Silverberg S J, Shane E, de la Cruz L, Segre G V, Clemens T L, Bilezikian J P
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
N Engl J Med. 1989 Feb 2;320(5):277-81. doi: 10.1056/NEJM198902023200503.
We investigated the parathyroid hormone-1,25-dihydroxyvitamin D3 (1,25(OH)2D) axis in osteoporosis by administering phosphate to 8 postmenopausal women with osteoporosis (49 to 78 years old) and to 10 normal women matched for age (50 to 74 years). All subjects responded with a similar increase in the serum phosphorus concentration (women with osteoporosis, 1.15 +/- 0.06 to 1.79 +/- 0.09 mmol per liter; controls, 1.14 +/- 0.05 to 1.73 +/- 0.08 mmol per liter) and a fall in the ionized calcium concentration (women with osteoporosis, 1.12 +/- 0.03 to 1.06 +/- 0.03 mmol per liter; controls, 1.17 +/- 0.01 to 1.11 +/- 0.02 mmol per liter). Parathyroid hormone levels rose 2.5-fold in the control group (15.4 +/- 2.2 to 37.9 +/- 6.1 pg per milliliter) but increased by only 43 percent in the group with osteoporosis (14.8 +/- 2.8 to 21.2 +/- 4.1 pg per milliliter), an increase similar to that previously reported in young normal subjects (53 percent). In healthy older and younger subjects, the levels of 1,25(OH)2D did not change; in the subjects with osteoporosis, however, they decreased significantly (50 percent). We conclude that older women require a greater parathyroid hormone stimulus than younger women to maintain vitamin D homeostasis, because of an age-related decline in the formation of 1,25(OH)2D in response to parathyroid hormone, and that in osteoporosis the age-appropriate parathyroid hormone response to the same hypocalcemic signal is diminished. Our results are consistent with the presence of an abnormality in parathyroid hormone secretory function in osteoporosis in addition to the universal decline in 1,25(OH)2D responsiveness associated with aging.
我们通过给8名绝经后骨质疏松症女性（49至78岁）和10名年龄匹配的正常女性（50至74岁）补充磷酸盐，研究了甲状旁腺激素 - 1,25 - 二羟基维生素D3（1,25(OH)2D）轴在骨质疏松症中的情况。所有受试者血清磷浓度均有相似程度的升高（骨质疏松症女性从1.15±0.06毫摩尔/升升至1.79±0.09毫摩尔/升；对照组从1.14±0.05毫摩尔/升升至1.73±0.08毫摩尔/升），同时离子钙浓度下降（骨质疏松症女性从1.12±0.03毫摩尔/升降至1.06±0.03毫摩尔/升；对照组从1.17±0.01毫摩尔/升降至1.11±0.02毫摩尔/升）。对照组甲状旁腺激素水平升高了2.5倍（从15.4±2.2皮克/毫升升至37.9±6.1皮克/毫升），而骨质疏松症组仅升高了43%（从14.8±2.8皮克/毫升升至21.2±4.1皮克/毫升），这一升高幅度与之前报道的年轻正常受试者相似（53%）。在健康的老年和年轻受试者中，1,25(OH)2D水平未发生变化；然而，骨质疏松症受试者的该水平显著下降（50%）。我们得出结论，由于随着年龄增长，甲状旁腺激素刺激下1,25(OH)2D的生成出现与年龄相关的下降，老年女性比年轻女性需要更大的甲状旁腺激素刺激来维持维生素D内稳态，并且在骨质疏松症中，针对相同低钙血症信号的适当甲状旁腺激素反应减弱。我们的结果与骨质疏松症中甲状旁腺激素分泌功能异常的存在一致，此外还与衰老相关的1,25(OH)2D反应性普遍下降有关。
