4-YEAR STUDY OF INTERMITTENT CYCLIC ETIDRONATE TREATMENT OF POSTMENOPAUSAL OSTEOPOROSIS - 3 YEARS OF BLINDED THERAPY FOLLOWED BY ONE-YEAR OF OPEN THERAPY

PURPOSE: To determine the effect of long-term intermittent cyclic etid ronate treatment on spinal bone density and vertebral fracture rates. PATIENTS AND METHODS: Postmenopausal osteoporotic women (n = 423) were randomized initially into a 2-year, double-blind, multicenter study; it was extended to a third year of blinded treatment followed by open- label treatment: 357 patients continued treatment in Year 3 (305 recei ving blinded therapy and 52 receiving calcium supplementation) and 277 in Year 4. During Years 1 through 3, patients received double-blind t reatment with phosphate (1.0 g) or placebo twice daily for 3 days, eti dronate (400 mg) or placebo daily for 14 days, and calcium (500 mg) da ily for the remainder of each 91-day treatment cycle. During Year 4, o pen-label intermittent cyclic etidronate therapy (without preceding ph osphate) was administered to all patients. Spinal bone density and ver tebral fracture rates were the main outcome measures. RESULTS: During Year 3, etidronate theraPY maintained the significant increases in spi nal bone mineral density of the first 2 years. Over the 3-year period, proximal femur bone density increased in etidronate-treated patients. Etidronate therapy for 3 years significantly decreased the vertebral fracture rate in patients at higher risk for fracture (low spinal bone density and three or more vertebral fractures at study entry), as com pared with nonetidronate treatment (228 versus 412 fractures per 1,000 patient-years, respectively; p < 0.05). After 1 year of open-label tr eatment, patients previously treated with etidronate maintained bone m ass, and vertebral fracture rates in all groups were lower than in any other study period. There were no apparent serious adverse effects. C ONCLUSIONS: Three years of intermittent cyclic etidronate therapy prod uced significant increases in spinal and hip bone density, with a sign ificant reduction in vertebral fracture rates in patients at higher fr acture risk. Maintenance of bone mass and low fracture rate were obser ved when etidronate was continued for an additional year.