Skip to main navigation menu Skip to main content Skip to site footer

Review article: Biomedical intelligence

Vol. 141 No. 0708 (2011)

Parkinson’s disease and the bones

  • Alain Kaelin-Lang
  • Markus Gnädinger
  • Hans-Ulrich Mellinghoff
DOI
https://doi.org/10.4414/smw.2011.13154
Cite this as:
Swiss Med Wkly. 2011;141:w13154
Published
14.02.2011

Summary

PRINCIPLES: Bone and joint problems in Parkinson’s disease (PD) are manifold: decreased mobility, abnormal posture, as well as the risk of falling may cause both acute and chronic damage to the musculoskeletal system. In patients with Parkinson’s disease, postural instability and falls are frequently observed. The aim of the study was to review the literature with respect to the bone health and risk of fractures in these patients.

METHODS: We conducted a review on bone health in patients with Parkinson’s disease.

RESULTS: There is evidence that patients with PD have an increased risk of fractures, especially of the hip, due to the elevated risk of falling. While rigidity, bradykinesia and postural instability (but not tremor) predict falls, fractures also correlate with bone mineral density, which is generally lowered in this group of patients as compared to age- and sex-matched controls. Typically PD patients have “high turnover osteoporosis” due to several causes.

CONCLUSIONS: Any newly diagnosed patient with PD should be evaluated for the risk of falling and osteoporosis and routinely be supplemented with vitamin D. In the case of osteoporosis, blood samples for detecting underlying and treatable conditions should be taken and bisphosphonates administered to the patient.

It is unclear whether drugs typically used for PD provoke or worsen osteoporosis. Nevertheless, every long-term medication should undergo safety studies to demonstrate lack of negative interference with bone metabolism. Drug admission authorities should demand these data when registering new substances or when renewing old admissions.

