[en] Osteoporosis treatments need to combine an unequivocally demonstrated reduction of fractures, at various skeletal sites, long-term safety, and a user-friendly profile, optimizing therapeutic adherence. Strontium ranelate is the first compound to simultaneously decrease bone resorption and stimulate bone formation. Its antifracture efficacy, at various skeletal sites, has been established up to 8 years, through studies of the highest methodological standards. Increases in bone mineral density, observed after 1 year of treatment, are predictive of the long-term fracture efficacy, hence suggesting, for the first time in osteoporosis, that bone densitometry can be used as a monitoring tool for both efficacy and compliance. Owing to a positive benefit/risk ratio, strontium ranelate may now be considered as a first-line treatment in the management of osteoporosis
Disciplines :
General & internal medicine
Author, co-author :
Reginster, Jean-Yves ; Université de Liège - ULiège > Département des sciences de la santé publique > Santé publique, Epidémiologie et Economie de la santé
Hiligsmann, Mickaël ; Université de Liège - ULiège > Département des sciences de la santé publique > Département des sciences de la santé publique
Bruyère, Olivier ; Université de Liège - ULiège > Département des sciences de la santé publique > Santé publique, Epidémiologie et Economie de la santé
Language :
English
Title :
Strontium ranelate: long-term efficacy against vertebral, nonvertebral and hip fractures in patients with postmenopausal osteoporosis
Adami, S., Giannini, S., Bianchi, G., Sinigaglia, L., Di Munno, O., Fiore, C.E. et al. (2009) Vitamin D status and response to treatment in post-menopausal osteoporosis. Osteoporos Int 20: 239-244.
Arlot, M.E., Jiang, Y., Genant, H.K., Zhao, J., Burt-Pichat, B., Roux, J.P. et al. (2008) Histomorphometric and microCT analysis of bone biopsies from postmenopausal osteoporotic women treated with strontium ranelate. J Bone Miner Res 23: 215-222.
Atkins, G., Welldon, K.J., Halbout, P. and Findlay, D.M. (2009) Strontium ranelate treatment of human primary osteoblasts promotes an osteocyte-like phenotype while eliciting an osteoprotegerin response. Osteoporos Int 20: 653-664.
Bain, S.D., Jerome, C., Shen, V., Dupin-Roger, I. and Ammann, P. (2009) Strontium ranelate improves bone strength in ovariectomized rat by positively influencing bone resistance determinants. Osteoporos Int 20: 1417-1428.
Baron, R. and Tsouderos, Y. ( 2002) In vitro effects of S12911-2 on osteoclast function and bone marrow macrophage differentiation. Eur J Pharmacol 450: 11-17.
Boivin, G., Farlay, D., Khebbab, M.T., Jaurand, X., Delmas, P.D. and Meunier, P.J. ( 2009) In osteoporotic women treated with strontium ranelate, strontium is located in bone formed during treatment with a maintained degree of mineralization. Osteoporos Int (Epub ahead of print).
Bonnelye, E., Chabadel, A., Saltel, F. and Jurdic, P. ( 2008) Dual effect of strontium ranelate: Stimulation of osteoblast differentiation and inhibition of osteoclast formation and resorption in vitro. Bone 42: 129-138.
Borgstrom, F., Strom, O., Coelho, J., Johansson, H., Oden, A., Mccloskey, E.V. et al. (2009) The cost-effectiveness of risedronate in the UK for the management of osteoporosis using the Frax(R). Osteoporos Int 21: 495-505.
Bréart, G., Cooper, C., Meyer, O., Speirs, C., Deltour, N. and Reginster, J.Y. ( 2009) Osteoporosis and venous thromboembolism: a retrospective cohort study in the UK General Practice Research Database (GPRD). Osteoporos Int (Epub ahead of print).
Brennan, T., Rybchyn, M.S., Green, W., Atwa, S., Conigrave, A.D. and Mason, R.S. (2009) Osteoblasts play key roles in the mechanisms of action of strontium ranelate. Br J Pharmacol 157: 1291-1300.
Bruyere, O., Roux, C., Badurski, J., Isaia, G., de Vernejoul, M.C., Cannata, J. et al. (2007 a) Relationship between change in femoral neck bone mineral density and hip fracture incidence during treatment with strontium ranelate. Curr Med Res Opin 23: 3041-3045.
Bruyere, O., Roux, C., Detilleux, J., Slosman, D.O., Spector, T.D., Fardellone, P. et al. (2007 b) Relationship between bone mineral density changes and fracture risk reduction in patients treated with strontium ranelate. J Clin Endocrinol Metab 92: 3076-3081.
