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Review
. 2026 Jan 26.
doi: 10.1038/s41391-026-01077-9. Online ahead of print.

Risk of bone fractures in patients with prostate cancer treated with maximal androgen blockade therapy: a systematic literature review and meta-analysis

Isabella Saporita  1 , Mariangela Calabrese  1 , Federica Maria Carfi  1 , Andrea Mogavero  1 , Marialuisa Puglisi  2   3 , Giorgio Treglia  4   5   6 , Ursula Maria Vogl  3 , Silke Gillessen  3   4 , Ricardo Pereira Mestre  3   4   7 , Martino Pedrani  3 , Giovanna Pecoraro  3   8 , Giuseppe Salfi  3   7 , Caroline-Claudia Erhart  3 , Hui-Ming Lin  3 , Luigi Tortola  3 , Massimo Di Maio  9 , Marcello Tucci  10 , Consuelo Buttigliero  1 , Fabio Turco  11
Affiliations
Review

Risk of bone fractures in patients with prostate cancer treated with maximal androgen blockade therapy: a systematic literature review and meta-analysis

Isabella Saporita et al. Prostate Cancer Prostatic Dis. .

Abstract

Background: Addition of an androgen receptor pathway inhibitor (ARPI) to androgen deprivation therapy (ADT) (ADT + ARPI, i.e., maximal androgen blockade, MAB) improves survival outcomes compared to ADT monotherapy in patients with prostate cancer (PC). It is known that ADT increases the risk of fractures in patients with PC, but it is unclear if this risk is higher with MAB. The aim of this study is to conduct a systematic review and meta-analysis to determine if MAB increases the incidence of fractures compared to ADT alone, and if the incidence of fractures was influenced by the type of ARPI.

Methods: Clinical trials assessing MAB versus ADT alone in patients with PC were identified using the PubMed/Medline and Cochrane library databases. The pooled odds ratio of developing fractures with MAB versus ADT alone was calculated for each type of ARPI in selected studies by random-effects modeling. The number of patients receiving bone-protecting agent (BPA) was also evaluated.

Results: We identified 17 studies comprising 16162 patients for the systematic review and meta-analysis (9240 patients treated with MAB, 6922 patients treated with ADT alone). Each type of ADT + ARPI resulted in a statistically significant increased risk of fractures compared to ADT alone (pooled OR ranging from 1.5 to 2.4). There was no difference in the magnitude of the risk of fractures among the different ARPIs. Only 7 studies reported the number of patients treated with a BPA.

Conclusions: In our meta-analysis, MAB resulted in a statistically significant increase in fracture risk compared to ADT alone, regardless of the type of ARPI. Since long-term MAB represents the standard of care in various settings of PC, the use of a BPA should be generally recommended. Dosing and frequency of BPA need to be adapted according to the specific PC setting.

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Conflict of interest statement

Competing interests: UMV reports speaker or consultancy honoraria from Accord (P), Astellas (I, P), Astra Zeneca (I), Bayer (I, P), European School of Oncology (ESO) (I) The healthbook Times (I, P) Janssen Cielag (I), Merck (I), MSD (I), Novartis AAA (I), Oncology Compass (I), SAKK (I), SAMO (I, P), travel grants from Astra Zenecka, Janssen, Merck and Ipsen (P), Grant Funding from Fond’Action Research Grant (I). SAKK PG UG president and Editor in Chief of the Healthbook Times. SG reports consulting fees from Tolremo, Ipsen, and Avalere Health; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Silvio Grasso Consulting, WebMD-Medscape, Peer Voice, European Society for Medical Oncology, Meister ConCept, Swiss Group for Clinical Cancer Research (SAKK), DESO, AdMeTech Foundation, EPG Health, and Intellisphere; support for attending meetings or travel from AstraZeneca, Bayer, Intellisphere, and Gilead; patents planned, issued, or pending for prostate cancer biomarkers (WO2009138392); participation on a data safety monitoring board or advisory board for Orion, Bayer, Astrazeneca, Myriad Genetic, Amgen, MSD, Bristol-Myers Squibb, Daiichi Sankyo, Boehringer Ingelheim, Innomedica, Macrogenics, Astellas, and Novartis; and leadership or fiduciary roles in other board, society, committee, or advocacy group, paid or unpaid for Pfizer, Unicancer, LinkinVax, University of Applied Sciences and Arts of Southern Switzerland, Advanced Prostate Cancer Consensus Conference Society, Fond’action, European Organisation for Research and Treatment of Cancer, American Society of Oncology. MDM received honoraria for consultancy or participation to advisory boards from AstraZeneca, Boehringer Ingelheim, Janssen, Merck Sharp & Dohme (MSD), Novartis, Pfizer, Roche, GlaxoSmithKline, Takeda, Viatris, Eisai, Daiichi Sankyo and institutional funding for work in clinical trials/contracted research from Beigene, Exelixis, MSD, Pfizer and Roche, all unrelated to the present work. FT reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Silvio Grasso Consulting, SAKK, Merck, Novartis and Bayer; support for attending meetings or travel from Bayer; and participation on a data safety monitoring board or advisory board for Bayer.

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