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The circulating sphingosine-1-phosphate level predicts incident fracture in postmenopausal women: a 3.5-year follow-up observation study

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Abstract

Summary

A high level of circulating sphingosine-1-phosphate (S1P) is associated with a high incidence of osteoporotic fracture and a high rate of an insufficient response to bisphosphonate therapy.

Introduction

Sphingosine-1-phosphate (S1P) is a significant regulator of bone metabolism. Recently, we found that a high plasma S1P level is associated with low bone mineral density (BMD), high levels of bone resorption markers (BRMs), and a high risk of prevalent vertebral fracture in postmenopausal women. We investigated the possibility that S1P is a predictor of incident fracture.

Methods

A total of 248 postmenopausal women participated in this longitudinal study and were followed up for a mean duration of 3.5 years (untreated [n = 76] or treated with bisphosphonate or hormone replacement therapy [n = 172]). The baseline plasma S1P level and prevalent and incident fracture occurrence were assessed.

Results

A high S1P level was significantly associated with a higher rate of prevalent fracture after adjusting for femoral neck (FN) BMD, BRM, and potential confounders (odds ratio = 2.05; 95 % confidence interval [CI] = 1.03–4.00). Incident fractures occurred more frequently in the highest S1P tertile (T3) than in the lower two tertiles (T1–2) after adjusting for confounders, including baseline FN BMD, prevalent fracture, antiosteoporotic medication, annualized changes in FN BMD, BRM, and potential confounders (hazard ratio = 5.52; 95 % CI = 1.04–56.54). Insufficient response to bisphosphonate therapy occurred more frequently in T3 than T1–2 (odds ratio = 4.43; 95 % CI = 1.02–21.25).

Conclusions

The plasma S1P level may be a potential predictor of fracture occurrence and an insufficient response to bisphosphonate therapy in postmenopausal women.

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Acknowledgments

This study was supported by grants from the Asan Institute for Life Sciences, Seoul, Republic of Korea (project no. 2015-568) and the Korea Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (project no. HI15C2792).

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Author notes

    Authors and Affiliations

    1. Health Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43 gil, Ulsan, Seoul, 05505, South Korea

      S. J. Bae

    2. Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-Ro 43-Gil, Songpa-gu, Seoul, 05505, South Korea

      S. H. Lee, H.-M. Kim, B.-J. Kim & J.-M. Koh

    3. Department of Endocrinology, Inha University School of Medicine, 27 Inhang-ro, Jung-Gu, Songpa-gu, Incheon, 22332, South Korea

      S. H. Ahn

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    Correspondence to J.-M. Koh.

    Ethics declarations

    All study participants provided written informed consent. This study was approved by the institutional review board of AMC.

    Conflict of interest

    Seung Hun Lee, Beom-Jun Kim, and Jung-Min Koh have patents registered in Korea (KR 10-1486368) and patent applications in the USA (US 13/865,688) for sphingosine-1-phosphate. Sung Jin Bae, Seong Hee Ahn, and Hyeon-Mok Kim have no conflicts of interest to declare.

    Additional information

    S. J. Bae and S. H. Lee contributed equally to this work.

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    Bae, S.J., Lee, S.H., Ahn, S.H. et al. The circulating sphingosine-1-phosphate level predicts incident fracture in postmenopausal women: a 3.5-year follow-up observation study. Osteoporos Int 27, 2533–2541 (2016). https://doi.org/10.1007/s00198-016-3565-z

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