Skip to main content
SpringerLink
Log in

The potential impact of new effervescent alendronate formulation on compliance and persistence in osteoporosis treatment

  • Review
  • Published:
Aging Clinical and Experimental Research Aims and scope Submit manuscript

Abstract

Osteoporotic fractures are a public health problem and their incidence and subsequent economic and social costs are expected to rise in the next future. Different drugs have been developed to reduce osteoporosis and the risk of osteoporotic fractures, and among them, antiresorptive agents, and in particular oral alendronate, are the most widely utilized. However, one of the most common problems with antiresorptive drugs is poor adherence to treatment, which is associated with a high fracture incidence and with an increase in hospitalization costs. One of the main reasons of poor adherence to these treatments is the occurrence of adverse events, mainly at gastrointestinal (GI) level, including dyspepsia, dysphagia, and esophageal ulcers. In light of these considerations the aim of this paper is to perform a literature review to show the pathophysiologic bases of GI alendronate-induced adverse events and how new bisphosphonate formulations like effervescent alendronate can improve compliance and persistence to treatment and decrease the fracture rate incidence in osteoporotic patients.

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

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Cauley JA, Thompson DE, Ensrud KC, Scott JC, Black D (2000) Risk of mortality following clinical fractures. Osteoporosis Int 11:556–561

    Article  CAS  Google Scholar 

  2. Johnell O, Kanis JA, Odén A, Sernbo I, Redlund-Johnell I, Petterson C, De Laet C, Jönsson B (2004) Mortality after osteoporotic fractures. Osteoporosis Int 15(1):38–42

    Article  CAS  Google Scholar 

  3. Johnell O, Kanis JA (2006) An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporosis Int 17(12):1726–1733

    Article  CAS  Google Scholar 

  4. Kanis JA, Reginster JY, Kaufman JM, Ringe JD, Adachi JD, Hiligsmann M, Rizzoli R, Cooper C (2012) A reappraisal of generic bisphosphonates in osteoporosis. Osteoporos Int 23:213–221

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Kanis JA, McCloskey EV, Johansson H, Strom O, Borgstrom F, Oden A (2009) How to decide who to treat. Best Pract Res Clin Rheumatol 23(6):711–726

    Article  CAS  PubMed  Google Scholar 

  6. Marcus R, Wong M, Heath H 3rd, Stock JL (2002) Antiresorptive treatment of postmenopausal osteoporosis: comparison of study designs and outcomes in large clinical trials with fracture as an endpoint. Endocrine Rev 23:16–37

    Article  CAS  Google Scholar 

  7. Siris ES, Selby PL, Saag KG, Borgström F, Herings RM, Silverman SL (2009) Impact of osteoporosis treatment adherence on fracture rates in North America and Europe. Am J Med 122(2 Suppl):S3–S13

    Article  PubMed  Google Scholar 

  8. Cranney A, Guyatt G, Griffith L, Wells G, Tugwell P, Rosen C; Osteoporosis Methodology Group and The Osteoporosis Research Advisory Group (2002) Meta-analyses of therapies for postmenopausal osteoporosis. IX: summary of meta-analyses of therapies for postmenopausal osteoporosis. Endocr Rev 23:570–578

    Article  Google Scholar 

  9. Siris ES, Harris ST, Rosen CJ, Barr CE, Arvesen JN, Abbott TA, Silverman S (2006) Adherence to bisphosphonate therapy and fracture rates in osteoporotic women: relationship to vertebral and nonvertebral fractures from 2 US claims databases. Mayo Clin Proc 81:1013–1022

    Article  PubMed  Google Scholar 

  10. Kayser J, Ettinger B, Pressman A (2001) Postmenopausal hormonal support: discontinuation of raloxifene versus estrogen. Menopause 8:328–332

    Article  CAS  PubMed  Google Scholar 

  11. Gallagher AM, Rietbrock S, Olson M, van Staa TP (2008) Fracture outcomes related to persistence and compliance with oral bisphosphonates. J Bone Miner Res 23:1569–1575