Canalis, E., Hott, M., Deloffre, P., Tsouderos, Y. and Marie, P.J. ( 1996) The divalent strontium salt S 12911 enhances bone cell replication and bone formation in vitro. Bone 18: 517-523.
Caverzasio, J. ( 2008) Strontium ranelate promotes osteoblastic cell replication through at least two different mechanisms. Bone 42: 1131-1136.
Delannoy, P., Bazot, D. and Marie, P.J. ( 2002) Long-term treatment with strontium ranelate increases vertebral bone mass without deleterious effect in mice. Metabolism 51: 906-911.
Emea (2007) Question and answers on the safety of protelos/osseor (strontium ranelate).
Ettinger, M.P. ( 2003) Aging bone and osteoporosis: strategies for preventing fractures in the elderly. Arch Intern Med 163: 2237-2246.
Fromigué, O., Haÿ, E., Barbara, A., Petrel, C., Traiffort, E., Ruat, M. and Marie, P.J. (2009) Calcium sensing receptor-dependent and -independent activation of osteoblast replication and survival by strontium ranelate. J Cell Mol Med 13: 2189-2199.
Grosso, A., Douglas, I., Hingorani, A., Macallister, R. and Smeeth, L. ( 2008) Post-marketing assessment of the safety of strontium ranelate; a novel case-only approach to the early detection of adverse drug reactions. Br J Clin Pharmacol 66: 689-694.
Hiligsmann, M., Bruyere, O. and Reginster, J.Y. (2010 a) Cost-effectiveness of strontium ranelate versus risedronate in the treatment of postmenopausal osteoporotic women aged over 75 years. Bone 46: 440-446.
Hiligsmann, M., Bruyere, O. and Reginster, J.Y. (2010 b) Cost-utility of long-term strontium ranelate treatment for postmenopausal osteoporotic women. Osteoporos Int 21: 157-165.
Hott, M., Deloffre, P., Tsouderos, Y. and Marie, P.J. ( 2003) S12911-2 reduces bone loss induced by short-term immobilization in rats. Bone 33: 115-123.
Hurtel-Lemaire, A.S., Mentaverri, R., Caudrillier, A., Cournarie, F., Wattel, A., Kamel, S. et al. (2009) The calcium-sensing receptor is involved in strontium ranelate-induced osteoclast apoptosis. New insights into the associated signaling pathways. J Biol Chem 284: 575-584.
Kanis, J.A., Burlet, N., Cooper, C., Delmas, P.D., Reginster, J.Y., Borgstrom, F. et al. (2008) European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 19: 399-428.
Kendler, D.L., Adachi, J.D., Josse, R.G. and Slosman, D.O. (2009) Monitoring strontium ranelate therapy in patients with osteoporosis. Osteoporos Int 20: 1101-1106.
Marie, P.J., Hott, M., Modrowski, D., de Pollak, C., Guillemain, J., Deloffre, P. et al. (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.
Marquis, P., Cialdella, P. and de La Loge, C. ( 2001) Development and validation of a specific quality of life module in post-menopausal women with osteoporosis: the QUALIOST. Qual Life Res 10: 555-566.
Marquis, P., Roux, C., de La Loge, C., Diaz-Curiel, M., Cormier, C., Isaia, G. et al. (2008) Strontium ranelate prevents quality of life impairment in post-menopausal women with established vertebral osteoporosis. Osteoporos Int 19: 503-510.
Mcclung, M.R., Geusens, P., Miller, P.D., Zippel, H., Bensen, W.G., Roux, C. et al. (2001) Effect of risedronate on the risk of hip fracture in elderly women. Hip intervention program study group. N Engl J Med 344: 333-340.
Meunier, P.J., Slosman, D.O., Delmas, P.D., Sebert, J.L., Brandi, M.L., Albanese, C. et al. (2002) Strontium ranelate: dose-dependent effects in established postmenopausal vertebral osteoporosis-a 2-year randomized placebo controlled trial. J Clin Endocrinol Metab 87: 2060-2066.
Meunier, P.J., Roux, C., Seeman, E., Ortolani, S., Badurski, J.E., Spector, T.D. 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.
Meunier, P.J., Roux, C., Ortolani, S., Diaz-Curiel, M., Compston, J., Marquis, P. et al. (2009) Effects of long-term strontium ranelate treatment on vertebral fracture risk in postmenopausal women with osteoporosis. Osteoporos Int 20: 1663-1673.
