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Drug-induced osteoporosis/osteomalacia: analysis in the French and Spanish pharmacovigilance databases

  • Pharmacoepidemiology and Prescription
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Abstract

Introduction

Osteomalacia and osteoporosis are two metabolic bone disorders that increase the risk of fracture due to several causes. In terms of drugs, apart from corticosteroids, which are known to induce bone disorders, several other drugs used in chronic disease management have also been linked with an increased risk of osteoporosis and osteomalacia.

Purpose

The aim of this study was to describe spontaneous reports of drug-induced osteoporosis and osteomalacia in the French (FPVDB) and Spanish (SPVDB) pharmacovigilance databases.

Methods

Data were provided by the FPVDB and SPVDB. All reports of osteoporosis and osteomalacia recorded from 1985 up to 31 December 2015 inclusive were selected. Taking the time to onset of bone loss into account, all cases occurring in less than 1 month were excluded.

Results

A total of 369 reports (44 cases of osteomalacia, 325 cases of osteoporosis) were registered in the FPVDB and 64 (22 cases of osteomalacia, 42 cases of osteoporosis) in the SPVDB. In France, the top 5 drugs involved in the onset of osteoporosis were corticosteroids accounting for approximately half of the reports (n = 170) followed by systemic antiviral (n = 87), antacid (n = 29), antiepileptic (n = 27) and antithrombotic (n = 24) drugs. The 2 main classes of drugs implicated in osteomalacia were systemic antiretroviral drugs for half of the reports (n = 21) and antiepileptic drugs (n = 15). In Spain, corticosteroids were involved in 35.7% of reported cases of osteoporosis (n = 15) followed by systemic antiviral drugs (n = 12). There was no spontaneous report for antacid drugs. For osteomalacia, the 2 main drug classes were systemic antiretroviral drugs (n = 18, 81.8%) followed by antiepileptics (n = 2, 9.0%). In both countries, concomitant administration of systemic corticosteroids with other suspected drugs did not significantly modify the time to onset of drug-induced osteoporosis.

Conclusion

Despite some differences between the French and Spanish PVDBs, our data consistently show that bone loss is not only restricted to glucocorticoids but also involves antivirals, antiepileptic drugs, antacid drugs or antidepressants. Further analysis might prove useful in exploring the characteristics of drug-induced bone loss on a larger scale.

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References

  1. Gifre L, Peris P, Monegal A, Martinez de Osaba MJ, Alvarez L, Guanabens N (2011) Osteomalacia revisited. A report on 28 cases. Clin Rheumatol 30:639–645

    Article  Google Scholar 

  2. Cooper C, Atkinson EJ, Jacobsen SJ, O’Fallon WM, Melton LJ (1993) Population-based study of survival after osteoporotic fractures. Am J Epidemiol 137:1001–1005

    Article  CAS  Google Scholar 

  3. Riggs BL, Melton LJ (1995) The worldwide problem of osteoporosis: insights afforded by epidemiology. Bone 17:505S–511S

    Article  CAS  Google Scholar 

  4. Kok C, Sambrook PN (2009) Secondary osteoporosis in patients with an osteoporotic fracture. Best Pract Res Clin. Rheumatol 23:769–779

    Article  CAS  Google Scholar 

  5. Bannwarth B (2007) Drug-induced musculoskeletal disorders. Drug Saf 30:27–46

    Article  CAS  Google Scholar 

  6. Davidge Pitts CJ, Kearns AE (2011) Update on medications with adverse skeletal effects. Mayo Clin Proc Mayo Clin 86:338–343

    Article  Google Scholar 

  7. Mazziotti G, Canalis E, Giustina A (2010) Drug-induced osteoporosis: mechanisms and clinical implications. Am J Med 123:877–884

    Article  CAS  Google Scholar 

  8. Keshav P, Gona A, Humphrey MB (2014) Medication-induced osteoporosis: screening and treatment strategies. Ther Adv Musculoskel Dis 6:185–202

    Article  Google Scholar 

  9. Vial T (2016) French pharmacovigilance. Missions, organization and perspectives. Therapie 71:143–150

    Article  Google Scholar 

  10. Manso G (2010) La situación actual del Sistema Español de Farmacovigilancia de Medicamentos de uso Humano. En: Manso G, Hidalgo A, Carvajal A, de Abajo FJ, coordinadores. Los primeros 25 años del Sistema Español de Farmacovigilancia de Medicamentos de Uso Humano. Oviedo: Universidad de Oviedo; P.19–23. Accessed 04/04/2019. Available at: https://www.unioviedo.es/gaife/documentos/libro25aniversario/Capitulos/Capitulo_01.pdf

