High Plasma Sphingosine 1-phosphate Levels Predict Osteoporotic Fractures in Postmenopausal Women: The Center of Excellence for Osteoporosis Research Study

BACKGROUND: Higher sphingosine 1-phosphate (S1P) plasma levels are associated with decreased bone mineral density (BMD), and increased risk of prevalent vertebral fracture. So, we hypothesized that postmenopausal women with increased baseline plasma S1P levels have a greater risk for future incident fracture (osteoporosis-related fractures [ORFs]). METHODS: This study was conducted in a prospective longitudinal cohort of 707 women recruited in 2004 and followed up annually for a mean period of 5.2±1.3 years. They were postmenopausal (aged ≥50 years). The primary outcome measure was the time to the first confirmed ORF event using radiographs and/or a surgical report. RESULTS: The plasma S1P levels (µmol/L) were significantly higher in the women with incident fracture (7.23±0.79) than in those without ORFs (5.02±0.51; P < 0.001). High S1P levels were strongly associated with increased fracture risk. After adjustment for age and other confounders, the hazard ratio (HR) was 6.12 (95% confidence interval [CI], 4.92−7.66) for each 1-standard deviation increase in plasma S1P levels. The women in the highest quartile of S1P levels had a significant increase in fracture risk (HR, 9.89; 95% CI, 2.83−34.44). Results were similar when we compared plasma S1P levels at the 1-year visit. CONCLUSIONS: The associations between plasma S1P levels and fracture risk were independent of BMD and other confounders. These findings demonstrate that high plasma S1P level at baseline and at years 1 to 5 is a strong and independent risk factor for future [ORFs] among postmenopausal women and could be a useful biomarker for fracture risk assessment in this population.

Recurrent intestinal perforations as a presentation of antiphospholipid syndrome

Antiphospholipid syndrome [APS] is a rare but important cause of thrombosis. It is suspected in patients who present with recurrent thrombosis or thrombosis in an unusual site. Gastrointestinal involvement is rare in this syndrome. Moreover, intestinal perforation in APS is very rare. We report a 19-year-old female patient who developed recurrent spontaneous intestinal perforations in which repeated laparotomies were undertaken and different diagnoses were entertained. The patient had received different treatments but without improvement. Antiphospholipid syndrome [APS] was suspected and diagnosed, and subsequently anticoagulant therapy was started. To our knowledge, this is a first report describing recurrent small intestinal perforation in a patient with APS