The Current Role of Osteoclast Inhibitors in Patients with Prostate Cancer

Abstract

Purpose Prostate cancer (PCa) is one of the most frequently diagnosed malignancies worldwide. Hormonal deprivation therapy is a well-established treatment for locally advanced or metastatic diseases but exposes patients to the risk of osteoporosis and fragility fractures. Furthermore, the tropism of the PCa cells to osseous metastases increases the incidence of skeletal-related events (SREs). Methods A nonsystematic review of the international literature was performed in respect to the use of osteoclast inhibitors zoledronic acid (ZA) and denosumab (DEN) in PCa patients. Results DEN and ZA have proved their efficacy in preventing osteoporosis and bone mass loss in patients treated with hormonal therapy with no proven superiority of one agent over the other. However, the effectiveness in reducing fragility fractures has been proved only for DEN so far. In metastatic-free castrate-sensitive high-risk PCa patients, ZA has not shown any efficacy in preventing osseous metastasis, and evidence is lacking in favor or against the use of DEN. The use of osteoclasts inhibitors had no evident positive effect in overall and disease-specific survival in this group of patients. In advanced castrate-refractory malignancy, DEN has shown clinical superiority over ZA in preventing new SRE but not in overall survival. Conclusion Superiority of DEN over ZA has been proved only in advanced castrate refractory disease in terms of preventing new SRE. In the rest of the cases, the selection of either agent should be based on the clinical condition of each patient and the cost of the treatment.

Bone health management in the continuum of prostate cancer disease: a review of the evidence with an expert panel opinion

“…In the setting of M0 HS disease on ADT, all BTTs at all schedules and doses used were able to prevent bone loss and/or improve BMD compared with placebo 69–74. However, whether this translates into reduced fractures remains unclear, as no RCTs were designed with fracture risk reduction as primary endpoint.…”

HO-1 Interactors Involved in the Colonization of the Bone Niche: Role of ANXA2 in Prostate Cancer Progression

“…Of note, we had previously published that HO-1 is involved in the bone physiology [14] and participates in PCa bone metastasis [13,14]. Although, men with PCa display in most cases osteoblastic metastases [54], an underlying osteoclastic component should not be overlooked [25]. To explore the contribution of HO-1 in the communication between prostate tumor cells and bone precursor cells, we used an indirect co-culture system between PC3 and Raw264.7 cell lines.…”

“…As mentioned above, the bone is a rich source of ANXA2 [22], a molecule produced by several cells, including osteoclasts and it is involved in osteoclast formation and bone resorption [24]. Although PCa bone metastasis are mainly osteoblastic, an underlying osteoclastic component should not be overlooked [25].To explore the contribution of HO-1 in the interaction between PCa cells and osteoclasts, our previous work documented that PCa cells exposed to conditioned medium from a co-culture system of PC3 and osteoclastic progenitor cells, displayed reduced membrane filopodia density and contact among cells, effects prevented by HO-1 induction in tumor cells [16]. Our results suggest that HO-1 prevents PCa cells from extravasation and invasion to other homing organs.…”

“…As mentioned above, the bone is a rich source of ANXA2 [22], a molecule produced by several cells, including osteoclasts and it is involved in osteoclast formation and bone resorption [24]. Although PCa bone metastasis are mainly osteoblastic, an underlying osteoclastic component should not be overlooked [25].…”

Apoptin as a Tumor-Specific Therapeutic Agent: Current Perspective on Mechanism of Action and Delivery Systems

“…Development of cancer-specific treatment regimens with no or minimum side-effects is the cornerstone of the modern cancer research globally which includes identification of novel vulnerabilities in cancer cells and targeted therapeutics such as anti-angiogenic agents, immunomodulators, monoclonal antibodies, nanoparticles, irreversible electroporation, thermal ablation, CRISPR/Cas9-based gene editing, exosome vehicles, etc. ( Amin and Hammers, 2018 ; Andreozzi et al, 2018 ; Bouvry et al, 2018 ; Dar et al, 2018 ; Darrason et al, 2018 ; Goedegebuure et al, 2018 ; Kozyrakis et al, 2018 ; Karimian et al, 2019 ; Kohnken and Mishra, 2019 ; Pacheco and Bunn, 2019 ; Wu et al, 2019 ; Xie et al, 2019 ; Zhang et al, 2019 ). These strategies can be used in combination with conventional treatment strategies to further ameliorate the health status of humans as well as other animal species.…”