Recker R R, Davies K M, Dowd R M, Heaney R P
Osteoporosis Research Center, School of Medicine, Creighton University, Omaha, Nebraska 68131, USA.
Ann Intern Med. 1999 Jun 1;130(11):897-904. doi: 10.7326/0003-4819-130-11-199906010-00005.
Hormone replacement therapy (HRT), the mainstay of osteoporosis prevention, is limited because of dose-related risks, side effects, and patient acceptance. The bone-sparing efficacy and tolerability of the lowest available doses of HRT have not been adequately studied in elderly women.
To determine the bone-sparing effect of continuous low-dose HRT in elderly women.
Randomized, double-blind, placebo-controlled trial.
University osteoporosis research and clinical center.
128 healthy white women (age > 65 years) with low bone mass recruited by word of mouth and by local advertisement. The principal eligibility criterion was spinal bone mineral density of 0.90 g/cm2 or less.
Continuous therapy with conjugated equine estrogen, 0.3 mg/d, and medroxyprogesterone, 2.5 mg/d, or matching placebo. Sufficient calcium supplementation was given to bring all calcium intakes above 1000 mg/d in both groups; supplemental oral 25-hydroxyvitamin D was given to maintain serum 25-hydroxyvitamin D levels of at least 75 nmol/L in both groups.
Bone mineral density of the spine, hip, total body, and forearm; serum total alkaline phosphatase and serum osteocalcin levels at 6-month intervals; and 24-hour urine creatinine and hydroxyproline excretion at baseline, 12 months, and 42 months.
During 3.5 years of observation, spinal bone mineral density increased by 3.5% (P < 0.001) in an intention-to-treat analysis and by 5.2% among patients with greater than 90% adherence to therapy. Significant increases were seen in total-body and forearm bone density (P < 0.01). Symptoms related to HRT (breast tenderness, spotting, pelvic discomfort, and mood changes) were mild and short-lived.
Continuous low-dose HRT with conjugated equine estrogen and oral medroxyprogesterone combined with adequate calcium and vitamin D provides a bone-sparing effect that is similar or superior to that provided by other, higher-dose HRT regimens in elderly women. This combination is well tolerated by most patients.
激素替代疗法（HRT）是预防骨质疏松症的主要方法，但由于与剂量相关的风险、副作用以及患者的接受度等因素，其应用受到限制。对于老年女性，最低可用剂量HRT的保骨疗效和耐受性尚未得到充分研究。
确定连续低剂量HRT对老年女性的保骨作用。
随机、双盲、安慰剂对照试验。
大学骨质疏松症研究和临床中心。
通过口碑和当地广告招募的128名健康白人女性（年龄>65岁），骨量较低。主要入选标准为脊柱骨密度为0.90g/cm2或更低。
连续服用结合马雌激素0.3mg/d和甲羟孕酮2.5mg/d，或匹配的安慰剂。两组均给予足够的钙补充剂，使所有患者的钙摄入量均高于1000mg/d；两组均给予口服补充25-羟维生素D，以维持血清25-羟维生素D水平至少为75nmol/L。
脊柱、髋部、全身和前臂的骨密度；每隔6个月测量血清总碱性磷酸酶和血清骨钙素水平；在基线、12个月和42个月时测量24小时尿肌酐和羟脯氨酸排泄量。
在3.5年的观察期内，意向性分析中脊柱骨密度增加了3.5%（P<0.001），在治疗依从性大于90%的患者中增加了5.2%。全身和前臂骨密度也有显著增加（P<0.01）。与HRT相关的症状（乳房压痛、点滴出血、盆腔不适和情绪变化）轻微且持续时间短。
连续低剂量结合马雌激素和口服甲羟孕酮的HRT联合充足的钙和维生素D，在老年女性中提供的保骨效果与其他更高剂量的HRT方案相似或更优。大多数患者对这种联合治疗耐受性良好。
