Prostate Cancer and Bone Metastases: The Underlying Mechanisms

Patients with advanced prostate cancer often develop bone metastases, leading to bone pain, skeletal fracture, and increased mortality. Bone provides a hospitable microenvironment to tumor cells. The disease manifestation is driven by the interaction between invading tumor cells, bone-forming osteoblasts, and bone-resorbing osteoclasts. The increased level of osteoclast-activating factor (parathyroid hormone-related peptide, PTHrP) is believed to induce bone resorption by upregulating receptor activator of nuclear factor-kappa B ligand (RANKL) and the release of various growth factors into the bone microenvironment to enhance cancer cell growth. However, the underlying molecular mechanisms remain poorly understood. This review outlines the possible molecular mechanisms involved in governing bone metastases driven by prostate cancer, which further provide the basis in searching for new molecular targets for the development of potential therapy.

Prominent Injury Types in Vehicle Underbody Blast

Background To fully understand the injury mechanisms during an underbody blast (UBB) event with military vehicles and develop new testing standards specific to military vehicles, one must understand the injuries sustained by the occupants. Methods Injury data from Service Members (SM) involved in UBB theater events that occurred from 2010 to 2014 were analyzed. Analysis included the investigation of prominent skeletal and visceral torso injuries. Results were categorized by killed-in-action (n = 132 SM) and wounded-in-action (n = 1,887 SM). Results Over 90% (553/606 SM) of casualties in UBB events with Abbreviated Injury Scale (AIS) 2+ injury sustained at least one skeletal fracture, when excluding concussion. The most frequent skeletal injuries from UBB were foot fractures (13% of injuries) for wounded-in-action and tibia/fibula fractures (10% of injuries) for killed-in-action. Only 1% (11/1037 SM) of all casualties with AIS 2+ injuries had visceral torso injuries without also sustaining skeletal fractures. In these few casualties, the coded injuries were likely due to trauma from a loading path other than direct UBB loading. Conclusion Skeletal fractures are the most frequent AIS 2+ injury resulting from UBB events. Visceral torso injuries are infrequent in individuals that survive and they generally occur in conjunction with skeletal injuries.

Determining the Incidence of Adult Fractures: How Accurate Are Emergency Department Data?

Various research methods have been used to obtain skeletal fracture data and report the incidence of fractures. A large number of British studies have used data collected in emergency departments, and not data derived from orthopaedic units. We hypothesised that fracture data will differ depending upon the methodology employed to capture it. Two commonly used sources of fracture data at our institution were compared, (the Emergency Department (ED) database and the Orthopaedic Trauma Unit (OTU) database), using a cohort of adult patients from our defined population as the study sample. We performed univariate analyses to identify differences between groups with accurate and inaccurate ED fracture diagnoses. We then performed a binary logistic regression analysis to determine the best predictors of diagnostic accuracy. In one year, 7,449 patients were referred to the OTU. Three-quarters were referred with fractures. The overall false positive fracture referral rate was 25%. Several fracture subtypes were commonly overdiagnosed in the ED. Regression analysis showed that patient age, patient gender, and the seniority of the referring clinician were independently predictive of an accurate fracture diagnosis. We suggest that studies making use of ED fracture data may potentially overestimate the incidence of adult fractures.