Wu et al.

SpringerPlus (2016) 5:1378

DOI 10.1186/s40064-016-3090-8

Open Access

RESEARCH

Increased migraine risk inosteoporosis

patients: a nationwide populationbased study
ChiehHsinWu3,4, ZiHaoZhang5, MingKungWu6, ChiuHuanWang7, YingYiLu1,2* andChihLungLin4,8*

Abstract
Background: Osteoporosis and migraine are both important public health problems and may have overlapping
pathophysiological mechanisms. The aim of this study was to use a Taiwanese population-based dataset to assess
migraine risk in osteoporosis patients.
Methods: The Taiwan National Health Insurance Research Database was used to analyse data for 40,672 patients
aged 20years who had been diagnosed with osteoporosis during 19962010. An additional 40,672 age-matched
patients without osteoporosis were randomly selected as the non-osteoporosis group. The relationship between
osteoporosis and migraine risk was estimated using Cox proportional hazard regression models.
Results: During the follow-up period, 1110 patients with osteoporosis and 750 patients without osteoporosis devel
oped migraine. After controlling for covariates, the overall incidence of migraine was 1.37-fold higher in the osteopo
rosis group than in the non-osteoporosis group (3.72 vs. 1.24 per 1000 person-years, respectively). Migraine risk factors
included high Charlson Comorbidity Index score, female gender, hypertension, depression, asthma, allergic rhinitis,
obesity, and tobacco use disorder.
Conclusions: Our results indicate that patients with a history of osteoporosis had a higher risk of migraine.
Keywords: Osteoporosis, Migraine, Nationwide population-based study
Background
Both osteoporosis and migraine are common conditions
that can affect quality of life and can impose large social
and economic burdens (Kuo et al. 2015; Manandhar
etal. 2015a, b; Mbewe etal. 2015; Rao etal. 2015; Steiner
etal. 2015; Lampl etal. 2016). The National Institutes of
Health Consensus Development Conference Statement
defines osteoporosis as a skeletal disorder characterized
by diminished bone strength resulting in increased fracture risk. Bone strength is measured in terms of both
bone mineral density (BMD) and bone quality (Nih Consensus Development Panel on Osteoporosis Prevention
and Therapy 2001). In elderly populations, osteoporosis
*Correspondence: actinp@hotmail.com; chihlung1@yahoo.com

Zi-Hao Zhang and Ming-Kung Wu have contributed equally to this work

1
Department ofDermatology, Kaohsiung Veterans General Hospital, No.
386 Dazhong 1st Rd, Kaohsiung81362, Taiwan
4
Department ofNeurosurgery, Kaohsiung Medical University Hospital,
Kaohsiung Medical University, No. 100 Tzyou 1st Road, Kaohsiung80708,
Taiwan
Full list of author information is available at the end of the article

affects approximately 30 % of women and 12 % of men

(Rachner et al. 2011). Migraine is a neurological disorder that manifests as a debilitating headache associated
with altered sensory perception (Goadsby et al. 2002;
Charles 2013; Baykan etal. 2015; Manandhar etal. 2015a,
b). The International Headache Society defines migraine
as a headache that lasts for 472 h and has at least two
of the following characteristics: pulsating quality, unilateral localization, moderate-to-severe pain intensity, and
aggravation by movement (Headache Classification Subcommittee of the International Headache 2004). Previous
studies have identified interacting relationships among
migraine, various sleep disorders, depression, psoriasis,
restless legs syndrome and cardiovascular disease (Kelman and Rains 2005; Pompili et al. 2009; Schurks et al.
2009; Cho etal. 2015; Egeberg etal. 2015; Kim etal. 2016;
Risal et al. 2016). Migraine is associated with episodes
of local sterile meningealinflammation, hypersensitized
pain pathways, and increased inflammatory cytokines
that contribute to the pathogenesis of osteoporosis, such

