoskelet Dis 2016; 8(6):225-35. https://doi.org/10.1177/1759720X16670154.

Bonjour JP, Chevalley T, Ferrari S, Rizzoli R. The Importance and Relevance of Peak Bone Mass in the Prevalence of Osteoporosis. Salud Publica Mex 2009; 51(Suppl 1):S5-17. https://doi.org/10.1590/s0036-36342009000700004.

Chevalley T, Rizzoli R. Acquisition of Peak Bone Mass. Best Pract Res Clin Endocrinol Metab 2022;36 (2):101616. https://doi.org/10.1016/j.beem.2022.101616.

Seeman E, Delmas PD. Bone Quality--the Material and Structural Basis of Bone Strength and Fragility. N Engl J Med 2006; 354(21): 2250-61. https://doi.org/10.1056/NEJMra053077.

Portal-Núñez S, Lozano D, de la Fuente M, Esbrit P. Fisiopatología del Envejecimiento Óseo. Rev. Esp. Geriatría Gerontol. 2012; 47 (3), 125–131. https://doi.org/10.1016/j.regg.2011.09.003.

Halloran BP, Ferguson VL, Simske SJ, Burghardt A, Venton LL, Majumdar S. Changes in Bone Structure and Mass with Advancing Age in the Male C57BL/6J Mouse. J Bone Miner Res Off J Am Soc Bone Miner Res 2002; 17(6): 1044-50. https://doi.org/10.1359/jbmr.2002.17.6.1044.

Wang Y, Zheng S, Luo Y, Xiao W, Huang C, Li, Y. Osteoimmunology and Aging: Mechanisms, Implications, and Therapeutic Perspectives. Ageing Res Rev 2025; 111: 102822. https://doi.org/10.1016/j.arr.2025.102822.

Zhang R, Gong H, Zhu D, Ma R, Fang J, Fan Y. Multi-Level Femoral Morphology and Mechanical Properties of Rats of Different Ages. Bone 2015; 76: 76–87. https://doi.org/10.1016/j.bone.2015.03.022.

Puelker SM, Castro SRR de, Souza RR de, Maifrino LBM, Nucci RAB, Sitta M do C. Age-Related Effects on Right Femoral Bone of Male Wistar Rats: A Morphometric and Biomechanical Study. J Health Allied Sci NU 2021; 12 (1): 67-70. https://doi.org/10.1055/s-0041-1730107.

Cao AB, McGrady LM, Wang M. Effect of Age on Femur Whole-Bone Bending Strength of Mature Rat. Clin Biomech Bristol Avon 2023; 101: 105828. https://doi.org/10.1016/j.clinbiomech.2022.105828.

Ferretti JL, Nocciolino LM, Lüscher SH, Mackler L, Beribé RS, González R, et al. Masa, calidad, direccionalidad. ¿Cuál es la verdadera diferencia entre ‘osteopenias’ y ‘osteoporosis’? Rev Fac Cienc. Médicas Univ Nac Rosario 2020;39-57. https://doi.org/10.35305/fcm.v1i.19.

Hernandez-Becerra E, Londoño-Restrepo SM, Hernández-Urbiola MI, Jiménez-Mendoza D, Aguilera-Barreiro M de L Á, Pérez-Torrero E, et al. Determination of Basal Bone Mineral Density in the Femur Bones of Male and Female Wistar Rats. Lab Anim 2021; 55 (1): 30-42. https://doi.org/10.1177/0023677220922566.

Rauchenzauner M, Schmid A, Heinz-Erian P, Kapelari K, Falkensammer G, Griesmacher A, et al. Sex- and Age-Specific Reference Curves for Serum Markers of Bone Turnover in Healthy Children from 2 Months to 18 Years. J Clin Endocrinol Metab 2007; 92(2): 443-9. https://doi.org/10.1210/jc.2006-1706.