Biological and clinical effects of abiraterone on anti-resorptive and anabolic activity in bone microenvironment
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Michele Iuliani1,*, Francesco Pantano1,*, Consuelo Buttigliero2, Marco Fioramonti1, Valentina Bertaglia2, Bruno Vincenzi1, Alice Zoccoli1, Giulia Ribelli1, Marcello Tucci2, Francesca Vignani2, Alfredo Berruti3, Giorgio Vittorio Scagliotti2, Giuseppe Tonini1 and Daniele Santini1
1 Translational Oncology Laboratory, Medical Oncology, University Campus Bio-Medico of Rome, Rome, Italy
2 Department of Oncology, University of Turin, San Luigi Hospital, Orbassano, Turin, Italy
3 U.O. Oncologia Medica, Ospedali Civili di Brescia, Brescia, Italy
* These authors have contributed equally to this work
Daniele Santini, email:
Keywords: abiraterone acetate, osteoclast, osteoblast, bone marker
Received: February 06, 2015 Accepted: March 03, 2015 Published: March 30, 2015
Abiraterone acetate (ABI) is associated not only with a significant survival advantage in both chemotherapy-naive and -treated patients with metastatic castration-resistant prostate cancer (mCRPC), but also with a delay in time to development of Skeletal Related Events and in radiological skeletal progression. These bone benefits may be related to a direct effect on prostate cancer cells in bone or to a specific mechanism directed to bone microenvironment. To test this hypothesis we designed an in vitro study aimed to evaluate a potential direct effect of ABI on human primary osteoclasts/osteoblasts (OCLs/OBLs). We also assessed changes in bone turnover markers, serum carboxy-terminal collagen crosslinks (CTX) and alkaline phosphatase (ALP), in 49 mCRPC patients treated with ABI.
Our results showed that non-cytotoxic doses of ABI have a statistically significant inhibitory effect on OCL differentiation and activity inducing a down-modulation of OCL marker genes TRAP, cathepsin K and metalloproteinase-9. Furthermore ABI promoted OBL differentiation and bone matrix deposition up-regulating OBL specific genes, ALP and osteocalcin. Finally, we observed a significant decrease of serum CTX values and an increase of ALP in ABI-treated patients.
These findings suggest a novel biological mechanism of action of ABI consisting in a direct bone anabolic and anti-resorptive activity.
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