Date 2013/March/4
Type of manuscript: research letter
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Manuscript title ：Alzheimer's disease correlates with increased risk of hip
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fracture in older people: a cohort in Taiwan
Running head：Alzheimer's disease and hip fracture
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Authors' full names:
Shih-Wei Lai1,2, Yu-Lung Chen1,2,Cheng-Li Lin3,4, Kuan-Fu Liao 5,6,7
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1
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2
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School of Medicine, 3Department of Public Health, and 5Graduate Institute of
Integrated Medicine, China Medical University, Taichung, Taiwan
Department of Family Medicine and 4Management Office for Health Data,
China Medical University Hospital, Taichung, Taiwan
6
Department of Internal Medicine, Taichung Tzu Chi General Hospital,
Taichung, Taiwan
7
Department of Health Care Administration, Central Taiwan University of
Science and Technology, Taichung, Taiwan
(The first two authors contributed equally to this study)
Corresponding author:
Kuan-Fu Liao, MD and MS
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
E-mail: kuanfuliao@yahoo.com.tw
1
Alzheimer's disease and hip fracture are two common disorders in older people and
both result in severe socioeconomic burden in the world. Growing evidence has
demonstrated that patients with Alzheimer's disease are associated with 2.1 to 3.2-fold
increased risk of hip fracture.1-3
To date, little evidence is available about the
relation between Alzheimer's disease and risk of hip fracture in older people in Taiwan.
Hence, we conducted this cohort study to explore this issue by analyzing the database
from the Taiwan National Health Insurance program. The details of insurance
program can be cited in previous studies.4,5 In this cohort study, the diagnosis of
Alzheimer's disease and hip fracture was based on the International Classification of
Diseases 9th Revision-Clinical Modification (ICD-9 codes). We chose 936 patients
aged 65 years or older with newly diagnosed Alzheimer's disease as the case group
(ICD-9 codes 331.0, 429 men and 507 women, mean age (standard deviation) 78.2 ±
6.8 years, mean follow-up period 3.5 ± 2.9 years) and 3744 subjects without
Alzheimer's disease as the companion group (1716 men and 2028 women, mean age
77.1 ±7.1 years, mean follow-up period 4.4 ±3.2 years), from 2000 to 2010. The index
date was defined as the date of diagnosing Alzheimer's disease. Both groups were
matched with gender, age and index year. Both groups were followed up to determine
the incidence of hip fracture (ICD-9 codes 820) until a subject received a diagnosis of
hip fracture or until December 31, 2010. Subjects with hip fracture, other dementia
2
(ICD-9 codes 290.0, 290.1, 290.2, 290.3, 290.4 and 294.1), or mental retardation
(ICD-9 codes 317–319) diagnosed before index date were excluded.
The Alzheimer's disease group had a significantly higher incidence of hip fracture
than that the non-Alzheimer's disease group did (27.8 vs. 11.7 per 1000 person-years,
95% CI =2.02, 2.80). The incidence rates, as stratified by gender, age and follow-up
period, were all significantly higher in the Alzheimer's disease group. Female subjects
with Alzheimer's disease had a higher incidence of hip fracture than male patients did
(30.8 vs. 24.0 per 1000 person-years). Subjects with Alzheimer's disease aged 75-84
had the highest incidence than other sub-groups did (incidence rate =37.8 per 1000
person-years). The stratified analysis by follow-up period showed a higher risk of
hip fracture among subjects with diagnosing Alzheimer's disease within 2 years
(incidence rate ratio =3.30, 95% CI =2.78, 3.92). Overall, 59.3% (54/91) of hip
fracture cases in Alzheimer's disease group occurred within 2 years after index date,
which was higher than that in non-Alzheimer's disease group (36.8% [70/190]).
So far, epidemiological studies have reported that Alzheimer's disease correlates with
increased risk of hip fracture in western countries.1-3 In this present study, we found
that the incidence rate ratio of hip fracture is 2.38 in subjects with Alzheimer's disease,
in comparison with the non-Alzheimer's disease group. We also found that the
incidence rates of hip fracture in our study among Alzheimer's disease group and
3
non-Alzheimer's disease group were higher than that in Baker et al’s study in United
Kingdom in 2011 (27.8 and 11.7 per 1000 person-years vs. 17.4 and 6.6 per 1000
person-years, respectively).3 This indicates that care quality of older people should be
further improved in our country. Furthermore, we found that the incidence of hip
fracture is higher within 2 years after index date. It means that patients with newly
diagnosed Alzheimer's disease during the first 2 years should be closely followed due
to higher risk of hip fracture.
We conclude that Alzheimer's disease is associated with 2.4-fold increased risk of hip
fracture in older people in Taiwan. Preventive strategy of falling should be intervened
to older people with Alzheimer's disease to reduce the risk of hip fracture.
4
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.
Specific author contributions
Shih-Wei Lai: substantial contributions to the conception of this article; conducted the
study and interpreted the data, initiated the draft of the article and critically revised
the article.
Yu-Lung Chen: conducted the study and interpreted the data, initiated the draft of the
article and critically revised the article.
Cheng-Li Lin: conducted the statistic analysis and critically revised the article.
Kuan-Fu Liao: conducted the study and critically revised the article.
Conflict of Interest Statement
The authors disclose no conflicts of interest.
5
References
1. Melton LJ, 3rd, Beard CM, Kokmen E, Atkinson EJ, O'Fallon WM. Fracture risk
in patients with Alzheimer's disease. J Am Geriatr Soc 1994;42:614-9.
2. Weller II. The relation between hip fracture and Alzheimer's disease in the
canadian national population health survey health institutions data, 1994-1995. A
cross-sectional study. Ann Epidemiol 2000;10:461.
3. Baker NL, Cook MN, Arrighi HM, Bullock R. Hip fracture risk and subsequent
mortality among Alzheimer's disease patients in the United Kingdom, 1988-2007. Age
Ageing 2011;40:49-54.
4. Lai SW, Liao KF, Liao CC, Muo CH, Liu CS, Sung FC. Polypharmacy correlates
with increased risk for hip fracture in the elderly: a population-based study. Medicine
(Baltimore) 2010;89:295-9.
5. Lai SW, Lin CH, Liao KF, Su LT, Sung FC, Lin CC. Association between
polypharmacy and dementia in older people: a population-based case-control study in
Taiwan. Geriatr Gerontol Int 2012;12:491-8.
6
Table 1. Incidence density of hip fracture for Alzheimer's disease group and non-Alzheimer's disease group
Non-Alzheimer's disease
All
gender
men
women
Alzheimer's disease
N
Case
Personyears
Incidence
rate
N
Case
Personyears
Incidence Incidence rate
rate
ratio (95% CI) †
3744
190
16292
11.7
936
91
3276
27.8
2.38(2.02, 2.80)
1716
2028
69
121
7655
8638
9.01
14.0
429
507
35
56
1459
1818
24.0
30.8
2.66(2.08, 3.42)
2.20(1.77, 2.73)
1288
2456
43
147
6863
9429
6.27
15.6
322
614
20
71
1396
1881
14.3
37.8
2.29(1.72, 3.04)
2.42(1.99, 2.94)
1097
2647
70
120
6382
9910
11.0
12.1
362
574
54
37
1491
1785
36.2
20.7
3.30(2.78, 3.92)
1.71(1.38, 2.13)
Age group (year)
65–74
75-84
Follow-up period
≤ 2 years
> 2 years
Incidence rate: per 1000 person-years
†
Incidence rate ratio: Alzheimer's disease vs. non-Alzheimer's disease
7