References

  1. Parkinson J. An essay on the shaking palsy. London, Wittingham and Rowland, 1817; chapt. 1.
  2. Bennet DA, Beckett LA, Murray AM, et al. Prevalence of parkinsonian signs and associated mortality in a community population of older people. N Engl J Med. 1996;334:71–6.
  3. Follet KA, Weaver FM, Stern M, et al. Pallidal versus subthalamic deep-brain stimulation for Parkinson’s disease. NEJM. 2010;362:2077–91.
  4. Katzenschlager R, Head J, Schrag A, et al. Fourteen-year final report of the randomized PDRG-UK trial comparing three initial treatments in PD. Neurology. 2008;71:474–80.
  5. Vaserman N, et al. Arthropatic appearances in Parkinson’s disease. Revue de Gériatrie 2001;26:2(95–104).
  6. Bloem BR, Grimbergen YA, Cramer M, et al. Prospective assessment of falls in Parkinson’s disease. J Neurol. 2001;248:950–8.
  7. Camicioli R, Majumdar SR. Relationship between mild cognitive impairment and falls in older people with and without Parkinson’s disease: 1-year prospective cohort study. Gait&Posture. 2010;87–91.
  8. Ashburn A, Fazakarley L, Ballinger C, et al. A randomized controlled trial of a home based exercise programme to reduce the risk of falling among people with Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2007;78:678–84.
  9. Gray P, Hildebrand K. Fall risk factors in Parkinson’s disease. J Neurosci Nurs. 2000;32:222–8.
  10. Koller WC, Glatt S, Vetere-Overfield B, et al. Falls and Parkinson’s disease. Clin Neuropharmacol. 1989;12:98–105.
  11. Matinolli M, Korpelainen JT, Korpelainen R, et al. Mobility and balance in Parkinson’s disease: a population-based study. Eur J Neurol. 2009;16:105–11.
  12. Sadowski CA, Jones CA, Gordon B. Knowledge of risk factors for falling reported by patients with Parkinson’s disease. J Neurosci Nursing. 2007;39:336–41.
  13. Balash Y, Peretz Ch, Leibovich G, et al. Falls in outpatients with Parkinson’s disease. J Neurol. 2005;252:1310–5.
  14. Deandra S, Lucenteforte E, Bravi F, et al. Risk factors for falls in community-dwelling older people. A systematic review and meta-analysis. Epidemiology. 2010;21:658–68.
  15. Wood BH, Bilclough JA, Bowron A, et al. Incidence and prediction of falls in Parkinson’s disease: a prospective multidisciplinary study. J Neurol Neurosurg Psychiatry. 2002;72:721–5.
  16. Williams DR, Watt HC, Lees AJ. Predictors of falls and fractures in bradykinetic rigid syndromes: a retrospective study. J Neurol Neurosurg Pschiatry. 2006;77:468–73.
  17. Kerr GK, Worringham CJ, Cole MH, et al. Predictors of future falls in Parkinson disease. Neurology. 2010;75:116–24.
  18. Dibble LE, Lange M. Predicting falls in individuals with Parkinson disease: a reconsideration of clinical balance measures. J Neurol Phys Ther. 2006;30:60–7.
  19. Chien SL, Lin SZ, Liang CC, et al. The efficacy of quantitative gait analysis by the GAITRite system in evaluation of parkinsonian bradykinesia. Parkinsonism Rel Dis. 2006;12:438–42.
  20. Frenklach A, Louie S, Miiler Koop M, et al. Excessive postural sway and the risk of falls at different stages of Parkinson’s disease. Mov Dis. 2009;24:377–85.
  21. Morris ME, Marin CL, Schenkman ML. Striding out with Parkinson Disease: Evidence-based physical therapy for gait disorders. Phys Ther. 2010;90:280–8.
  22. Rochester L, Burn DJ, Woods G, et al. Does auditory rhythmical cueing improve gait in people with Parkinson’s disease and cognitive impairment? A feasibility study. Mov Dis. 2009;24:839–45.
  23. Ashburn A, Fazakarley, Ballinger C, et al. A randomized controlled trial of a home based exercise programme to reduce the risk of falling among people with Parkinson’s disease. J Neurol Neurosurg Psych. 2007;78:678–84.
  24. Allen NE, Canning CG, Sherrington C, et al. The effects of an exercise program on fall risk factors in people with Parkinson’s disease: a randomized controlled trial. Mov Dis. 2010;25:1217–25.
  25. Buracchio T, Arvanitakis Z. Parkinsonian signs and incident falls in older persons without Parkinson’s disease (Letter to the editor). J Am Geriatr Soc. 2010;58:205–6.
  26. Klawans HL, Topel JL. Parkinsonism as a falling sickness. JAMA. 1974;230:1555–7.
  27. Chung KA, Lobb BM, Nutt JG, et al. Effects of a central cholinesterase inhibitor on reducing falls in Parkinson disease. Neurology. 2010;75:1263–9.
  28. Moro E, Hamani C Poon YY, et al. Unilateral pedunculopontine stimulation improves falls in Parkinson’s disease. Brain. 2010;133:215–24.
