Rubin Mishaela R, Schussheim Debra H, Kulak Carolina A M, Kurland Etah S, Rosen Clifford J, Bilezikian John P, Shane Elizabeth
Department of Medicine, College of Physicians & Surgeons, Columbia University, 630 West 168th Street, New York, N.Y. 10032, USA.
Osteoporos Int. 2005 May;16(5):526-33. doi: 10.1007/s00198-004-1716-0. Epub 2004 Aug 5.
Although osteoporosis predominantly affects older postmenopausal women, low bone mineral density also occurs in men and younger women. In men, it is often unexplained by recognized secondary causes. These men with idiopathic osteoporosis have reductions in serum IGF-I as well as indices of reduced bone formation. Younger women also experience bone loss of unknown etiology (IOP). Whether premenopausal women with IOP have similar decreases in IGF-I levels and reduced indices of bone formation is unknown. We prospectively evaluated a group of premenopausal women with unexplained low bone mass and compared them to normal premenopausal women with respect to serum concentrations of IGF-I. Thirteen premenopausal women (34.2+/-2.3 years) with low bone density (mean lumbar spine T-score -2.26+/-0.20) were compared with 13 premenopausal women (35.7+/-1.7 years) with normal bone density of similar age, height and ethnic composition. Body mass index (BMI) was lower in subjects than controls (20.5+/-0.7 versus 25.2+/-1.1 kg/m(2), P<0.01). A family history of osteoporosis and a history of fragility fractures were found more frequently in subjects than controls (P< or =0.05). Calciotropic hormones did not differ between the two groups. In contrast to our observations in men with idiopathic osteoporosis, mean serum IGF-I concentrations did not differ between subjects and controls (subjects: 22.5+/-2.2 nmol/l versus controls: 20.8+/-1.6 nmol/l; NS). Moreover, serum IGF-I levels did not correlate significantly with serum estradiol or with BMD at either the lumbar spine or femoral neck. However, lower follicular phase serum estradiol levels among non-oral contraceptive users were found in subjects as compared to controls (subjects: 124.1+/-13 pmol/l versus controls 194.9+/-24 pmol/l, P=0.06). Calculated free, bioavailable estradiol levels were significantly lower overall in subjects than controls (0.6+/-0.1 versus 1.2+/-0.2 pmol/l, P<0.05). Total serum estradiol levels correlated with BMD at the femoral neck (r=+0.50; P<0.05). Free, bioavailable estradiol correlated with BMD and BMAD at the lumbar spine (r=+0.54, P<0.01 and r=+0.54, P<0.05, respectively) and femoral neck (r=+0.60 and r=+0.55 respectively, both P<0.01). Urinary NTX excretion, although within the normal premenopausal range, was 45% higher in subjects than controls (41.6+/-5.9 nmol BCE/l versus 28.3+/-2.4 nmol BCE/l; P<0.05). Bone-specific alkaline phosphatase activity was also higher (17.4+/-1.6 ng/ml versus 14.7+/-0.8 ng/ml), although the difference was not statistically significant. These results suggest differences in the pathogenesis of idiopathic osteoporosis in women as compared to men with IOP.
虽然骨质疏松症主要影响绝经后的老年女性,但男性和年轻女性也会出现低骨矿物质密度。在男性中,其往往无法用公认的继发性病因来解释。这些患有特发性骨质疏松症的男性血清胰岛素样生长因子-I(IGF-I)水平降低,且骨形成指标也降低。年轻女性也会经历病因不明的骨质流失(IOP)。绝经前患有IOP的女性IGF-I水平是否会有类似降低以及骨形成指标是否会降低尚不清楚。我们对一组绝经前不明原因低骨量的女性进行了前瞻性评估,并将她们与绝经前正常女性的IGF-I血清浓度进行了比较。13名骨密度低(腰椎平均T值为-2.26±0.20)的绝经前女性(34.2±2.3岁)与13名年龄、身高和种族构成相似、骨密度正常的绝经前女性(35.7±1.7岁)进行了比较。研究对象的体重指数(BMI)低于对照组(20.5±0.7对25.2±1.1kg/m²,P<0.01)。骨质疏松症家族史和脆性骨折史在研究对象中比对照组更常见(P≤0.05)。两组间促钙激素无差异。与我们对特发性骨质疏松症男性的观察结果相反,研究对象和对照组的平均血清IGF-I浓度无差异(研究对象:22.5±2.2nmol/l对对照组:20.8±1.6nmol/l;无显著性差异)。此外,血清IGF-I水平与血清雌二醇、腰椎或股骨颈的骨密度均无显著相关性。然而,与对照组相比,研究对象中非口服避孕药使用者的卵泡期血清雌二醇水平较低(研究对象:124.1±13pmol/l对对照组194.9±24pmol/l,P=0.06)。总体而言,研究对象计算出的游离、生物可利用雌二醇水平显著低于对照组(0.6±0.1对1.2±0.2pmol/l,P<0.05)。血清总雌二醇水平与股骨颈骨密度相关(r=+0.50;P<0.05)。游离、生物可利用雌二醇与腰椎(r=+0.54,P<0.01和r=+0.54,P<0.05,分别)和股骨颈(r=+0.60和r=+0.55,均P<0.01)的骨密度和骨小梁面积密度相关。尿NTX排泄量虽然在绝经前正常范围内,但研究对象比对照组高45%(4l.6±5.9nmol BCE/l对28.3±2.4nmol BCE/l;P<0.05)。骨特异性碱性磷酸酶活性也较高(17.4±1.6ng/ml对14.7±0.8ng/ml),尽管差异无统计学意义。这些结果表明,与患有特发性骨质疏松症的男性相比,女性特发性骨质疏松症的发病机制存在差异。