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Medication Use Before and After Hip Fracture: A Population-Based Cohort and Case-Control Study

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Abstract

Background

Osteoporosis, together with age, is the main risk factor for hip fracture, the incidence of which has also been associated with an increased risk of falling or co-morbidities and related pharmacological treatments.

Objectives

The aim of this study was to investigate changes in concomitant pharmacological treatments prescribed before and after hip fracture in elderly patients compared with treatments prescribed to a matched cohort of subjects without hospitalisation for fractures.

Methods

Data relating to the study population were extracted from a large population-based administrative database of the Italian National Health Authorities. A retrospective analysis was conducted involving female patients (6,431) aged ≥65 years and hospitalised for a hip fracture. The control group comprised age-matched subjects (38,586) not hospitalised for fracture. Changes in drug prescriptions 1 year before and 1 year after hip fracture and differences versus controls were compared.

Results

Prior to the fracture, patients were taking more anti-Parkinson medications, antidepressants, medications for chronic obstructive pulmonary disease (COPD), bisphosphonates and calcium–vitamin D supplements, although the intake of the routinely monitored drug classes was significantly infrequent. Polypharmacy was less frequent in fractured women before fracture than in controls (22 vs. 25 %, respectively; P < 0.001), but it was more frequent (30 %, P < 0.001) post-fracture. The incidence of fracture was associated with a significant increase in the use of a number of drug classes: insulin, NSAIDs or analgesics, gastroprotectants, loop diuretics, β-blockers, antidepressants, antiparkinson drugs, antiepileptics and drugs for COPD.

Conclusion

Our study confirms a strong association between the use of some drugs (antidepressants, antiparkinson drugs, drugs for COPD) and the risk of hip fracture, but drug use is globally less common than in controls. Hip fracture is associated with a significant increase in drug use, suggesting a global deterioration of health conditions.

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References

  1. Hernlund E, Svedbom A, Ivergård M, et al. Osteoporosis in the European Union: medical management, epidemiology and economic burden. A report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Arch Osteoporos. 2013;8:136.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Rossini M, Piscitelli P, Fitto F, et al. Incidence and socioeconomic burden of hip fractures in Italy. Reumatismo. 2005;57:97–102.

    CAS  PubMed  Google Scholar 

  3. Piscitelli P, Iolascon G, Gimigliano F, et al. Incidence and costs of hip fractures compared to acute myocardial infarction in the Italian population: a 4-year survey. Osteoporos Int. 2007;18:211–9.

    Article  CAS  PubMed  Google Scholar 

  4. Stevens JA, Anne Rudd R. Declining hip fracture rates in the United States. Age Ageing. 2010;39:500–3.

    Article  PubMed  Google Scholar 

  5. Piscitelli P, Gimigliano F, Gatto S, et al. Hip fractures in Italy: 2000–2005 extension study. Osteoporos Int. 2010;21:1323–30.

    Article  CAS  PubMed  Google Scholar 

  6. Kanis JA, Oden A, McCloskey EV, et al. A systematic review of hip fracture incidence and probability of fracture worldwide. Osteoporos Int. 2012;23:2239–56.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Oden A, McCloskey EV, Johansson H, et al. Assessing the impact of osteoporosis on the burden of hip fractures. Calcif Tissue Int. 2013;92:42–9.

    Article  CAS  PubMed  Google Scholar 

  8. Wilkin TJ, Devendra D. Bone densitometry is not a good predictor of hip fracture. BMJ. 2001;323:795–9.

    Article  CAS  PubMed  Google Scholar 

  9. Kaptoge S, Benevolenskaya LI, Bhalla AK, et al. Low BMD is less predictive than reported falls for future limb fractures in women across Europe: results from the European Prospective Osteoporosis Study. Bone. 2005;36:387–98.

    Article  CAS  PubMed  Google Scholar 

  10. Wainwright SA, Marshall LM, Ensrud KE, et al. Hip fracture in women without osteoporosis J Clin Endocrinol Metab. 2005;90:2787–93.

    Article  CAS  Google Scholar 

  11. Edwards MH, Jameson K, Denison H, et al. Clinically risk factors, bone density and fall history in the prediction of incident fracture among men and women. Bone. 2013;52:541–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Wei TS, Hu CH, Wang SH, et al. Fall characteristics, functional mobility and bone mineral density as risk factors of hip fracture in the community-dwelling ambulatory elderly. Osteoporos Int. 2001;12:1050–5.

    Article  CAS  PubMed  Google Scholar 

  13. Norton R, Campbell J, Lee-Joe T, et al. Circumstances of falls resulting in hip fractures among older people. J Am Geriatr Soc. 1997;45:1108–12.

