Bone Health Management in the Continuum of Prostate Cancer Disease

Abstract

Prostate cancer (PCa) is the second-leading cause of cancer-related deaths in men. PCa cells require androgen receptor (AR) signaling for their growth and survival. Androgen deprivation therapy (ADT) is the preferred treatment for patients with locally advanced and metastatic PCa disease. Despite their initial response to androgen blockade, most patients eventually will develop metastatic castration-resistant prostate cancer (mCRPC). Bone metastases are common in men with mCRPC, occurring in 30% of patients within 2 years of castration resistance and in >90% of patients over the course of the disease. Patients with mCRPC-induced bone metastasis develop lesions throughout their skeleton; the 5-year survival rate for these patients is 47%. Bone-metastasis-induced early changes in the bone that proceed the osteoblastic response in the bone matrix are monitored and detected via modern magnetic resonance and PET/CT imaging technologies. Various treatment options, such as targeting osteolytic metastasis with bisphosphonates, prednisone, dexamethasone, denosumab, immunotherapy, external beam radiation therapy, radiopharmaceuticals, surgery, and pain medications are employed to treat prostate-cancer-induced bone metastasis and manage bone health. However, these diagnostics and treatment options are not very accurate nor efficient enough to treat bone metastases and manage bone health. In this review, we present the pathogenesis of PCa-induced bone metastasis, its deleterious impacts on vital organs, the impact of metastatic PCa on bone health, treatment interventions for bone metastasis and management of bone- and skeletal-related events, and possible current and future therapeutic options for bone management in the continuum of prostate cancer disease.

Identification of novel bone-resorption markers by osteoclastsin vitroandin vivo

“…This increase in type 1 collagen markers is associated with stimulation of osteoclastogenesis through RANKL expression and increased cathepsin K activity. 20–22 In our lung cancer cohort, we previously showed changes in a number of our bone markers in the last weeks of life. 13 Two of the COL1A1-specific collagen peptides reported here progressively increased in urine over the course of time leading up to death, from greater than three months up to the last week before death; these were the dipeptide phenylalanyl-hydroxyproline and the highest molecular weight COL1A1 fragment observed here (marker #22; Table 1).…”

Prostate cancer genotyping for risk stratification and precision treatment

“…These treatments can be combined with oral or intravenous bisphosphonates for pain relief in patients with hormone-relapsed metastatic PC when other treatments, including analgesics and palliative radiotherapy, do not provide satisfactory pain relief. [34,35]…”

A comparative study of spinal cord compression management in metastatic prostate cancer: Teaching versus non‐teaching hospitals in the United States

“…Bone metastases are a common complication of patient with prostate cancer, occurring in over 90% of patients over disease course 6 . Bone metastases are detected through a variety of imaging techniques including MRI, CT, and PET scans 7,8 .…”

“…Bone metastases are a common complication of patient with prostate cancer, occurring in over 90% of patients over disease course. 6 Bone metastases are detected through a variety of imaging techniques including MRI, CT, and PET scans. 7 , 8 In patients with bone metastases, complications are often collectively referred to as skeletal‐related events (SRE), which include pathologic fractures, the need for radiation or surgery, or spinal cord compression.…”