Abstract
Strontium ranelate has been shown to decrease the risk of fractures in postmenopausal women. Its efficacy in clinical studies results from its unique mode of action, on both bone resorption and bone formation. Pharmacological studies in animals have shown that strontium ranelate decreases bone resorption and increases bone formation, resulting in increased bone mass. In ovariectomized rats, strontium ranelate prevented the reduction in bone mineral content and the decrease in trabecular bone volume induced by estrogen deficiency. In this model, strontium ranelate decreased bone resorption, whereas bone formation was maintained at a high level as documented by plasma biochemical markers and histomorphometric indices of bone formation. In the model of osteopenia induced by hind-limb immobilization in rats, strontium ranelate reduced histomorphometric parameters of bone resorption and partially prevented long-bone loss, as assessed by bone mineral content, bone volume, and biochemical indices of bone resorption. In intact mice, strontium ranelate increased bone formation and vertebral bone mass. In intact growing rats, strontium ranelate increased the bone trabecular volume without alteration of mineralization. The unique mode of action of strontium ranelate on bone formation and resorption was supported by in vitro studies. In rat calvaria culture systems and rat osteoblastic cell cultures, strontium ranelate enhanced preosteoblastic cell replication and increased collagen synthesis by osteoblasts. Moreover, strontium ranelate decreased bone resorption in organ cultures and decreased the resorbing activity of isolated mouse osteoclasts. The assessment of bone markers in a clinical trial [Spinal Osteoporosis Therapeutic Intervention (SOTI)] supports the mode of action of strontium ranelate: bone alkaline phosphatase levels increased and C-telopeptide of type I collagen levels decreased in treated patients compared with the placebo group at all time points. Thus, pharmacological and clinical studies suggest that strontium ranelate optimizes bone resorption and bone formation, resulting in increased bone mass, which may be of great value in the treatment of osteoporosis.
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Marie PJ (1996) Effects of strontium on bone formation and bone cells. In: Neve J, Chappuis P, Lamand M (eds) Therapeutic uses of traces elements. Plenum Press, New York, pp 277–282
Marie PJ, Ammann P, Boivin G, Rey C (2001) Mechanisms of action and therapeutic potential of strontium in bone. Calcif Tissue Int 69:121–129
Marie PJ (2003) Optimizing bone metabolism in osteoporosis: insight into the pharmacologic profile of strontium ranelate. Osteoporos Int 14 [Suppl 3]:S9–12
Modrowski D, Miravet L, Feuga M, Marie PJ (1993) Increased proliferation of osteoblast precursor cells in estrogen-deficient rats. Am J Physiol 264:E190–196
Marie PJ, Hott M, Modrowski D, de Pollak C, Guillemain J, Deloffre P, Tsouderos Y (1993) An uncoupling agent containing strontium prevents bone loss by depressing bone resorption and maintaining bone formation in estrogen-deficient rats. J Bone Miner Res 8:607–615
Arlot ME, Braillon P, Roux JP, Deloffre P, Tsouderos Y, Meunier PJ (1992) A new agent containing strontium (S12911) has a protective effect on bone loss in ovariectomized rats (abstract). Bone 13:A1
Hott M, Deloffre P, Tsouderos Y, Marie PJ (2003) S12911-2 reduces bone loss induced by short-term immobilization in rats. Bone 33:115–123
Delannoy P, Bazot D, Marie PJ (2002) Long-term treatment with strontium ranelate increases vertebral bone mass without deleterious effect in mice. Metabolism 51:906–911
Ammann P, Shen V, Robin B, Mauras Y, Bonjour JP, Rizzoli R (2004) Strontium ranelate improves bone resistance by increasing bone mass and improving architecture in intact female rats. J Bone Miner Res (in press)
Buehler J, Chappuis P, Saffar JL, Tsouderos Y, Vignery A (2001) Strontium ranelate inhibits bone resorption while maintaining bone formation in alveolar bone in monkeys (Macaca fascicularis). Bone 29:176–179
Canalis E, Hott M, Deloffre P, Tsouderos Y, Marie PJ (1996) The divalent strontium salt S12911 enhances bone cell replication and bone formation in vitro. Bone 18:517–523
Barbara A, Delannoy P, Denis BG, Marie PJ (2004) Normal matrix mineralization induced by strontium ranelate in MC3T3-E1 osteogenic cells. Metabolism 53: 532–537
Takahashi N, Sasaki T, Tsouderos Y, Suda T (2003) S 12911-2 inhibits osteoclastic bone resorption in vitro. J Bone Miner Res 18:1082–1087
Baron R, Tsouderos Y (2002) In vitro effects of S12911-2 on osteoclast function and marrow macrophage differentiation. Eur J Pharmacol 450:11–17
Meunier PJ, Roux C, Seeman E, Ortolani S, Badurski JE, Spector TD, et al (2004) The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med 350:459–468
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Marie, P.J. Strontium ranelate: a novel mode of action optimizing bone formation and resorption. Osteoporos Int 16 (Suppl 1), S7–S10 (2005). https://doi.org/10.1007/s00198-004-1753-8
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DOI: https://doi.org/10.1007/s00198-004-1753-8