Biomechanical Computed Tomography Facilitates the Diagnosis of Osteoporosis and Fracture Prediction in Patients with High-Risk Prostate Cancer
Abstract
Prostate cancer (PCa) is a major cause of morbidity and mortality among males. The American Cancer Society estimates that, in 2021 alone, there will be 248,530 new cases of PCa in 2021 with 34,130 deaths. Fortunately, as a result of earlier diagnosis and better treatment, men with PCa are living longer with less morbidity. Androgen deprivation therapy (ADT) is the mainstay of such therapy. However, ADT has an important downside in that it is associated with a 13% annual decrease in bone mineral density (BMD), mostly within the first year, which combined with decreased muscle mass and increased falls leads to a 10-20% increased risk of fractures, especially vertebral fractures, within 5 years of initiation. These fractures are associated with worse quality of life, ADT discontinuation, and a threefold increase in mortality. Moreover, when ADT is combined with other hormonal agents that either block testosterone action on its target tissue or block androgen production from the adrenals (which standard ADT does not do), the impact on bone loss is even more severe. These effects of ADT on bone are well known. National guidelines, such as those from the National Comprehensive Cancer Network (NCCN) and American Cancer Society, recommend performing bone density measurements prior to and during ADT and initiating antiresorptive therapy if substantial bone loss is observed. However, these recommendations are seldom followed. In a recent study, we observed that only one third of Veterans with PCa receive baseline screening prior to initiating ADT. Other studies have shown similar results. The standard means of bone testing is the determination of bone mineral density (BMD) via DXA (dual energy x-ray absorptiometry). However, an important limitation of this method when applied to older males is that this population tends to have a substantial amount of degenerative changes, especially in the spine, which artifactually increases the apparent amount of bone detected in the usual mode of DXA scanning. Thus, even if the NCCN recommendations are followed, the extent of bone loss in the older male population, the population most likely to present with PCa, is underestimated. We are proposing to use a newer technology, biomechanical computed tomography (BCT), to address the under diagnosis of bone loss in the PCa population. BCT was developed to estimate bone strength as well as BMD in a non-invasive manner. It conducts a virtual stress test to determine the force needed to fracture the bone of interest. BCT has been validated in clinical studies and generally outperforms both CT and DXA with respect to fracture prediction. The use of PET-CT and CT scans for initial staging and routine surveillance of PCa provides an opportunity to retrospectively evaluate the extent of osteoporosis in men with high-risk or very-high risk PCa, including metastatic disease; determine the degree to which this diagnosis was either not considered or missed by current practice; and determine whether BCT could improve the prediction of future fractures subsequent to the initial PET-CT scan. Our overall hypothesis is that BCT of staging and surveillance CT scans of men with high-risk or very high-risk prostate cancer, including metastatic disease, improves detection and management of osteoporosis compared to usual care. We have four aims: 1. Determine the prevalence of osteoporosis using BCT. 2. Determine what proportion of men found to have osteoporosis by BCT were diagnosed with osteoporosis prior to BCT using DXA or other imaging modalities. 3. Determine the relationship between BCT and incident fracture. 4. Determine whether race/ethnicity modifies the relationship between BCT-derived bone strength and BMD and 5- and 10-year fracture risk. We plan to evaluate all CT, including PET-CT scans, that include the hip and/or spine used in the staging of men with high-risk or very-high risk PCa obtained during th
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210150
Entities
People
- Daniel D Bikle
Organizations
- San Francisco VA Medical Center
- United States Army