[en] The aim of the strontium ranelate (SR) for treatment of osteoporosis (STRATOS) trial was to investigate the efficacy and safety of different doses of SR, a novel agent in the treatment of postmenopausal osteoporosis. A randomized, multicenter, double-blind, placebo-controlled trial was undertaken in 353 osteoporotic women with at least one previous vertebral fracture and a lumbar T-score <-2.4. Patients were randomized to receive placebo, 0.5 g, 1 g, or 2 g SR/d for 2 yr. The primary efficacy endpoint was lumbar bone mineral density (BMD), assessed by dual-energy x-ray absorptiometry. Secondary outcome measures included femoral BMD, incidence of new vertebral deformities, and biochemical markers of bone metabolism. Lumbar BMD, adjusted for bone strontium content, increased in a dose-dependent manner in the intention-to-treat population: mean annual slope increased from 1.4% with 0.5 g/d SR to 3.0% with 2 g/d SR, which was significantly higher than placebo (P < 0.01). There was a significant reduction in the number of patients experiencing new vertebral deformities in the second year of treatment with 2 g/d SR [relative risk 0.56; 95% confidence interval (0.35; 0.89)]. In the 2 g/d group, there was a significant increase in serum levels of bone alkaline phosphatase, whereas urinary excretion of cross-linked N-telopeptide, a marker of bone resorption, was lower with SR than with placebo. All tested doses were well tolerated; the 2 g/d dose was considered to offer the best combination of efficacy and safety. In conclusion, SR therapy increased vertebral BMD and reduced the incidence of vertebral fractures.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Meunier, P. J.
Slosman, D. O.
Delmas, P. D.
Sebert, J. L.
Brandi, M. L.
Albanese, C.
Lorenc, R.
Pors-Nielsen, S.
de Vernejoul, M. C.
Roces, A.
Reginster, Jean-Yves ; Université de Liège - ULiège > Département des sciences de la santé publique > Epidémiologie et santé publique
Language :
English
Title :
Strontium ranelate: Dose-dependent effects in established postmenopausal vertebral osteoporosis - A 2-year randomized placebo controlled trial
Eastell R. (1998) Treatment of postmenopausal osteoporosis. N Engl J Med 338:736-746.
Arlot M.E., Roux J.P., Boivin G., Perrat B., Tsouderos Y., Deloffre P., Meunier P.J. (1995) Effects of strontium salt (S 12911) in both tibial metaphysis and epiphysis in normal growing rats. J Bone Miner Res , Abstract M415; 10(SUPPL. 1).
Canalis E., Hott M., Deloffre P., Tsouderos Y., Marie P.J. (1996) The divalent salt S 12911 enhances bone cell replication and bone formation in vitro. Bone 18:517-523.
Su Y., Bonnett J., Deloffre P., Tsouderos Y., Baron R. (1992) The strontium salt S 12911 inhibits the expression of carbonic anhydrase and the vitronectin receptor in chicken bone marrow cultures and bone resorption in mouse calvaria and isolated rat osteoclasts. J Bone Miner Res , Abstract 853; 7(SUPPL. 1).
Marie P.J., 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.
Marie P.J. (1996) Effects of strontium on bone formation and bone cells. Therapeutic use of trace elements , Neve J, ed. New York: Plenum Press; 277-282.
Boivin G., Deloffre P., Perrat B., Panczer G., Boudeulle M., Mauras Y., Allain P., Tsouderos Y., Meunier P.J. (1996) Strontium distribution and interactions with bone mineral in monkey iliac bone after strontium salt (S12911) administration. J Bone Miner Res 11:1302-1311.
Reginster J.Y., Roux C., Tsouderos Y., Juspin I. (1998) Role of strontium ranelate in prevention of early postmenopausal bone loss: A double-blind, prospective, randomised, placebo-controlled study. Arthritis Rheum , Abstract 580; 41(SUPPL.).
Note for guidance on involutional osteoporosis in women, CPMP/EWP/552/95; 1997.
