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Zoledronate treatment exerts sex-independent effects on bone and dental physicochemical properties in mice jaw necrosis

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Abstract

Introduction

Bisphosphonate (BF) therapy is strongly related to the occurrence of medication-related osteonecrosis of the jaw (ONJ). However, no previous study has evaluated if there are sex-related differences on the ONJ establishment together with bone biomechanical alterations, and if they could have a synergy with the ZA treatment.

Materials and Methods

This study aimed to analyze the physicochemical properties of mineralized tissues in a zoledronate (ZA)-related osteonecrosis mouse model, by a 2 × 2-factorial design, considering sex (female/male) and treatment (ZA/Saline) factors (n = 8/group). After three ZA (1.0 mg/kg) or saline administrations (days 0, 7, 14), the lower left second molar was extracted (day 42). Further ZA administration (day 49) and euthanasia (day 70) were conducted. After confirmation of ZA-induced jaw necrosis (histologic and microtomographic analysis), spectroscopic and mechanical parameters were assessed.

Results

ZA-treated groups presented lower bone density due to impaired healing of tooth extraction socket. Sex-related alterations were also observed, with lower bone density in females. Regarding biomechanical parameters, sex and treatment exerted independent influences. ZA, although decreasing flexural modulus and yield stress, increases stiffness mainly due to a higher bone volume. Females show less resistance to higher loads compared to males (considering dimension-independent parameters). Additionally, ZA increases crystallinity in bone and dental structure (p < 0.05). In summary, although strongly related to osteonecrosis occurrence, ZA modifies bone and dental mineral matrix, improving bone mechanical properties.

Conclusion

Despite sex-dependent differences in bone biomechanics and density, osteonecrosis was established with no sex influence. No synergistic association between sex and treatment factors was observed in this study.

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Acknowledgements

The authors would like to thank the National Council for the Improvement of Higher Education (CAPES) and Central Analítica-UFC/CT-INFRA/MCTI-SISANO/Pró-Equipamentos CAPES for their support. The authors also thank Charles Alves Silva, mechanical engineer, for technical support.

Funding

Brazilian funding agencies CAPES (Coordination of Superior Level Staff Improvement) and CNPq (National Council for Scientific and Technological Development) provided financial support for this research.

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Authors and Affiliations

  1. Faculty of Pharmacy, Dentistry and Nursing, Postgraduate Program in Dentistry, Federal University of Ceará (UFC), Rua Monsenhor Furtado, S/N, Rodolfo Teofilo, Fortaleza, CE, Brazil

    Maria Elisa Quezado Lima-Verde, Maria Imaculada de Queiroz Rodrigues, Paulo Goberlânio de Barros Silva, Fabrício Bitu Sousa, Mário Rogério Lima Mota & Ana Paula Negreiros Nunes Alves

  2. Health Sciences Center, Graduate Program in Dentistry, Federal University of Paraíba, Joao Pessoa, PB, Brazil

    Basílio Rodrigues Vieira

  3. Aeronautical and Aerospace Engineering Division, Technological Institute of Aeronautics (ITA), São José Dos Campos, SP, Brazil

    Francisco Tarcísio Guedes Lima-Verde Neto

  4. Department of Physics, Science Center, Federal University of Ceará, Fortaleza, CE, Brazil

    Enzo Victorino Hernandez Agressott & Alexandre Rocha Paschoal

  5. Department of Morphology, Health Sciences Center, Federal University of Paraíba, Joao Pessoa, PB, Brazil

    Frederico Barbosa de Sousa

Authors
  1. Maria Elisa Quezado Lima-Verde
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  11. Ana Paula Negreiros Nunes Alves
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Contributions

MEQ L-V: conceptualization, investigation, writing—original draft; MIdQR: investigation; BRV: formal analysis, data curation; FTGLVN: formal analysis, data curation; EVHA: formal analysis, data curation; FBdS: formal analysis, data curation; ARP: formal analysis, data curation; PGdBS: formal analysis, data curation; FBS: writing—review and editing, supervision; MRLM: writing—review and editing, supervision; APNNA: conceptualization, methodology, writing—review and editing, supervision, project administration.

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Correspondence to Maria Elisa Quezado Lima-Verde.

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Lima-Verde, M.E.Q., de Queiroz Rodrigues, M.I., Vieira, B.R. et al. Zoledronate treatment exerts sex-independent effects on bone and dental physicochemical properties in mice jaw necrosis. J Bone Miner Metab 41, 760–771 (2023). https://doi.org/10.1007/s00774-023-01465-4

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  • DOI: https://doi.org/10.1007/s00774-023-01465-4

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