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Physiology and Biochemistry

The impact of obesity on bone health: molecular pathways, metabolic interactions, and associated pathologies

International Journal of Obesity volume 50, pages 87–115 (2026)Cite this article

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Abstract

Obesity, characterized by excessive body fat accumulation, is a growing global health concern with significant implications for both metabolic and skeletal health. The increasing prevalence of obesity, particularly among children, adolescents, and postmenopausal women, is associated with various bone-related disorders. Obesity and non-alcoholic fatty liver disease (NAFLD) collectively influence bone metabolism through systemic factors such as chronic inflammation, insulin resistance, dyslipidemia, and alterations in adipose tissue function. Key mediators, including adipokines like leptin and adiponectin, along with pro-inflammatory cytokines, play crucial roles in modulating bone formation and resorption, thereby contributing to conditions such as osteopenia and osteoporosis. Moreover, the interplay between obesity, NAFLD, and bone health involves complex mechanisms, including gut microbiota dysbiosis and impaired vitamin D metabolism. Understanding these multifaceted interactions is essential for developing targeted interventions to prevent or mitigate the adverse effects of obesity and NAFLD on bone health. This review explores the molecular pathways, metabolic interactions, and associated pathologies linking obesity and NAFLD to bone health.

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Acknowledgements

We would like to express our gratitude to BioRender (www.biorender.com) for providing the software used to create all figures in this article.

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Authors and Affiliations

  1. Bone and Joint Reconstruction Research Center, Shafa Orthopedic Hospital, Iran University of Medical Sciences, Baharestan Square, Tehran, Iran

    Abolfazl Bagherifard

  2. Shohadaye Haftom-e-Tir Hospital, Department of Orthopaedic, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Ahmad Hemmatyar

  3. Bone and Joint Reconstruction Research Center, Department of Orthopedics, School of Medicine, Iran University of Medical Science, Tehran, Iran

    Karo Khosravi & Hooman Yahyazedeh

  4. Dezful University of Medical Sciences, Dezful, Iran

    Ali Rouzbahani

  5. Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran

    Khatere Mokhtari

  6. Department of Orthopedic Surgery, Farhikhtegan Hospital, Faculty of Medicine, Tehran Medical Sciences Islamic Azad University, Tehran, Iran

    Hooman Yahyazedeh

  7. Antimicrobial Resistance Research Center, Basic Science Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Hamid Tanzadehpanah

Authors
  1. Abolfazl Bagherifard
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  2. Ahmad Hemmatyar
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  4. Ali Rouzbahani
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Contributions

Conceptualization: AH; Data curation: AB, KK, and HT; Investigation: AB and AH; Supervision: HY. Validation: KM; Writing—original draft: AB, KK, and KM; Writing—review & editing: HY and HT.

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Correspondence to Hooman Yahyazedeh or Hamid Tanzadehpanah.

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Bagherifard, A., Hemmatyar, A., Khosravi, K. et al. The impact of obesity on bone health: molecular pathways, metabolic interactions, and associated pathologies. Int J Obes 50, 87–115 (2026). https://doi.org/10.1038/s41366-025-01907-1

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