Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) study
Reginster, Jean-Yves; Seeman, E.; De Vernejoul, M. C.et al.
2005 • In Journal of Clinical Endocrinology and Metabolism, 90 (5), p. 2816-2822
Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis Treatment of Peripheral Osteoporosis (TROPOS) study.pdf
[en] Background: Strontium ranelate, a new oral drug shown to reduce vertebral fracture risk in postmenopausal women with osteoporosis, was studied in the Treatment of Peripheral Osteoporosis (TROPOS) study to assess its efficacy and safety in preventing nonvertebral fractures also. Methods: Strontium ranelate (2 g/d) or placebo were randomly allocated to 5091 postmenopausal women with osteoporosis in a double-blind placebo-controlled 5-yr study with a main statistical analysis over 3 yr of treatment. Findings: In the entire sample, relative risk (RR) was reduced by 16% for all nonvertebral fractures (P = 0.04), and by 19% for major fragility fractures (hip, wrist, pelvis and sacrum, ribs and sternum, clavicle, humerus) (P = 0.031) in strontium ranelate-treated patients in comparison with the placebo group. Among women at high risk of hip fracture ( age ≥ 74 yr and femoral neck bone mineral density T score ≤-3, corresponding to -2.4 according to NHANES reference) (n = 1977), the RR reduction for hip fracture was 36% (P = 0.046). RR of vertebral fractures was reduced by 39% (P < 0.001) in the 3640 patients with spinal x-rays and by 45% in the subgroup without prevalent vertebral fracture. Strontium ranelate increased bone mineral density throughout the study, reaching at 3 yr (P < 0.001): +8.2% (femoral neck) and +9.8% (total hip). Incidence of adverse events (AEs) was similar in both groups. Conclusion: This study shows that strontium ranelate significantly reduces the risk of all nonvertebral and in a high-risk subgroup, hip fractures over a 3-yr period, and is well tolerated. It confirms that strontium ranelate reduces vertebral fractures. Strontium ranelate offers a safe and effective means of reducing the risk of fracture associated with osteoporosis.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Reginster, Jean-Yves ; Université de Liège - ULiège > Département des sciences de la santé publique > Epidémiologie et santé publique
Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) study
Publication date :
May 2005
Journal title :
Journal of Clinical Endocrinology and Metabolism
ISSN :
0021-972X
eISSN :
1945-7197
Publisher :
Endocrine Soc, Chevy Chase, United States - Maryland
Center JR, Nguyen TV, Schneider D, Sambrook PN, Eisman JA 1999 Mortality after all major types of osteoporotic fracture in men and women: an observational study. Lancet 353:878-882
Cummings RS, Melton 3rd LJ 2002 Epidemiology and outcomes of osteoporotic fractures. Lancet 359:1761-1767
Youm T, Koval KJ, Kummer FJ, Zuckerman JD 1999 Do all hip fractures result from a fall? Am J Orthop 28:190-194
Seeman E 2002 Pathogenesis of bone fragility in women and men. Lancet 359:1841-1850
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
Baron R, Tsouderos Y 2002 In vitro effects of S12911-2 on osteoclast function and bone marrow macrophage differentiation. Eur J Pharmacol 450:11-17
Takahashi N, Sasaki N, Tsouderos Y, Suda T 2003 S12911-2 inhibits osteoclastic bone resorption in vitro. J Bone Miner Res 18:1082-1087
Meunier PJ, Roux C, Seeman E, Ortolani S, Badurski J, Spector T, Cannata J, Balogh A, Lemmel EM, Pors-Nielsen S, Rizzoli R, Genant HK, Reginster JY 2004 The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med 350:459-468
Committee for Proprietary Medicinal Products 2001 Note for guidance on post menopausal osteoporosis in women rev. 1
Food and Drug Administration 1994 Draft guidance postmenopausal osteoporosis. Preclinical and clinical evaluation of agents used in the prevention or treatment of postmenopausal osteoporosis
Genant HK, Wu CY, van Kuijk C, Nevitt MC 1993 Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 8:1137-1148
Slosman D, Provvedini DM, Meunier PJ, Delmas PD, Sebert JL, De Vernejoul MC, Tsouderos Y, Reginster JY 1999 The use of different dual x-ray absorptiometry brands in a multicenter clinical trial. J Clin Densitom 2:37-44
Donaldson LJ, Cook A, Thomson RG 1990 Incidence of fractures in a geographically defined population. J Epidemiol Community Health 44:241-245
McClung MR, Geusens P, Miller PD, Zippel H, Bensen WG, Roux C, Adami S, Fogelman I, Diamond T, Eastell R, Meunier PJ, Reginster JY 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
Chapuy MC, Arlot M, Delmas P, Meunier PJ 1994 Effect of calcium and cholecalciferol treatment for three years on hip fractures in elderly women. BMJ 308:1081-1082
Harris ST, Watts NB, Genant HK, McKeever CD, Hangartner T, Keller M, Chesnut CH, Brown J, Eriksen EF, Hoseyni MS, Axelrod DW, Miller PD 1999 Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis. J Am Med Assoc 282:1344-1352
Reginster JY, Minne HW, Sorensen OH, Hooper M, Roux C, Brandi ML, 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 post-menopausal osteoporosis. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group. Osteoporos Int 11:83-91
Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC, Bauer DC, Genant HK, Haskell WL, Marcus R, Ott SM, Torner JC, Quandt SA, Reiss TF, Ensrud KE 1996 Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet 348:1535-1541
Cummings SR, Black DM, Thompson DE, Applegate WB, Barrett-Connor E, Musliner TA, Palermo L, Prineas R, Rubin SM, Scott JC, Vogt T, Wallace R, Yates AJ, LaCroix AZ 1998 Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. J Am Med Assoc. 280:2077-2082
Meunier PJ, Slosman D, Delmas PD, Sebert JL, Brandi ML, Albanese C, Lorenc R, Pors-Nielsen S, De Vernejoul MC, Roces A, Reginster JY 2002 Strontium ranelate: dose-dependent effects in established post menopausal vertebral osteoporosis. The Stratos 2-year randomized placebo controlled trial. J Clin Endocrinol Metab 87:2060-2066
Reginster JY, Deroisy R, Dougados M, Jupsin I, Colette J, Roux C 2002 Prevention of early postmenopausal bone loss by strontium ranelate: the randomized, two-year, double-masked, dose-ranging, placebo-controlled PREVOS trial. Osteoporos Int 13:925-931
Ammann P, Rizzoli R, Deloffre P, Tsouderos Y, Meyer JM, Bonjour JP 1996 The increase in vertebral bone mass induced in intact rats by long-term administration of the strontium salt S-12911 is directly correlated with vertebral bone strength. Osteoporos Int 6(Suppl 1):259
Coulombe J, Faure H, Robin B, Tsouderos Y, Ruat M 2002 Activation of the rat and mouse cation-sensing receptor by strontium ranelate and its modulation by extracellular calcium. Osteoporos Int 13(suppl 1):P70MO
Pi M, Quarles LD 2004 A novel cation-sensing mechanism in osteoblasts is a molecular target for strontium. J Bone Miner Res 19:862-869
