Nationwide study on the risk of unprovoked venous thromboembolism in non-traumatic osteonecrosis of femoral head
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Endothelial dysfunction is a risk factor for osteonecrosis of femoral head (ONFH) and venous thromboembolism (VTE) [defined as deep venous thrombosis (DVT) or pulmonary embolism (PE)]. However, the risk of unprovoked VTE in non-traumatic ONFH patients remains unclear.
We investigated the relationship between ONFH and VTE using Taiwan National Health Insurance Research Database (NHIRD). Between 1997 and 2010, a total of 1514 non-traumatic ONFH patients were identified from 1,000,000 general populations after excluding initially concomitant diagnoses of DVT and PE, and subjects undergoing lower limb surgery within one year since enrollment. The comparison group (n = 15,140) without ONFH was set up by matching study cohort with age, gender, income and urbanization in a 1:10 ratio. Subjects diagnosed with VTE within one year after surgery were also excluded.
The patients with non-traumatic ONFH had significantly higher frequency of unprovoked VTE, including DVT, than general population (1.19 vs. 0.5%, p < 0.0007), whereas the frequency of PE was similar between these two groups (p = 0.4922). The cumulative incidence of VTE and DVT was also remarkably higher in the ONFH than non-ONFH group (all p < 0.001). After adjusting for age, gender, medications and comorbidities with multivariate analysis, the ONFH patients had a 2.3-fold increase in risk of DVT compared with non-ONFH counterparts (95% CI 1.28 to 4.13, p = 0.0053). Apart from ONFH, age > 65 years and hypertension were also identified as risk factors for DVT occurrence.
The incidence and risk of unprovoked VTE were significantly increased in the non-traumatic ONFH population.
KeywordsOsteonecrosis of femoral head Venous thromboembolism (VTE) Deep venous thrombosis (DVT) Population-based cohort study Endothelial dysfunction
Osteonecrosis of femoral head
Venous thromboembolic events
Deep vein thrombosis
National Health Insurance Research Database
National Health Research Institute
We would like to thank Institute of Occupational Medicine and Industrial Hygiene, College of Public Health, National Taiwan University, Taiwan for data acquisition. We also thank Health Information and Epidemiology Laboratory of Chang Gung Memorial Hospital, Chia-yi Branch, Taiwan (CLRPG6G0041) for the comments and assistance in data analysis. In addition, this study was supported by a grant from Chia-yi Chang Gung Memorial Hospital, and based on the National Health Insurance Research Database offered by the Bureau of National Health Insurance, Department of Health, Taiwan. We analyzed and interpreted the retrieved data for academic purpose, and therefore the viewpoint is not represented by the Bureau of National Health Insurance, Department of Health, or National Health Research Institutes.
P.H.S and H.J.C. participated in the design of the study, data acquisition, and analysis as well as drafting the manuscript. Y.H.Y and C.J.C. were responsible for the data acquisition and troubleshooting. J.Y.C. and H.K.Y. participated in data analysis, and interpretation. M.S.L. conceived of the study, participated in its design and coordination, and helped to draft the manuscript. All authors read and approved the final manuscript.
Compliance with ethical standards
Conflict of interest
This article is the sole work of the authors. All authors report no conflict of interest.
Ethical review committee statement
This study was approved by the Ethics Institutional Review Board of Chang Gung Memorial Hospital (No. 201600738B1).
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