Villa M L, Packer E, Cheema M, Holloway L, Marcus R
Aging Study Unit, VA Medical Center Palo Alto, California 94304.
J Clin Endocrinol Metab. 1991 Dec;73(6):1256-61. doi: 10.1210/jcem-73-6-1256.
In previous studies we proposed that estrogen increases circulating calcitriol in postmenopausal women by reducing plasma phosphorus concentrations. For this model to be plausible, a reduction in plasma phosphorus must be itself be sufficient to increase circulating calcitriol in elderly women. To assess this question we studied the effects of Al(OH)3 on daylong circulating levels of phosphorus, calcium, PTH, and calcitriol in 14 postmenopausal women. Subjects were studied on two 7-day periods of dietary control, in which calculated intakes for phosphorus, calcium, and sodium were 950, 800, and 3000 mg/day, respectively. During one randomly assigned period, subjects were given Al(OH)3 with each meal. Al(OH)3 significantly lowered daylong plasma phosphorus concentrations by 17% (0.95 +/- 0.02 mmol/L vs. 1.15 +/- 0.02, P less than 0.0005) (2.94 +/- 0.06 mg/dL vs. 3.57 +/- 0.07), and this was associated with a 38% rise in circulating calcitriol from 61.8 +/- 10.3 pmol/L to 85.2 +/- 10.1 pmol/L (25.7 +/- 4.3 pg/ml to 35.5 +/- 4.2 pg/ml) (P less than 0.0001). The rise in calcitriol correlated significantly with the reduction in phosphorus (r = 0.51, P = 0.03). Al(OH)3 did not significantly alter average daily circulating total calcium (2.32 +/- 0.008 vs. 2.32 +/- 0.005 mmol/L) (9.31 +/- 0.03 vs. 9.29 +/- 0.02 mg/dL), ionized calcium (1.19 +/- 0.003 vs. 1.19 +/- .004 mmol/L), or intact PTH (24.6 +/- 0.6 vs. 24.2 +/- 0.8 ng/L). Moreover, neither the renal phosphorus reabsorption maximum (TmP/GFR), baseline excretion of cAMP, nor the phosphaturic, cAMP, or calcitriol responses to infused hPTH(1-34) were altered by Al(OH)3. We conclude that Al(OH)3 treatment of older women lowers plasma phosphorus concentrations by restricting intestinal phosphorus absorption, and that older women retain the capacity to increase calcitriol levels in response to phosphorus restriction.
在之前的研究中,我们提出雌激素通过降低血浆磷浓度来增加绝经后女性循环中的骨化三醇。要使该模型合理,血浆磷的降低本身必须足以增加老年女性循环中的骨化三醇。为评估这个问题,我们研究了氢氧化铝对14名绝经后女性全天循环中的磷、钙、甲状旁腺激素(PTH)和骨化三醇水平的影响。在两个为期7天的饮食控制阶段对受试者进行研究,其中磷、钙和钠的计算摄入量分别为950、800和3000毫克/天。在一个随机分配的阶段,受试者每餐都服用氢氧化铝。氢氧化铝使全天血浆磷浓度显著降低了17%(从1.15±0.02毫摩尔/升降至0.95±0.02毫摩尔/升,P<0.0005)(从3.57±0.07毫克/分升降至2.94±0.06毫克/分升),这与循环中的骨化三醇升高38%相关,从61.8±10.3皮摩尔/升升至85.2±10.1皮摩尔/升(从25.7±4.3皮克/毫升升至35.5±4.2皮克/毫升)(P<0.0001)。骨化三醇的升高与磷的降低显著相关(r = 0.51,P = 0.03)。氢氧化铝并未显著改变平均每日循环中的总钙(2.32±0.008毫摩尔/升对2.32±0.005毫摩尔/升)(9.31±0.03毫克/分升对9.29±0.02毫克/分升)、离子钙(1.19±0.003毫摩尔/升对1.19±0.004毫摩尔/升)或完整的PTH(24.6±0.6纳克/升对24.2±0.8纳克/升)。此外,氢氧化铝并未改变肾磷重吸收最大值(TmP/GFR)、环磷酸腺苷(cAMP)的基线排泄量,也未改变对注入的人甲状旁腺激素(1 - 34)的磷尿、cAMP或骨化三醇反应。我们得出结论,用氢氧化铝治疗老年女性可通过限制肠道磷吸收来降低血浆磷浓度,并且老年女性仍有能力因磷限制而增加骨化三醇水平。