Skip to main content
SpringerLink
Log in

Statistical Analysis for Comparing Antifracture Efficacy among Antiresorptive Agents

Alendronate versus Alfacalcidol and Calcitonin

  • Clinical Use
  • Published:
Clinical Drug Investigation Aims and scope Submit manuscript

Abstract

Objective: To develop a method that estimates and compares the antifracture efficacy [relative risk reduction (RRR) and number needed to treat (NNT)] of various antiresorptive agents when fracture trials are not available.

Design, Setting and Patients: Statistical analysis using efficacy data from clinical trials of postmenopausal women with osteoporosis.

Interventions: Oral alendronate 5mg, oral alfacalcidol lμg, or intranasal calcitonin 200IU daily.

Methods: We used the effects on bone mineral density (BMD) in head-to-head trials together with the relationship between BMD changes and fracture risk reductions reported in published meta-analyses of antifracture trials to predict and compare RRR and NNT.

Results: The predicted RRR was similar to the published values in large clinical trials, thus validating the method. With an incidence of 12% over 3 years in untreated women with pre-existing vertebral fractures (based on a large epidemiological study), the predicted NNT to prevent a new vertebral fracture was 17 for alendronate and 29 for alfacalcidol; similar results were observed for alendronate versus calcitonin. For nonvertebral fractures, the NNT was three to four times lower for alendronate, compared with alfacalcidol and calcitonin.

Conclusions: There is currently insufficient evidence of antifracture efficacy from randomised trials to recommend the use of alfacalcidol or calcitonin for treating osteoporosis. Furthermore, our analyses indicate that alendronate is substantially more effective for reducing vertebral and nonvertebral fracture risk than alfacalcidol or calcitonin.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Table II
Table III
Table IV

Similar content being viewed by others

References

  1. Kanis JA, Delmas P, Burckhardt P, et al. Guidelines for diagnosis and management of osteoporosis. Osteoporos Int 1997; 7: 390–406

    Article  PubMed  CAS  Google Scholar 

  2. Johnell O. The socioeconomic burden of fractures: today and in the 21st century. Am J Med 1997; 103: 20S–6S.

    Article  PubMed  CAS  Google Scholar 

  3. Garnero P, Sornay-Rendu E, Chapuy M-C, et al. Increased bone turnover in late postmenopausal women is a major determinant of osteoporosis. J Bone Miner Res 1996; 11: 337–49

    Article  PubMed  CAS  Google Scholar 

  4. Guyatt GH. Evidence-based management of patients with osteoporosis. J Clin Densitom 1998; 1: 395–402

    Article  PubMed  CAS  Google Scholar 

  5. Cummings SR, Chapurlat RD. What PROOF proves about calcitonin and clinical trials. Am J Med 2000; 109: 330–1

    Article  PubMed  CAS  Google Scholar 

  6. Wasnich RD, Miller PD. Antifracture efficacy of antiresorptive agents are related to changes in bone density. J Clin Endocrinol Metab 2000; 85: 231–6

    Article  PubMed  CAS  Google Scholar 

  7. Hochberg MC. Preventing fractures in postmenopausal women with osteoporosis: a review of recent controlled trials of antiresorptive agents. Drugs & Aging 2000; 17(4): 317–30

    Article  CAS  Google Scholar 

  8. Black DM, Reiss TF, Nevitt MC, et al. Design of the Fracture Intervention Trial. Osteoporos Int 1993; 3: S29–39

    Article  PubMed  Google Scholar 

  9. Shiraki M, Kushida K, Fukunaga M, et al. A double-masked multicenter comparative study between alendronate and alfacalcidol in Japanese patients with osteoporosis. Osteoporos Int 1999; 10: 183–92

    Article  PubMed  CAS  Google Scholar 

  10. Downs RW Jr, Bell NH, Ettinger MP, et al. Comparison of alendronate and intranasal calcitonin for treatment of osteoporosis in postmenopausal women. J Clin Endocrinol Metab 2000; 85: 1783–8

    Article  PubMed  CAS  Google Scholar 

  11. Adami S, Passeri M, Ortolani S, et al. Effects of oral alendronate and intranasal salmon calcitonin on bone mass and biochemical markers of bone turnover in postmenopausal women with osteoporosis. Bone 1995; 17(4): 383–90

    Article  PubMed  CAS  Google Scholar 

  12. Miller PD, Hochberg MC, Greenspan S, et al. Increases in bone mineral density explain the reduction in incidence of non-vertebral fractures seen with antiresorptive therapy in women with postmenopausal osteoporosis. J Clin Densitom. In press

  13. Black DM, Pearson J, Harris F, et al. Predicting the effect of antiresorptive treatments on risk of vertebral fractures: a meta-analysis [abstract]. J Bone Miner Res 1999; 14Suppl. 1: S137