2016 The Author(s). This article is distributed under the terms of the Creative Commons Attribution 4.0 International License
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Wu et al. SpringerPlus (2016) 5:1378

as interleukins (ILs) or tumor necrosis factor- (Braun

and Schett 2012; Egeberg et al. 2015). Like osteoporosis and other inflammatory conditions, migraine is also
apparently associated with systemic endothelial dysfunction (Vanmolkot et al. 2007; Sacco et al. 2013; Steyers
and Miller 2014). Although no recent studies have suggested a link between osteoporosis and migraine, both
conditions are independent risk factors for cardiovascular disease (Sumino et al. 2008; Bigal et al. 2010; Hyder
etal. 2010), and both are comorbid with pain-related and
psychiatric conditions (Kalaydjian and Merikangas 2008;
Radaei etal. 2014). We therefore investigated the impact
of osteoporosis on migraine risk in a nationwide cohort
in Taiwan.

Methods
Database

This population-based cohort study used data obtained

from the Taiwan National Health Insurance Research
Database (NHIRD) maintained by the national health
care system of Taiwan. The NHIRD is an encrypted secondary database containing medical data for approximately 99 % of the 23.74 million residents of Taiwan.
The Taiwan national health insurance program allows
researchers to access this database of administrative data
for patients. The NHIRD files are composed of comprehensive use and enrollment information of the patients.
Besides, under regulations of the Personal Electronic
Data Protection Law of Taiwan, all citizens and hospital identities in the NHIRD database were decoded. This
retrospective cohort study analysed 19962010 data contained in a subset of the NHIRD, the Longitudinal Health
Insurance Database 2010, which comprises data for 1
million beneficiaries randomly sampled from the primary
NHIRD. In this study, diseases were identified and classified according to the diagnostic codes of the International Classification of Diseases, Ninth Revision, Clinical
Modification (ICD-9-CM).

Page 2 of 8

code assigned by an orthopaedist, and at least one BMD

examination. The index date was defined as the date of
the first clinical visit for osteoporosis. A migraine (ICD9-CM code 346) was defined as a history of two or more
migraine diagnoses in ambulatory visits or one or more
migraine diagnoses in inpatient care as well as a record
of an ICD-9 code for migraine assigned by a neurologist. The date of diagnosis was defined as the date of the
first diagnosis of osteoporosis. Matching control subjects
were assigned an identical pseudo date of diagnosis,
which was the date of diagnosis in matched cases. The
exclusion criteria were diagnosis of migraine before or on
the index date, incomplete information, and age younger
than 20years.
The ratio of osteoporosis to non-osteoporosis patients
was kept at 1:1 to enhance the power of statistical tests
and to obtain a sufficient number of migraine cases for
stratified analyses. The patients in the non-osteoporosis cohort were selected by a simple random sampling
method in which one insured patient without osteoporosis was randomly selected and frequency matched
with each person in the osteoporosis cohort in the same
period by age, gender, and year of osteoporosis diagnosis. A post hoc sample size was calculated to determine
statistical power. Logistic regression analysis was used to
obtain a 4-digit match of the propensity score for each
patient with the covariates, including age and gender. As
a result, 40,672 subjects were enrolled in the non-osteoporosis cohort. Figure 1 shows a flowchart of the study
procedure.
Outcome andcomorbidities

The patients in both the osteoporosis and non-osteoporosis cohorts were followed up until diagnosis with

Ethical approval

The study was performed in accordance with the Declaration of Helsinki guidelines and was also evaluated and
approved by the Institutional Review Board of Kaohsiung Medical University Hospital (KMUHIRB-EXEMPT
(II)-20160016).
Study population

The study cohort included 40,672 patients aged 20years

or older who had been diagnosed with osteoporosis
(ICD-9-CM code 733.0) during 19962010. To maximize
accuracy, the analysis was limited to patients who had a
record of 2 osteoporosis diagnoses during ambulatory
visits or 1 diagnoses during inpatient care, an ICD-9

