Strontium ranelate: a novel concept for the treatment of osteoporosis

Abstract

The di-strontium salt strontium ranelate, a novel orally active agent consisting of two atoms of stable strontium and the organic moiety ranelic acid, has been developed for the treatment of osteoporosis. It has been shown to enhance osteoblastic cell replication and increase collagen synthesis while decreasing pre-osteoclast differentiation and bone-resorbing activity of mature osteoclasts in vitro. Studies performed in healthy animals have shown that strontium ranelate not only increases bone mass at various skeletal sites but also improves mechanical properties of femoral, humeral and vertebral bones. In estrogen-deficient animals, strontium ranelate effectively inhibits increased bone resorption while maintaining bone formation. Similar results have been obtained from studies in hind limb-immobilized animals. Strontium ranelate has been investigated in a large phase III program which includes two extensive multinational, randomized, double-blind, placebo-controlled clinical trials for the treatment of severe postmenopausal osteoporosis. Before inclusion in these two studies, patients were subjected to a run-in study in order to initiate normalization of their calcium and vitamin D status. The SOTI study, aimed at assessing strontium ranelate's effect on the risk of vertebral fractures, revealed a significant reduction in the risk of new vertebral fractures in the group treated with strontium ranelate. The TROPOS study, which aimed at evaluating the effect of strontium ranelate on nonvertebral fractures, showed a significant reduction in the risk of new nonvertebral fractures and also, in a high-risk subgroup, a significant reduction in the risk of hip fractures. In both studies, the reduction in fracture risk was accompanied by an increase in bone mineral density. The increase remained significant also after correction of the bone mineral density for the higher atomic mass of strontium compared to calcium. Furthermore, an increase in serum levels of a bone formation marker and a decrease in serum levels of a bone resorption marker were observed. The spectrum of side effects comprised mild diarrhea, particularly within the first weeks of treatment, and also a slightly increased risk of venous thromboembolic events. Strontium ranelate thus appears to be a new, effective treatment to prevent fractures in postmenopausal osteoporosis with a novel mechanism of action. It can be expected for the near future that strontium ranelate will also be evaluated for other types of osteoporosis, such as male osteoporosis.