Abstract
Background
Although recent studies provide clinical evidence that sphingosine-1-phosphate (S1P) may primarily affect bone resorption in humans, rather than bone formation or the osteoclast–osteoblast coupling phenomenon, those studies could not determine which bone resorption mechanism is more important, i.e., chemorepulsion of osteoclast precursors via the blood to bone marrow S1P gradient or receptor activator of NF-κB ligand (RANKL) elevation in osteoblasts via local S1P.
Aim
To investigate how S1P mainly contributes to increased bone resorption in humans, we performed this case–control study at a clinical unit in Korea.
Methods
Blood and bone marrow samples were contemporaneously collected from 70 patients who underwent hip surgery due to either osteoporotic hip fracture (HF) (n = 10) or other causes such as osteoarthritis (n = 60).
Results
After adjusting for sex, age, BMI, smoking, alcohol, previous fracture, diabetes, and stroke, subjects with osteoporotic HF demonstrated a 3.2-fold higher plasma/bone marrow S1P ratio than those without HF, whereas plasma and bone marrow S1P levels were not significantly different between these groups. Consistently, the risk of osteoporotic HF increased 1.38-fold per increment in the plasma/bone marrow S1P ratio in a multivariate adjustment model. However, the odds ratios for prevalent HF according to the increment in the plasma and bone marrow S1P level were not statistically significant.
Conclusion
Our current results using simultaneously collected blood and bone marrow samples suggest that the detrimental effects of S1P on bone metabolism in humans may depend on the S1P gradient between the peripheral blood and bone marrow cavity.
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Acknowledgments
This study was supported by grants from the Korea Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (Project Nos. HI13C1432 and HI14C2185) and the National Research Foundation (NRF) that is funded by the Korean government (Project No. KRF-2010-0025271).
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This study was approved by the Institutional Review Board of Asan Medical Center and was conducted according to the Ethical Principles for Medical Research Involving Human Subjects, as defined by the Declaration of Helsinki.
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All enrolled participants provided written informed consent.
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B.-J. Kim and K.-O. Shin contributed equally to this work.
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Kim, BJ., Shin, KO., Kim, H. et al. The effect of sphingosine-1-phosphate on bone metabolism in humans depends on its plasma/bone marrow gradient. J Endocrinol Invest 39, 297–303 (2016). https://doi.org/10.1007/s40618-015-0364-x
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DOI: https://doi.org/10.1007/s40618-015-0364-x