Fig.1 Flow diagram of the present study from the National Health
Insurance Research Database in Taiwan. LHIDlongitudinal Health
Insurance Database

Wu et al. SpringerPlus (2016) 5:1378

migraine, withdrawal from insurance, or the end of 2010,

whichever occurred first. Baseline comorbidities identified by ICD-9-CM codes in the claims records before
the index date included hypertension (ICD-9-CM codes
401-405), diabetes mellitus (ICD-9-CM code 250), hyperlipidemia (ICD-9-CM code 272), depression (ICD-9-CM
codes 296.2, 296.3, 300.4 and 311), asthma (ICD-9-CM
code 493), allergic rhinitis (ICD-9-CM code 477), psoriasis (ICD-9-CM code 696.1), obesity (ICD-9-CM code
278), tobacco use disorder (ICD-9-CM code 350.1), and
alcohol attributed disease (ICD-9-CM codes 291.0-9,
303, 305.0, 357.5, 425.5, 535.3, 571.0-3, 980.0 and V11.3).
The Charlson Comorbidity Index (CCI) score was used
to assess the severity of comorbidities, i.e., myocardial
infarction, congestive heart failure, peripheral vascular
disease, cerebrovascular disease, dementia, chronic pulmonary disease, rheumatic disease, peptic ulcer disease,
liver disease (mild, moderate, or severe), diabetes (with
or without chronic complication), hemiplegia or paraplegia, renal disease, any malignancy (including lymphoma
and leukemia but excluding skin malignancy), metastatic
solid tumor, human immunodeficiency virus infection
and acquired immune deficiency syndrome. The CCI
scores were then categorized into four levels: 0, 12, 34
and 5.
Statistical analyses

Chi square test was used to compare distributions of

categorical demographics and clinical characteristics
between the osteoporosis and non-osteoporosis cohorts.
The Student t test and Wilcoxon rank-sum test were
used as appropriate to compare mean age and followup time (y) between the two cohorts. The KaplanMeier
method was used to estimate cumulative incidence,
and the differences between the curves were tested by
2-tailed log-rank test. For osteoporosis patients, survival
was calculated until hospitalization, an ambulatory visit
for migraine, or the end of the study period (December
31, 2010), whichever occurred first. Incidence rates of
migraine estimated in 1000 person-years were compared
between the two cohorts. Univariable and multivariable Cox proportional hazard regression models were
used to calculate hazard ratios (HRs) and 95 % confidence intervals (CIs) for migraine if the proportional
hazards assumption was satisfied. The multivariable Cox
models were adjusted for age, gender, CCI score, and
relevant comorbidities. A 2-tailed P value of <0.05 was
considered statistically significant. All data processing
and statistical analyses were performed using Statistical
Analysis Software, version 9.4 (SAS Institute, Cary, NC,
USA).

Page 3 of 8

Results
Baseline characteristics ofpatients withand
withoutosteoporosis

The baseline demographic characteristics and comorbidities in the two cohorts are presented in Table 1. In the
osteoporosis cohort, 82.48% patients were female. Compared to the non-osteoporosis cohort, the osteoporosis
cohort had significantly higher percentages of patients
with hypertension (70.12 vs. 54.07, P < 0.001), diabetes mellitus (38.58 vs. 27.71, P < 0.001), hyperlipidemia
(61.28 vs. 43.96, P < 0.001), depression (21.21 vs. 11.71,
P<0.001), asthma (28.77 vs. 19.20, P<0.001), allergic rhinitis (44.62 vs. 32.38, P < 0.001), psoriasis (2.15 vs. 1.43,
P<0.001), obesity (2.64 vs. 2.11, P<0.001), tobacco use
disorder (1.91 vs. 1.04, P<0.001) and alcohol-attributable
disease (2.63 vs. 1.92, P<0.001). The osteoporosis cohort
also had higher CCI scores. During a median observation time of 3.5 years, 2.73 % (1110) of the osteoporosis
patients had migraine (interquartile range [IQR] 1.56.2).
The migraine incidence of osteoporosis cohort was significantly (P < 0.001) higher than that in the non-osteoporosis patients (751 with migraine out of 40,672 age- and
gender-matched controls [1.85 %]) during a median
observation time of 7.2 years [IQR 4.810.5]). Migraine
development was significantly faster in the osteoporosis group (3.5 years) compared to the non-osteoporosis
group (7.2years) for the respective observation periods.
Migraine incidence andrisk

