Calcified Tissue International

, Volume 74, Issue 2, pp 129–135

Risedronate Rapidly Reduces the Risk for Nonvertebral Fractures in Women with Postmenopausal Osteoporosis

  • J. T. Harrington
  • L. -G. Ste-Marie
  • M. L. Brandi
  • R. Civitelli
  • P. Fardellone
  • A. Grauer
  • I. Barton
  • S. Boonen
Clinical Investigations

Abstract

Prevention of nonvertebral fractures, which account for a substantial proportion of osteoporotic fractures, is an important goal of osteoporosis treatment. Risedronate, a pyridinyl bisphosphonate, significantly reduces clinical vertebral fracture incidence within 6 months. To determine the effect of risedronate on osteoporosis-related nonvertebral fractures, data from four large, randomized, double-blind, placebo-controlled, Phase III studies were pooled and analyzed. The population analyzed consisted of postmenopausal women, with and without vertebral fractures, who had low bone mineral density (lumbar spine T-score <−2.5). Patients received placebo (N = 608) or risedronate 5 mg daily (N = 564) for 1 to 3 years. At baseline, 58% had at least one prevalent vertebral fracture, and the mean lumbar spine T-score was −3.4. Among placebo-treated patients, the presence of prevalent vertebral fractures did not increase the risk of incident nonvertebral fractures overall, although fractures of the humerus and hip and pelvis were more common in patients who had prevalent vertebral fractures than in those who did not. Risedronate 5 mg significantly reduced the incidence of nonvertebral fractures within 6 months compared with control. After 1 year, nonvertebral fracture incidence was reduced by 74% compared with control (P = 0.001), and after 3 years, the incidence was reduced by 59% (P = 0.002). The results indicate that risedronate significantly reduces the incidence of osteoporosis-related nonvertebral fractures within 6 months.

