strontium ranelate; vertebral and nonvertebral fractures risk reduction; women > 80 years of age
Abstract :
[en] Introduction: About 25-30% of the population burden of all fragility fractures in the community arise from women >= 80 years of age, because this population is at high risk for all types of fracture, particularly nonvertebral fractures. Despite this, evidence that therapies reduce the risk of both vertebral and nonvertebral fractures in this group is lacking. The aim of this study was to determine whether strontium ranelate, an agent that reduces the risk of vertebral and nonvertebral fractures in postmenopausal women > 50 years of age, also reduces fractures in the elderly. Materials and Methods: An analysis based on preplanned pooling of data from two international, phase 111, randomized, placebo-controlled, double-blind studies (the Spinal Osteoporosis, Therapeutic Intervention [SOTI] and TReatment Of Peripheral OSteoporosis [TROPOS]) included 1488 women between 80 and 100 years of age followed for 3 years. Yearly spinal X-rays were performed in 895 patients. Only radiographically confirmed nonvertebral fractures were included. Results: Baseline characteristics did not differ in placebo and treatment arms. In the intent-to-treat analysis, the risk of vertebral, nonvertebral, and clinical (symptomatic vertebral and nonvertebral) fractures was reduced within I year by 59% (p = 0.002), 41% (p = 0.027), and 37% (p = 0.012), respectively. At the end of 3 years, vertebral, nonvertebral, and clinical fracture risks were reduced by 32% (p = 0.013), 31% (p = 0.011), and 22% (p = 0.040), respectively. The medication was well tolerated, and the safety profile was similar to that in younger patients. Conclusions: Treatment with strontium ranelate safely reduces the risk of vertebral and nonvertebral fractures in women with osteoporosis >= 80 years of age. Even in the oldest old, it is not too late to reduce fracture risk.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Seeman, E.
Vellas, B.
Benhamou, C. L.
Aquino, J. P.
Semler, J.
Kaufman, J. M.
Hoszowski, K.
Varela, A. R.
Fiore, C.
Brixen, K.
Reginster, Jean-Yves ; Université de Liège - ULiège > Département des sciences de la santé publique > Epidémiologie et santé publique
Boonen, S.
Language :
English
Title :
Strontium ranelate reduces the risk of vertebral and nonvertebral fractures in women eighty years of age and older
Publication date :
July 2006
Journal title :
Journal of Bone and Mineral Research
ISSN :
0884-0431
eISSN :
1523-4681
Publisher :
Amer Soc Bone & Mineral Res, Washington, United States - Washington
Population Division of the Department of Economic and Social Affairs of the Nations Secretariat 2002 World Population Prospects: The 2002 Revision and World Urban Prospects. Available online at http://esa.un.org/unpp. Accessed January 2006.
Ettinger MP 2003 Aging bone and osteoporosis: Strategies for preventing fractures in the elderly. Arch Intern Med 163:2237-2246.
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. JAMA 280:2077-2082.
Ettinger B, Black DM, Mitlak BH, Knickerbocker RK, Nickelsen T, Genant HK, Christiansen C, Delmas PD, Zanchetta JR, Stakkestad J, Gluer CC, Krueger K, Cohen FJ, Eckert S, Ensrud KE, Avioli LV, Lips P, Cummings SR 1999 Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: Results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA 282:637-645.
Harris ST, Watts NB, Genant HK, McKeever CD, Hangartner T, Keller M, Chesnut CH III, 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: A randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group. JAMA 282:1344-1352.
Reginster J, 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 postmenopausal osteoporosis. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group. Osteoporos Int 11:83-91.
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.
Boonen S, McClung MR, Eastell R, El-Hajj Fuleihan G, Barton IP, Delmas P 2004 Safety and efficacy of risedronate in reducing fracture risk in osteoporotic women aged 80 and older: Implications for the use of antiresorptive agents in the old and oldest old. J Am Geriatr Soc 52:1832-1839.
Boonen S, Marin F, Mellstrom D, Xie L, Desaiah D, Krege JH, Rosen CJ 2006 Safety and efficacy of teriparatide in elderly women with established osteoporosis: Bone anabolic therapy from a geriatric perspective. J Am Geriatr Soc (in press).
Marie PJ, Amman P, Boivin G, Rey C 2001 Mechanisms of action and therapeutic potential of strontium in bone. Calcif Tissue Int 69:121-129.