The migraine incidence and HRs by gender, age and

comorbidity are stratified in Table2. During the follow-up
period, migraine developed in 2.73% (1110) of the osteoporosis patients and in 1.85% (750) of the non-osteoporosis
patients. The overall migraine risk was 1.37 times greater in
the osteoporosis group compared to the non-osteoporosis
group (3.72 vs. 1.24 per 1000 person-years, respectively)
after adjusting for age, gender, CCI, and related comorbidities (hypertension, diabetes mellitus, hyperlipidemia,
depression, asthma, allergic rhinitis, psoriasis, obesity,
tobacco use disorder and alcohol-attributable disease).
The gender-specific analyses showed that, in both
cohorts, the incidence of osteoporosis was higher in
women than in men (3.61 vs. 2.28 per 1000 person-years,
respectively, in the osteoporosis cohort; 1.35 vs. 0.73 per
1000 person-years, respectively, in the non-osteoporosis
cohort). Additionally, the osteoporosis group had a significantly higher migraine risk in both genders (adjusted
HR 1.34, 95% CI 1.191.49 for women; adjusted HR 1.66,
95% CI 1.192.31 for men).
Although the incidence of migraine was consistently
higher in all age groups in the osteoporosis cohort

Wu et al. SpringerPlus (2016) 5:1378

Page 4 of 8

Table1 Baseline characteristics ofpatients withand withoutosteoporosis

Variables

Osteoporosis
Yes (N=40,672)

Migraine patients, n (%)

1110 (2.73)

Period of developing migraine, median (IQR), years

Mean age at diagnosis of migraine, years

3.5 (1.56.2)
57.9 (10.4)

P value
No (N=40,672)
751 (1.85)
7.2 (4.810.5)
62.6 (10.3)

<0.001
<0.001
<0.001

Age group, n (%)

2049
50

7361 (18.10)

7361 (18.10)

33,311 (81.90)

33,311 (81.90)

1.000

Gender, n (%)
Men
Women

7125 (17.52)

7125 (17.52)

33,547 (82.48)

33,547 (82.48)

1.000

Charlson Comorbidity Index, n (%)

0

1912 (4.70)

12

9667 (23.77)

7744 (19.04)
14,437 (35.50)

34

11,911 (29.29)

9861 (24.25)

17,182 (42.25)

8630 (21.22)

<0.001

Co-morbidity, n (%)
Hypertension

28,521 (70.12)

21,991 (54.07)

<0.001

Diabetes mellitus

15,693 (38.58)

11,272 (27.71)

<0.001

Hyperlipidemia

24,923 (61.28)

17,879 (43.96)

<0.001

8625 (21.21)

4764 (11.71)

<0.001

Depression
Asthma

11,700 (28.77)

7807 (19.20)

<0.001

Allergic rhinitis

18,146 (44.62)

13,168 (32.38)

<0.001

Psoriasis

874 (2.15)

583 (1.43)

<0.001

Obesity

1073 (2.64)

857 (2.11)

<0.001

Tobacco use disorder

Alcohol attributed disease

776 (1.91)

422 (1.04)

<0.001

1069 (2.63)

780 (1.92)