    Article  PubMed  Google Scholar 

  12. Yood RA, Emani S, Reed Jl, Reed JI, Lewis BE, Charpentier M, Lydick E (2003) Compliance with pharmacologic therapy for osteoporosis. Osteoporos Int 14:965–968

    Article  CAS  PubMed  Google Scholar 

  13. McCombs JS, Thiebaud P, McLaughlin-Miley C, Shi J (2004) Compliance with drug therapies for the treatment and prevention of osteoporosis. Maturitas 15;48(3):271-87

  14. Adachi JD, Adami S, Miller PD, Olszynski WP, Kendler DL, Silverman SL, Licata AA, Li Z, Gomez-Panzani E (2001) Tolerability of risedronate in post-menopausal women intolerant of alendronate. Aging 13(5):347–354

    CAS  PubMed  Google Scholar 

  15. http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2012/202344s000ltr.pdf

  16. Briesacher BA, Andrade SE, Fouayzi H, Chan KA (2008) Comparison of drug adherence rates among patients with seven different medical conditions. Pharmacotherapy. 28:437–443

    Article  PubMed Central  PubMed  Google Scholar 

  17. Rabenda V, Hiligsmann M, Reginster JY (2009) Poor adherence to oral bisphosphonate treatment and its consequences: a review of the evidence. Expert Opin Pharmacother 10(14):2303–2315

    Article  CAS  PubMed  Google Scholar 

  18. De Groen PC, Lubbe DF, Hirsch LJ, Daifotis A, Stephenson W, Freedholm D, Pryor-Tillotson S, Seleznick MJ, Pinkas H, Wang KK (1996) Esophagitis associated with the use of alendronate. N Engl J Med 3;335(14):1016–1021

    Article  Google Scholar 

  19. Peter CP, Handt LK, Smith SM (1998) Esophageal irritation due to alendronate sodium tablets possible mechanisms. Dig Dis Sci 43(9):1998–2002

    Article  CAS  PubMed  Google Scholar 

  20. Varenna M, Bertoldo F, Di Monaco M et al (2013) Il profilo di sicurezza per i farmaci per il trattamento dell’osteoporosi. Revisione critica della letteratura. Reumatismo 65(4):143–166

    CAS  Google Scholar 

  21. Perkinks AC, Blackshaw E, Hay PD et al (2008) Esophageal transit and in vivo disintegration of branded risedronate sodium tablets and two generic formulations of alendronic acid tablets: a single-center single-blind, six-period crossover study in healthy female subjects. Clin Ther 30(5):834–844

    Article  Google Scholar 

  22. Abraham SC, Cruz-Correa M, Lee L, Yardley JH, Wu TT (1999) Alendronate-associated esophageal injury: pathologic and endoscopic features. Mod Pathol 12:1152–1157

    CAS  PubMed  Google Scholar 

  23. Argenzio RA, Eisemann J (1996) Mechanisms of acid injury in porcine gastroe-sophageal mucosa. Am J Vet Res 57:564–573

    CAS  PubMed  Google Scholar 

  24. Barbosa CD, Balp MM, Kulich K et al (2012) A literature review to explore the link between treatment satisfaction and adherence, compliance, and persistence. Patient Prefer Adherence 6:39–48

    Article  PubMed Central  PubMed  Google Scholar 

  25. Fleisch H, Russell RGG, Bisaz S, Casey PA, Mtihlbaner RC (1968) The influence of pyrophosphate analogues (diphosphonates) on the precipitation and dissolution of calcium phosphate in vitro and in vivo. Calcif Tissue Res 2(suppl):10–10A

    Article  Google Scholar 

  26. Fleisch H, Russell RGG (1970) Pyrophosphate and polyphosphate. In: Encyclopaedia (Int.) of pharmacology and therapeutics Section S l: Pharmacology of the endocrine system and related drugs, Pergamon, New York, 61–100

  27. Fleisch H, Russell RGG, Straumann F (1966) Effect of pyrophosphonate on bydroxyapatite and its implications in calcium homeostasis. Nature 212:901–903

