Kim B-J, Shin K-O, Kim H, Ahn S H, Lee S H, Seo C-H, Byun S-E, Chang J S, Koh J-M, Lee Y-M
Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 138-736, Korea.
College of Pharmacy and MRC, Chungbuk National University, Cheongju, 361-763, Korea.
J Endocrinol Invest. 2016 Mar;39(3):297-303. doi: 10.1007/s40618-015-0364-x. Epub 2015 Jul 29.
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.
To investigate how S1P mainly contributes to increased bone resorption in humans, we performed this case-control study at a clinical unit in Korea.
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).
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.
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.
尽管最近的研究提供了临床证据，表明1-磷酸鞘氨醇（S1P）可能主要影响人类的骨吸收，而非骨形成或破骨细胞-成骨细胞偶联现象，但这些研究无法确定哪种骨吸收机制更为重要，即破骨细胞前体通过血液至骨髓的S1P梯度产生的化学排斥作用，还是局部S1P导致成骨细胞中核因子κB受体活化因子配体（RANKL）升高。
为了研究S1P如何主要导致人类骨吸收增加，我们在韩国的一个临床单位开展了这项病例对照研究。
同期收集了70例因骨质疏松性髋部骨折（HF）（n = 10）或骨关节炎等其他原因（n = 60）接受髋关节手术患者的血液和骨髓样本。
在对性别、年龄、体重指数、吸烟、饮酒、既往骨折、糖尿病和中风进行校正后，骨质疏松性HF患者的血浆/骨髓S1P比值比无HF患者高3.2倍，而两组间血浆和骨髓S1P水平无显著差异。同样，在多变量调整模型中，血浆/骨髓S1P比值每增加1倍，骨质疏松性HF的风险增加1.38倍。然而，根据血浆和骨髓S1P水平增加情况得出的HF患病率的比值比无统计学意义。
我们目前使用同时采集的血液和骨髓样本得出的结果表明，S1P对人类骨代谢的有害影响可能取决于外周血和骨髓腔之间的S1P梯度。
