Pathophysiology of Bone Loss in Patients with Prostate Cancer Receiving Androgen-Deprivation Therapy and Lifestyle Modifications for the Management of Bone Health: A Comprehensive Review

Abstract

Androgen-deprivation therapy (ADT) is a systemic therapy administered for the management of advanced prostate cancer (PCa). Although ADT may improve survival, long-term use reduces bone mass density (BMD), posing an increased risk of fracture. Considering the long natural history of PCa, it is essential to preserve bone health and quality-of-life in patients on long-term ADT. As an alternative to pharmacological interventions targeted at preserving BMD, current evidence recommends lifestyle modifications, including individualized exercise and nutritional interventions. Exercise interventions include resistance training, aerobic exercise, and weight-bearing impact exercise, and have shown efficacy in preserving BMD. At the same time, it is important to take into account that PCa is a progressive and debilitating disease in which a substantial proportion of patients on long-term ADT are older individuals who harbor axial bone metastases. Smoking cessation and limited alcohol consumption are commonly recommended lifestyle measures in patients receiving ADT. Contemporary guidelines regarding lifestyle modifications vary by country, organization, and expert opinion. This comprehensive review will provide an evidence-based, updated summary of lifestyle interventions that could be implemented to preserve bone health and maintain quality-of-life throughout the disease course of PCa.

Exercise Effects on Bone Mineral Density in Men

“…Nevertheless, some studies do not report pre-study exercise status (Table 3) or pharmacologic therapy (Table 2). Consequently, there is some evidence that failure of an intervention effect on BMD might be related to (a) diseases/pharmaceutic therapy [33][34][35]), (e.g., Androgen Deprivation Therapy that induces adverse metabolic effects, including reduced muscle mass, increased fat mass and loss of bone mineral density (BMD) [36]) with striking impact on bone metabolism or/and (b) low difference between pre-intervention and intervention exercise with a corresponding lack of effective stimuli for bone. This might also relate to studies with an active control group (e.g., [21,37]) and potentially effective exercise characteristics that dilute differences between EG and CG.…”

Bone Targeting Agents in Patients with Prostate Cancer: General Toxicities and Osteonecrosis of the Jaw

“…The implicated mechanisms are mainly two: induction of sarcopenia, which increases the percentage of fat body mass, and increased bone turnover, that induces rapid and non-reversible microarchitectural damage and slow body mass loss. These quantitative and qualitative bone alterations result in an elevated risk of pathological and non-pathological fractures, typically occurring during the first year of therapy, because of rapid bone turnover [26]. So, skeletal involvement in PCa can be caused by two mechanisms: drug related, creating the so-called "cancer treatment-induced bone loss" (CTIBL), and disease related, due to the presence of metastases, causing complications known as SREs.…”

Salute ossea in corso di trattamento adiuvante anti-ormonale nella patologia oncologica: rischio fratturativo e temporizzazione della terapia

“…Oltre al trattamento farmacologico, diversi interventi non farmacologici sono raccomandati nei pazienti a rischio di CTIBL: abolizione del fumo di sigaretta, riduzione dell'introito di alcol, esercizio fisico costante, adeguato apporto di calcio (500-1500 mg/die) e mantenimento di livelli di vitamina D tra 30 e 40 ng/dl [15,27].…”

“…Le recenti linee guida della European Society for Medical Oncology (ESMO) del 2020 [29], in accordo con il Joint Position Statement pubblicato nel 2017 sul Journal of Bone Oncology [27], raccomandano di iniziare la terapia antiriassorbitiva solo in caso di aumentato rischio fratturativo, identificato da:…”