Combination treatment with estrogen and calcitriol in the prevention of age-related bone loss.
Combination treatment with estrogen and calcitriol in the prevention of age-related bone loss.
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DOI：
10.1210/jcem.86.8.7703
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发表时间：
2001-08
期刊：
影响因子：
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通讯作者：
J. Gallagher;S. Fowler;J. R. Detter;S. Sherman
中科院分区：
文献类型：
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作者：
J. Gallagher;S. Fowler;J. R. Detter;S. Sherman
由于骨化三醇水平降低或肠道对骨化三醇的抵抗力导致的雌激素缺乏和钙吸收下降是与年龄相关的骨质流失发病机制的重要因素。本研究的主要目的是检查雌激素和 1,25-二羟基维生素 D 单独或联合治疗对老年女性骨质流失的影响。 489 名年龄在 65-77 岁之间骨密度正常的老年妇女参与了一项随机双盲、安慰剂对照试验。女性被随机分为四组之一：没有子宫的女性使用结合雌激素（0.625 毫克，每天）（雌激素替代疗法），有子宫的女性使用醋酸甲羟孕酮（2.5 毫克，每天）（激素替代疗法），骨化三醇（0.25 微克，每天两次），激素替代疗法/雌激素替代疗法的组合 治疗加骨化三醇或安慰剂 3 年。主要结果是股骨颈和脊柱骨矿物质密度的变化。在意向治疗分析中，激素治疗（激素替代疗法/雌激素替代疗法）使股骨颈骨矿物质密度平均（+/-1 SD）增加2.98%（+/-5.45%）（P < 0.0001），使脊柱骨矿物质密度平均（+/-1 SD）增加4.36%（+/-6.42%）（P < 0.0001）。总髋部和转子骨矿物质密度平行增加。骨化三醇使股骨颈骨密度增加 0.10% (+/- 4.27%) (P = 0.57)，使脊柱骨密度增加 1.65% (+/- 4.83%) (P < 0.0124)。激素替代疗法/雌激素替代疗法+骨化三醇的组合使股骨颈处的骨矿物质密度增加了3.80%（+/-4.95%）（P<0.001），脊柱处的骨矿物质密度增加了4.91%（+/-6.0%）（P<0.0001），并且全髋部和转子处的骨矿物质密度也发生了平行变化。所有三个治疗组在脊柱方面与安慰剂以及股骨颈、脊柱、全髋和转子方面的激素替代疗法/雌激素替代疗法组均显着不同。在意向治疗分析中，联合疗法与激素替代疗法/单独雌激素替代疗法在任何部位的骨矿物质密度方面均无显着差异。在对坚持治疗的女性效果的二次分析中，骨化三醇对脊柱（P = 0.003）和全髋部（P = 0.004）有更显着的影响。与意向治疗组相比，坚持治疗组的女性骨矿物质密度的增加总是更高。与单独的激素替代疗法/雌激素替代疗法相比，联合疗法在转子（P = 0.007）和总髋骨矿物质密度（P = 0.0017）方面产生了显着更大的反应。总之，单独使用激素替代疗法/雌激素替代疗法以及与骨化三醇疗法相结合，对于骨密度正常的老年女性组来说，在减少骨吸收并增加髋部和其他临床相关部位的骨矿物质密度方面非常有效。骨化三醇可有效增加脊柱骨矿物质密度。在坚持治疗的女性中，激素替代疗法/雌激素替代疗法和骨化三醇的联合疗法比单独的激素替代疗法/雌激素替代疗法显着增加了全髋部和转子的骨矿物质密度。
Estrogen deficiency and declining calcium absorption due to reduced calcitriol levels or intestinal resistance to calcitriol, are important factors in the pathogenesis of age-related bone loss. The main objective of this study was to examine the effect of estrogen and 1,25-dihydroxyvitamin D therapy given individually or in combination on bone loss in elderly women. Four hundred eighty-nine elderly women with normal bone density for their age, aged 65-77 yr, were entered into a randomized double blind, placebo-controlled trial. Women were randomized to one of four groups: conjugated estrogens (0.625 mg, daily) to women without a uterus (estrogen replacement therapy) plus medroxyprogesterone acetate (2.5 mg, daily) to women with a uterus (hormone replacement therapy), calcitriol (0.25 microg twice daily), a combination of hormone replacement therapy/estrogen replacement therapy plus calcitriol, or placebos for 3 yr. The primary outcome was the change in bone mineral density of the femoral neck and spine. In the intent to treat analysis, hormone therapy (hormone replacement therapy/estrogen replacement therapy) produced a mean (+/-1 SD) increase in bone mineral density of 2.98% (+/-5.45%) at the femoral neck (P < 0.0001) and 4.36% (+/-6.42%) at the spine (P < 0.0001). There were parallel increases in total hip and trochanter bone mineral density. Calcitriol increased bone mineral density 0.10% (+/- 4.27%) at the femoral neck (P = 0.57) and 1.65% (+/- 4.83%) at the spine (P < 0.0124). The combination of hormone replacement therapy/estrogen replacement therapy + calcitriol increased bone mineral density 3.80% (+/-4.95%) at the femoral neck (P < 0.001), 4.91% (+/-6.0%) at the spine (P < 0.0001), and parallel changes at the total hip and trochanter. All three treatment groups differed significantly from placebo at the spine and for the hormone replacement therapy/estrogen replacement therapy groups at the femoral neck, spine, total hip and trochanter. There were no significant differences between combination therapy and hormone replacement therapy/estrogen replacement therapy alone on bone mineral density at any site in the intent to treat analysis. In a secondary analysis of the effect in women who were adherent to treatment, calcitriol had a more significant effect on spine (P = 0.003) and total hip (P = 0.004). The increase in bone mineral density in the adherent groups of women was always higher compared with the intent to treat groups. Combination therapy compared with hormone replacement therapy/estrogen replacement therapy alone produced a significantly greater response in trochanter (P = 0.007) and total hip bone mineral density (P = 0.0017). In summary, hormone replacement therapy/estrogen replacement therapy alone and in combination with calcitriol therapy was highly effective in reducing bone resorption and increasing bone mineral density at the hip and other clinically relevant sites in a group of elderly women, with normal bone density for their age. Calcitriol was effective in increasing spine bone mineral density. In the adherent women, combination therapy with hormone replacement therapy/estrogen replacement therapy and calcitriol increased bone mineral density significantly more in the total hip and trochanter than did hormone replacement therapy/estrogen replacement therapy alone.