    CAS  PubMed  Google Scholar 

  14. Kanis JA, Borgstrom F, De Laet C, et al. Assessment of fracture risk. Osteoporos Int. 2005;16:581–9.

    Article  PubMed  Google Scholar 

  15. Dennison EM, Compston JE, Flahive J, et al. Effect of co-morbidities on fracture risk: findings from the Global Longitudinal Study of Osteoporosis in Women (GLOW). Bone. 2012;50:1288–93.

    Article  PubMed  Google Scholar 

  16. Lawlor DA, Patel R, Ebrahim S. Association between falls in elderly women and chronic diseases and drug use: cross sectional study. BMJ. 2003;327:712.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Leveille SG, Jones RN, Kiely DK, et al. Chronic musculoskeletal pain and the occurrence of falls in an older population. JAMA. 2009;302:2214–21.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Vestergaard R, Rejnmark L, Mosekilde L. Fracture risk in patients with chronic lung diseases treated with bronchodilator drugs and inhaled and oral corticosteroids. Chest. 2007;132:1599–607.

    Article  CAS  PubMed  Google Scholar 

  19. Prieto-Alhambra D, Nogues X, Javaid MK, et al. An increased rate of falling leads to a rise in fracture risk in postmenopausal women with self-reported osteoarthritis: a prospective multinational cohort study (GLOW). Ann Rheum Dis. 2013;72:911–7.

    Article  PubMed  Google Scholar 

  20. Janghorbani M, Feskanich D, Willett WC, et al. Prospective study of diabetes and risk of hip fracture: the Nurses’ Health Study. Diabetes Care. 2006;29:1573–8.

    Article  PubMed  Google Scholar 

  21. Cumming RG, Klineberg RJ. Psychotropics, thiazide diuretics and hip fractures in the elderly. Med J Aust. 1993;158:414–7.

    CAS  PubMed  Google Scholar 

  22. Cumming RG, Le Couteur DG. Benzodiazepines and risk of hip fractures in older people: a review of the evidence. CNS Drugs. 2003;17:825–37.

    Article  CAS  PubMed  Google Scholar 

  23. Leipzig RM, Cumming RG, Tinetti ME. Drugs and falls in older people: a systematic review and meta-analysis: II. Cardiac and analgesic drugs. J Am Geriatr Soc. 1999;47:40–50.

    CAS  PubMed  Google Scholar 

  24. Leipzig RM, Cumming RG, Tinetti ME. Drugs and falls in older people: a systematic review and meta-analysis: I. Psychotropic drugs. J Am Geriatr Soc. 1999;47:30–9.

    CAS  PubMed  Google Scholar 

  25. Barrett-Connor E, Weiss TW, McHorney CA, et al. Predictors of falls among postmenopausal women: results from the National Osteoporosis Risk Assessment (NORA). Osteoporos Int. 2009;20:715–22.

    Article  CAS  PubMed  Google Scholar 

  26. Evans JG. Drugs and falls in later life. Lancet. 2003;361:448.

    Article  PubMed  Google Scholar 

  27. Neutel CI, Perry S, Maxwell C. Medication use and risk of falls. Pharmacoepidemiol Drug Saf. 2002;11:97–104.

    Article  PubMed  Google Scholar 

  28. Woolcoot JC, Richardson KJ, Wiens MO, et al. Meta-analysis of the impact of 9 classes on falls in elderly persons. Arch Intern Med. 2009;169:1952–60.

    Article  Google Scholar 

  29. Darowsky A, Chambers SACF, Chambers DJ. Antidepressants and falls in the elderly. Drugs Aging. 2009;26:381–94.

    Article  Google Scholar 

  30. van den Brand MW, Pouwels S, Samson MM, et al. Use of anti-depressants and the risk of fracture of the hip or femur. Osteoporos Int. 2009;20:1705–13.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Carbone LD, Johnson KC, Bush AJ, et al. Loop diuretic use and fracture in postmenopausal women: findings from the Women’s Health Initiative. Arch Intern Med. 2009;169:132–40.

    Article  PubMed  Google Scholar 

  32. Pouwels S, van Staa TP, Egberts AC, et al. Antipsychotic use and the risk of hip/femur fracture: a population-based case–control study. Osteoporos Int. 2009;20:1499–506.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Carbone LD, Johnson KC, Robbins J, et al. Antiepileptic drug use, falls, fractures, and BMD in postmenopausal women: findings from the women’s health initiative (WHI). J Bone Miner Res. 2010;25:873–81.

    CAS  PubMed Central  PubMed  Google Scholar 

  34. Riche DM. Travis King S. Bone loss and fracture risk associated with thiazolidinedione therapy. Pharmacotherapy. 2010;30:716–27.

