Higher circulating sphingosine 1-phosphate levels are associated with lower bone mineral density and higher bone resorption marker in humans.
BACKGROUND
Several in vivo and in vitro studies suggest that sphingosine-1-phosphate (S1P) is known to act as a coupling factor, to stimulate osteoclastogenesis, to control the migration of osteoclast precursors between the blood and bone, and to stimulate the proliferation, migration, and survival of osteoblasts.


OBJECTIVE
Using the determination of circulating S1P levels, we investigated which kinds of processes may be primarily affected by S1P in humans.


METHODS
This was a cross-sectional study conducted in two clinical units in Korea.


METHODS
Men (n = 86), premenopausal women (n = 94), and postmenopausal women (n = 357) participated in the study.


METHODS
We measured S1P levels and their relationships with bone mineral density, biochemical bone turnover markers, and uncoupling indices.


RESULTS
S1P levels were significantly higher in the postmenopausal women than in the premenopausal women and men. High S1P concentrations were significantly associated with low bone mineral density values at some femur sites in the postmenopausal women (P = 0.015 to 0.049), at the lumbar spine in the premenopausal women (P = 0.017), and at all sites in men (P = 0.001 to 0.036) after adjustments with multiple covariates. S1P levels were positively correlated with bone resorption markers (P = 0.003 to 0.049), but not with formation markers in postmenopausal women. Higher S1P levels were associated with lower uncoupling indices (P = <0.001 to 0.048) in postmenopausal women.


CONCLUSIONS
These findings suggest that S1P may primarily affect bone resorption, resulting in bone loss.
Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea.
Seung Hun
SH
Lee
Sun-Young
SY
Lee
Young-Sun
YS
Lee
Beom-Jun
BJ
Kim
Kyeong-Hye
KH
Lim
Eun-Hee
EH
Cho
Sang-Wook
SW
Kim
Jung-Min
JM
Koh
Ghi Su
GS
Kim
D000328:Adult; D000368:Aged; D015519:Bone Density; D001862:Bone Resorption / Q000097:blood*; D024042:Collagen Type I / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008246:Lysophospholipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000097:blood; D017698:Postmenopause; D012189:Retrospective Studies; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D024042:Collagen Type I; D008246:Lysophospholipids; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; C052929:collagen type I trimeric cross-linked peptide; C060506:sphingosine 1-phosphate; D013110:Sphingosine