Mathematical Analysis of Osteoporotic Progression Induced by Androgen Deprivation Therapy (ADT)

ABSTRACT Prostate cancer originates in the prostate gland and is influenced by androgens, which are enzymatically converted into dihydrotestosterone (DHT). This conversion is linked to the stimulation of epithelial cell growth and increased PSA levels. In early stages, androgen dependency is observed, and apoptotic responses in malignant cells are triggered through therapeutic androgen reduction. Based on progression, prostate cancer is classified as non‐metastatic, metastatic, or castration‐resistant. Hormonal therapies such as continuous (CADT) and intermittent (IADT) androgen suppression have been adopted. Within androgen deprivation therapy (ADT), GnRH antagonists (e.g., degarelix) are employed to suppress testicular testosterone synthesis, while abiraterone acetate is used to inhibit CYP17A1, reducing systemic androgen levels. The role of testosterone in bone physiology is emphasized, and its reduction through ADT is implicated in osteoporotic changes. Denosumab, a RANKL inhibitor, is administered to counteract ADT‐induced bone loss by preventing osteoclast activation. A quantitative evaluation of osteoporosis linked to CADT and IADT regimens has been conducted, with testosterone's bone‐regulatory functions analyzed. Two patient scenarios are modeled: One examining bone deterioration via ADT, and the other assessing denosumab's therapeutic role. Graphical simulations, stability analysis and sensitivity analyses are used to assess treatment efficacy and guide osteoporosis management strategies in prostate cancer patients.