• Giuseppe Gargano, Simona M Pagano, and Nicola Maffulli.
• Department of Trauma and Orthopaedic Surgery, Hospital San Francesco D'Assisi, Via Michele Clemente, Oliveto Citra, SA 84020, Italy.
• Br. Med. Bull. 2025 Jan 16; 153 (1).

BackgroundOsteoporosis (OP) is a metabolic bone disease producing reduction in bone mass with consequent bone fragility. Circular ribonucleic acid (CircRNA) is a form of RNA that forms a loop structure rather than a linear one. CircRNA can be used for therapeutic purposes, including molecular targets or to test new therapies.Sources Of DataA systematic search of different databases to July 2024 was performed to define the role of circRNA in OP therapy. Seventeen suitable studies were identified.Areas Of AgreementCircRNAs may be useful in studying metabolic processes in OP and identify possible therapeutic targets and new drug therapies.Areas Of ControversyThe metabolic processes involved in OP are regulated by many genes and cytokines that can be targeted by CircRNAs. However, it is not easy to predict whether the in vitro responses of the studied CircRNAs and their interaction with drugs are also applicable in vivo.Growing PointsMetabolic processes can be affected by gene dysregulation of CircRNAs on various growth factors. Areas timely for developing research: Despite the predictability of CircRNA pharmacological response in vitro, such pharmacological response cannot be expected to be replicated in vivo.Data AvailabilityThe data that support the findings of this study are available from the corresponding author.© The Author(s) 2025. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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