sphingosine-1-phosphate and Osteoporosis--Postmenopausal

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.

Topics: Aged; Bone Density; Female; Follow-Up Studies; Fractures, Bone; Humans; Longitudinal Studies; Lysophospholipids; Middle Aged; Osteoporosis, Postmenopausal; Postmenopause; Risk Factors; Sphingosine

Although sphingosine 1-phosphate (S1P) plays diverse roles in bone metabolism, the most prominent role seems to be the augmentation of bone resorption.. The objective of the study was to investigate the possibility of using S1P as a predictor for osteoporotic vertebral fracture (VF) risk.. This was a case-control study conducted in a clinical unit in Korea.. Sixty-nine cases having radiological VF and 69 age- and body mass index-matched controls among 460 eligible postmenopausal women participated in the study.. Lateral thoracolumbar radiographs, bone mineral density (BMD), bone turnover markers, and plasma S1P levels were obtained from all subjects.. S1P levels were markedly higher in subjects with VF (7.49±3.44 μmol/liter) than in those without VF (5.58±2.01 μmol/liter; P=0.001) and increased in a dose-response manner as the number of VF increased (P for the trend<0.001), even after adjustment for lumbar spine BMD and potential confounders. The odds ratio for VF was markedly higher in subjects in the highest S1P quartile category compared with those in the lowest S1P quartile category after adjustment for confounders (odds ratio 9.33, 95% confidence interval 2.68-32.49). S1P levels were inversely correlated with BMD at various sites (P=0.015 to 0.044), whereas they were positively correlated with bone resorption markers (P=0.016 to 0.098).. These findings suggest that plasma S1P may be a potential biomarker for the risk of VF, independent of BMD, in postmenopausal women.

Topics: Aged; Bone Density; Case-Control Studies; Female; Humans; Lumbar Vertebrae; Lysophospholipids; Middle Aged; Osteoporosis, Postmenopausal; Predictive Value of Tests; Radiography; Risk Factors; Sphingosine; Spinal Fractures; Thoracic Vertebrae

Therapeutics targeting sphingosine-1-phosphate (S1P), a kind of lipid mediator regulating immune cell trafficking, has been emerging rapidly as a novel line of regimen for autoimmune diseases, including rheumatoid arthritis (RA). Here, we propose that S1P-targeted therapy is beneficial not only for limiting inflammation but for preventing bone-resorptive disorders, such as osteoporosis, by controlling the migratory behavior of osteoclast precursors and therefore would be good for treating elderly female RA patients who suffer from postmenopausal osteoporosis and arthritis simultaneously.

Topics: Age Factors; Aged; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Female; Humans; Lysophospholipids; Mice; Osteoclasts; Osteoporosis, Postmenopausal; Receptors, Lysosphingolipid; Sphingosine; Treatment Outcome

Osteoclasts, the cells that degrade bone, differentiate from bone marrow-derived myeloid precursors. Recent work by Ishii et al. shows that sphingosine-1 phosphate in blood attracts osteoclast precursors into the bloodstream to keep them away from bone surfaces. These findings point to a novel mechanism to inhibit bone degradation and prevent bone loss.

Topics: Animals; Bone Remodeling; Female; Humans; Lysophospholipids; Mice; Models, Biological; Osteoclasts; Osteoporosis, Postmenopausal; Receptors, Lysosphingolipid; Sphingosine; Sphingosine-1-Phosphate Receptors