Reginster J.Y., Compston J.E. (1995) Recommendations for the registration of new chemical entities used in the prevention and treatment of osteoporosis. Calcif Tissue Int 57:247-250.
Slosman D.O., Rizzoli R., Pichard C., Donath A., Bonjour J.P. (1994) Longitudinal measurement of regional and whole body bone mass in young healthy adults. Osteoporos Int 4:185-190.
Chapuy M.C., Arlot M.E., Delmas P.D., Meunier P.J. (1994) Effect of calcium and cholecalciferol treatment for three years on hip fractures in elderly women. Br Med J 308:1081-1082.
Slosman D.O., Provvedini D.M., Meunier P.J., Delmas P.D., Sebert J.L., De Vernejoul M.C., Tsouderos Y., Reginster J.Y. (1999) The use of different dual x-ray absorptiometry brands in a multicenter clinical trial. J Clin Densitom 2:37-44.
Pors-Nielsen S., Slosman D., Sorensen O.H., Basse-Cathalinat B., De Cassin P., Roux C., Meunier P.J. (1999) Influence of strontium on bone mineral density and bone mineral content measurements by dual x-ray absorptiometry. J Clin Densitom 2:371-379.
Dahl S.G., Allain P., Marie P.J., Mauras Y., Boivin G., Ammann P., Tsouderos Y., Delmas P.D., Christiansen C. (2001) Incorporation and distribution of strontium in bone. Bone 28:446-453.
Cranney A., Guyatt G., Krolicki N., Welch V., Griffith L., Adachi J.D., Shea B., Tugwell P., Wells G. (2001) A meta-analysis of etidronate for the treatment of postmenopausal osteoporosis. Osteoporos Int 12:140-151.
Lees B., Stevenson J.C. (2001) The prevention of osteoporosis using sequential low-dose hormone replacement therapy with estradiol-17 beta and dydrogesterone. Osteoporos Int 12:251-258.
Lufkin E.G., Wahner H.W., O'Fallon W.M., Hodgson S.F., Kotowicz M.A., Lane A.W., Judd H.L., Caplan R.H., Riggs B.L. (1992) Treatment of postmenopausal osteoporosis with transdermal estrogen. Ann Intern Med 117:1-9.
Storm T., Thamsborg G., Steiniche T., Genant H.K., Sorensen O.H. (1990) Effect of intermittent cyclical etidronate therapy on bone mass and fracture rate in women with postmenopausal osteoporosis. N Engl J Med 322:1265-1271.
Guidelines for preclinical and clinical evaluation of agents used in the prevention or treatment of postmenopausal osteoporosis, USA: Division of Metabolism and Endocrine Drug Products, FDA; 1994.
Ettinger B., Black D.M., Mitlak B.H., Knickerbocker R.K., Nickelsen T., Genant H.K., Christiansen C., Delmas P.D., Zanchetta J.R., Stakkestad J., Gluer C.C., Krueger K., Cohen F.J., Eckert S., Ensrud K.E., Avioli L.V., Lips P., Cummings S.R. (1999) Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: Results from a 3-year randomized clinical trial. JAMA 282:637-645.
Liberman U.A., Weiss S.R., Broll J., Minne H.W., Quan H., Bell N.H., Rodriguez-Portales J., Downs R.W. Jr., Dequeker J., Favus M. (1995) Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. The Alendronate Phase III Osteoporosis Treatment Study. N Engl J Med 333:1437-1443.
Reginster J., Minne H.W., Sorensen O.H., Hooper M., Roux C., Brandi M.L., Lund B., Ethgen D., Pack S., Roumagnac I., Eastell R. (2000) Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group. Osteoporos Int 11:83-91.
Boivin G., Schenker E., Tupinon-Mathieu I., Meunier P.J. (1999) Uptake and distribution of strontium in human bone, evolution of the degree of mineralisation after strontium ranelate administration. J Bone Miner Res 14(SUPPL. 1):284.
