sphingosine-1-phosphate and Spinal-Fractures

The primary objective was to quantify changes in vascular micro-environment in spinal metastases (SM) patients treated with stereotactic body radiotherapy (SBRT) with multi-parametric dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI). The secondary objective was to study plasma biomarkers related to endothelial apoptosis.. Patients were imaged with DCE-MRI at baseline/1-week/12-weeks post-SBRT. Metrics including normalised time-dependent leakage (Ktrans), permeability surface product (PS), fractional plasma volume (Vp), extracellular volume (Ve) and perfusion (F) were estimated using distributed parameter model. Serum acid sphingomyelinase (ASM) and sphingosine-1-phosphate (S1P) were quantified using ELISA. Clinical outcomes including physician-scored and patient-reported toxicity were collected.. Twelve patients (with varying primary histology) were recruited, of whom 10 underwent SBRT. Nine patients (with 10 lesions) completed all 3 imaging assessment timepoints. One patient died due to pneumonia (unrelated) before follow-up scans were performed. Median SBRT dose was 27 Gy (range: 24-27) over 3 fractions (range: 2-3). Median follow-up for alive patients was 42-months (range: 22.3-54.3), with local control rate of 90% and one grade 2 or higher toxicity (vertebral compression fracture). In general, we found an overall trend of reduction at 12-weeks in all parameters (Ktrans/PS/Vp/Ve/F). Ktrans and PS showed a reduction as early as 1-week. Ve/Vp/F exhibited a slight rise 1-week post-SBRT before reducing below the baseline value. There were no significant changes, post-SBRT, in plasma biomarkers (ASM/S1P).. Tumour vascular micro-environment (measured by various metrics) showed a general trend towards downregulation post-SBRT. It is likely that vascular-mediated cell killing contributes to excellent local control rates seen with SBRT. Future studies should evaluate the effect of SBRT on primary-specific spinal metastases (e.g., renal cell carcinoma).

Topics: Fractures, Compression; Humans; Prospective Studies; Radiosurgery; Spinal Fractures; Spinal Neoplasms; Tumor Microenvironment

Although sphingosine 1-phosphate (S1P) plays diverse roles in bone metabolism, the most prominent role seems to be the augmentation of bone resorption.. The objective of the study was to investigate the possibility of using S1P as a predictor for osteoporotic vertebral fracture (VF) risk.. This was a case-control study conducted in a clinical unit in Korea.. Sixty-nine cases having radiological VF and 69 age- and body mass index-matched controls among 460 eligible postmenopausal women participated in the study.. Lateral thoracolumbar radiographs, bone mineral density (BMD), bone turnover markers, and plasma S1P levels were obtained from all subjects.. S1P levels were markedly higher in subjects with VF (7.49±3.44 μmol/liter) than in those without VF (5.58±2.01 μmol/liter; P=0.001) and increased in a dose-response manner as the number of VF increased (P for the trend<0.001), even after adjustment for lumbar spine BMD and potential confounders. The odds ratio for VF was markedly higher in subjects in the highest S1P quartile category compared with those in the lowest S1P quartile category after adjustment for confounders (odds ratio 9.33, 95% confidence interval 2.68-32.49). S1P levels were inversely correlated with BMD at various sites (P=0.015 to 0.044), whereas they were positively correlated with bone resorption markers (P=0.016 to 0.098).. These findings suggest that plasma S1P may be a potential biomarker for the risk of VF, independent of BMD, in postmenopausal women.

Topics: Aged; Bone Density; Case-Control Studies; Female; Humans; Lumbar Vertebrae; Lysophospholipids; Middle Aged; Osteoporosis, Postmenopausal; Predictive Value of Tests; Radiography; Risk Factors; Sphingosine; Spinal Fractures; Thoracic Vertebrae