Multidisciplinary Consensus on the Prevention and Treatment of Osteoporosis and Fragility Fractures in Patients with Prostate Cancer Receiving Androgen-Deprivation Therapy

Abstract

Patients with prostate cancer (PCa) on androgen-deprivation therapy (ADT) are at high risk of osteoporosis and fragility fractures. We aimed to provide some practical insights into the delivery of optimal bone health care for PCa patients, particularly those on ADT. An interdisciplinary group of experts, including urologists and rheumatologists developed recommendations based on their expertise, current evidence and guidelines. The multidisciplinary group's main recommendations are: fragility fracture risk should be assessed in all PCa patient, especially, in those under ADT. FRAX® tool may be incorporated into clinical practice to identify patients at high risk of fracture. Bone mineral density (BMD) should be measured routinely by dual energy X-ray absorptiometry in all patients scheduled for or on ADT. Thoracic and lumbar spine X-ray may be performed at the initial evaluation of patients with the diagnosis of osteoporosis and in case of suspected clinical vertebral fracture. Basic laboratory tests are recommended to exclude secondary osteoporosis. Treatment with bisphosphonates or denosumab should be considered in patients on ADT with fragility fracture, osteoporosis (BMD T-score ≤−2.5), or high risk of fracture according to FRAX®. Referral to a bone metabolism specialist should be contemplated in some cases. The recommendations provided in this document, tailored for clinicians treating PCa patients, may be of help to identify and treat patients at high risk of fracture.

Insights and implications of sexual dimorphism in osteoporosis

“… 424 Denosumab can also increase BMD in males with primary osteoporosis or prostate cancer undergoing androgen deprivation therapy. 203 , 425 Despite the efficacy in improving BMD and reducing the incidence of fractures, several side effects may restrict the use of denosumab in specific patient populations. Upon discontinuation, the effects of denosumab rapidly reversed, which resulted in increased bone turnover and BMD loss, 426 with the vertebral fracture rate increasing, even back to the level in untreated patients.…”

Frailty of Prostate Cancer Patients Receiving Androgen Deprivation Therapy: A Scoping Review

“…No study has explored the relationship between social factors and frailty. ADT is a treatment for lowering testosterone levels, which can be closely related to psychological side effects, cognitive impairment, and difficulties with masculinity and self-image, which lead to social isolation [ 17 45 46 47 ]. Therefore, it is difficult to define and characterize frailty experienced by patients with PC receiving ADT through the frailty phenotype described by Fried et al [ 4 ] which does not include psychological, cognitive, and social domains.…”

“…Recently, androgen deprivation therapy (ADT) that lowers testosterone secretion to below-normal levels has been used not only for the treatment of metastatic PC but also as a conservative treatment for radiation therapy in local or locally advanced cancer [ 15 ]. Low testosterone levels due to ADT decrease energy levels, leading to frailty-related falls, osteoporosis, and metabolic syndromes [ 16 17 18 ]. In detail, a recent systematic review found that ADT significantly decreased bone mineral density in patients with PC receiving ADT [ 19 ].…”

Improving Bone Health in Patients with Metastatic Prostate Cancer with the Use of Algorithm-Based Clinical Practice Tool

“…The ASCO endorsed the Cancer Care Ontario (CCO) guidelines on Bone Health and Bone-Targeted Therapies for Prostate Cancer in 2020 [ 18 ]. The guidelines aim to guide oncologists toward the optimal use of bone-modifying agents (BMAs) in men with PCa in various settings based on evidence gathered from several studies conducted to guide indications for therapy with BMAs [ 19 , 20 ]. Despite strong evidence, the implementation of these guidelines remains inconsistent [ 21 , 22 ].…”