A 4-YEAR RANDOMIZED CONTROLLED TRIAL OF HORMONE REPLACEMENT AND BISPHOSPHONATE, ALONE OR IN COMBINATION, IN WOMEN WITH POSTMENOPAUSAL OSTEOPOROSIS

PURPOSE: Hormone replacement therapy (HRT) with estrogen and treatment with bisphosphonates have been shown to increase bone mineral density (BMD) in postmenopausal women. This 4-year prospective randomized stu dy was carried out to assess the effectiveness of the combined HRT plu s etidronate on BMD in postmenopausal women with established osteoporo sis. PATIENTS AND METHODS: Seventy-two postmenopausal women (mean age 64.9 +/- 0.5 years) attending metabolic bone disease outpatient clinic s with established osteoporosis were randomly allocated into one of fo ur treatment groups and monitored for 4 years. All patients enrolled i n this study including the control group (n = 18) received 1.0 g eleme ntal calcium and 400 units vitamin D per day. The HRT group (n = 18) r eceived cyclical estrogen and progesterone; the etidronate group (n = 17) received intermittent cyclical etidronate; and the combined therap y group (n = 19) received both HRT and etidronate. BMD was measured in the lumbar spine and the hip before treatment and at 2 and 4 years af ter treatment. Changes in height were recorded, and the occurrence of new vertebral fractures were documented in comparison with the baselin e radiographic evaluation. In 40 patients (10 patients per group), ana lysis of bone histomorphometry was carried out after 4 years of treatm ent. RESULTS: In patients who received the combined therapy, BMD incre ased in the lumbar spine by 10.4% (P < 0.001) and in the hip by 7.0% ( P < 0.001) at 4 years. For patients treated with ICE, these increases were 7.3% (P < 0.001) and 0.9% (P < 0.05), and with HRT, the increases were 7.0% (P (0.001) and 4.8% (P < 0.01) in the vertebrae and femora, respectively. The group treated with calcium and vitamin D lost 2.5% (P < 0.05) and 4.4% (P < 0.01) of BMD in the vertebrae and femora, res pectively, after 4 years. Patients who received combined therapy had s ignificantly higher BMD in both the vertebrae and in the femora (P < 0 .05) in comparison with patients who were treated with HRT or etidrona te alone after 4 years. In comparison with patients in the control gro up, there was a trend toward a lower rate of new vertebral fractures i n the treatment groups. Height loss was significantly less in all thre e active treatment groups (HRT [P < 0.001], etidronate [P < 0.02], and combined therapy group [P < 0.0001]), in comparison with the control group. The combined therapy group did not have a significant height lo ss, in comparison with the HRT (P < 0.02) and the etidronate (P < 0.00 1) groups. None of the patients had histomorphometric evidence of oste omalacia CONCLUSION: This 4-year randomized study showed an additive e ffect of etidronate and HRT on hip and spine BMD in postmenopausal wom en with established osteoporosis.