Abstract
Summary
The aim of the study was to determine fracture risk in incident Parkinson’s disease (PD) patients. This study showed that fracture risk assessment may be indicated among patients with PD, in particular when they have recently used selective serotonin re-uptake inhibitors or high-dose antipsychotics, or have a history of fracture, falling, low body mass index (BMI) or renal disease.
Introduction
PD is a movement disorder associated with falling and detrimental effects on bone. Both are recognized risk factors for fracture. Therefore, the aim was to determine fracture risk in incident PD patients stratified by treatment, severity, duration of disease and related comorbidities.
Methods
We conducted a retrospective cohort study using the UK General Practice Research Database (1987–2011). Each PD patient was matched by age, sex, calendar time and practice to a control patient without history of PD.
Results
We identified 4,687 incident PD patients. Compared to controls, a statistically significant increased risk was observed for any fracture (adjusted hazard ratio [AHR], 1.89; 95 % confidence interval [CI], 1.67–2.14), osteoporotic fracture (AHR, 1.99; 95 % CI, 1.72–2.30) and hip fracture (AHR 3.08; 95 % CI, 2.43–3.89). Fracture risk further increased with history of fracture, falling, low BMI, renal disease, antidepressant use and use of high-dose antipsychotics.
Conclusion
This study showed that incident PD patients have a statistically significant increased risk of fracture. Therefore, fracture risk assessment may be indicated among PD patients, who, besides the general risk factors for fracture, like increasing age and female gender, have recently used selective serotonin re-uptake inhibitors or high-dose antipsychotics or have a history of fracture, falling, low BMI or renal disease.
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References
Nussbaum RL, Ellis CE (2003) Alzheimer’s disease and Parkinson’s disease. N Engl J Med 348:1356
Burch D, Sheerin F (2005) Parkinson’s disease. Lancet 365(9459):622–627
Pickering RM, Grimbergen YA, Rigney U, Ashburn A, Mazibrada G, Wood B, Gray P, Kerr G, Bloem BR (2007) A meta-analysis of six prospective studies of falling in Parkinson’s disease. Mov Disord 22(13):1892–1900
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 20:410–415
Sato Y, Kikuyama M, Oizumi K (1997) High prevalence of vitamin D deficiency and reduced bone mass in Parkinson’s disease. Neurology 49:1273–1278
Kao CH, Chen CC, Wang SJ, Chia LG (1994) Bone mineral density in patients with Parkinson’s disease measured by dual photon absorptiometry. Nucl Med Commun 15:173–177
Sato Y, Iwamoto J, Honda Y (2011) Amelioration of osteoporosis and hypovitaminosis D by sunlight exposure in Parkinson’s disease. Parkinsonism Relat Disord 17(1):22–26
Lees AJ, Hardy J, Revesz T (2009) Parkinson’s disease. Lancet 373(2055):2066, Review. Erratum in Lancet 2009;374(9691):684
Vaserman N (2005) Parkinson’s disease and osteoporosis. Joint Bone Spine 72:484–488
Becker C, Brobert GP, Johansson S, Jick SS, Meier CR (2011) Risk of incident depression in patients with Parkinson disease in the UK. Eur J Neurol 18(3):448–453
Bolluk B, Ozel-Kizil ET, Akbostanci MC, Atbasoglu EC (2010) Social anxiety in patients with Parkinson’s disease. J Neuropsychiatry Clin Neurosci 22(4):390–394
Aarsland D, Andersen K, Larsen JP, Lolk A, Nielsen H, Kragh-Sorensen P (2001) Risk of dementia in Parkinsons disease: a community-based, prospective study. Neurology 56(6):730–736
Eng ML, Welty TE (2010) Management of hallucinations and psychosis in Parkinson’s disease. Am J Geriatr Pharmacother 8(4):316–330
Baker NL, Cook MN, Arrighi HM, Bullock R (2011) Hip fracture risk and subsequent mortality among Alzheimer’s disease patients in the United Kingdom, 1988-2007. Age Ageing 40(1):49–54
van den Brand MW, Samson MM, Pouwels S, van Staa TP, Thio B, Cooper C, Leufkens HG, Egberts AC, Verhaar HJ, de Vries F (2009) Use of anti-depressants and the risk of fracture of the hip or femur. Osteoporos Int 20(10):1705–1713
Pouwels S, van Staa TP, Egberts AC, Leufkens HG, Cooper C, de Vries F (2009) Antipsychotic use and the risk of hip/femur fracture: a population-based case–control study. Osteoporos Int 20(9):1499–1506
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(2):89–93
Schneider JL, Fink HA, Ewing SK, Ensrud KE, Cummings SR (2008) Study of Osteoporotic Fractures (SOF) Research Group. The association of Parkinson’s disease with bone mineral density and fracture in older women. Osteoporos Int 19(7):1093–1097
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 34:21–24
