Second-generation hormonotherapy in prostate cancer and bone microenvironment

Abstract

Prostate cancer (Pca) is the most commonly diagnosed cancer affecting men in France. Before the age of 75 years old, 1 in 8 French men will have Pca. Androgen deprivation therapies (ADT) remain the standard of care. Such therapies induces significant bone loss. Bone-remodelling cycle depends on the androgen synthesis signalling pathways. Furthermore, age-specific hormonal decline plays a key role in the decrease in bone mass. As a result, the older the patients, the more likely they are to have osteoporosis if they are treated with hormone therapy. Their risk of osteoporotic fracture has an impact on their quality of live and their capacity of independent living. In recent years, newer hormone therapies (acetate abiraterone, enzalutamide, apalutamide and darolutamide) have proved efficient in metastatic castration-resistant Pca (mCRPC) patients as well as in hormone naïve patients, and actually in non-metastatic diagnosis. The combination of these treatments with ADT highly inhibit androgen production pathways. They are prescribed to aged patients undergoing bone density loss after first generation anti-androgen treatment. Specific recommendations for bone health management in Pca patients are currently lacking. To date, bone mineral density in patients treated with second-generation hormone therapy has never been assessed in a prospective study. This review aims at reviewing what is known about the impact of second-generation hormonotherapy on bone microenvironment.

Celebrating the 80th anniversary of hormone ablation for prostate cancer

“…In 'Second-generation hormonotherapy in prostate cancer and bone microenvironment', Bouleftour et al (2021) discuss the effect of androgen ablation and secondgeneration anti-androgens on the bone. Proper functioning of the AR is essential both for bone development and for bone mass maintenance (Bellido et al 1995, Kawano et al 2003, Chen et al 2019.…”

“…Despite this, prostate cancer patients, especially those who are older, suffer significantly from bone loss and related side effects. Bouleftour et al (2021) argue that currently, specific recommendations for bone health management in prostate cancer patients are lacking, and prospective studies assessing bone mineral density in patients treated with second-generation hormone therapy has not been conducted. It may be hoped that the collection of information provided in this issue would pave the way for such a study.…”

Changes in bone and mineral homeostasis after short-term androgen deprivation therapy with or without androgen receptor signalling inhibitor – substudy of a single-centre, double blind, randomised, placebo-controlled phase 2 trial

“…However, data on bone health of these newer drugs remain limited. [8][9][10] Importantly, fractures inversely correlate with overall survival in PCa patients; overall mortality risk increases with 38% in PCa patients experiencing a fracture. 11 Guidelines from both urological and endocrinological societies advice routine screening for bone health in PCa patients treated with ADT.…”