Meunier PJ, Roux C, Seeman E, Ortolani S, Badurski JE, Spector TD, 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.
Reginster JY, Seeman E, De Vernejoul MC, Adami S, Compston J, Phenekos C, Devogelaer JP, Curiel MD, Sawicki A, Goemaere S, Sorensen OH, Felsenberg D, Meunier PJ 2005 Strontium ranelate reduces the risk of non vertebral fractures in postmenopausal women with osteoporosis: TReatment Of Peripheral OSsteoporosis (TROPOS) Study. J Clin Endocrinol Metab 90:2816-2822.
Committee for Proprietary Medicinal Products 2001 Note for Guidance on Post Menopausal Osteoporosis in Women Rev. 1 (CPMP adopted January 2001). European Agency for Evaluation of Medicinal Products, London, UK.
Food and Drug Adminstration 1994 Draft Guidance Postmenopausal Osteoporosis. Preclinical and Clinical Evaluation of Agents Used in the Prevention or Treatment of Postmenopausal Osteoporosis. Division of Metabolic and Endocrine Drug Products, Food and Drug Administration, Rockville, MD, USA.
Genant HK, Wu CY, van Kuijk C, Nevitt MC 1993 Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 8:1137-1148.
Reginster JY, Janssen C, Deroisy R, Zegels B, Albert A, Franchimont P 1995 Bone mineral density of the spine and the hip measured with dual energy X-ray absorptiometry: Normal range and fracture threshold for western European (Belgian) postmenopausal females. Clin Rheumatol 14:68-75.
Looker AC, Wahner HW, Dunn WL, Calvo MS, Harris TB, Heyse SP, Johnston CC Jr, Lindsay R 1998 Updated data on proximal femur bone mineral levels of US adults. Osteoporos Int 8:468-489.
Slosman DO, Provvedini DM, Meunier PJ, Delmas P, 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.
Schuit SC, van der Klift M, Weel AE, de Laet CE, Burger H, Seeman E, Hofman A, Uitterlinden AG, van Leeuwen JP, Pols HA 2004 Fracture incidence and association with bone mineral density in elderly men and women: The Rotterdam Study. Bone 34:195-202.
Sanders KM, Nicholson GC, Watts JJ, Pasco JA, Henry MJ, Kotowicz MA, Seeman E 2006 Half the burden of fragility fractures in the community occur in women without osteoporosis. When is fracture prevention cost effective? Bone (in press).
Chrischilles E, Shireman T, Wallace R 1994 Costs and health effects of osteoporotic fractures. Bone 15:377-386.
Autier P, Haentjens P, Bentin J, Baillon JM, Grivegnee AR, Closon MC, Boonen S 2000 Costs induced by hip fractures: A prospective controlled study in Belgium. Belgian Hip Fracture Study Group. Osteoporos Int 11:373-380.
Cooper C, Atkinson EJ, Jacobsen SJ, O'Fallon WM, Melton LJ III 1993 Population-based study of survival after osteoporotic fractures. Am J Epidemiol 137:1001-1005.
Dahl SG, Allain P, Marie PJ, Mauras Y, Boivin G, Ammann P, Tsouderos Y, Delmas PD, Christiansen C 2001 Incorporation and distribution of strontium in bone. Bone 28:446-453.
Nielsen SP, Slosman D, Sorensen OH, Basse-Cathalinat B, De Cassin P, Roux CR, Meunier PJ 1999 Influence of strontium on bone mineral density and bone mineral content measurements by dual X-ray absorptiometry. J Clin Densitom 2:371-379.
Slosman DO, Rizzoli R, Pichard C, Donath A, Bonjour JP 1994 Longitudinal measurement of regional and whole body bone mass in young healthy adults. Osteoporos Int 4:185-190.
Briancon D, de Gaudemar JB, Forestier R 2004 Management of osteoporosis in women with peripheral osteoporotic fractures after 50 years of age: A study of practices. Joint Bone Spine 71:128-130.
Feldstein AC, Nichols GA, Elmer PJ, Smith DH, Aickin M, Herson M 2003 Older women with fractures: Patients falling through the cracks of guideline-recommended osteoporosis screening and treatment. J Bone Joint Surg Am 85:2294-2302.