    Article  CAS  PubMed  Google Scholar 

  35. Pouwels S, Lalmohamed A, van Staa T, et al. Use of organic nitrates and the risk of hip fracture: a population-based case-control study. J Clin Endocrinol Metab. 2010;95:1924–31.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Pouwels S, Lalmohamed A, Souverein P, et al. Use of proton pump inhibitors and risk of hip/femur fracture: a population-based case-control study. Osteoporos Int. 2011;22:903–10.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Solomon DH, Mogun H, Garneau K, et al. Risk of fractures in older adults using antihypertensive medications. J Bone Miner Res. 2011;26:1561–7.

    Article  CAS  PubMed  Google Scholar 

  38. Yang S, Nguyen ND, Center JR, et al. Association between beta-blocker use and fracture risk: the Dubbo Osteoporosis Epidemiology Study. Bone. 2011;48:451–5.

    Article  CAS  PubMed  Google Scholar 

  39. Kwok CS, Yeong JKY, Loke YK. Meta-analysis: risk of fractures with acid-suppressing medication. Bone. 2011;48:768–76.

    Article  CAS  PubMed  Google Scholar 

  40. Abrahamsen B, Eiken P, Eastell R. Proton pump inhibitor use and the antifracture efficacy of alendronate. Arch Intern Med. 2011;171:998–1004.

    PubMed  Google Scholar 

  41. Diem SJ, Blackwell TL, Stone KL, et al. Use of antidepressant medications and risk of fracture in older women. Calcif Tissue Int. 2011;88:476–84.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Miller M, Stürmer T, Azrael D, et al. Opioid analgesics and the risk of fractures in older adults with arthritis. J Am Geriatr Soc. 2011;59:430–8.

    Article  PubMed Central  PubMed  Google Scholar 

  43. Arbouw ME, Movig KL, van Staa TP, et al. Dopaminergic drugs and the risk of hip or femur fracture: a population-based case-control study. Osteoporos Int. 2011;22:2197–204.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  44. Wu Q, Qu W, Crowell MD, et al. Tricyclic antidepressant use and risk of fractures: a meta-analysis of cohort and case-control studies. J Bone Miner Res. 2013;28:753–63.

    Article  PubMed  Google Scholar 

  45. Wu Q, Bencaz AF, Hentz JG, et al. Selective serotonin reuptake inhibitor treatment and risk of fractures: a meta-analysis of cohort and case-control studies. Osteoporos Int. 2012;23:365–75.

    Article  CAS  PubMed  Google Scholar 

  46. Eom CS, Lee HK, Ye S, et al. Use of selective serotonin reuptake inhibitors and risk of fracture: a systematic review and meta-analysis. J Bone Miner Res. 2012;27:1186–95.

    Article  CAS  PubMed  Google Scholar 

  47. Rabenda V, Bruyère O, Reginster JY. Risk of non vertebral fractures among elderly postmenopausal women using antidepressants. Bone. 2012;51:674–9.

    Article  CAS  PubMed  Google Scholar 

  48. Vestergaard P, Preto-Alhambra D, Javaid MK, et al. Fractures in users of antidepressants and anxiolytics and sedatives: effects of age and dose. Osteoporos Int. 2013;24:671–80.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Khong TP, de Vries F, Goldenberg JS, et al. Potential impact of benzodiazepine use on the rate of hip fractures in five large European countries and the United States. Calcif Tissue Int. 2012;91:24–31.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  50. Eom CS, Park SM, Myung SK, et al. Use of acid-suppressive drugs and risk of fracture: a meta-analysis of observational studies. Ann Fam Med. 2011;9:257–67.

    Article  PubMed Central  PubMed  Google Scholar 

  51. Fraser LA, Leslie WD, Targownik LE, et al. The effect of proton pump inhibitors on fracture risk: report from the Canadian Multicenter Osteoporosis Study. Osteoporos Int. 2013;24:1161–8.

    Article  CAS  PubMed  Google Scholar 

  52. Vestergaard P, Hermann P, Jensen JE, et al. Effects of paracetamol, non-steroidal anti-inflammatory drugs, acetylsalicylic acid, and opioids on bone mineral density and risk of fracture: results of the Danish Osteoporosis Prevention Study (DOPS). Osteoporos Int. 2012;23:1255–65.

    Article  CAS  PubMed  Google Scholar 

  53. Williams LJ, Pasco JA, Henry MJ, et al. Paracetamol (acetaminophen) use, fracture and bone mineral density. Bone. 2011;48:1277–81.

    Article  CAS  PubMed  Google Scholar 

  54. Degli Esposti L, Adami S, Iolascon G, et al. Il costo delle fratture da osteoporosi in Italia. Risultati dello studio BLOCK (Bone Loss and Osteoporosis: Cost-of-illness Knowledge). Farmeconomia e Percorsi Terapeutici. 2011;12:89–95.

    Google Scholar 

  55. Motheral BR, Fairman KA. The use of claims databases for outcomes research: rationale, challenges, and strategies. Clin Ther. 1997;19:346–66.