  11. Miremont-Salamé G, Théophile H, Haramburu F, Bégaud B (2016) Causality assessment in pharmacovigilance: the French method and its successive updates. Therapie 71:179–186

    Article  Google Scholar 

  12. Edwards IR, Aronson JK (2000) Adverse drug reactions: definitions, diagnosis, and management. Lancet 356:1255–1259

    Article  CAS  Google Scholar 

  13. Brown DEG, Wood L, Wood S (1999) The Medical Dictionary for Regulatory Activities (MedDRA). Drug Saf 20:109–117

    Article  CAS  Google Scholar 

  14. Woolf AD, Pfleger B (2003) Burden of major musculoskeletal conditions. Bull World Health Organ 81:646–656

    PubMed  PubMed Central  Google Scholar 

  15. Van Staa TP, Leufkens HGM, Abenhaim L, Zhang B, Cooper C (2005) Use of oral corticosteroids and risk of fractures. J Bone Miner Res 20:1486–1493

    Article  Google Scholar 

  16. Carvajal A, Macias D, Sáinz M, Ortega S, Martín Arias LH, Velasco A, Bagheri H, Lapeyre-Mestre M, Montastruc JL (2006) HMG CoA reductase inhibitors and impotence: two case series from the Spanish and French drug monitoring systems. Drug Saf 29:143–149

    Article  CAS  Google Scholar 

  17. Montastruc F, Scotto S, Vaz IR, Guerra LN, Escudero A, Sáinz M, Falomir T, Bagheri H, Herdeiro MT, Venegoni M, Montastruc JL, Carvajal A (2014) Hepatotoxicity related to agomelatine and other new antidepressants: a case/noncase approach with information from the Portuguese, French, Spanish, and Italian pharmacovigilance systems. J Clin Psychopharmacol 34:327–330

    Article  CAS  Google Scholar 

  18. Nguyen KD, Bagheri B, Bagheri H (2018) Drug-induced bone loss: a major safety concern in Europe. Expert Opin Drug Saf 17:1005–1014

    Article  CAS  Google Scholar 

  19. Haney EM, Warden SJ, Bliziotes MM (2010) Effects of selective serotonin reuptake inhibitors on bone health in adults: time for recommendations about screening, prevention and management. Bone 46:13–17

    Article  CAS  Google Scholar 

  20. Bliziotes MM, Eshleman A, Zhang X, Wiren K (2001) Neurotransmitter action in osteoblasts: expression of a functional system for serotonin receptor activation and reuptake. Bone 29:477–486

    Article  CAS  Google Scholar 

  21. Warden SJ, Robling AG, Sanders MS, Bliziotes MM, Turner CH (2005) Inhibition of the serotonin (5-hydroxytryptamine) transporter reduces bone accrual during growth. Endocrinology 146:685–693

    Article  CAS  Google Scholar 

  22. Bradaschia-Correa V, Josephson AM, Mehta D, Mizrahi M, Neibart SS, Liu C, Kennedy OD, Castillo AB, Egol KA, Leucht P (2017) The selective serotonin reuptake inhibitor fluoxetine directly inhibits osteoblast differentiation and mineralization during fracture healing in mice. J Bone Miner Res 32:821–833

    Article  CAS  Google Scholar 

  23. Yadav VK, Ryu JH, Suda N, Tanaka KF, Gingrich JA, Schütz G, Glorieux FH, Chiang CY, Zajac JD, Insogna KL, Mann JJ, Hen R, Ducy P, Karsenty G (2008) LRP5 controls bone formation by inhibiting serotonin synthesis in the duodenum. Cell 135:825–837

    Article  CAS  Google Scholar 

  24. Lavoie B, Roberts JA, Haag MM, Spohn SN, Margolis KG, Sharkey KA, Lian JB, Mawe GM (2019) Gut-derived serotonin contributes to bone deficits in colitis. Pharmacol Res 140:75–84

    Article  CAS  Google Scholar 

  25. Lavoie B, Lian JB, Mawe GM (2017) Regulation of bone metabolism by serotonin. Adv Exp Med Biol 1033:35–46

    Article  CAS  Google Scholar 

  26. Weaver J, Kawsky J, Corboy A (2019) Antipsychotic use and fracture risk: an evaluation of incidence at a Veterans Affairs Medical Center. Ment Health Clin 9:6–11