  29. Grimbergen YAM, Munneke M, Bloem BR, et al. Falls in Parkinson’s disease. Curr Opin Neurol. 2004;17:405–15.
  30. Johnell O, Melton LJ, Atkinson EJ, et al. Fracture risk in patients with parkinsonism: a population-based study in Olmsted county, Minnesota. Age Ageing. 1992;21:32–8.
  31. Genever RW, Downes TW, Medcalf P. Fracture rates in Parkinson’s disease compared with age- and gender-machted controls: a retrospective cohort study. Age Ageing. 2005;34:21–4.
  32. Schneider JL, Fink HA, Ewing SK, et al. The association of Parkinson’s disease with bone mineral density and fracture in older women. Osteoporosis Int. 2008;19:1093–7.
  33. Fink HA, Kuskowski MA, Taylor BC, et al. Association of Parkinson’s disease with accelerated bone loss, fractures and mortality in older men: the osteoporotic fractures in men (MrOs) study. Osteoporosis Int. 2008;19:1277–82.
  34. Grisso JA, Kelsey JL, Storm BL, et al. Risk factors for falls as a cause of hip fracture in women. N Engl J Med. 1991;324:1326–31.
  35. Taylor BC, Schreiner PJ, Stone KL, et al. Long-term prediction of incident hip fracture risk in elderly white women: study of osteoporotic fractures. J Am Geriatr Soc. 2004;52:1479–86.
  36. Nguyen T, Sambrook P, Kelly P, et al. Prediction of osteoporotic fractures by postural instability and bone density. BMJ. 1993;307:1111–5.
  37. Vestergaard P, Rejmark L, Mosekilde L. Fracure risk associatred with parkinsonism and anti-parkinson drugs. Calcif Tissue Int. 2007;81:153–61.
  38. The North American Menopause Society: Management of osteoporosis in postmenopausal women: 2010 position statement. Menopause. 2010;17:25–54.
  39. Diem-Zangerl A, Seppi K, Wenning GK, et al. Mortality in Parkinson’s disease: a 20-year follow-up study. Mov Dis. 2009;24:819–25.
  40. Berger K, Breteler MMB, Helmer C, et al. Prognosis with Parkinson’s disease in Europe: a coccaborative study of population-based cohorts. Neurology. 2000;54:S24–7.
  41. Herlofson K, Lie AS, Arsland D, et al. Mortality and Parkinson’s disease. A community based study. Neurology. 2004;62:937–42.
  42. Hely MA, Morris JGL, Reid WGJ, et al. Sydney multicenter study of Parkinson’s disease: non-L-dopa-responsive problems dominate at 15 years. Mov Dis. 2005;20:190–9.
  43. Hobson P, Meara J, Ishihara-Paul L. The estimated life expectancy in a community cohort of Parkinson’s disease patients with and without dementia, compared with the UK population. J Neurol Neurosurg Psychiatry. 2010;81:193–8.
  44. Rajput AHR, Uitti RJ, Rajput A, et al. Mortality in Parkinson’s disease (Letter). Mov Dis. 2010;25:507–8.
  45. Mylne AQN, Griffiths C, Rooney C, et al. Trends in Parkinson’s disease related mortality in England and Wales, 1993–2006. Eur J Neurol. 2009;16:1010–6.
  46. Fall PA, Saleh A, Fredrickson M, et al. Survival time, mortality, and cause of death in elderly patients with Parkinson’s disease: a 9-year follow-up. Mov Dis. 2003;18:1312–6.
  47. D’Amelio M, Ragonese P, Morgante L, et al. Lont-erm survival of Parkinson’s disease. A population-based study. J Neurol. 2006;253:33–7.
  48. Pennington S, Snell K, Lee M, et al. The cause of death in idiopathic Parkinson’s disease. Park Rel Dis. 2010;16:434–7.
  49. Ebmeier KP, Calder SA, Crawford JR, et al. Mortality and causes of death in idiopathic Parkinson’s disease: results from the Aberdeen whole population study. Scot Med J. 1990;35:173–5.
  50. Vinogradova Y, Hippisley-Cox J, Coupland C. Identification of new risk factors for pneumonie: population-based case-control study. Br J Gen Pract. 2009; DOI: 10.3399/bjgp09X472629.
  51. Hristova DR. Standardized mortality ratio and seasonal fluctuations of mortality in Parkinson’s disease. Folia Mecica. 2009;51:40–5.
  52. Kao CH, Chen CC, Wang SJ, et al. Bone mineral density in patients with Parkinson’s disease measured by dual photon absorptiometry. Nucl Med Comm. 1994;15:173–7.
  53. Taggart H, Crawford V. Reduced bone density of the hip in elderly patients with Parkinson’s disease. Age Ageing. 1995;24:326–8.
  54. Lorefält B, Toss G, Granérus AK, et al. Bone mass in elderly patients with Parkinson’s disease. Acta Neurol Scand. 2007;116:248–54.
  55. Abou-Raya S, Helmii M, Abou-Raya A. Bone and mineral metabolism in older adults with Parkinson’s disease. Age Ageing. 2009;38:675–80.
  56. Bezza A, Ouzzif Z, Naji H, et al. Prevalence and risk factors of osteoporosis in patients with Parkinson’s disease. Rheumatol Int. 2008;28:1205–9.
