ABSTRACT
OBJECTIVE: Our objective was to analyze the relationship between bone mineral density (BMD) changes and fracture incidence during 3-yr treatment with strontium ranelate. PATIENTS: Women from the strontium ranelate arm of the Spinal Osteoporosis Therapeutic Intervention study and the TReatment Of Peripheral OSteoporosis study were evaluated. OUTCOME MEASURES: The outcome measures included BMD at the lumbar spine, femoral neck, and total proximal femur assessed at baseline and after a follow-up of 1 and 3 yr; semiquantitative visual assessment of vertebral fractures; and nonvertebral fractures based on written documentation. RESULTS: After 3 yr of strontium ranelate treatment, each percentage point increase in femoral neck and total proximal femur BMD was associated with a 3% (95% adjusted confidence interval, 1-5%) and 2% (1-4%) reduction in risk of a new vertebral fracture, respectively. The 3-yr changes in femoral neck and total proximal femur BMD explained 76% and 74%, respectively, of the reduction in vertebral fractures observed during the treatment. Three-year changes in spine BMD were not statistically associated with the incidence of new vertebral fracture (P = 0.10). No significant associations were found between 3-yr changes in BMD and incidence of new nonvertebral fractures, but a trend was found for femoral neck BMD (P = 0.09) and for total proximal femur BMD (P = 0.07). An increase in femoral neck BMD after 1 yr was significantly associated with the reduction in incidence of new vertebral fractures observed after 3 yr (P = 0.04). CONCLUSION: During 3-yr strontium ranelate treatment, an increase in femoral neck BMD was associated with a proportional reduction in vertebral fracture incidence.
Subject(s)
Bone Density/drug effects , Fractures, Bone/prevention & control , Organometallic Compounds/therapeutic use , Thiophenes/therapeutic use , Aged , Calcium/therapeutic use , Double-Blind Method , Female , Femur/drug effects , Femur Neck/drug effects , Follow-Up Studies , Fractures, Bone/epidemiology , Humans , Logistic Models , Middle Aged , Osteoporosis/drug therapy , Risk Reduction Behavior , Spinal Fractures/epidemiology , Spine/drug effects , Treatment Outcome , Vitamin D/therapeutic useABSTRACT
BACKGROUND: Osteoporotic structural damage and bone fragility result from reduced bone formation and increased bone resorption. In a phase 2 clinical trial, strontium ranelate, an orally active drug that dissociates bone remodeling by increasing bone formation and decreasing bone resorption, has been shown to reduce the risk of vertebral fractures and to increase bone mineral density. METHODS: To evaluate the efficacy of strontium ranelate in preventing vertebral fractures in a phase 3 trial, we randomly assigned 1649 postmenopausal women with osteoporosis (low bone mineral density) and at least one vertebral fracture to receive 2 g of oral strontium ranelate per day or placebo for three years. We gave calcium and vitamin D supplements to both groups before and during the study. Vertebral radiographs were obtained annually, and measurements of bone mineral density were performed every six months. RESULTS: New vertebral fractures occurred in fewer patients in the strontium ranelate group than in the placebo group, with a risk reduction of 49 percent in the first year of treatment and 41 percent during the three-year study period (relative risk, 0.59; 95 percent confidence interval, 0.48 to 0.73). Strontium ranelate increased bone mineral density at month 36 by 14.4 percent at the lumbar spine and 8.3 percent at the femoral neck (P<0.001 for both comparisons). There were no significant differences between the groups in the incidence of serious adverse events. CONCLUSIONS: Treatment of postmenopausal osteoporosis with strontium ranelate leads to early and sustained reductions in the risk of vertebral fractures.
