The Effects of Strontium Ranelate on the Risk of Vertebral Fracture in Women With Postmenopausal Osteoporosis

Abstract

Strontium ranelate is an orally active agent that stimulates new bone formation and decreases bone resorption. A recent phase 2 placebo-controlled study of postmenopausal women with osteoporosis indicated a reduction in vertebral fractures and increased bone mineral density (BMD). The present phase 3 trial, the Spinal Osteoporosis Therapeutic Intervention study, evaluated strontium ranelate, given orally in a dose of 2 g daily for 3 years, in women aged 50 years and older who had been postmenopausal for at least 5 years, had had at least 1 spinal fracture, and had a lumbar spine BMD of 0.84 g/cm2 or lower. A total of 1442 women were randomized to receive strontium ranelate or placebo and were included in an intention-to-treat analysis. All women received calcium and vitamin D supplements. BMD was estimated at 6-month intervals, and spinal radiographs were obtained each year. After 12 months, the risk of a new vertebral fracture was 49% lower in women given strontium ranelate (6.4% vs. 12.2%) for a relative risk of 0.51. Symptomatic fractures were decreased 52%. The reduction in risk of a new spinal fracture persisted throughout the 3-year study period. The risk of having more than 1 new vertebral fracture was 6.4% in the study group and 9.8% in placebo recipients. Fewer patients in the study group lost 1 cm or more in height (30.1% vs. 37.5%). Nonvertebral fractures were similarly frequent in the 2 groups. BMD in the lumbar spine increased by 12.7% in strontium-treated women. None of 14 bone biopsies disclosed osteomalacia or signs of a primary defect in mineralization. Compliance rates were 83% and 85% in the study and placebo groups, respectively. Diarrhea, the most common adverse gastrointestinal effect, tended to resolve after 3 months of treatment. Serum calcium levels were lower and serum phosphate levels higher in strontium-treated women. Strontium ranelate provides a rapid and lasting reduction in the risk of vertebral fractures in postmenopausal women with osteoporosis.