<0.001

IQR interquartile range, SD standard deviation

compared to the non-osteoporosis cohort, the migraine

risk decreased with age. Age-specific risk comparisons showed that, compared to the non-osteoporosis
cohort, the osteoporosis cohort had a significantly
higher migraine risk in patients under 50 years old
(adjusted HR 1.46, 95 % CI 1.171.82, P < 0.001) than
in patients over 50 years old (HR 1.34, 95 % CI 1.20
1.50, P < 0.001). Regardless of comorbidities, migraine
risk was higher in osteoporosis patients than in nonosteoporosis patients. However, the migraine risk contributed by osteoporosis decreased in the presence of
comorbidity.
The KaplanMeier curves for the cumulative incidence
of migraine between the osteoporosis and non-osteoporosis groups at the 15-year follow up are compared in
Fig. 2. The KaplanMeier curves showed a significantly
higher cumulative incidence of migraine in the osteoporosis cohort compared to the non-osteoporosis cohort
(log-rank test P<0.001).

Risks factors formigraine inosteoporosis patients

The Cox regression analysis revealed the following risk

factors for migraine in the osteoporosis group: high CCI
score, female gender, hypertension, depression, asthma,
allergic rhinitis, obesity, and tobacco use disorder. Risk
factors for migraine were female gender (adjusted HR
1.51, 95% CI 1.231.85), hypertension (adjusted HR 1.19,
95 % CI 1.021.38), depression (adjusted HR 2.36, 95 %
CI 2.092.66), asthma (adjusted HR 1.28, 95% CI 1.13
1.45), allergic rhinitis (adjusted HR 1.46, 95 % CI 1.29
1.66), obesity (adjusted HR 1.79, 95 % CI 1.402.28),
tobacco use disorder (adjusted HR 2.30, 95 % CI 1.78
2.97) and high CCI (adjusted HR 1.57, 95% CI 1.441.71)
(Table3).

Discussion
To our knowledge, this is the first nationwide populationbased study of the relationship between osteoporosis and
subsequent migraine in an Asian population. During the

Wu et al. SpringerPlus (2016) 5:1378

Page 5 of 8

Table2 Incidence andhazard ratios ofmigraine bydemographic characteristics andcomorbidity amongpatients withor
withoutosteoporosis
Variables

Patients withosteoporosis

Overall

Patients withoutosteoporosis

Compared tonon- osteoporosis

Migraine

PYs

Rate

Migraine

PYs

Rate

CrudeHRa (95% CI)

Adjusted HRa (95%

CI)

1110

324,126.20

3.42

751

604,550.99

1.24

2.48 (2.252.73)c

1.37 (1.231.51)c

104

45,604.93

2.28

78

106,313.43

0.73

2.80 (2.043.85)c

1.66 (1.192.31)d

1.34 (1.191.49)c

Gender
Men
Women

1006

278,521.27

3.61

573

498,237.56

1.35

2.39 (2.172.66)

252

64,474.34

3.91

130

109,506.02

1.19

2.97 (2.393.68)c

1.46 (1.171.82)c

1.34 (1.201.50)c

Stratify by age
2049
50
Comorbidity
No
Yes

858

259,651.83

3.30

621

495,044.97

1.25

2.37 (2.122.64)

19

20,949.87

0.91

43

127,923.68

0.34

2.41 (1.404.14)e

1.78 (1.033.06)f

1.49

1.34 (1.221.49)c

1091

303,176.33

3.59

708

476,627.31

2.18 (1.972.41)

PYs person-years, Rate incidence rate in per 1000 person-years, 95% CI 95% confidence interval, HR hazard ratio
a

Model adjusted for age, gender, Charlson Comorbidity Index and relevant comorbidities (hypertension, diabetes mellitus, hyperlipidemia, depression, asthma,
allergic rhinitis, psoriasis, obesity, tobacco use disorder and alcohol attributed disease)

Patients with any examined comorbidities, including hypertension, diabetes mellitus, hyperlipidemia, depression, asthma, allergic rhinitis, psoriasis, obesity, tobacco
use disorder and alcohol attributed disease, were classified as the comorbidity group

