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Association of circulating levels of total and protein-bound sphingosine 1-phosphate with osteoporotic fracture
  1. Ha Eun Song1,
  2. Seung Hun Lee2,
  3. Su Jung Kim1,
  4. Beom-Jun Kim2,
  5. Hyun Ju Yoo1,
  6. Jung-Min Koh2
  1. 1Department of Convergence Medicine, Asan Institute for Life Sciences, Seoul, Korea (the Republic of)
  2. 2Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea (the Republic of)
  1. Correspondence to Dr Jung-Min Koh, Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea (the Republic of); jmkoh{at}; Professor Hyun Ju Yoo, Department of Convergence Medicine, Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, South Korea; yoohyunju{at}


The biological activity and effects of circulating sphingosine 1-phosphate (S1P) might be dependent on the carrier protein. Although S1P is known to be a biomarker for osteoporotic fracture (OF), its role according to its carrier protein (high-density lipoprotein (HDL), low-density lipoprotein (LDL), or albumin) has not yet been studied. We measured the protein-bound S1P levels and bone mineral density (BMD) in 58 postmenopausal women with OF and 58 age-matched and body mass index–matched postmenopausal women without OF. Albumin-bound S1P was the most abundant. Before adjustment, women with OF had higher total S1P (p=0.046) and albumin-bound S1P (p=0.026) levels than those without OF, but there was no difference in the levels of HDL-bound or LDL-bound S1P. After adjustment for confounders including BMD, women with OF had only higher levels of total S1P than those without OF (p=0.047). Before adjustment, the OR for OF was higher in subjects in the highest quartile for total S1P (OR 5.36, 95% CI 1.22 to 23.63) or albumin-bound S1P (OR 4.48, 95% CI 1.22 to 16.42). After adjustment for confounders including BMD, statistical significance persisted only for total S1P (OR 2.23, 95% CI 1.12 to 4.81). These findings suggest that the positive association of S1P with OF is mainly due to level of total plasma S1P and not due to the differing contributions from specific carrier protein-bound fractions.

  • Osteoporotic fractures
  • Biological markers
  • Lipoproteins
  • Serum albumin

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  • HES and SHL are joint first authors.

  • Correction notice This article has been corrected since it was first published. Hyun Ju Yoo has been added as a joint corresponding author. Additionally, the author’s institution has been added to the second affiliation: ‘University of Ulsan College of Medicine’.

  • Contributors HJY and J-MK contributed to the study conception and design. Acquisition and analysis of data were performed by HES, SHL, SJK, and B-JK. Interpretation of data was performed by SHL, HJY, and J-MK.The first draft of the manuscript was written by HES and SHL. All authors read and approved the final manuscript.

  • Funding This study was supported by grants from the Korea Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (project no. HI15C2792), from the Basic Science Research Program, Ministry of Science, ICT, & Future Planning, Republic of Korea (2016R1D1A1B03935517), and from the Asan Institute of Life Sciences, Asan Medical Center, Republic of Korea (2017IL0540).

  • Disclaimer The funding body had no role in in the study design; in the collection, analysis, and interpretation of the data; in the writing of the report; and in the decision to submit the paper for publication.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; internally peer reviewed.