COMBINED THERAPY WITH ESTROGEN AND ETIDRONATE HAS AN ADDITIVE EFFECT ON BONE-MINERAL DENSITY IN THE HIP AND VERTEBRAE - 4-YEAR RANDOMIZED STUDY

BACKGROUND: Administration of estrogen or etidronate has been shown to increase bone mineral density in postmenopausal women. This 4-year, p rospective, randomized study was carried out to monitor any added bene ficial effect on bone mineral density when hormone-replacement therapy (HRT) was combined with etidronate. PATIENTS AND METHODS: Fifty-eight early postmenopausal women attending metabolic bone disease outpatien t clinics were randomly allocated into four treatment groups and monit ored for up to 4 years. All patients received 1.0 g/d of elemental cal cium. In addition, group 1 received percutaneously administered HRT in = 15); group 2, intermittent cyclical etidronate (ICE) tn = 14); grou p 3, HRT and ICE (n = 15); and group 4, calcium alone (n = 14). The bo ne mineral density (measured by dual-energy x-ray absorptiometry), bio chemical variables of bone turnover, including bone-specific alkaline phosphatase, and urinary hydroxyproline:creatinine ratios were measure d before treatment and at 2 and 4 years after treatment. RESULTS: In p atients who received the combined therapy, bone mineral density was in creased in the vertebrae by 10.9% (P <0.001) and in the femora by 7.25 % (P <0.001) at 4 years. For patients treated with ICE, the increase w as 6.79% (P <0.001) and 1.20% (P <0.05), and with HRT, 6.78% (P <0.001 ) and 4.01% (P <0.01) in the vertebrae and femora, respectively. The g roup treated with calcium alone lost 3.81% (P <0.01) and 4.96% (P <0.0 1) of bone mineral density in vertebrae and femora. Patients who recei ved no specific therapy lost 8.58% (P <0.01) from vertebrae, and 7.83% (P <0.01) from the femora over 4 years. Patients who received combine d therapy had significantly higher bone mineral density in both verteb rae (P <0.05) and femora (P <0.01), in comparison to patients who were treated with HRT, or ICE, alone. Three of 9 patients (33%) in the ICE group developed osteomalacia, as shown by bone histomorphometry, wher eas in women who received combined HRT and ICE therapies, none of the 11 patients tested had evidence of bone mineralization defects. CONCLU SION: This 4-year, prospective, randomized study in early postmenopaus al women showed an additive effect of ICE and HRT on the bone mineral density in both vertebrae and the hip. Furthermore, the combined thera py prevented the occurrence of osteomalacia associated with etidronate . This is the first study to demonstrate the effects of etidronate in early postmenopausal women, and the additive beneficial effects of HRT and ICE on bone mineral density.