  57. Kamanli A, Ardicoglu O, Ozgocmen S, et al. Bone mineral density in patients with Parkinson’s disease. Aging Clin Exp Res. 2008;20:277–9.
  58. Lam K, Li M, Mok V, et al. A case control study on bone mineral density in Chinese patients with Parkinson’s disease. Park Rel Dis. 2010;16:471–4.
  59. Sato Y, Manabe S, Kuno H, et al. Amelioration of osteopenia and hypovitaminosis D by 1α-hydroxyvitamin D3 in elderly patients with Parkinson’s disease. J Neurol Neurosurg Psychiatry. 1999;66:64–8.
  60. Sato Y, Honda Y, Kaji M, et al. Amelioration of osteoporosis by menatetrenone in elderly female Parkinson’s disease patients with vitamin D deficiency. Bone. 2002;31:114–8.
  61. Ishizaki F, Harada T, Katayama S, et al. Relationship between osteopenia and clinical characteristics of Parkinson’s disease. Movement Disorders. 1993;8:507–11.
  62. Sato Y, Iwamoto J, Kanoko T, et al. Alendronate and vitamin D2 for prevention of hip fracture in Parkinson’s disease: a randomized controlled trial. Movement disorders. 2006;21:924–9.
  63. Sato Y, Honda Y, Iwamoto J. Risedronate and ergocalciferol prevent hip fracture in elderly men with Parkinson’s disease. Neurology. 2007;68:911–5.
  64. Evatt ML, DeLong MR, Khazai N, et al. Prevalence of vitamin D insufficiency in patients with Parkinson disease and Alzheimer disease. Arch Neurol. 2008;65:1348–52.
  65. Sato Y, Kikuyama M, Oizumi K. High prevalence of vitamin D deficiency and reduced bone mass in Parkinson’s disease. Neurology. 1997;49:1273–8.
  66. Sato Y, Iwamoto J, Honda Y. Amelioration of osteoporosis and hypovitaminosis D by sunlight exposure in Parkinson’s disease. Parkinson Rel Dis 2010; DOI; 10.1016/j.parkreldis.2010.10.008.
  67. Rico H, Vazquez A, Cabranes JA, et al. Long-term influence of levodopa on bone mass and growth hormone in postmenopausal women with Parkinson’s disease. Clin Neuropharmacol. 1987;10:87–91.
  68. Arbouw MEL, Movig KLL, von Staa TP, et al. Dopaminergic drugs and the risk of hip or femur fracture: a population-based case-control study. Osteoporosis Int 2010; DOI 10.1007/s00198-010-1455-3.
  69. Inglis GC, Kenyon CJ. Effects of long-term infusions of dopa and carbidopa on renin and steroid secretion in the rat. Endocrinology. 1992;131:2941–5.
  70. Luippold G, Küster E, Joos TO, et al. Dopamine D3 receptor activation modulates renal function in anesthetized rats. Naunyn-Schmiedeberg’s Arch Pharmacol. 1998;358:690–3.
  71. Luippold G, Mühlbauer B. Dopamine D2 receptors mediate glomerular hyperfiltration due to amino acids. J Pharamacol Exp Ther. 1998;286:1248–52.
  72. Bliziotes M, McLoughlin S, Gunness M, et al. Bone histomorphometric and biomechanical abnormalities in mice homozygous for deletion of the dopamine transporter gene. Bone. 2000;26:15–9.
  73. Kytömäki O, Nousiainen R, Pekkarinen A, et al. Plasma growth hormone and insulin response to levodopa and amantadine. J Neural Transmission. 1973;34:145–51.
  74. Rhee EJ, Oh KW, Lee WY, et al. Age, body mass index, current smoking history, and serum insulin-like growth factor-I levels associated with bone mineral density in middle-aged Korean men. J Bone Miner Metab. 2004;22:392–8.
  75. Diebold J, Bätge B, Stein H, et al. Osteoporosis in longstanding acromegaly: characteristic changes of vertebral trabecular architecture and bone matrix composition. Virchows Archiv A Pathol Anat. 1991;419:209–15.
  76. Bellomo G, Santambrogio L, Fiacconi M, et al. Plasma profiles of adrenocorticotropic hormone, cortisol, growth hormone and prolactin in patients with untreated Parkinson’s disease. J Neurol. 1991;238:19–22.
  77. O’Suilleabhain PE, Bottiglieri T, Dewey RB, et al. Modest increase in plasma homocysteine follows levodopa initiation in Parkinson’s disease. Mov Dis. 2004;19:1403–8.
  78. Sato Y, Iwamoto J, Kanoko T, et al. Homocysteine as a predictive factor for hip fracture in elderly women with Parkinson’s disease. Am J Med. 2005;118:1250–55.
  79. Lee SH, Kim MJ, Kim BJ, et al. Hyperhomocysteinemia due to levodopa treatment as a risk factor for osteoporosis in patients with Parkinson’s disease. Calcif Tissue Int. 2010;86:132–41.
  80. vanMeurs JBJ, Dhonukshe-Rutten RAM, Pluijm SMF, et al. Homocysteine levels and the risk of osteoporotic fracture. NEJM. 2004;350:2033–41.
  81. Lee SH, Kim MJ, Kim BJ, et al. Homocysteine-lowering therapy or antioxidant therapy for bone loss in Parkinson’s disease. Mov Dis. 2010;25:332–40.
