S. Pors-Nielsen

The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal Osteoporosis

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/cm 2 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.

Relationship Between Bone Mineral Density Changes and Fracture Risk Reduction in Patients Treated With Strontium Ranelate

Numerous randomized, controlled trials have shown that drugs can improve bone mineral density (BMD) and lower the risk of fracture, but in the case of antiresorptive agents the predictive value of changes in BMD remains controversial. Strontium ranelate has reduced bone resorption and increased bone formation at the same time in preclinical models, and recently was reported to significantly lower the risk of vertebral and other fractures in women with postmenopausal osteoporosis. The present study monitored vertebral and other fractures and BMD at several sites (lumbar spine, femoral neck, total proximal femur) during 1-3 years of treatment with strontium ranelate. A 3-year increase in BMD at the femoral neck and total proximal femur, but not in the spine, was significantly associated with a reduced incidence of new vertebral fractures. For each percentage point increase in femoral neck or total proximal femur BMD noted after 3 years, the risk of a new vertebral fracture developing after 3 years decreased by 3%. The 3-year changes in femoral neck and total proximal femur BMD accounted for 76% and 74%, respectively, of the reduction in vertebral fractures. No significant association was found between 3-year changes in BMD and the risk of new nonvertebral fractures. Nevertheless, an increase in femoral neck BMD after 1 year was significantly associated with the reduction in new vertebral fractures observed after 3 years of treatment.