Skip to content
BY 4.0 license Open Access Published by De Gruyter Open Access April 18, 2022

Effects of zoledronic acid on bone structure and organization of nanocomposites in rats with obesity and limited mobility

  • N.M. Kostyshyn and I.I. Shtablavyi
From the journal Cell Pathology


Background: Some investigations show that obesity is associated with increase in bone mass due to excessive mechanical exertion. However, these data are contradictory as loss of mineral density of bone tissue and, respectively, the risk of fractures in this population group is higher. The aim of the research was to investigate impact of drug therapy with zoledronic acid on nanostructure of bones in rats with limited mobility and high-calorie diet.

Methods: Rats (n = 56) were distributed into three groups: control (n = 18) – standard vivarium conditions, І experimental group (n = 18) – rats, which were on a high-calorie diet with limited mobility (HCD+LM), ІІ experimental group (n = 18) – HCD+LM+zoledronic acid. Zoledronic acid was injected at the dose 0.025 mg/kg intramuscularly every four weeks for six months. X-ray structure analysis, scanning electron microscopy and atomic absorption spectrometry were used for investigation of ultrastructure and quantitative assessment of mineral component loss in the femoral neck.

Results: Obesity and limited mobility reduced the level of the mineral component in the femoral neck (−31.5%) compared with control. It is significant that zoledronic acid did not permit decrease in mineral component of the bone throughout the entire experiment compared with group I (+41.8%), and all parameters were higher than in control group (+15%).

Conclusions: Obesity and limited mobility negatively affect mineral bone mass. Zoledronic acid induces increase in the mineral component as a result of remodeling inhibition under conditions of obesity and limited mobility modeling.


[1] Smith KB, Smith MS. Obesity statistics. Prim Care. 2016 Mar;43(1):121-35. 10.1016/j.pop.2015.10.001Search in Google Scholar

[2] Villareal DT, Apovian CM, Kushner RF, Klein S; American Society for Nutrition; NAASO, The Obesity Society. Obesity in older adults: technical review and position statement of the American Society for Nutrition and NAASO, The Obesity Society. Obes Res. 2005 Nov;13(11):1849–63.10.1038/oby.2005.228Search in Google Scholar

[3] Yarrow JF, Toklu HZ, Balaez A, Phillips EG, Otzel DM, Chen C, et al. Fructose consumption does not worsen bone deficits resulting from high-fat feeding in young male rats. Bone. 2016 Apr;85:99–106.10.1016/j.bone.2016.02.004Search in Google Scholar

[4] Pang MY, Lau RW, Yip SP. The effects of whole-body vibration therapy on bone turnover, muscle strength, motor function, and spasticity in chronic stroke: a randomized controlled trial. Eur J Phys Rehabil Med. 2013 Aug;49(4):439–50.Search in Google Scholar

[5] Cao J. Effects of obesity on bone metabolism. J Orthop Surg Res. 2011 Jun;6:30.10.1186/1749-799X-6-30Search in Google Scholar

[6] Compston J. Obesity and bone. Curr Osteoporos Rep. 2013 Mar;11(1):30–5.10.1007/s11914-012-0127-ySearch in Google Scholar

[7] Cao JJ, Sun L, Gao H. Diet-induced obesity alters bone remodeling leading to decreased femoral trabecular bone mass in mice. Ann N Y Acad Sci. 2010 Mar;1192(1):292–7.10.1111/j.1749-6632.2009.05252.xSearch in Google Scholar

[8] Recker RR, Delmas PD, Halse J, Reid IR, Boonen S, García-Hernandez PA, et al. Effects of intravenous zoledronic acid once yearly on bone remodeling and bone structure. J Bone Miner Res. 2008 Jan;23(1):6–16.10.1359/jbmr.070906Search in Google Scholar

[9] Raje N, Terpos E, Willenbacher W, Shimizu K, García-Sanz R, Durie B, et al. Denosumab versus zoledronic acid in bone disease treatment of newly diagnosed multiple myeloma: an international, double-blind, double-dummy, randomised, controlled, phase 3 study. Lancet Oncol. 2018 Mar;19(3):370–81.10.1016/S1470-2045(18)30072-XSearch in Google Scholar

[10] Khajuria DK, Disha C, Razdan R, Mahapatra DR, Vasireddi R. Prophylactic effects of propranolol versus the standard therapy on a new model of disuse osteoporosis in rats. Sci Pharm. 2013 Dec;82(2):357–74.10.3797/scipharm.1310-06Search in Google Scholar

[11] Khajuria DK, Razdan R, Mahapatra DR. Effect of combined treatment with zoledronic acid and propranolol on mechanical strength in an rat model of disuse osteoporosis. Rev Bras Reumatol. 2015 Nov-Dec;55(6):501–11.10.1016/j.rbre.2014.07.007Search in Google Scholar

[12] Wellington K, Goa KL. Zoledronic acid: a review of its use in the management of bone metastases and hypercalcaemia of malignancy. Drugs. 2003;63(4):417–37.10.2165/00003495-200363040-00009Search in Google Scholar

[13] Pozzi S, Vallet S, Mukherjee S, Cirstea D, Vaghela N, Santo L, et al. High-dose zoledronic acid impacts bone remodeling with effects on osteoblastic lineage and bone mechanical properties. Clin Cancer Res. 2009 Sep;15(18):5829–39.10.1158/1078-0432.CCR-09-0426Search in Google Scholar

