Objective:To evaluate the tolerance and effectiveness of transdermal estrogen for women with established postmenopausal osteoporosis and vertebral fractures.
Design:Double-blind, randomized, placebo-controlled clinical trial lasting 1 year.
Setting:Referral-based outpatient clinic.
Patients:Seventy-five postmenopausal women, 47 to 75 years of age, with one or more vertebral fractures due to osteoporosis.
Interventions:Thirty-nine women received dermal patches delivering 0.1 mg of 17β-estradiol for days 1 to 21 and oral medroxyprogesterone acetate for days 11 to 21 of a 28-day cycle. Another 39 women received placebo.
Measurements:Bone turnover assessed by biochemical markers and iliac bone histomorphometry; bone loss assessed by serial measurement of bone density; and vertebral fracture rate.
Results:Compared with the placebo group, the median annual percentage change in bone mineral density in the estrogen group reflected increased or steady-state bone mineral density at the lumbar spine (5.3 compared with 0.2;P= 0.007), femoral trochanter (7.6 compared with 2.1;P= 0.03), and midradius (1.0 compared with - 2.6,P< 0.001) but showed no significant difference at the femoral neck (2.6 compared with 1.4;P= 0.17). Estrogen treatment uniformly decreased bone turnover as assessed by several methods including serum osteocalcin concentration (median change, - 0.35 compared with 0.02 nmol/L;P< 0.001). Histomorphometric evaluation of iliac biopsy samples confirmed the effect of estrogen on bone formation rate per bone volume (median change, - 12.9 compared with - 6.2% per year;P= 0.004). Also, 8 new fractures occurred in 7 women in the estrogen group, whereas 20 occurred in 12 women in the placebo group, yielding a lower vertebral fracture rate in the estrogen group (relative risk, 0.39; 95% Cl, 0.16 to 0.95).
Conclusions:Transdermal estradiol treatment is effective in postmenopausal women with established osteoporosis.
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