J Bone Metab.  2018 May;25(2):87-98. 10.11005/jbm.2018.25.2.87.

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

• Ardawi MS
• Rouzi AA
• Al-Senani
• Qari MH
• Elsamanoudy AZ
• Mousa SA

• KMID: 2413370
• DOI: http://doi.org/10.11005/jbm.2018.25.2.87

Abstract

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.

Keyword

Osteoporosis; Osteoporotic fractures; Postmenopausal; Sphingosine 1 phosphate

MeSH Terms

Animals
Bone Density
Cohort Studies
Ecthyma, Contagious
Female
Humans
Open Reading Frames
Osteoporosis*
Osteoporotic Fractures*
Outcome Assessment (Health Care)
Plasma*
Prospective Studies
Risk Assessment
Risk Factors
Sphingosine*
Sphingosine

Figure

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  Fig. 1 Study design and measurements.

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  Fig. 2 Cumulative incidence of fractures among the studied women with sphingosine 1-phosphate levels in the highest quartile compared with that in all other quartiles. CI, confidence interval.

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  Fig. 3 Multivariable-adjusted hazard ratios for the risk of osteoporosis-related fractures, according to the quartile of plasma sphingosine 1-phosphate (S1P) concentration. Plasma S1P (µmol/L) quartiles were: Q1<4.85; Q2=4.86–5.24; Q3=5.25–5.81; and Q4≥5.82. The y axis is on a log scale. The reference group is quartile 1. The I bars denote 95% confidence intervals.

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