Keywords

Risedronate Nonvertebral fractures Postmenopausal women Osteoporosis 

References

  1. 1.
    NIH2001Consensus Development Panel on Osteoporosis Prevention, Diagnosis, and Therapy. Osteoporosis prevention, diagnosis, and therapy.JAMA285785795PubMedGoogle Scholar
  2. 2.
    Melton III, LJ, Chrischilles, EA, Cooper, C, Lane, AW, Riggs, BL 1992Perspective. How many women have osteoporosis?J Bone Miner Res710051010PubMedGoogle Scholar
  3. 3.
    O’Neill, TW, Felsenberg, D, Varlow, J, Cooper, C, Kanis, JA, Silman, AJ 1996The prevalence of vertebral deformity in European men and women: the European Vertebral Osteoporosis Study.J Bone Miner Res1110101018PubMedGoogle Scholar
  4. 4.
    Melton III, LJ, Lane, AW, Cooper, C, Eastell, R, O’Fallon, WM, Riggs, BL 1993Prevalence and incidence of vertebral deformities.Osteoporos Int3113119PubMedGoogle Scholar
  5. 5.
    Eastell, R, Reid, DM, Compston, J,  et al. 2001Secondary prevention of osteoporosis: When should a non-vertebral fracture be a trigger for action?QJM94575597CrossRefPubMedGoogle Scholar
  6. 6.
    Melton III, LJ, Atkinson, EJ, Cooper, C, O’Fallon, WM, Riggs, BL 1999Vertebral fractures predict subsequent fractures.Osteoporos Int10214221CrossRefPubMedGoogle Scholar
  7. 7.
    Seeley, DG, Browner, WS, Nevitt, MC, Genant, HK, Scott, JC, Cummings, SR 1991Which fractures are associated with low appendicular bone mass in elderly women? The Study of Osteoporotic Fractures Research Group.Ann Intern Med115837842PubMedGoogle Scholar
  8. 8.
    Black, DM, Cummings, SR, Genant, HK, Nevitt, MC, Palermo, L, Browner, W 1992Axial and appendicular bone density predict fractures in older women.J Bone Miner Res7633638PubMedGoogle Scholar
  9. 9.
    Harris, ST, Watts, NB, Genant, HK,  et al. 1999Effects of risedronate treatment on vertebral and non-vertebral fractures in women with postmenopausal osteoporosis. A randomized controlled trial.JAMA28213441352, for the Vertebral Efficacy with Risedronate Therapy (VERT) Study GroupPubMedGoogle Scholar
  10. 10.
    Cohen, S, Levy, RM, Keller, M,  et al. 1999Risedronate therapy prevents corticosteroid-induced bone loss.Arthritis Rheum4223092318CrossRefPubMedGoogle Scholar
  11. 11.
    Reid, DM, Hughes, RA, Laan, RF, Sacco-Gibson, NA, Wenderoth, DH, Adami, S, Eusebio, RA, Devogelaer, JP 2000Efficacy and safety of daily risedronate in the treatment of corticosteroid-induced osteoporosis in men and women: a randomized trial.J Bone Miner Res1510061013, for the European Corticosteroid-Induced Osteoporosis Treatment StudyPubMedGoogle Scholar
  12. 12.
    Hooper, M, Ebeling, P, Roberts, A, D’Emden, M, Nicholson, G, Crusan, C, Wenderoth, D, Ethgen, D 1999Risedronate prevents bone loss in early postmenopausal women (abstract).Calcif Tissue Int64S69, for the Australian Risedronate Prevention Study GroupGoogle Scholar
  13. 13.
    Reginster, J, Minne, HW, Sorensen, OH, Hooper, M, Roux, C, Brandi, ML, Lund, B, Ethgen, D, Pack, S, Roumagnac, I, Eastell, R 2000Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis.Osteoporos Int118391, on behalf of the Vertebral Efficacy with Risedronate Therapy (VERT) Study GroupPubMedGoogle Scholar
  14. 14.
    McClung, M, Bensen, W, Bolognese, M,  et al. 1998Risedronate increases bone mineral density at the hip, spine and radius in postmenopausal women with low bone mass (abstract).Osteoporos Int8111Google Scholar
  15. 15.
    Fogelman, I, Ribot, C, Smith, R, Ethgen, D, Sod, E, Reginster, JY 2000Risedronate reverses bone loss in postmenopausal women with low bone mass: results from a multinational, double-blind, placebo-controlled trial.J Clin Endocrinol Metab8518951900PubMedGoogle Scholar
  16. 16.
    McClung, MR, Geusens, P, Miller, PD,  et al. 2001Effect of risedronate on the risk of hip fracture in elderly women.N Engl J Med344333340, for the Hip Intervention Program Study GroupCrossRefPubMedGoogle Scholar
  17. 17.
    Watts, NB, Adami, S, Chesnut, CH 2001Risedronate reduces the risk of clinical vertebral fractures in just 6 months (abstract).J Bone Miner Res16S407Google Scholar
  18. 18.
    Lindsay, R, Burge, RT, Strauss, DM 2001The expected cost of new fractures in the year following a vertebral fracture (abstract).J Bone Miner Res16S275Google Scholar
  19. 19.
    Lindsay, R, Silverman, SL, Cooper, C,  et al. 2001Risk of new vertebral fracture in the year following a fracture.JAMA285320323PubMedGoogle Scholar
  20. 20.
    Black, DM, Thompson, DE, Bauer, DC, Ensrud, K, Musliner, T, Hochberg, MC, Nevitt, MC, Suryawanshi, S, Cummings, SR 2000Fracture risk reduction with alendronate in women with osteoporosis: the Fracture Intervention Trial.J Clin Endocrinol Metab8541184124, for the Fracture Intervention Trial Research GroupPubMedGoogle Scholar
  21. 21.
    Pols, HAP, Felsenberg, D, Hanley, DA, Stych, B,  et al. 1999Multinational, placebo-controlled, randomized trial of the effects of alendronate on bone density and fracture risk in postmenopausal women with low bone mass: results of the FOSIT study.Osteoporos Int9461468, for the Fosamax International Trial Study GroupCrossRefPubMedGoogle Scholar
