Abstract
BackgroundOsteoporosis is a skeletal disorder characterized by compromised bone strength, resulting in increased fracture risk. Patients with prostate cancer may have multiple risk factors contributing to bone fragility: advanced age, hypogonadism, and long-term use of androgen-deprivation therapy. Despite absence of metastatic disease, patients with nonmetastatic castrate-resistant prostate cancer receiving newer androgen receptor inhibitors can experience decreased bone mineral density. A systematic approach to bone health care has been hampered by a simplistic view that does not account for heterogeneity among prostate cancer patients or treatments they receive. This review aims to raise awareness in oncology and urology communities regarding the complexity of bone health, and to provide a framework for management strategies for patients with nonmetastatic castrate-resistant prostate cancer receiving androgen receptor inhibitor treatment.MethodsWe searched peer-reviewed literature on the PubMed database using key words “androgen-deprivation therapy,” “androgen receptor inhibitors,” “bone,” “bone complications,” and “nonmetastatic prostate cancer” from 2000 to present.ResultsWe discuss how androgen inhibition affects bone health in patients with nonmetastatic castrate-resistant prostate cancer. We present data from phase 3 trials on the three approved androgen receptor inhibitors with regard to effects on bone. Finally, we present management strategies for maintenance of bone health.ConclusionsIn patients with nonmetastatic castrate-resistant prostate cancer, aging, and antiandrogen therapy contribute to bone fragility. Newer androgen receptor inhibitors were associated with falls or fractures in a small subset of patients. Management guidelines include regular assessment of bone density, nutritional guidance, and use of antiresorptive bone health agents when warranted.
Highlights
USA 5 Mayo Clinic AZ, Scottsdale, AZ, USA 6 MD Anderson Cancer Center, Houston, TX, USA 7 Indiana University School of Medicine, Indianapolis, IN, USAOsteoporosis is a skeletal disorder that compromises bone strength and increases the risk of fractures [1]
Bone fragility in patients with metastases has been studied extensively; these studies have led to two US Food and Drug Administration (FDA) approvals, for zoledronic acid and denosumab, for the prevention of metastasisrelated skeletal-related events (SREs) in this high-risk population [4, 6, 7]
The approved generation androgen receptor inhibitors (ARIs)—apalutamide, darolutamide, and enzalutamide—have demonstrated efficacy in patients with nmCRPC in the SPARTAN, ARAMIS, and PROSPER phase 3 trials respectively; each trial evaluated potential risk of falls and fractures [15,16,17]. These three agents were each added to androgen-deprivation therapy (ADT) and evaluated against placebo in designed studies of nmCRPC with prostate-specific antigen doubling time (PSADT) ≤10 months, with the primary endpoint being metastasisfree survival
Summary
We discuss how androgen inhibition affects bone health in patients with nonmetastatic castrate-resistant prostate cancer. We present data from phase 3 trials on the three approved androgen receptor inhibitors with regard to effects on bone. We present management strategies for maintenance of bone health
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