P<0.001

P=0.003

P=0.001

P=0.037

Fig.2 Cumulative incidence of migraine for adult patients with osteoporosis and the general population control cohort

follow-up period, migraine developed in 2.73 % (1110)

patients with osteoporosis and in 1.85 % (750) patients
without osteoporosis. After controlling for potential
confounding factors, migraine risk was 1.37-fold higher
in the osteoporosis group than in the non-osteoporosis
group. Patients with osteoporosis, particularly those with
high CCI score, female gender, hypertension, depression,
asthma, allergic rhinitis, obesity, and tobacco use disorder, had a high migraine risk.
The exact mechanisms underlying the relationship
between migraine and osteoporosis are likely to be elusive. However, several lines of evidence in the literature
suggest that osteoporosis and migraine have a shared

pathophysiology. First, bone density is significantly associated with magnesium, an essential micronutrient with a
wide range of metabolic, structural and regulatory functions (Jahnen-Dechent and Ketteler 2012). In humans,
magnesium deficiency contributes to osteoporosis. Low
serum magnesium is a co-contributing factor in osteopenia in adults with sickle cell anemia (Elshal et al. 2012).
Moreover, an association between serum magnesium
and bone density has been identified in pre- and postmenopausal women (Saito etal. 2004; Song etal. 2007).
Magnesium deficiency also has a strong association
with migraine attacks (Welch and Ramadan 1995). Gallai etal. showed that individuals suffering from migraine

Wu et al. SpringerPlus (2016) 5:1378

Page 6 of 8

Table
3Cox regression model: significant predictors
ofmigraine afterosteoporosis
Variables

Adjusted HRa

(95% CI)

P value

Age

0.76

(0.720.81)

<0.001

Charlson Comorbidity Index

1.57

(1.441.71)

<0.001
<0.001

Female gender

1.51

(1.231.85)

Hypertension

1.19

(1.021.38)

0.027

Depression

2.36

(2.092.66)

<0.001

Asthma

1.28

(1.131.45)

0.001

Allergic rhinitis

1.46

(1.291.66)

<0.001

Obesity

1.79

(1.402.28)

<0.001

Tobacco use disorder

2.30

(1.782.97)

<0.001

The adjusted HR and 95% CI were estimated by a stepwise the Cox proportional
hazards regression method
HR hazard ratio, 95% CI 95% confidence interval
a

Model adjusted for age, gender, Charlson Comorbidity Index and relevant
comorbidities (hypertension, diabetes mellitus, hyperlipidemia, depression,
asthma, allergic rhinitis, psoriasis, obesity, tobacco use disorder and alcohol
attributed disease)

headaches had lower plasma and saliva magnesium levels between the attacks compared to controls without
migraine headaches (Gallai etal. 1992). Both osteoporosis and migraine are associated with hypomagnesemia,
which suggests an interplay between osteoporosis and
migraine. Second, the relationship between migraine and
osteoporosis might be explained at least partly by their
common inflammatory mediators. Neurogenic inflammation resulting from activation of the trigeminal vascular system is the main cause of the pain produced by
migraine. Stimulation of trigeminal ganglion nociceptors
induces the release of proinflammatory substances, particularly calcitonin gene-related peptide (CGRP) (Silberstein 2004; Dalkara etal. 2006; DAndrea and Leon 2010).
Individuals with osteoporosis also had elevated CGRP
levels (Lin etal. 2001). Experimental injections of CGRP
into eviratated rats indicate that CGRP may also affect
the release of osteoblastic cytokines and may indi-rectly
regulate the suppressed bone resorption of osteoclasts
(Valentijn et al. 1997). Inflammatory cytokines associated with osteoporosis such as tumor necrosis factorand IL-6 (Braun and Schett 2012; Wiseman etal. 2014)
are elevated at the onset of migraine attacks (Perini etal.
2005). Finally, C-reactive protein, which increases during systemic inflammation, is elevated in both osteoporosis and migraine (Vanmolkot and de Hoon 2007; de
Pablo et al. 2012). Thus, the inflammatory state caused
by osteoporosis may increase the frequency or severity
of migraine headaches by exacerbating the inflammatory
response.
The strength of our study is the use of a large sample
that is highly representative of the general population

