Taiwanese Journal of Obstetrics & Gynecology 55 (2016) 258e262
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Original Article
Risk factor for first-incident hip fracture in Taiwanese postmenopausal women Fang-Ping Chen a, *, Kuang-Hung Hsu b, Tsai-Sheng Fu c, An-Shine Chao a, Yu-Wei Yu d, Chih-Ming Fan e, Chen-Ming Sung e, Ingrid Ying-Yu Chern f a
Department of Obstetrics and Gynecology, Keelung Chang Gung Memorial Hospital and Chang Gung University, Taiwan Department of Health Care Management, College of Management, Chang Gung University, Taiwan Department of Orthopaedic Surgery, Keelung Chang Gung Memorial Hospital and Chang Gung University, Taiwan d Department of Medical Research and Development, Keelung Chang Gung Memorial Hospital and Chang Gung University, Taiwan e Department of Radiology, Keelung Chang Gung Memorial Hospital and Chang Gung University, Taiwan f School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan b c
a r t i c l e i n f o
a b s t r a c t
Article history: Accepted 1 December 2015
Objective: The variation in hip fracture risk between countries is greater than 10-fold. The present study aimed at identifying risk factors that resulted in the first occurrence of hip fracture in Taiwanese postmenopausal women. Materials and Methods: A caseecontrol study with a patient group of 50 postmenopausal women, who were admitted to Keelung Chang Gung Hospital, Keelung, Taiwan due to the first incident of accidental hip fracture, was used to examine potential risk factors, including bone mass. Fifty women without hip fracture, selected from those undergoing general health evaluation at the Gynecology Outpatient Clinic at Keelung Chang Gung Hospital, were used as the control group and were matched to the case patients according to age. Evaluation consisted of a questionnaire, interview to document risk factors, physical examination (to record body height and body weight), and examination [dual-energy X-ray absorptiometry used to measure bone mineral density (BMD) of the hip and spine]. Results: The average age of participants of both groups was 79.6 years. Lower level of education, younger age at menopause, increased body height, weight-bearing exercise less than three times per week, and lower BMD were associated with first-incident hip fracture. Total hip BMD was a stronger predictor than the BMD of different sites. Participants in the control group had a significantly higher prevalence of chronic diseases and a history of cataracts or glaucoma compared with those in the patient group. Conclusion: While total hip BMD is the strongest predictor of hip fracture, increasing awareness of osteoporosis prevention by educating people about good lifestyle habits and how to maintain BMD is prioritized for preventing the first-incident hip fracture in Taiwanese women. Copyright © 2016, Taiwan Association of Obstetrics & Gynecology. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/).
Keywords: bone mineral density dual-energy X-ray absorptiometry first occurrence of hip fracture level of education Taiwanese postmenopausal women
Introduction Osteoporosis has been recognized as a major threat for public health because it may progress without symptoms until a fracture occurs. Due to estrogen deficiency, postmenopausal women have a higher incidence of osteoporosis and fracture than men. The hip, spine, and wrist are the most susceptible areas to fracture in
* Corresponding author. Department of Obstetrics and Gynecology, Keelung Chang Gung Memorial Hospital, 222 Mai-Chin Road, Taiwan. E-mail address:
[email protected] (F.-P. Chen).
postmenopausal women. Furthermore, hip fractures are considered to be of greater concern because these may result in personal disability and mortality, and therefore, place a higher burden on family and society expenditure. According to the inpatient database of Taiwan's National Health Insurance (NHI) program from 1996 to 2000, the incidence of hip fracture was 1.6 times higher and occurred 5 years earlier among women than men [1]. The 5-year age-adjusted incidence of hip fracture in Taiwan was 505 per 100,000 women [1]. According to an analysis of Taiwan's NHI database from 1996 to 2002, it has been estimated that approximately one-third of women would
http://dx.doi.org/10.1016/j.tjog.2015.12.017 1028-4559/Copyright © 2016, Taiwan Association of Obstetrics & Gynecology. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
F.-P. Chen et al. / Taiwanese Journal of Obstetrics & Gynecology 55 (2016) 258e262
experience at least one vertebral, hip, or wrist fracture in their lifetime [2]. Moreover, Taiwan not only is considered to be a highrisk area for hip fracture, but also has the highest incidence of hip fracture compared with other Asian countries [3]. According to records from the NHI, the rate of mortality following hip fractures in the elderly within the 1st year is about 15% for women [1], which is almost equivalent to the mortality rate of patients with Stages III and IV breast cancer. Hip fractures not only result in personal disability and have a high mortality rate, but also account for a heavy monetary burden. The average medical expenditure for an inpatient with a hip fracture is United States (US) $3243 per patient [4], along with a financial burden on the patient's family and society that is difficult to estimate. The risk for subsequent fracture in women with a hip fracture is 2.5 times higher than for those without a hip fracture [5]. Potential risk factors for hip fracture, which were previously evaluated in Caucasian women, include low bone density, lower body weight, cigarette smoking, caffeine intake, use of long-acting sedatives, and inactivity [6,7]. Since