Clinical effect of bisphosphonate and vitamin D on osteoporosis: reappraisal of a multicenter double-blind clinical trial comparing etidronate and alfacalcidol.

As inhibitors of bone resorption, bisphosphonates and vitamin D derivatives have been extensively used for the treatment of osteoporosis in various parts of the world, but the clinical effects of these two groups of agents have rarely been compared in detail. A multicenter, prospective, double-blind controlled study was started comparing the effects of etidronate and alfacalcidol (1-alpha-hydroxycholecalciferol) in 414 patients with established osteoporosis from 36 centers. Among these patients, 135 were given 400 mg etidronate daily at bedtime for 2 weeks followed by 10 weeks off treatment, and this cycle was repeated four times along with a placebo indistinguishable from the alfacalcidol capsule daily throughout the 48 weeks of study (Group A, High Dose Etidronate Group). In 133 patients, 200 mg etidronate was used instead of 400 mg (Group B, Low Dose Etidronate Group). In 138 patients, 1 microg alfacalcidol was given daily throughout the 48-week study period along with a placebo indistinguishable from the etidronate tablet in four separate periods of 2 weeks (Group C, Control Group). Dual-energy X-ray absorptiometry of the lumbar spine (L2-L4) was performed before the beginning of the study and every 12 weeks thereafter. Changes in spinal deformity were also assessed based on the lateral thoracic and lumbar spine X-ray films taken before and after the study. The lumbar spine bone mineral density (BMD) changes were +3.4% +/- 0.6% (mean +/- SEM) in Group A, +2.4% +/- 0.5% in Group B, and -0.5% +/- 0.4% in Group C, the former two being significantly higher than the last. New occurrence of spinal compression fracture was also significantly reduced in Group A compared to Group C. In patients without previous fracture at entry, incident fracture was 10.2% in Group C, but 0% in Groups A and B. In patients with prevalent fracture at entry, corresponding figures were 21.5% (Group C), 12.0% (Group A), and 13.2% (Group B), respectively. Alfacalcidol maintained lumbar spine BMD, preventing a decrease for 48 weeks, and etidronate significantly increased it further, demonstrating its usefulness in the treatment of established osteoporosis.