Musette, P., Brandi, M.L., Cacoub, P., Kaufman, J.M., Rizzoli, R. and Reginster, J.Y. ( 2009) Treatment of osteoporosis: recognizing and managing cutaneous adverse reactions and drug-induced hypersensitivity. Osteoporos Int (Epub ahead of print).
Naves, M., Diaz-Lopez, J.B., Gomez, C., Rodriguez-Rebollar, A., Rodriguez-Garcia, M. and Cannata-Andia, J.B. ( 2003) The effect of vertebral fracture as a risk factor for osteoporotic fracture and mortality in a Spanish population. Osteoporos Int 14: 520-524.
Rabenda, V., Vanoverloop, J., Fabri, V., Mertens, R., Sumkay, F., Vannecke, C. et al. (2008) Low incidence of anti-osteoporosis treatment after hip fracture. J Bone Joint Surg Am 90: 2142-2148.
Reginster, J.Y. and Meunier, P.J. ( 2003) Strontium ranelate phase 2 dose-ranging studies: PREVOS and STRATOS studies. Osteoporos Int 14(Suppl 3): S56-S65.
Reginster, J.Y., Seeman, E., de Vernejoul, M.C., Adami, S., Compston, J., Phenekos, C. et al. (2005) Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) Study. J Clin Endocrinol Metab 90: 2816-2822.
Reginster, J.Y., Malaise, O., Neuprez, A. and Bruyere, O. ( 2007) Strontium ranelate in the prevention of osteoporotic fractures. Int J Clin Pract 61: 324-328.
Reginster, J.Y., Felsenberg, D., Boonen, S., Diez-Perez, A., Rizzoli, R., Brandi, M.L. et al. (2008) Effects of long-term strontium ranelate treatment on the risk of nonvertebral and vertebral fractures in postmenopausal osteoporosis: results of a five-year, randomized, placebo-controlled trial. Arthritis Rheum 58: 1687-1695.
Reginster, J.Y., Bruyere, O., Sawicki, A., Roces-Varela, A., Fardellone, P., Roberts, A. et al. (2009) Long-term treatment of postmenopausal osteoporosis with strontium ranelate: results at 8 years. Bone 45: 1059-1064.
Roux, C., Reginster, J.Y., Fechtenbaum, J., Kolta, S., Sawicki, A., Tulassay, Z. et al. (2006) Vertebral fracture risk reduction with strontium ranelate in women with postmenopausal osteoporosis is independent of baseline risk factors. J Bone Miner Res 21: 536-542.
Roux, C., Fechtenbaum, J., Kolta, S., Isaia, G., Andia, J.B. and Devogelaer, J.P. ( 2008) Strontium ranelate reduces the risk of vertebral fracture in young postmenopausal women with severe osteoporosis. Ann Rheum Dis 67: 1736-1738.
Seeman, E., Vellas, B., Benhamou, C., Aquino, J.P., Semler, J., Kaufman, J.M. et al. (2006) Strontium ranelate reduces the risk of vertebral and nonvertebral fractures in women eighty years of age and older. J Bone Miner Res 21: 1113-1120.
Seeman, E., Devogelaer, J.P., Lorenc, R., Spector, T., Brixen, K., Balogh, A. et al. (2008) Strontium ranelate reduces the risk of vertebral fractures in patients with osteopenia. J Bone Miner Res 23: 433-438.
Shea, B., Wells, G., Cranney, A., Zytaruk, N., Robinson, V., Griffith, L. et al. (2004) Calcium supplementation on bone loss in postmenopausal women. Cochrane Database Syst Rev CD004526.
Suzuki, A., Sekiguchi, S., Asano, S. and Itoh, M. ( 2008) Pharmacological topics of bone metabolism: recent advances in pharmacological management of osteoporosis. J Pharmacol Sci 106: 530-535.
Takahashi, N., Sasaki, T., Tsouderos, Y. and Suda, T. ( 2003) S 12911-2 inhibits osteoclastic bone resorption in vitro. J Bone Miner Res 18: 1082-1087.
Tas, S. and Simonart, T. ( 2003) Management of drug rash with eosinophilia and systemic symptoms (DRESS syndrome): an update. Dermatology 206: 353-356.
United Nations (2003) World Population Prospects: The 2002 Revision.
United Nations (2008) World Urbanization Prospects: The 2007 Revision.
van Staa, T.P., Leufkens, H.G. and Cooper, C. ( 2002) Does a fracture at one site predict later fractures at other sites? A British cohort study. Osteoporos Int 13: 624-629.