Prostate cancer and bone health

Introduction Both prostate cancer (PC) and its treatment have important effects on bone and body composition. Three distinct mechanisms affect bone; androgen deprivation therapy (ADT); use of chemotherapy and systemic glucocorticoids (GC), and bone metastases (BM). Work undertaken in this thesis investigates the effect of ADT on bone density, microarchitecture, strength, physical performance, frailty, biomarkers of bone turnover and body composition. The second section explores the role of biomarkers in predicting the development of PC BM. Methods The ANTELOPE trial recruited men receiving ADT or ADT and chemotherapy/GC for PC, and healthy controls. A comprehensive bone health assessment was undertaken at baseline and 12 months to identify changes associated with ADT. The biomarker discovery project applied proteomic methods to PC cell lines to quantify the expression of CAPG, GIPC1 and DOCK4 proteins and sought to relate expression to their predicted metastatic potential. Results ADT was associated with loss of bone density at all skeletal sites. There was significant loss of volumetric density at the radius, along with microarchitectural deterioration and reduced bone strength and stiffness. ADT increased bone turnover, and led to sarcopenic obesity with marked effects in upper limb composition. Frailty increased and physical performance and strength deteriorated in association with ADT. The biomarkers GIPC1 and DOCK4 showed differential expression across PC cell lines and may have a role in the early stages of metastasis, but do not appear to predict BM development. Conclusions ADT has profound effects on bone density, structure, strength and body composition, and has important effects on frailty and physical performance. Assessment of bone health is an unmet need in this population and must be incorporated into clinical practice to reduce risk of fractures and their associated morbidity and mortality. Studies should explore the effects of bone targeted therapies on density and microstructure in order to select the most appropriate treatment for this population. Proteomic techniques allow the identification of predictive biomarkers of BM in PC, and further work should explore GIPC1 and DOCK4 in PC cell lines and tissue models.