Calcified Tissue International

, Volume 81, Issue 3, pp 153–161

Fracture Risk Associated with Parkinsonism and Anti-Parkinson Drugs

Article

Abstract

We studied fracture risk associated with parkinsonism (including Parkinson’s disease) and drugs used to treat these conditions in a case-control study. Cases were all subjects with any fracture during the year 2000 (n = 124,655). For each case, three controls (n = 373,962) matched on age and gender were randomly drawn from the background population. Exposure was a diagnosis of parkinsonism or use of anticholinergic drugs, levodopa alone or in combination with carbidopa, and/or catechol-O-methyl transferase (COMT) inhibitors, dopamine agonists, or monoamine oxidase B (MAO-B) inhibitors and a number of other confounders. Parkinsonism was associated with a crude odds ratio (OR) of any fracture of 2.2 (95% confidence interval [95% CI] 2.0–2.5) and an adjusted OR of 1.2 (95% CI 1.0–1.4), the risk being higher especially in males younger than 75 years. Levodopa was associated with an increased overall fracture risk and an increased risk of hip fractures in high doses. Dopamine agonists, anticholinergic drugs, and MAO-B inhibitors were not associated with increased fracture risk except for hip fractures at high doses for MAO-B inhibitors and hip fractures at median doses for dopamine agonists. Neuroleptics were associated with increased risk of fractures in almost all skeletal sites and doses. In conclusion, parkinsonism was associated with increased risk of fractures, especially among males younger than 75 years, and the risk was significantly attenuated upon adjustment for confounders. Use of neuroleptics and, to some degree, levodopa was associated with increased risk of fractures.

