Date 2013/March/5 Title Page:
Manuscript title: No association between chronic osteomyelitis and Parkinson's disease in older people in Taiwan
Running head: Chronic osteomyelitis and Parkinson's disease Authors' full names:
Shih-Wei Lai1,2,Juhn-Cherng Liu1,3,Chun-Hung Tseng1,4,Chih-Hsin Muo5,6,Kuan-Fu Liao 7,8
1School of Medicine, 5Department of Public Health, and 7Graduate Institute of Integrated Medicine, andChina Medical University, Taichung, Taiwan
2Department of Family Medicine, 3Department of Radiology, 4Department of Neurology, and 6Management Office for Health Data, China Medical
University Hospital, Taichung, Taiwan
8Department of Internal Medicine, Taichung Tzu Chi General Hospital, Taichung, Taiwan
Corresponding author: Kuan-Fu Liao, Department of Internal Medicine, Taichung Tzu Chi General Hospital, No.66, Sec. 1, Fongsing Road, Tanzi District, Taichung City, 427, Taiwan
Phone: 886-4-2205-2121 Fax: 886-4-2203-3986
ABSTRACT
The aim of this study is to explore whether chronic osteomyelitis is associated with an increased risk of Parkinson's disease in older people in Taiwan. By using the database from the Taiwan National Health Insurance program, this case-control study consisted of 4686 subjects aged 65 years or older with newly diagnosed Parkinson's disease as the case group and 18744 subjects without Parkinson's disease as the control group. After adjusting for cofounding factors, multivariable logistic regression analysis showed no association between chronic osteomyelitis and Parkinson's disease in both gender (odds ratio = 0.71, 95% CI = 0.37-1.36 in men, and odds ratio = 0.90, 95% CI = 0.45-1.83 in women, respectively). We conclude that no association can be detected between chronic osteomyelitis and Parkinson's disease in older people in Taiwan.
Parkinson's disease is a common neurodegenerative disease mainly affecting the older people. Despite the real causes of Parkinson's disease remain unknown, extensive evidence has shown that chronic neuroinflammation associated with central and systemic inflammation might play a key role in the pathogenesis of Parkinson's disease.1-3 On the other hand, chronic osteomyelitis is also a chronic inflammatory
disorder mainly caused by bacterial infection. Therefore, we make a hypothesis that chronic osteomyelitis could be associated with an increased risk of Parkinson's disease through chronic inflammatory process. In order to explore this issue, we conducted this case-control study by utilizing the database from the Taiwan National Health Insurance program. The details of insurance program can be cited in previous studies.6-8 This present study included 4686 subjects aged 65 years or older with new diagnosis of Parkinson's disease as the cases (2457 men, mean age 77.0 years and standard deviation 6.18 years, and 2229 women, mean age 76.3 years and standard deviation 6.51 years, respectively) (based on International Classification of Diseases 9th Revision-Clinical Modification, ICD-9 332), and 18744 subjects without
Parkinson's disease as the controls (9828 men, mean age 76.4 years and standard deviation 6.64 years, and 8916 women, mean age 75.6 years and standard deviation 7.02 years, respectively). The date of diagnosing Parkinson's disease was defined as the index date. The cases and the controls were matched with age, gender, and index date from 2000 to 2010. Chronic osteomyelitis (ICD-9 730.1x) was diagnosed before
cases (0.53%) and 55 subjects with chronic osteomyelitis among controls (0.56%) (Chi-square test for P > 0.05). In women, there were 12 subjects with chronic osteomyelitis among Parkinson disease cases (0.54%) and 37 subjects with chronic osteomyelitis among control subjects (0.41%) (Chi-square test for P > 0.05). After controlling for cofounding factors, multivariable logistic regression analysis showed that no association could be detected between chronic osteomyelitis and Parkinson's disease in both gender (odds ratio = 0.71, 95% CI = 0.37-1.36 in men, and odds ratio = 0.90, 95% CI = 0.45-1.83 in women, respectively) (Table 1).