and provides sufficient statistical power to identify an

association between osteoporosis and migraine risk.
However, several limitations must be considered when
interpreting these findings. One limitation is that the
analysis only included observational data, i.e., ICD9-CM codes, the accuracy of which depends on the
clinical performance of individual physicians. That
is, the accuracy of diagnostic codes in the database is
a potential limitation. Notably, however, the Taiwan
National Health Insurance program requires all insurance claims to be reviewed and audited by medical
reimbursement specialists in the Bureau of National
Health Insurance, which supports the validity and accuracy of the observed associations between osteoporosis
and migraine. Furthermore, many studies have already
used the NHIRD database because of its large size and
long follow-up period (Chiu etal. 2015; Chu etal. 2015;
Wu et al. 2015, 2016a, b, c, d). A second limitation is
that the NHIRD does not contain detailed data that
can be used to identify osteoporosis risk factors such
as exercise capacity, body mass index, smoking, alcohol
consumption, and dietary habits. A third limitation is
that the Taiwan population analysed in this study was
mostly of Chinese descent. Therefore, caution is needed
when extrapolating the results to other ethnic groups;
further studies are needed to determine whether these
findings can be generalized to other ethnicities. Finally,
this retrospective cohort study may have been biased
by unrecognized or unadjusted confounding variables,
despite the use of statistical methods for reducing their
confounding effects.

Conclusions
In summary, this nationwide population-based cohort
study revealed that adult patients with osteoporosis
had a significantly higher risk of developing subsequent
migraine compared to controls without osteoporosis.
Clinicians should be aware that osteoporosis is a potential risk factor for migraine. Further studies are recommended to confirm this association and to explore its
mechanisms.
Abbreviations
BMD: bone mineral density; CGRP: calcitonin gene-related peptide; CCI: Charl
son Comorbidity Index; CI: confidence interval; HR: hazard ratio; ICD-9-CM:
International Classification of Diseases, Ninth Revision, Clinical Modification; IL:
interleukin; NHIRD: National Health Insurance Research Database.
Authors contributions
CHW participated in study design, interpreted result and drafted the manu
script. ZHZ participated in study design and performed the statistical analysis.
MKW participated in study design and helped to draft the manuscript. CHW
helped to perform the statistical analysis and coordination. YYL and CLL con
ceived of the study, participated in its design, coordination and revising the
manuscript. All authors read and approved the final manuscript.

Wu et al. SpringerPlus (2016) 5:1378

Author details
1
Department ofDermatology, Kaohsiung Veterans General Hospital, No.
386 Dazhong 1st Rd, Kaohsiung81362, Taiwan. 2Cosmetic Applications
andManagement Department, Yuh-Ing Junior College ofHealth Care
andManagement, Kaohsiung, Taiwan. 3Graduate Institute ofMedicine,
College ofMedicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
4
Department ofNeurosurgery, Kaohsiung Medical University Hospital,
Kaohsiung Medical University, No. 100 Tzyou 1st Road, Kaohsiung80708,
Taiwan. 5Department ofNeurosurgery, The No. 7 Peoples Hospital ofHebei
Province, Dingzhou073000, Hebei, Peoples Republic ofChina. 6Department
ofPsychiatry, Kaohsiung Chang Gung Memorial Hospital andChang Gung
University College ofMedicine, Kaohsiung807, Taiwan. 7Department ofNurs
ing, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No.
100 Tzyou 1st Road, Kaohsiung80708, Taiwan. 8Department ofNeurosurgery,
Faculty ofMedicine, College ofMedicine, Kaohsiung Medical University,
Kaohsiung, Taiwan.
Competing interests
All authors declare that they have no competing interests.
Received: 12 July 2016 Accepted: 17 August 2016

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