    Article  Google Scholar 

  27. Poly TN, Islam MM, Yang HC, Wu CC, Li YJ (2019) Proton pump inhibitors and risk of hip fracture: a meta-analysis of observational studies. Osteoporos Int 30:103–114

    Article  CAS  Google Scholar 

  28. Zhou B, Huang Y, Li H, Sun W, Liu J (2016) Proton-pump inhibitors and risk of fractures: an update meta-analysis. Osteoporos Int 27:339–347

    Article  CAS  Google Scholar 

  29. Liu J, Li X, Fan L, Yang J, Wang J, Sun J, Wang Z (2019) Proton pump inhibitors therapy and risk of bone diseases: an update meta-analysis. Life Sci 218:213–223

    Article  CAS  Google Scholar 

  30. Munson JC, Bynum JPW, Bell JE, McDonough C, Wang Q, Tosteson T, Tosteson ANA (2018) Impact of prescription drugs on second fragility fractures among US Medicare patients. Osteoporos Int 29:2771–2779

    Article  CAS  Google Scholar 

  31. Hussain S, Siddiqui AN, Habib A, Hussain MS, Najmi AK (2018) Proton pump inhibitors’ use and risk of hip fracture: a systematic review and meta-analysis. Rheumatol Int 38:1999–2014

    Article  Google Scholar 

  32. Ahmad AN, Ahmad SN, Ahmad N (2017) HIV infection and bone abnormalities. Open Orthop J 21:777–784

    Article  Google Scholar 

  33. Wei Z, He JW, Fu WZ, Zhang ZL (2016) Osteomalacia induced by long-term low-dose adefovir dipivoxil: clinical characteristics and genetic predictors. Bone. 93:97–103

    Article  CAS  Google Scholar 

  34. Lucey JM, Hsu P, Ziegler JB (2013) Tenofovir-related Fanconi’s syndrome and osteomalacia in a teenager with HIV. BMJ Case Rep pii 2013:bcr2013008674. https://doi.org/10.1136/bcr-2013-008674

    Article  Google Scholar 

  35. Mehsen-Cêtre N, Cazanave C (2017) Osteoarticular manifestations associated with HIV infection. Joint Bone spine 84:29–33

    Article  Google Scholar 

  36. Hamed SA (2016) Markers of bone turnover in patients with epilepsy and their relationship to management of bone diseases induced by antiepileptic drugs. Expert Rev Clin Pharmacol 9:267–286

    Article  CAS  Google Scholar 

  37. Hazell L, Shakir SA (2006) Under-reporting of adverse drug reactions: a systematic review. Drug Saf 29:385–396

    Article  Google Scholar 

Download references

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Authors and Affiliations

  1. Service de Pharmacologie Médicale et Clinique, Centre de Pharmacovigilance, de Pharmacoépidémiologie et d’Informations sur le Médicament, INSERM U1027, Faculté de Médecine, Centre Hospitalier Universitaire, Toulouse, France

    Quentin Dardonville, Vanessa Rousseau, Leila Chebane, Jean Louis Montastruc & Haleh Bagheri

  2. Departamento de Medicina, Área de Farmacología, Universidad de Oviedo, Oviedo, Spain

    Esther Salguiero

  3. Département de Pharmacologie Médicale et Toxicologie, Centre de Pharmacovigilance, Hospitalier Universitaire, 34295, Montpellier, France

    Jean Luc Faillie

  4. Centre Regional de Pharmacovigilance de Lille, UnivLille, INSERM, CHU Lille, Lille, France

    Sophie Gautier

  5. Centro de Estudios sobre la Seguridad de Medicamentos, School of Medicine, University of Valladolid, Valladolid, Spain

    Alfonso Carvajal

Authors
  1. Quentin Dardonville
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  2. Esther Salguiero
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  3. Vanessa Rousseau
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  4. Leila Chebane
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  5. Jean Luc Faillie
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  8. Alfonso Carvajal
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  9. Haleh Bagheri
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Correspondence to Haleh Bagheri.

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Dardonville, Q., Salguiero, E., Rousseau, V. et al. Drug-induced osteoporosis/osteomalacia: analysis in the French and Spanish pharmacovigilance databases. Eur J Clin Pharmacol 75, 1705–1711 (2019). https://doi.org/10.1007/s00228-019-02743-9

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  • DOI: https://doi.org/10.1007/s00228-019-02743-9

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