    Article  CAS  PubMed  Google Scholar 

  28. Lin JH (1996) Bisphosphonates: a review of their pharmacokinetic properties. Bone 18(2):75–85

    Article  CAS  PubMed  Google Scholar 

  29. Tosteson AN, Grove, Hammond CS, Moncur MM, Ray GT, Hebert GM, Pressman AR, Ettinger B (2003) Early discontinuation of treatment for osteoporosis. Am J Med 15(115(3)):209–216

    Google Scholar 

  30. Gertz BJ, Holland SD, Kline WF, Matuszewski BK, Porras AG (1993) Clinical pharmacology of alendronate sodium. Osteopor Int 3(suppl. 3):513–516

    Google Scholar 

  31. Spivacow FR, Zanchetta JR, Kerzberg EM, Frigeri A, Fiasche R (1996) Tolerability of oral pamidronate in elderly patients with osteoporosis and other bone diseases. Curr Ther Res 57:123–130

    Article  CAS  Google Scholar 

  32. Twist IM, Pas O, Ramp-Koopmanschap W, Den Hartigh J, Vermeij P (1999) The effects of nitrogen-containing bisphosphonates on human epithelial (Caco-2) cells, an in vitro model for intestinal epithelium. J Bone Miner Res 14:784–791

    Article  Google Scholar 

  33. Saunders RL Jr (1997) Appearance of a gastric ulcer during diphosphonate therapy in a woman with CRST syndrome. South Med J 70(11):1327–1329

    Google Scholar 

  34. Lufkin EG, Argueta R, Whitaker MD, Cameron AL, Wong V, Egan KS, O’Fallon WM, Riggs BL (1994) Pamidronate: an unrecognized problem in gastrointestinal tolerability. Osteoporosis Int 4(6):320–322

    Article  CAS  Google Scholar 

  35. Reginster JYL (1992) Oral tiludronate: pharmacological properties and potential usefulness in Paget’s disease of bone and osteoporosis. Bone 13(5):351–354

    Article  CAS  PubMed  Google Scholar 

  36. Chesnut CH 3rd, McClung MR, Ensrud KE, Bell NH, Genant HK, Harris ST, Singer FR, Stock JL, Yood RA, Delmas PD (1995) Alendronate treatment of the postmenopausal osteoporotic woman: effect of multiple dosages on bone mass and bone remodeling. Am J Med 99:144–152

    Article  CAS  PubMed  Google Scholar 

  37. Abid S, Mumtaz K, Jafri W, Hamid S, Abbas Z, Shah HA, Khan AH (2005) Pill-induced esophageal injury: endoscopic features and clinical outcomes. Endoscopy 37(8):740–744

    Article  CAS  PubMed  Google Scholar 

  38. Olovson GS, Bjorkman JA, Ek L, Hauu N (1983) The ulcerogenic effect on the esophagus of three b-adrenoceptor antagonists, investigated in a new porcine esophagus test model. Acta Pharmacol Toxicol (Copenh). 53(5):385–391

    Article  CAS  PubMed  Google Scholar 

  39. Bozymski EM, Isaacs KL (1995) Medications reported to cause esophageal damage. In: Yamada T (ed) Textbook of gastroenterology, vol 1, 2nd edn. JB Lippincott, Philadelphia, pp 1283–1301

    Google Scholar 

  40. Castell DO (1996) “pill esophagitis”—the case of alendronate. N Engl J Med 3(335(14)):1058–1059

    Article  Google Scholar 

  41. Blank MA, Gibson GW, Myers WR, Dierckman TA, Phipps RJ, Smith PN (2000) Gastric damage in the rat with nitrogen-containing bisphosphonates depends on pH. Aliment Pharmacol Ther 14(9):1215–1223

    Article  CAS  PubMed  Google Scholar 

  42. Aihara E, Hayashi S, Amagase K, Kato S, Takeuchi K (2007) Prophylactic effect of rebamipide against the irritative and healing impairment actions of alendronate in rat stomachs. Inflammopharmacology 15(5):196–202

