CYCLICAL ETIDRONATE IN THE TREATMENT OF POSTMENOPAUSAL OSTEOPOROSIS -EFFICACY AND SAFETY AFTER 7 YEARS OF TREATMENT

PURPOSE: TO determine the efficacy and safety of cyclical etidronate f or up to 7 years in the treatment of postmenopausal osteoporosis and t o examine the effects of discontinuing treatment after 2 or 5 years of therapy. PATIENTS AND METHODS: Patients were randomized at entry into the original study in 1986 to blinded treatment for 2 years with eith er a calcium (placebo) or an intermittent cyclical etidronate regimen, which most patients continued for a third year. Following this phase of the study, patients were enrolled into an open-label, follow-up stu dy (years 4 and 5), during which all patients received cyclical etidro nate treatment. In the present double-blind study (years 6 and 7), pat ients were rerandomized to receive intermittent cyclical therapy with either etidronate or placebo; all patients received calcium. The treat ment regimen consisted of 400 mg/day etidronate or placebo for 14 days , followed by 76 days of elemental calcium (500 mg/day); this cycle wa s repeated approximately 4 times in each year. Of the 193 patients who continued in years 6 and 7 of the study, 93 were randomized to receiv e cyclical etidronate and 100 were randomized to receive calcium only. For purposes of efficacy analyses, patients were categorized by their total years of cumulative etidronate treatment (7, 5, 4, or 2 years). There were 51, 46, 42, and 54 patients in the 7-, 5-, 4-, and 2-year groups, respectively. Annual assessments included lumbar spine bone mi neral density (BMD), as measured by densitometry, and vertebral radiog raphs.RESULTS: The groups receiving cyclical etidronate during this 2- year study period (7- and 4-year groups) had statistically significant mean percent increases in spinal BMD of 1.8% and 2.2%, respectively ( P <0.05) at the week 104 observation time. The 5- and 2-year groups, w hich did not receive etidronate during this period, had mean values of 1.4% and 0.2%, respectively (not significant) at week 104. In the 7-, 5-, 4-, and 2-year groups, the increases in spinal BMD at the end of 7 years were 7.6%, 8.6%, 8.1%, and 3.9%, respectively; these values we re statistically significant for all groups compared with original bas eline (year 0) (P <0.05). BMD of the femur and wrist was maintained th roughout the 7-year period. The incidence and rate of vertebral fractu res were lowest in patients with the longest exposure to etidronate. E tidronate was well tolerated during the study, with low incidences of gastrointestinal side effects and nonvertebral fractures. CONCLUSIONS: Long-term cyclical etidronate is a safe, effective, and well-tolerate d treatment for postmenopausal osteoporosis. Bone mass is maintained f or at least 2 years after treatment with etidronate is stopped; howeve r, further gains in spinal bone mass are seen in patients who continue therapy. (C) 1997 by Excerpta Medica, Inc.