Keywords

Fracture risk Parkinsonism Anti-Parkinson drug 

References

  1. 1.
    Genever RW, Downes TW, Medcalf P (2005) Fracture rates in Parkinson’s disease compared with age- and gender-matched controls: a retrospective cohort study. Age Ageing 34:21–24PubMedCrossRefGoogle Scholar
  2. 2.
    Johnell O, Melton LJ III, Atkinson EJ, O’Fallon WM, Kurland LT (1992) Fracture risk in patients with parkinsonism: a population-based study in Olmsted County, Minnesota. Age Ageing 21:32–38PubMedCrossRefGoogle Scholar
  3. 3.
    Taylor BC, Schreiner PJ, Stone KL, Fink HA, Cummings SR, Nevitt MC, Bowman PJ, Ensrud KE (2004) Long-term prediction of incident hip fracture risk in elderly white women: study of osteoporotic fractures. J Am Geriatr Soc 52:1479–1486PubMedCrossRefGoogle Scholar
  4. 4.
    Wielinski CL, Erickson-Davis C, Wichmann R, Walde-Douglas M, Parashos SA (2005) Falls and injuries resulting from falls among patients with Parkinson’s disease and other parkinsonian syndromes. Mov Disord 20:410–415PubMedCrossRefGoogle Scholar
  5. 5.
    Williams DR, Watt HC, Lees AJ (2006) Predictors of falls and fractures in bradykinetic rigid syndromes: a retrospective study. J Neurol Neurosurg Psychiatry 77:468–473PubMedCrossRefGoogle Scholar
  6. 6.
    Melton LJ III, Leibson CL, Achenbach SJ, Bower JH, Maraganore DM, Oberg AL, Rocca WA (2006) Fracture risk after the diagnosis of Parkinson’s disease: influence of concomitant dementia. Mov Disord 21:1361–1367PubMedCrossRefGoogle Scholar
  7. 7.
    Yamanashi A, Yamazaki K, Kanamori M, Mochizuki K, Okamoto S, Koide Y, Kin K, Nagano A (2005) Assessment of risk factors for second hip fractures in Japanese elderly. Osteoporos Int 16:1239–1246PubMedCrossRefGoogle Scholar
  8. 8.
    Di Monaco M, Vallero F, Di Monaco R, Tappero R, Cavanna A (2006) Bone mineral density in hip-fracture patients with Parkinson’s disease: a case-control study. Arch Phys Med Rehabil 87:1459–1462PubMedCrossRefGoogle Scholar
  9. 9.
    Taggart H, Crawford V (1995) Reduced bone density of the hip in elderly patients with Parkinson’s disease. Age Ageing 24:326–328PubMedCrossRefGoogle Scholar
  10. 10.
    Sato Y, Kikuyama M, Oizumi K (1997) High prevalence of vitamin D deficiency and reduced bone mass in Parkinson’s disease. Neurology 49:1273–1278PubMedGoogle Scholar
  11. 11.
    Sato Y, Manabe S, Kuno H, Oizumi K (1999) Amelioration of osteopenia and hypovitaminosis D by 1alpha-hydroxyvitamin D3 in elderly patients with Parkinson’s disease. J Neurol Neurosurg Psychiatry 66:64–68PubMedCrossRefGoogle Scholar
  12. 12.
    Sato Y, Honda Y, Kaji M, Asoh T, Hosokawa K, Kondo I, Satoh K (2002) Amelioration of osteoporosis by menatetrenone in elderly female Parkinson’s disease patients with vitamin D deficiency. Bone 31:114–118PubMedCrossRefGoogle Scholar
  13. 13.
    Sato Y, Kaji M, Tsuru T, Oizumi K (2001) Risk factors for hip fracture among elderly patients with Parkinson’s disease. J Neurol Sci 182:89–93PubMedCrossRefGoogle Scholar
  14. 14.
    Sato Y, Iwamoto J, Kanoko T, Satoh K (2005) Homocysteine as a predictive factor for hip fracture in elderly women with Parkinson’s disease. Am J Med 118:1250–1255PubMedCrossRefGoogle Scholar
  15. 15.
    Dorrington J, Gore-Langton RE (1981) Prolactin inhibits oestrogen synthesis in the ovary. Nature 290:600–602PubMedCrossRefGoogle Scholar
  16. 16.
    Frank L (2000) Epidemiology. When an entire country is a cohort. Science 287:2398–2399PubMedCrossRefGoogle Scholar
  17. 17.
    Andersen TF, Madsen M, Jørgensen J, Mellemkjær L, Olsen JH (1999) The Danish National Hospital Register. Dan Med Bull 46:263–268PubMedGoogle Scholar
  18. 18.
    Vestergaard P, Mosekilde L (2002) Fracture risk in patients with celiac disease, Crohn’s disease, and ulcerative colitis: a nation-wide follow-up study in 16,416 patients in Denmark. Am J Epidemiol 156:1–10PubMedCrossRefGoogle Scholar
  19. 19.
    Wacholder S, McLaughlin JK, Silverman DT, Mandel JS (1992) Selection of controls in case-control studies. I. Principles. Am J Epidemiol 135:1019–1028PubMedGoogle Scholar
  20. 20.
    Capella D (1993) Descriptive tools and analysis. In: Dukes MNG (ed) Drug utilization studies: methods and uses. WHO Regional Publications, European Series 45, Copenhagen, pp 55–78Google Scholar
  21. 21.
    Nielsen GL, Sørensen HT, Zhou W, Steffensen FH, Olsen J (1997) The pharmaco-epidemiologic prescription database of north Jutland. Int J Risk Saf Med 10:203–205Google Scholar
  22. 22.
    Munk-Jørgensen P, Mortensen PB (1997) The Danish Psychiatric Central Register. Dan Med Bull 44:82–84PubMedGoogle Scholar
  23. 23.
    Miettinen OS (1985) Theoretical epidemiology: principles of occurrence research in medicine. Wiley, New YorkGoogle Scholar
  24. 24.
    Vestergaard P, Mollerup CL, Frøkjær VG, Christiansen P, Blichert-Toft M, Mosekilde L (2000) Cohort study of risk of fracture before and after surgery for primary hyperparathyroidism. BMJ 321:598–602PubMedCrossRefGoogle Scholar
  25. 25.
    Vestergaard P, Rejnmark L, Mosekilde L (2006) Anxiolytics, sedatives, antidepressants, neuroleptics and the risk of fracture. Osteoporos Int 17:807–816PubMedCrossRefGoogle Scholar
  26. 26.
    Ensrud KE, Blackwell TL, Mangione CM, Bowman PJ, Whooley MA, Bauer DC, Schwartz AV, Hanlon JT, Nevitt MC (2002) Central nervous system-active medications and risk for falls in older women. J Am Geriatr Soc 50:1629–1637PubMedCrossRefGoogle Scholar
  27. 27.
    Pollock BG (1999) Adverse reactions of antidepressants in elderly patients. J Clin Psychiatry 60 Suppl 20:4–8Google Scholar
  28. 28.
    Steiger MJ, Thompson PD, Marsden CD (1996) Disordered axial movement in Parkinson’s disease. J Neurol Neurosurg Psychiatry 61:645–648PubMedGoogle Scholar
  29. 29.
    Aita JF (1982) Why patients with Parkinson’s disease fall. JAMA 247:515–516PubMedCrossRefGoogle Scholar
  30. 30.
    Sambrook PN, Cameron ID, Chen JS, Cumming RG, Lord SR, March LM, Schwarz J, Seibel MJ, Simpson JM (2007) Influence of fall related factors and bone strength on fracture risk in the frail elderly. Osteoporos Int 18:603–610PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Peter Vestergaard
    • 1
  • Lars Rejnmark
    • 1
  • Leif Mosekilde
    • 1
  1. 1.Department of Endocrinology and Metabolism C, Aarhus AmtssygehusAarhus University HospitalAarhus CDenmark

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