  82. Sato Y, Honda Y, Iwamoto J, et al. Effect of folate and mecobalamin on hip fractures in patients with stroke. JAMA. 2005;293:1082–8.
  83. Tanaka C, Tanaka S, Itokawa Y, et al. Skeletal changed induced by dopa decarboxylase inhibitor in rats. Japan J Pharmacol. 1973;23:123–5.
  84. Schärer K. Special developmental derangements of the rat skeleton after administration of DL-Serine-(2,3,4-trihydroxybenzyl) hydrazide] (German). Beitr Path. 1974;152:127–50.
  85. Savica R, Rocca WA, Ahlskog JE. When does Parkinson disease start? Arch Neurol. 2010;67:798–801.
  86. Karachi C, Grabli D, Bernard FA, et al. Cholinergic mesencephalic neurons are involved in gait and postural disorders in Parkinson disease. J Clin Invest. 2010;120:2745–54.
  87. Zaidel A, Arkadir D, Israel Z, et al. Akineto-rigid vs. tremor syndromes in parkinsonism. Curr Opin Neurol. 2009;22:387–93.
  88. Mak MKY, Pang MYC. Fear of falling is independently associated with recurrent falls in patients with Parkinson’s disease: a 1-year prospective study. J Neurol. 2009;256:1689–95.
  89. Tinetti ME, Kumar C. The patient who falls / “It’s always a trade-off”. JAMA. 2010;303(3):258–66.
  90. The American Geriatrics Society: Clinical practice Guideline: Prevention of falls in older persons. http://www.americangeriatrics.org/health_care_professionals/clinical_practice/clinical_guidelines_recommendations/2010/
  91. Gillespie LD, Robertson MC, Gillespie WJ, et al. Interventions for preventing falls in older people living in the community. Cochrane Database of Systematic Reviews 2009, Issue 2. Art. No.: CD007146. DOI: 10.1002/14651858.CD007146.pub2.
  92. Petroni MI, Albani G, Bicchiega V, et al. Body composition in advanced-stage Parkinson’s disease: Acta Diabetol. 2003;40:S187–90.
  93. Invernizzi M, Carda S, Sguazzini Visconti G, et al. Osteoporosis in Parkinson’s disease. Parkinsonism Rel Dis. 2009;15:339–46.
  94. Knekt P, Kilkkinen A, Rissanen H, et al. Serum Vitamin D and the risk of Parkinson disease. Arch Neurol. 2010;67:808–11.
  95. Sato Y, Oizumi K, Kuno H, et al. Effect of immobilization upon renal synthesis of 1,25-dihydroxyvitamin D in disabled elderly stroke patients. Bone. 1999;24:271–5.
  96. Blumenkrantz N, Asboe-Hansen G. Inhibitory effect of L-dopa on collagen biosynthsis. Acta Med Scand. 1974;195:37–8.
  97. Lubec B, Fang-Kircher S, Lubec T, et al. Evidence for McKusick’s hypothesis of deficient collagen cross-linking in patients with homocysteinuria. Biochimica et Biophysica Acta. 1996;1315:159–62.
  98. Zoccolella S, dell’Aquila C, Abruzzese G, et al. Hyperhomocysteinemia in levodopa-treated patients with Parkinson’s disease dementia.
  99. Huang T, Yuan G, Zhang Z, et al. Cardivascular pathogenesis in hyperhomocysteinemia. Asia Pac J Clin Nutr. 2008;17:8–16.
  100. Marti-Carvajal AJ, Sola I, Lathyris D, et al. Homocysteine lowering interventions for preventing cardiovascular events. Cochrane Database of Systematic Reviews 2009; Issue 4 Art. No.: CD006612. DOI: 10.1002/14651858.CD006612.pub2.
  101. Zoccolella S, Lamberti P, Armenise E, et al. Plasma homocysteine levels in Parkinson’s disease: role of antiparkinsonian medications. Parkinsonism and Related Disorders. 2005;11:131–3.
  102. Lamberti P, Zoccolella S, Iliceto G, et al. Effects of levodopa and COMT-inhibitors on plasma homocysteine in Parkinsons’ disease patients. Mov Dis. 2005;20:69–72.
  103. Farhat G, Yamout B, Mikati MA, et al. Effect of antiepileptic drugs on bone density in ambulatory patients. Neurology. 2002;58:1348–53.
  104. Fiore CE, Tamburino C, Foti R, et al. Reduced axial bone mineral content in patients taking an oral anticoagulant. South Med J. 1990;83:538–42.
  105. Grey A, Bolland M, Gamble G, et al. The peroxisome proliferator-activated receptor-gamma agonist rosiglitazone decreases bone formation and bone mineral density in healthy postmenopausal women: a randomized, controlled trial. J Clin Endocrinol Metab. 2007;92:1305–10.
  106. Diem SJ, Blackwell TL, Stone KL, et al. Use of antidepressants and rates of hip bone loss in older women. Arch Intern Med. 2007;167:1240–5.
  107. Yang YX, Lewis JD, Epstein S, et al. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006;296(24):2947–53.
  108. Mukherjee D. Nonsteroidal anti-inflammatory drugs and the heart: what is the danger? Congestive heart failure. 2008;14:5–82.

Most read articles by the same author(s)