[14] Kostyshyn NM, Gzhegotskyi MR, Kostyshyn LP, Mudry SI. Effect of zoledronic acid on bone nanocomposites organization and prevention of bone mineral density loss in ovariectomized rats. Drug Metab Pers Ther. 2021 Mar;36(3):239–45.10.1515/dmpt-2020-0187Search in Google Scholar

[15] Clark SM, Iball J. The x-ray crystal analysis of bone. Prog Biophys Biophys Chem. 1957;7:225–53.10.1016/S0096-4174(18)30127-6Search in Google Scholar

[16] Bunaciu AA, Udriştioiu EG, Aboul-Enein HY. X-ray diffraction: instrumentation and applications. Crit Rev Anal Chem. 2015;45(4):289–99.10.1080/10408347.2014.949616Search in Google Scholar

[17] Piga G, Solinas G, Thompson TJ, Brunetti A, Malgosa A, Enzo S. Is X-ray diffraction able to distinguish between animal and human bones? J Archaeol Sci. 2013;40(1):778–85.10.1016/j.jas.2012.07.004Search in Google Scholar

[18] Tadano S, Giri B. X-ray diffraction as a promising tool to characterize bone nanocomposites. Sci Technol Adv Mater. 2012 Jan;12(6):064708.10.1088/1468-6996/12/6/064708Search in Google Scholar

[19] Kostyshy N, Kulyk Y, Kostyshyn L, Gzhegotskyi M. Metabolic and Structural Response of Bone to Whole-Body Vibration in Obesity and Sedentary Rat Models for Osteopenia. Rom J Diabetes Nutr Metab Dis. 2020;27:200–8.Search in Google Scholar

[20] Shah FA, Ruscsák K, Palmquist A. 50 years of scanning electron microscopy of bone-a comprehensive overview of the important discoveries made and insights gained into bone material properties in health, disease, and taphonomy. Bone Res. 2019 May;7(1):15.10.1038/s41413-019-0053-zSearch in Google Scholar

[21] Alexander B, Daulton TL, Genin GM, Lipner J, Pasteris JD, Wopenka B, et al. The nanometre-scale physiology of bone: steric modelling and scanning transmission electron microscopy of collagen-mineral structure. J R Soc Interface. 2012 Aug;9(73):1774–86.10.1098/rsif.2011.0880Search in Google Scholar

[22] Boyde A. Scanning electron microscopy of bone. In: Idris AI, editor. Bone Research Protocols. New York (NY): Humana Press; 2019. pp. 571–616.10.1007/978-1-4939-8997-3_31Search in Google Scholar

[23] Miskovic-Stankovic V, Erakovic S, Jankovic A, Vukasinovic-Sekulic M, Mitric M, Jung YC, et al. Electrochemical synthesis of nanosized hydroxyapatite/graphene composite powder. Carbon lett. 2015 Oct;16(4):233-240.10.5714/CL.2015.16.4.233Search in Google Scholar

[24] Hellenbrandt M. The inorganic crystal structure database (ICSD)—present and future. Crystallogr Rev. 2004;10(1):17–22.10.1080/08893110410001664882Search in Google Scholar

[25] Premaor MO, Comim FV, Compston JE. Obesity and fractures. Arq Bras Endocrinol Metabol. 2014 Jul;58(5):470–7.10.1590/0004-2730000003274Search in Google Scholar

[26] Liu Y, Côté MM, Cheney MC, Lindeman KG, Rushin CC, Hutter MM, et al. Zoledronic acid for prevention of bone loss in patients receiving bariatric surgery. Bone Rep. 2021 Mar;14:100760.10.1016/j.bonr.2021.100760Search in Google Scholar

[27] Wessel JH, Dodson TB, Zavras AI. Zoledronate, smoking, and obesity are strong risk factors for osteonecrosis of the jaw: a case-control study. J Oral Maxillofac Surg. 2008 Apr;66(4):625–31.10.1016/j.joms.2007.11.032Search in Google Scholar

[28] Walsh JS, Vilaca T. Obesity, type 2 diabetes and bone in adults. Calcif Tissue Int. 2017 May;100(5):528–35.10.1007/s00223-016-0229-0Search in Google Scholar

[29] Kostyshyn NM, Grzegotsky MR, Servetnyk MI. Assessment of structural and functional condition of rats bone tissue under the influence of various parameters of vibration. Curr Issues Pharm Med Sci. 2018;31(3):148–53.10.1515/cipms-2018-0029Search in Google Scholar

[30] Lespessailles E, Jaffré C, Beaupied H, Nanyan P, Dolléans E, Benhamou CL, et al. Does exercise modify the effects of zoledronic acid on bone mass, microarchitecture, biomechanics, and turnover in ovariectomized rats? Calcif Tissue Int. 2009 Aug;85(2):146–57.10.1007/s00223-009-9269-zSearch in Google Scholar

[31] Zhu Y, Huang Z, Wang Y, Xu W, Chen H, Xu J, et al. The efficacy and safety of denosumab in postmenopausal women with osteoporosis previously treated with bisphosphonates: A review. J Orthop Translat. 2019 Sep;22:7–13.10.1016/ in Google Scholar PubMed PubMed Central

Received: 2021-11-04
Accepted: 2022-03-20
Published Online: 2022-04-18

© 2020 N.M. Kostyshyn et al., published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

Downloaded on 3.3.2024 from
Scroll to top button