PRECLINICAL MODEL OF OSTEOBLASTIC-OSTEOLYTIC BONE METASTASES DEMONSTRATES SARCOPENIA WITH IMAGING BIOMARKERS

Metastasized cancer cells disturb bone remodeling, leading to an increased formation of low-quality bone. In addition to changes to the bone, 61% of patients with prostate cancer experience sarcopenia (generalized muscle weakening). Systemic treatment with docetaxel (DTX) and bisphosphonates [Zoledronic Acid (ZA)] for prostate cancer are known to have an impact on musculoskeletal health. Research on the relationship between the atrophy of both tissues, known as osteosarcopenia, has been limited. This increases the frequency of falls and fractures, and an overall lowered quality of life. This study aims to determine imaging biomarkers from the psoas muscle in the presence of metastatic prostate cancer. Twenty-four athymic, 5-week-old male rats were randomly assigned to the following groups: healthy control, healthy treated, ACE-1 cell injected control, and ACE-1 cell injected treated. Institutional approval was obtained, and the ARRIVE guidelines were followed. Under anaesthesia 19 rats received an intra-cardiac injection of luciferase-transfected ACE-1 canine prostate cancer cells (1.5x106 cells/200 µL). Grip strength tests (Grip Strength Test, Bioseb), µMRI (NanoScan, Mediso, with Gadolinium contrast), µCT (NanoScan, Mediso), and bioluminescence imaging (IVIS Spectrum) monitored muscle and bone changes (Figure 1). Rats were injected with docetaxel (5 mg/kg,i.v), or zoledronic acid (Zometa; 60µg/kg, s.c.) on day 9 post-tumour cell injection. All animals tolerated the procedures well. The rats were sacrificed on day 21, for ex-vivo vertebral imaging using high-resolution μCT (µCT100, Scanco, 34.4µm isotropic voxels) to assess trabecular bone architectural properties. Psoas muscles were manually segmented from fused in-vivo MR/CT images to investigate imaging biomarkers like muscle L2-normalized-psoas-volume and attenuation (Figure 2). Bioluminescence and ex-vivo µCT images confirmed mixed metastases in 9 rats (Figure 1). The presence of sarcopenia in rats with metastatic disease was confirmed by a significantly lower normalized psoas volume in cell-injected animals compared to healthy animals (p Sarcopenia was observed with imaging biomarkers of muscle volume and attenuation in this preclinical model of bone metastases secondary to prostate cancer. This study will provide a more thorough understanding of the relationship between treatments, osteopenia, and prostate cancer tumour burden. The imaging biomarkers evaluated in this study may facilitate the earlier diagnosis of osteosarcopenia in prostate cancer patients, leading to earlier intervention and increasing the quality of life. For any figures or tables, please contact the authors directly.