  22. 22.
    Neer, RM, Arnaud, CD, Zanchetta, JR,  et al. 2001Effect of parathyroid hormone (1–34) on fractures and bone mineral density in postmenopausal women with osteoporosis.N Engl J Med34414341441PubMedGoogle Scholar
  23. 23.
    Ettinger, B, Black, DM, Mitlak, BH,  et al. 1999Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial.JAMA282637645, for the Multiple Outcomes of Raloxifene Evaluation (MORE) InvestigatorsPubMedGoogle Scholar
  24. 24.
    Delmas, PD 2002Different effects of antiresorptive therapies on vertebral and nonvertebral fractures in postmenopausal osteoporosis.Bone301417CrossRefPubMedGoogle Scholar
  25. 25.
    Black, DM, Arden, NK, Palermo, L, Pearson, J, Cummings, SR 1999Prevalent vertebral deformities predict hip fractures and new vertebral deformities but not wrist fractures.J Bone Miner Res14821828, for the Study of Osteoporotic Fractures Research GroupPubMedGoogle Scholar
  26. 26.
    Ross, PD, Davis, JW, Epstein, RS, Wasnich, RD 1991Pre-existing fractures and bone mass predict vertebral fracture incidence in women.Ann Intern Med114919923PubMedGoogle Scholar
  27. 27.
    Lauritzen, JB, Lund, B 1993Risk of hip fracture after osteoporosis fractures: 451 women with fracture of lumbar spine, olecranon, knee or ankle.Acta Orthop Scand64297300PubMedGoogle Scholar
  28. 28.
    Fujiwara, S, Kasagi, F, Yamada, M, Kodama, K 1997Risk factors for hip fracture in a Japanese cohort.J Bone Miner Res129981004Google Scholar
  29. 29.
    Kotowicz, MA, Melton III, LJ, Cooper, C, Atkinson, EJ, O’Fallon, WM, Riggs, BL 1994Risk of hip fracture in women with vertebral fracture.J Bone Miner Res9599605PubMedGoogle Scholar
  30. 30.
    Cummings, SR, Kelsey, JL, Nevitt, MC, O’Dowd, KJ 1985Epidemiology of osteoporosis and osteoporotic fractures.Epidemiol Rev7178208PubMedGoogle Scholar
  31. 31.
    Melton III, LJ, Cummings, SR 1987Heterogeneity of age-related fractures: implications for epidemiology.Bone Miner2321331Google Scholar
  32. 32.
    Jones, G, Nguyen, T, Sambrook, PN, Kelly, PJ, Gilbert, C, Eisman, JA 1994Symptomatic fracture incidence in elderly men and women: the Dubbo Osteoporosis Epidemiology Study (DOES).Osteoporos Int4277282PubMedGoogle Scholar
  33. 33.
    Donaldson, LJ, Cook, A, Thomson, RG 1990Incidence of fractures in a geographically defined population.J Epidemiol Community Health44241245PubMedGoogle Scholar
  34. 34.
    Johansen, A, Evans, RJ, Stone, MD, Richmond, PW, Lo, SV, Woodhouse, KW 1997Fracture incidence in England and Wales: a study based on the population of Cardiff.Injury28655660CrossRefPubMedGoogle Scholar
  35. 35.
    Ismail, AA, Cockerill, W, Cooper, C,  et al. 2001Prevalent vertebral deformity predicts incident hip though not distal forearm fracture: results from the European Prospective Osteoporosis Study.Osteoporos Int128590CrossRefPubMedGoogle Scholar
  36. 36.
    Watts, N, Bockman, R, Smith, C, Li, Z, Eastell, R, Pack, S, Lindsay, R 2000BMD change explains only a fraction of the observed fracture risk reduction in risedronate-treated patients (abstract).Osteoporosis Int11S203CrossRefGoogle Scholar
  37. 37.
    Li, Z, Meredith, MP, Hoseyni, MS 2001A method to assess the proportion of treatment effect explained by a surrogate endpoint.Stat Med2031753188CrossRefPubMedGoogle Scholar
  38. 38.
    Cummings, SR, Black, DM, Pearson, JB, Karpf, DB, Harris, F, Genant, HK, LaCroix, AZ 1999How much of the reduction in risk of vertebral fractures by alendronate is explained by increased spine BMD? (abstract).J Bone Miner Res14SI59Google Scholar
  39. 39.
    Sarkar, S, Mitlak, BH, Wong, M, Stock, JL, Black, DM, Harper, KD 2002Relationships between bone mineral density and incident vertebral fracture risk with raloxifene therapy.J Bone Miner Res17110PubMedGoogle Scholar
  40. 40.
    van Staa, TP, Dennison, EM, Leufkens, HG, Cooper, C 2001Epidemiology of fractures in England and Wales.Bone29517522CrossRefPubMedGoogle Scholar
  41. 41.
    Cummings, SR, Nevitt, MC, Browner, WS, Stone, K, Fox, KM, Ensrud, KE, Cauley, J, Black, D, Vogt, TM 1995Risk factors for hip fracture in white women.N Engl J Med332767773, the Study of Osteoporotic Fractures Research GroupPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • J. T. Harrington
    • 1
  • L. -G. Ste-Marie
    • 2
  • M. L. Brandi
    • 3
  • R. Civitelli
    • 4
  • P. Fardellone
    • 5
  • A. Grauer
    • 6
  • I. Barton
    • 7
  • S. Boonen
    • 8
  1. 1.University of Wisconsin Medical School, Madison, WIUSA
  2. 2.Centre de Recherche du CHUMHôspital Saint-Luc Montreal, QuebecCanada
  3. 3.University of Florence Medical School, FlorenceItaly
  4. 4.Division of Bone & Mineral DiseasesWashington University School of Medicine, St. Louis, MOUSA
  5. 5.Hospital Nord, AmiensFrance
  6. 6.Procter & Gamble PharmaceuticalsMason, Ohio, USA
  7. 7.Procter & Gamble Pharmaceuticals, EghamUnited Kingdom
  8. 8.Leuven University Center for Metabolic Bone Diseases and Division of Geriatric Medicine, LeuvenBelgium

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