    Article  CAS  PubMed  Google Scholar 

  56. Birnbaum HG, Cremieux PY, Greenberg PE, et al. Using healthcare claims data for outcome research and pharmacoeconomic analyses. Pharmacoeconomics. 1999;16:1–8.

    Article  CAS  PubMed  Google Scholar 

  57. Fulton MM, Allen ER. Polypharmacy in the elderly: a literature review. J Am Acad Nurse Pract. 2005;17:123–32.

    Article  PubMed  Google Scholar 

  58. Cameron ID, Chen JS, March LM, et al. Hip fracture causes excess mortality owing to cardiovascular and infectious disease in institutionalized older people: a prospective 5-year study. J Bone Miner Res. 2010;25:866–72.

    PubMed  Google Scholar 

  59. De Laet C, Kanis JA, Oden A, et al. Body mass index as a predictor of fracture risk: a meta-analysis. Osteoporos Int. 2005;16:1330–8.

    Article  PubMed  Google Scholar 

  60. Tang X, Liu G, Kang J, et al. Obesity and risk of hip fracture in adults: a meta-analysis of prospective cohort studies. PLoS One. 2013;8:e55077.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  61. Roerholt C, Eiken P, Abrahamsen B. Initiation of anti-osteoporotic therapy in patients with recent fractures: a nationwide analysis of prescription rates and persistence. Osteoporos Int. 2009;20:299–307.

    Article  CAS  PubMed  Google Scholar 

  62. Leslie WD, Giangregorio LM, Yogendran M, et al. A population-based analysis of the post-fracture care gap 1996–2008: the situation is not improving. Osteoporos Int. 2012;23:1623–9.

    Article  CAS  PubMed  Google Scholar 

  63. Adami S, Bertoldo F, Brandi ML, et al. Guidelines for the diagnosis, prevention and treatment of osteoporosis. Reumatismo. 2009;61:260–84.

    CAS  PubMed  Google Scholar 

  64. van Helden S, Cals J, Kessels F, et al. Risk of new clinical fractures within 2 years following a fracture. Osteoporos Int. 2006;17:348–54.

    Article  PubMed  Google Scholar 

  65. Center JR, Bliuc D, Nguyen TV, et al. Risk of subsequent fracture after low-trauma fracture in men and women. JAMA. 2007;297:387–94.

    Article  CAS  PubMed  Google Scholar 

  66. Silverman SL, Watts NB, Delmas PD, et al. Effectiveness of bisphosphonates on nonvertebral and hip fractures in the first year of therapy: the risedronate and alendronate (REAL) cohort study. Osteoporos Int. 2007;18:25–34.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  67. Harris ST, Reginster JY, Harley C, et al. Risk of fracture in women treated with monthly oral ibandronate or weekly bisphosphonates: the eValuation of IBandronate Efficacy (VIBE) database fracture study. Bone. 2009;44:758–65.

    Article  CAS  PubMed  Google Scholar 

  68. Kragh A, Elmstahl S, Atroshi I. Older adults’ medication use 6 months before and after hip fracture: a population-based cohort study. J Am Geriatr Soc. 2011;59:863–8.

    Article  PubMed  Google Scholar 

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Acknowledgments

Funding sources

This study was supported by independent research grants from Amgen Dompe and GlaxoSmithKline. The grant providers had no role in the study design, data collection, statistical analysis, or manuscript preparation and submission.

Conflict of interest

S.A. has received consultancy honoraria from Merck and Amgen, and speaking fees from Amgen, Abiogen, Merck, Eli-Lilly, Pfizer, Novartis and GSK. O.V. has received speaking fees from Merck and Pfizer. L.I. has received speaking fees from Novartis. L.D.E. has received speaking fees from Amgen and Eli-Lilly. D.G. has received speaking fees from Amgen, Abiogen, Merck, Eli-Lilly and Pfizer. All other authors have declared no conflicts of interest.

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Authors and Affiliations

  1. Rheumatology Unit, Department of Medicine, University of Verona, Policlinico Borgo Roma, Piazzale Scuro, 10, 37134, Verona, Italy

    Maurizio Rossini, Ombretta Viapiana, Silvano Adami, Luca Idolazzi & Davide Gatti

  2. CliCon S.r.l. Health, Economics and Outcomes Research, Ravenna, Italy

    Stefano Buda, Chiara Veronesi & Luca Degli Esposti

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  1. Maurizio Rossini
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  2. Ombretta Viapiana
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Correspondence to Maurizio Rossini.

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Rossini, M., Viapiana, O., Adami, S. et al. Medication Use Before and After Hip Fracture: A Population-Based Cohort and Case-Control Study. Drugs Aging 31, 547–553 (2014). https://doi.org/10.1007/s40266-014-0184-2

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