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Gastrointestinal and renal side effects of bisphosphonates: differentiating between no proof of difference and proof of no difference

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Abstract

Background

This study was aimed at comparing the safety of bisphosphonates in women with osteoporosis by application of equivalence testing.

Methods

Gastrointestinal and renal side effects were evaluated based on information published in randomized controlled trials.

Results

The data on gastrointestinal side effects (47 trials) indicated that alendronate, risedronate etidronate, and zolendronate have similar rates of the adverse effects; application of Bayesian network meta-analysis showed that equivalence was demonstrated according to margins around ±10 %. The data on renal safety were more sparse and suffered from the use of different outcome measures; hence, a single trial could be evaluated. This trial showed a similar effect of alendronate and risedronate on renal function at 12 months; equivalence was based on differences between the two agents in renal function with margins of less than ±10.4 ml/min.

Conclusion

Our study provided quantitative information to determine to what extent bisphosphonates can be considered equivalent in terms of gastrointestinal and renal side effects.

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References

  1. Mascha EJ (2010) Equivalence and noninferiority testing in anesthesiology research. Anesthesiology 113(4):779–781

    Article  PubMed  Google Scholar 

  2. Ahn S, Park SH, Lee KH (2013) How to demonstrate similarity by using noninferiority and equivalence statistical testing in radiology research. Radiology 267(2):328–338

    Article  PubMed  Google Scholar 

  3. Messori A, Fadda V, Gatto R, Maratea D, Trippoli S (2014) Differentiating between “no proof of difference” and “proof of no difference” for new oral anticoagulants. BMJ 348:g1955. doi:10.1136/bmj.g1955

    Article  PubMed  Google Scholar 

  4. Walker E, Nowacki AS (2011) Understanding equivalence and noninferiority testing. J Gen Intern Med 26(2):192–196

    Article  PubMed Central  PubMed  Google Scholar 

  5. Migliore A, Broccoli S, Massafra U, Cassol M, Frediani B (2013) Ranking antireabsorptive agents to prevent vertebral fractures in postmenopausal osteoporosis by mixed treatment comparison meta-analysis. Eur Rev Med Pharmacol Sci 17(5):658–667

    CAS  PubMed  Google Scholar 

  6. Tadrous M, Wong L, Mamdani MM, Juurlink DN, Krahn MD, Lévesque LE, Cadarette SM (2014) Comparative gastrointestinal safety of bisphosphonates in primary osteoporosis: a network meta-analysis. Osteoporos Int 25(4):1225–1235

    Article  CAS  PubMed  Google Scholar 

  7. Messori A, Fadda V, Maratea D, Trippoli S, Marinai C (2014) Anti-reabsorptive agents in women with osteoporosis: determining statistical equivalence according to evidence-based methods. J Endocrinol Invest 37(8):769–773

  8. Fadda V (2014) Gastrointestinal adverse events of bisphosphonates. PubMedCommons. http://www.ncbi.nlm.nih.gov/pubmed/24287510#cm24287510_5074. Accessed 2 Jul 2014

  9. Lumley T (2002) Network meta-analysis for indirect treatment comparisons. Stat Med 21(16):2313–2324

    Article  PubMed  Google Scholar 

  10. Hoaglin DC, Hawkins N, Jansen JP et al (2011) Conducting indirect-treatment-comparison and network-meta-analysis studies: report of the ISPOR task force on indirect treatment comparisons good research practices—part 2. Value Health 14:429–437

    Article  PubMed  Google Scholar 

  11. Sobieraj DM, Cappelleri JC, Baker WL, Phung OJ, White CM, Coleman CI (2013) Methods used to conduct and report Bayesian mixed treatment comparisons published in the medical literature: a systematic review. BMJ Open 3(7). doi: 10.1136/bmjopen-2013-003111

  12. Greco T, Landoni G, Biondi-Zoccai G, D’Ascenzo F, Zangrillo A (2013) A Bayesian network meta-analysis for binary outcome: how to do it. Stat Methods Med Res [Epub ahead of print]

  13. Messori A (2014) Bayesian models implemented under Winbugs: can they be considered the new standard for conducting a network meta-analysis? PubMed Commons. http://www.ncbi.nlm.nih.gov/pubmed/23970014#cm23970014_6256. Accessed 15 Sep 2014

  14. NICE Clinical Guidelines, No. 92 (2010) National clinical guideline centre—acute and chronic conditions (UK). London Royal College of Physicians (UK). http://www.ncbi.nlm.nih.gov/books/NBK116530/. Accessed 14 Aug 2014

  15. Bucher HC, Guyatt GH, Griffith LE, Walter SD (1997) The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J Clin Epidemiol 50(6):683–691

    Article  CAS  PubMed  Google Scholar 

  16. Jones PW, Beeh KM, Chapman KR, Decramer M, Mahler DA, Wedzicha JA (2014) Minimal clinically important differences in pharmacological trials. Am J Respir Crit Care Med 189(3):250–255

    Article  PubMed  Google Scholar 

  17. Norman G, Monteiro S, Salama S (2012) Sample size calculations: should the emperor’s clothes be off the peg or made to measure? BMJ 23(345):e5278. doi:10.1136/bmj.e5278

    Article  Google Scholar 

  18. Tanaka S, Kinjo Y, Kataoka Y, Yoshimura K, Teramukai S (2012) Statistical issues and recommendations for noninferiority trials in oncology: a systematic review. Clin Cancer Res 18(7):1837–1847

    Article  CAS  PubMed  Google Scholar 

  19. Yanik B, Bavbek N, Yanik T, Inegöl I, Kanbay M, Turgut FH, Uz E, Akçay A (2007) The effect of alendronate, risedronate, and raloxifene on renal functions, based on the Cockcroft and Gault method, in postmenopausal women. Ren Fail 29(4):471–476

    Article  CAS  PubMed  Google Scholar 

  20. Miller PD, Jamal SA, Evenepoel P, Eastell R, Boonen S (2013) Renal safety in patients treated with bisphosphonates for osteoporosis: a review. J Bone Miner Res 28(10):2049–2059. doi:10.1002/jbmr.2058

    Article  CAS  PubMed  Google Scholar 

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Conflict of interest

V. Fadda, D. Maratea, S. Trippoli and A. Messori declared they have no conflict of interest.

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Fadda, V., Maratea, D., Trippoli, S. et al. Gastrointestinal and renal side effects of bisphosphonates: differentiating between no proof of difference and proof of no difference. J Endocrinol Invest 38, 189–192 (2015). https://doi.org/10.1007/s40618-014-0211-5

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  • DOI: https://doi.org/10.1007/s40618-014-0211-5

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