    Article  CAS  PubMed  Google Scholar 

  43. Sener G, Kapucu C, Cetinel S, Cikler E, Ayanoğlu-Dülger G (2005) Gastroprotective effect of leukotriene receptor blocker montelukast in alendronat-induced lesions of the rat gastric mucosa. Prostaglandins Leukot Essent Fatty Acids 72(1):1–11

    Article  CAS  PubMed  Google Scholar 

  44. Sener G, Sehirli O, Cetinel S, Midillioğlu S, Gedik N, Ayanoğlu-Dülger G (2005) Protective effect of taurine against alendronate-induced gastric damage in rats. Fundam Clin Pharmacol 19(1):93–100

    Article  CAS  PubMed  Google Scholar 

  45. Sener G, Goren FO, Ulusoy NB, Ersoy Y, Arbak S, Dülger GA (2005) Protective effect of melatonin and omeprazole against alendronate-induced gastric damage. Dig Dis Sci 50(8):1506–1512

    Article  CAS  PubMed  Google Scholar 

  46. Ohashi Y, Aihara E, Takasuka H, Takahashi K, Takeuchi K (2009) Antral ulcers induced by alendronate, a nitrogen-containing bisphophonate, in rat stomachs-prophylactic effect of rebamipide. J Physiol Pharmacol 60(3):85–93

    CAS  PubMed  Google Scholar 

  47. Takeuchi K, Kato S, Amagase K (2011) Gastric ulcerogenic and healing impairment actions of alendronate, a nitrogen-containing bisphosphonate-prophylactic effects of rebamipide. Curr Pharm Des 17(16):1602–1611

    Article  CAS  PubMed  Google Scholar 

  48. Pytlik M, Cegieła U, Folwarczna J, Nowińska B (2012) Proton pump (H+/K+-ATPase) inhibitors weaken the protective effect of alendronate on bone mechanical properties in estrogen-deficient rats. Pharmacol Rep 64(3):625–634

    Article  CAS  PubMed  Google Scholar 

  49. Katsumi H, Takashima M, Sano J, Nishiyama K, Kitamura N, Sakane T, Hibi T, Yamamoto A (2011) Development of polyethylene glycol-conjugated alendronate, a novel nitrogen-containing bisphosphonate derivative: evaluation of absorption, safety, and effects after intrapulmonary administration in rats. J Pharm Sci 100(9):3783–3792

    Article  CAS  PubMed  Google Scholar 

  50. Gomez Acotto C, Antonelli C, Flynn D, McDaid D, Roldan EJ (2012) Upper gastrointestinal tract transit times of tablet and drinkable solution formulations of alendronate: a bioequivalence and a quantitative, randomized study using video deglutition. Calcif Tissue Int 91(5):325–334

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  51. Hodges LA, Connolly SM, Winter J, Schmidt T, Stevens HNE, Hayward M, Wilson CG (2012) Modulation of gastric pH by a buffered soluble effervescent formulation: a possible means of improving gastric tolerability of alendronate. Int J Pharm 432:57–62

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

Marco Invernizzi, Stefano Carda and Carlo Cisari declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Physical and Rehabilitative Medicine, Department of Health Sciences, University of Eastern Piedmont “A. Avogadro”, Viale Piazza D’Armi 1, 28100, Novara, Italy

    Marco Invernizzi & C. Cisari

  2. Società Italiana per lo Studio delle Disabilità Muscolo-Scheletriche-SISDIM, Novara, Italy

    Marco Invernizzi & C. Cisari

  3. Department of Neurorehabilitation and Neuropsychology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland

    S. Carda

Authors
  1. Marco Invernizzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Cisari
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Carda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marco Invernizzi.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Invernizzi, M., Cisari, C. & Carda, S. The potential impact of new effervescent alendronate formulation on compliance and persistence in osteoporosis treatment. Aging Clin Exp Res 27, 107–113 (2015). https://doi.org/10.1007/s40520-014-0256-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40520-014-0256-5

Keywords

Search

Navigation