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 21:32–38
Fink HA, Kuskowski MA, Taylor BC, Schousboe JT, Orwoll ES, Ensrud KE (2008) Osteoporotic Fractures in Men (MrOS) Study Group. Association of Parkinson’s disease with accelerated bone loss, fractures and mortality in older men: the Osteoporotic Fractures in Men (MrOS) study. Osteoporos Int 19(9):1277–1282
Vestergaard P, Rejnmark L, Mosekilde L (2007) Fracture risk associated with parkinsonism and anti-Parkinson drugs. Calcif Tissue Int 81:153–161
Arbouw ME, Movig KL, van Staa TP, Egberts AC, Souverein PC, de Vries F (2011) Dopaminergic drugs and the risk of hip or femur fracture: a population-based case–control study. Osteoporos Int 22(7):2197–2204
Walley T, Mantgani A (1997) The UK General Practice Research Database. Lancet 350:1097–1099
Van Staa TP, Abenhaim L (1994) The quality of information recorded on a UK database of primary care records: a study of hospitalization due to hypoglycemia and other conditions. Pharmacoepidemiol Drug Saf 3:15–21
Van Staa TP, Abenhaim L, Cooper C, Begaud B, Zhang B, Leufkens HG (2000) The use of a large pharmaco-epidemiological database to study exposure to oral glucocorticoids and risk of fractures: validation of study population and results. Pharmacoepidemiol Drug Saf 9:359–366
Kanis JA, Oden A, Johnell O, Jonsson B, de Laet C, Dawson A (2001) The burden of osteoporotic fractures: a method for setting intervention thresholds. Osteoporos Int 12(5):417–427
Hoehn M, Yahr M (1967) Parkinsonism: onset, progression and mortality. Neurology 17(5):427–442
NICE (2006) Parkinson’s disease. Diagnosis and management in primary and secondary care (NICE clinical guideline 35). National Collaborating Centre for Chronic Conditions, London
Norwegian Institute of Public Health (2012) WHO International Working Group for drug statistics methodology. Norwegian Institute of Public Health, WHO International Working Group for drug statistics methodology. http://www.whocc.no/atcddd/. Accessed May 11, 2012
Hernán MA, Logroscino G, Rodríguez LA (2004) A prospective study of alcoholism and the risk of Parkinson’s disease. J Neurol 251(7):vII14–vII17
Vestergaard P, Rejnmark L, Mosekilde L (2006) Anxiolytics, sedatives, antidepressants, neuroleptics and the risk of fracture. Osteoporos Int 17(6):807–816
Verdel BM, Souverein PC, Egberts TC, van Staa TP, Leufkens HG, de Vries F (2010) Use of antidepressant drugs and risk of osteoporotic and non-osteoporotic fractures. Bone 47(3):604–609
Liu B, Anderson G, Mittmann N, To T, Axcell T, Shear N (1998) Use of selective serotonin-reuptake inhibitors or tricyclic antidepressants and risk of hip fractures in elderly people. Lancet 351(9112):1303–1307
de Vries F, Setakis E, Zhang B, van Staa TP (2010) Long-acting {beta}2-agonists in adult asthma and the pattern of risk of death and severe asthma outcomes: a study using the GPRD. Eur Respir J 36(3):494–502
Bazelier M, Gallagher A, van Staa T, Cooper C, Leufkens H, Vestergaard P, De Vries F (2011) Use of thiazolidinediones and risk of osteoporotic fracture: disease or drugs? Pharmacoepidemiology and Drug Safety 20:S26
Iwamoto J, Takeda T, Matsumoto H (2011) Efficacy of oral bisphosphonates for preventing hip fracture in disabled patients with neurological diseases: a meta-analysis of randomized controlled trials among the Japanese population. Curr Med Res Opin 27(6):1141–1148
Acknowledgments
This work was funded in part by the European Calcified Tissue Society and the NIHR, Biomedical Research Unit in Musculoskeletal Sciences, Nuffield Orthopaedic Centre, Oxford.
Conflicts of interest
The department of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, employing SP, MTB, AB and FV has received unrestricted research funding from the Netherlands Organisation for Health Research and Development (ZonMW), the Dutch Health Care Insurance Board (CVZ), the Royal Dutch Pharmacists Association (KNMP), the private–public funded Top Institute Pharma (www.tipharma.nl) (includes cofunding from universities, government and industry), the EU Innovative Medicines Initiative (IMI), EU 7th Framework Program (FP7), the Dutch Medicines Evaluation Board, the Dutch Ministry of Health and industry (including GlaxoSmithKline, Pfizer and others). CC, WW and CN report no disclosures.
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Pouwels, S., Bazelier, M.T., de Boer, A. et al. Risk of fracture in patients with Parkinson’s disease. Osteoporos Int 24, 2283–2290 (2013). https://doi.org/10.1007/s00198-013-2300-2
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DOI: https://doi.org/10.1007/s00198-013-2300-2