Cancer Treatment and Bone Health

Considerable advances in oncology over recent decades have led to improved survival, while raising concerns about long-term consequences of anticancer treatments. In patients with breast or prostate malignancies, bone health is a major issue due to the high risk of bone metastases and the frequent prolonged use of hormone therapies that alter physiological bone turnover, leading to increased fracture risk. Thus, the onset of cancer treatment-induced bone loss (CTIBL) should be considered by clinicians and recent guidelines should be routinely applied to these patients. In particular, baseline and periodic follow-up evaluations of bone health parameters enable the identification of patients at high risk of osteoporosis and fractures, which can be prevented by the use of bone-targeting agents (BTAs), calcium and vitamin D supplementation and modifications of lifestyle. This review will focus upon the pathophysiology of breast and prostate cancer treatment-induced bone loss and the most recent evidence about effective preventive and therapeutic strategies

Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

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

Medical Prevention and Treatment of Bone Metastases.

The presence of metastatic bone disease is a devastating complication that has signifcant impact on morbidity and mortality in cancer patients. Although the type, incidence, and consequences of bone metastases (BM) may vary between primary cancer sites, all patients with BM require consideration as to how both their primary tumour and their bone disease should be managed in terms of avoiding complications and maximizing both quality of life and survival. This chapter will describe normal bone turnover, the pathophysiology of BM, and the most common clinical sequelae. We will then explain the current evidence for the prevention and treatment of BM for the most osteotropic tumours (breast, prostate, lung, and renal)

Setting Research Priorities in Partnership with Patients to Provide Patient-centred Urological Cancer Care.

There is a well-documented discrepancy in prioritisation of research agendas between patients and researchers. Patient involvement in urological research from the outset is critical for well-prioritised research.Ni