    Google Scholar 

  14. Laupacis A, Sackett DL, Roberts RS. An assessment of clinically useful measures of the consequences of treatment. N Engl J Med 1988; 318: 1728–33

    Article  PubMed  CAS  Google Scholar 

  15. Chatellier G, Zapletal E, Lemaitre D, et al. The number needed to treat: a clinically useful nomogram in its proper context. BMJ 1996; 312: 426–9

    Article  PubMed  CAS  Google Scholar 

  16. Cook RJ, Sackett DL. The number needed to treat: a clinically useful measure of treatment effect. BMJ 1995; 310: 452–4

    Article  PubMed  CAS  Google Scholar 

  17. Liberman UA, Weiss SR, Broil J, et al. Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. N Engl J Med 1995; 333: 1437–43

    Article  PubMed  CAS  Google Scholar 

  18. Black DM, Cummings SR, Karpf DB, et al. Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Lancet 1996; 348: 1535–41

    Article  PubMed  CAS  Google Scholar 

  19. Black DM, Arden NK, Palermo L, et al. Prevalent vertebral deformities predict hip fractures and new vertebral deformities but not wrist fractures. J Bone Miner Res 1999; 14: 821–8

    Article  PubMed  CAS  Google Scholar 

  20. Cummings SR, Black DM, Thompson DE, et al. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. JAMA 1998; 280: 2077–82

    Article  PubMed  CAS  Google Scholar 

  21. Black DM, Thompson DE, Bauer D, et al. Fracture risk reduction with alendronate in women with osteoporosis: The Fracture Intervention Trial. J Clin Endocrinol Metab 2000; 85(11): 4118–24

    Article  PubMed  CAS  Google Scholar 

  22. Meunier PJ. Evidence-based medicine and osteoporosis: a comparison of fracture risk reduction data from osteoporosis randomised clinical trials. Int J Clin Pract 1999; 53: 122–9

    PubMed  CAS  Google Scholar 

  23. Orimo H, Shiraki M, Hayashi Y, et al. Effects of 1 alpha-hydroxyvitamin D3 on lumbar bone mineral density and vertebral fractures in patients with postmenopausal osteoporosis. Calcif Tissue Int 1994; 54: 370–6

    Article  PubMed  CAS  Google Scholar 

  24. Windeier J, Lange S. Events per person year —a dubious concept. BMJ 1995; 310: 454–6

    Article  Google Scholar 

  25. Shiraki M, Kushida K, Yamazaki K, et al. Effects of 2 years’ treatment of osteoporosis with 1 alpha-hydroxy vitamin D3 on bone mineral density and incidence of fracture: a placebo-controlled, double-blind prospective study. Endocr J 1996; 43: 211–20

    Article  CAS  Google Scholar 

  26. Chesnut CH, Silverman S, Andriano K, et al. Arandomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the Prevent Recurrence of Osteoporotic Fractures study. Am J Med 2000; 109: 267–76

    Article  PubMed  CAS  Google Scholar 

  27. Tonino RP, Meunier PJ, Emkey R, et al. Skeletal benefits of alendronate: 7-year treatment of postmenopausal osteoporotic women. J Clin Endocrinol Metab 2000; 85(9): 3109–15

    Article  PubMed  CAS  Google Scholar 

  28. Lips P, Graafmans WC, Ooms ME, et al. Vitamin D supplementation and fracture incidence in elderly persons. A randomized, placebo-controlled clinical trial. Ann Intern Med 1996; 124: 400–6

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank Dr Philip Ross, Merck & Co., Inc., for assistance with the analysis and preparation of the manuscript.

Author information

Authors and Affiliations

  1. Department of Public Health, Nagasaki University School of Medicine, 1-12-4 Sakamoto, Nagasaki, Japan, 852-8523

    Kiyoshi Aoyagi

  2. Research Institute and Practice for Involutional Diseases, Nagano, Japan

    Masataka Shiraki

  3. Department of Radiology, Nagasaki University School of Medicine, Nagasaki, Japan

    Masako Ito

  4. Department of Orthopedic Surgery, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan

    Toshitaka Nakamura

Authors
  1. Kiyoshi Aoyagi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masataka Shiraki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Masako Ito
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Toshitaka Nakamura
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kiyoshi Aoyagi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Aoyagi, K., Shiraki, M., Ito, M. et al. Statistical Analysis for Comparing Antifracture Efficacy among Antiresorptive Agents. Clin. Drug Investig. 21, 415–422 (2001). https://doi.org/10.2165/00044011-200121060-00004

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00044011-200121060-00004

Keywords

Search

Navigation