Despite the literature has shown that chronic inflammatory process might be involved in chronic osteomyelitis and Parkinson’s disease,1-5 however, no relevantstudies can be cited to date. In this present study, no association is found between chronic osteomyelitis and Parkinson's disease in both genders. However, only 117 patients with chronic osteomyelitis were selected. That is, the number of chronic osteomyelitis is probable too small to reach clinical significance. Therefore, additional studies with large sample size are warranted to clarify this issue.
Funding
This study was supported in part by Taiwan Department of Health Clinical Trial and Research Center of Excellence (DOH102-TD-B-111-004).The funding agency did not influence the study design, data collection and analysis, decision to publish, or
preparation of the manuscript. Acknowledgements
The authors thank the National Health Research Institute in Taiwan for providing the insurance claims data.
Conflict of Interest Statement
REFERENCES
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Table 1. Odds ratio and 95% confidence interval of Parkinson's disease associated with chronic osteomyelitis and other co-morbidities
Men Women
Crude Adjusted † Crude Adjusted †
Variable OR (95%CI) OR (95%CI) OR (95%CI) OR (95%CI)
Age (every one year) 1.02 (1.01-1.02) 1.01 (1.00-1.02) 1.01 (1.01-1.02) 1.01 (1.00-1.02) Co-morbidities before
index date (yes vs. no)*
Chronic osteomyelitis 0.95 (0.52-1.73) 0.71 (0.37-1.36) 1.30 (0.68-2.50) 0.90 (0.45-1.83) Obesity 1.17 (0.64-2.12) -- 1.74 (1.17-2.60) 1.43 (0.94-2.19) Diabetes mellitus 1.36 (1.23-1.51) 0.86 (0.77-0.97) 1.52 (1.38-1.68) 0.98 (0.87-1.09) Hyperlipidemia 1.85 (1.68-2.04) 1.23 (1.11-1.37) 1.49 (1.35-1.63) 0.96 (0.86-1.07) Hypertension 2.51 (2.24-2.80) 1.48 (1.31-1.68) 2.80 (2.44-3.20) 1.82 (1.58-2.11) Cerebrovascular disease 1.86 (1.67-2.07) 1.30 (1.15-1.46) 1.67 (1.48-1.89) 1.12 (0.98-1.28) Dementia 4.70 (3.94-5.60) 3.29 (2.72-3.98) 4.79 (3.99-5.76) 3.44 (2.82-4.19) Major depressive disorder 3.41 (2.88-4.05) 2.09 (1.74-2.52) 3.32 (2.77-3.76) 2.19 (1.86-2.58) Chronic kidney disease 1.61 (1.37-1.88) 0.99 (0.83-1.17) 1.44 (1.19-1.74) 0.99 (0.81-1.21) Head injury 1.59 (1.40-1.79) 1.29 (1.13-1.48) 1.67 (1.47-1.91) 1.31 (1.13-1.50)
Tobacco use 1.75 (1.16-2.64) 1.32 (0.84-2.05) --
--Alcoholism 1.76 (1.13-2.75) 1.24 (0.76-2.03) 3.33 (1.02-1.09) 2.80 (0.81-9.69) Polypharmacy 4.03 (3.67-4.43) 3.17 (2.85-3.52) 3.64 (3.30-4.01) 2.85 (2.55-3.17) *The co-morbidities included before index date were as follows: chronic osteomyelitis (ICD-9 730.1x), obesity (ICD-9 278.00 and 278.01), diabetes mellitus (ICD-9 250), hyperlipidemia (ICD-9 272.0, 272.1, 272.2, 272.3 and 272.4), hypertension (ICD-9 401-405), cerebrovascular disease (ICD-9 430– 438), dementia (ICD-9 290.0, 290.1, 290.2, 290.3, 290.4, 294.1 and 331.0), major depressive disorder (ICD-9 296.2, 296.3, 300.4 and 311), chronic kidney disease (ICD-9 585, 586, 588.8 and 588.9), head injury (ICD-9 850-854 and 959.01), tobacco use (ICD-9 305.1) and alcoholism (ICD-9 303, 305.00, 305.01, 305.02, 305.03 and V11.3). Polypharmacy was defined as the daily average use of 5 or more
