title: The circulating sphingosine-1-phosphate level predicts incident fracture in postmenopausal women: a 3.5-year follow-up observation study.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  The plasma S1P level may be a potential predictor of fracture occurrence and an insufficient response to bisphosphonate therapy in postmenopausal women.
authors.affiliation: Health Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43 gil, Ulsan, Seoul, 05505, South Korea.
authors.forename: S J
authors.initials: SJ
authors.lastname: Bae
authors.affiliation: 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.
authors.forename: S H
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Endocrinology, Inha University School of Medicine, 27 Inhang-ro, Jung-Gu, Songpa-gu, Incheon, 22332, South Korea.
authors.forename: S H
authors.initials: SH
authors.lastname: Ahn
authors.affiliation: 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.
authors.forename: H-M
authors.initials: HM
authors.lastname: Kim
authors.affiliation: 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.
authors.forename: B-J
authors.initials: BJ
authors.lastname: Kim
authors.affiliation: 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. jmkoh@amc.seoul.kr.
authors.forename: J-M
authors.initials: JM
authors.lastname: Koh
mesh_terms: D000368:Aged; D015519:Bone Density; D005260:Female; D005500:Follow-Up Studies; D050723:Fractures, Bone / Q000097:blood*; D006801:Humans; D008137:Longitudinal Studies; D008246:Lysophospholipids / Q000097:blood*; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000097:blood*; D017698:Postmenopause; D012307:Risk Factors; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D013110:Sphingosine
keywords: Biomarker; Bisphosphonate; Insufficient response; Osteoporotic fracture; Sphingosine-1-phosphate