Date 2013/March/4
Type of manuscript: research letter
Manuscript title ：Alzheimer's disease correlates with increased risk of hip fracture in older people: a cohort in Taiwan
Running head：Alzheimer's disease and hip fracture
Authors' full names:
Shih-Wei Lai1,2, Yu-Lung Chen1,2,Cheng-Li Lin3,4, Kuan-Fu Liao 5,6,7
1School of Medicine, 3Department of Public Health, and 5Graduate Institute of
Integrated Medicine, China Medical University, Taichung, Taiwan
2Department of Family Medicine and 4Management Office for Health Data,
China Medical University Hospital, Taichung, Taiwan
6Department of Internal Medicine, Taichung Tzu Chi General Hospital,
Taichung, Taiwan
7Department 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
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. 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
(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
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.
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
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.
Table 1. Incidence density of hip fracture for Alzheimer's disease group and non-Alzheimer's disease group Non-Alzheimer's disease Alzheimer's disease
N Case Person-years Incidence rate N Case Person-years Incidence rate Incidence rate ratio (95% CI) † All 3744 190 16292 11.7 936 91 3276 27.8 2.38(2.02, 2.80) gender men 1716 69 7655 9.01 429 35 1459 24.0 2.66(2.08, 3.42) women 2028 121 8638 14.0 507 56 1818 30.8 2.20(1.77, 2.73)
Age group (year)
65–74 1288 43 6863 6.27 322 20 1396 14.3 2.29(1.72, 3.04)
75-84 2456 147 9429 15.6 614 71 1881 37.8 2.42(1.99, 2.94)
Follow-up period
≤ 2 years 1097 70 6382 11.0 362 54 1491 36.2 3.30(2.78, 3.92)
> 2 years 2647 120 9910 12.1 574 37 1785 20.7 1.71(1.38, 2.13)
Incidence rate: per 1000 person-years
