Bone mineral density response to estrogen replacement in frail elderly women - A randomized controlled trial

Context Although hormone replacement therapy (HRT) is an established approa ch for osteoporosis prevention, little is known about the osteoprotective e ffects of HRT in frail elderly women. Objective To determine whether HRT increases bone mineral density (BMD) in frail elderly women. Design and Setting Randomized, double-blind, placebo-controlled trial condu cted in a US university-based research center from September 1995 to August 2000. Participants Sixty-seven women aged 75 years or older with mild-to-moderate physical frailty. Intervention Participants were randomly assigned to receive conjugated estr ogens, 0.625 mg/d, plus trimonthly medroxyprogesterone acetate, 5 mg/d for 13 days (n=45), or matching placebo (n=22), for 9 months. Main Outcome Measures The primary outcome measure was 9-month change in BMD of the lumbar spine and hip, measured by dual-energy x-ray absorptiometry. Secondary outcomes were changes in markers of bone turnover. Results Based on intention-to-treat analyses, HRT resulted in significantly larger increases in BMD of the lumbar spine than placebo (mean change, 4.3 % vs 0.4%; between-group difference, 3.9%; 95% confidence interval [CI], 3. 5%-4.3%) and total hip (mean change, 1.7% vs -0.1%; between-group differenc e, 1.8%; 95% Cl, 1.5%-2.1%). Compared with placebo, HRT resulted in signifi cant decreases in serum bone-specific alkaline phosphatase levels (mean cha nge, -24% vs 6%; between-group difference, -30%; 95% Cl, -26% to -33%) and urine N-telopeptide levels (mean change, -48% vs 4%; between-group differen ce, -52%; 95% CI, -47% to -55%). Conclusions In physically frail elderly women, 9 months of HRT significantl y increased BMD compared with placebo in clinically important skeletal regi ons. Further studies are needed to determine whether these osteogenic effec ts of HRT in elderly women are associated with a reduction in osteoporotic fractures.