the prevalence of hip fracture in Taiwanese postmenopausal women is higher than that of their Western counterparts, except for in Northern Europe, the risk factors for first-incident hip fracture in Taiwanese postmenopausal women should be reassessed. Risk factor identification is critical so as to optimize treatment to prevent first-incident hip fracture, avert subsequent fractures, and improve both outcome and quality of life after a hip fracture. This study was designed as a caseecontrol study to identify those with potential risk factors and to measure bone mass for postmenopausal women with first-incident hip fracture. Materials and methods Study design and participants In this caseecontrol study, women with a hip fracture (case group) were compared with those without a hip fracture (control group) to determine if potential risk factors and bone mass differed between the two groups. This study was approved by the Ethical Medicine Committee at Chang Gung Memorial Hospital, Keelung, Taiwan. All participants signed an informed consent form. The case patients were admitted to Keelung Chang Gung Hospital for the first incident of accidental hip fracture from March 2014 to February 2015. Patients were excluded if they were (1) severely cognitively impaired and completely unable to follow orders, (2) terminally ill, or (3) refused to participate. A total of 50 postmenopausal women were enrolled in the patient group. To achieve a control group with a similar background to the patient group, 50 postmenopausal women (without a hip fracture) undergoing general health evaluation were recruited from the gynecology outpatient clinic at Keelung Chang Gung Hospital from March 2014 to February 2015 and were matched to the patient group according to age. Assessment of risk factors Questionnaire and interview All participants were questioned and examineddthe patient group during admission and the control group while at the outpatient clinic. All the interviews were conducted in person. We ascertained their level of education, body height and weight, age at menopause, parity, whether they underwent bilateral oophorectomy prior to the age of 45 years, history of fracture, parental history of fracture, current or previous therapy with estrogen within the past year, smoking habits, alcohol and coffee intake, calcium supplement, sun exposure for > 30 min/d, and weight-bearing
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exercise three or more times per week. We also inquired about physician-diagnosed fractures, hyperthyroidism, diabetes mellitus, chronic diseases (including coronary heart disease, renal disease, epilepsy, parkinsonism, and cancer), rheumatoid arthritis, stroke, cataracts or glaucoma, visual impairment, and walking aids. Furthermore, participants were asked about their current medication, including hormone therapy, steroid, psychological medications (including tranquilizers, and antianxiety and antipsychological medications), osteoporosis medication, and diuretics (including thiazide and behyd). Examination Body weight, height, and bone mineral density (BMD) were measured. Baseline lumbar spine and hip BMD were measured by dual-energy X-ray absorptiometry (GE-Lunar; iDAX, Madision, WL, USA) installed at Keelung Chang Gung Memorial Hospital. Statistical analyses Summary statistics for the study variables were calculated and compared between the hip fracture and no hip fracture groups. Mean and standard deviation for continuous variables, frequency, and percentage for categorical variables were applied to descriptive statistics. Independent t tests were used to assess differences of numerical variables between the two study groups, and the Chisquare test was used to examine differences between categorical variables. Multiple logistic regression analysis was used to calculate multivariate-adjusted odd ratios of the study variables associated with hip fracture. In the multiple regression analyses, regression diagnostics, such as residual analysis, and multicollinearity were performed to ensure model robustness. All analyses were performed using SAS software, version 9.1 (SAS Institute, Cary, NC, USA). Results The characteristics of the study population are presented in Table 1. The average age of both groups was 79.6 years. A number of risk factors were associated with first-incident hip fracture, which included lower level of education, younger age at menopause, increased body height, weight-bearing exercise for less than three times per week, and poor BMD. However, patients in the control group had a significantly higher prevalence of chronic diseases, including coronary heart disease, renal disease, epilepsy, Parkinsonism, and cancer, and a prior history of cataracts or glaucoma compared with those in the patient group. Many putative risk factors for osteoporosis were not associated with first-incident hip fracture risk. These factors included body weight, body mass index, parity, bilateral oophorectomy prior to the age of 45 years, estrogen therapy, a prior history of fracture, parental fracture, hyperthyroidism, diabetes mellitus, stroke, visual impairment, and rheumatoid arthritis. Furthermore, aside from weight-bearing exercise, other life-style risk factors were not related to first-incident hip fracture. These life-style risk factors included walking aids, current smoking, alcohol, sun exposure for > 30 min/d, calcium supplement, and both coffee and alcohol consumption. Use of psychological medication, including tranquilizers, antianxiety and antipsychological medications, and diurectics (including thiazide diuretics and behyd) also did not increase hip fracture risk. As aforementioned, BMD was a strong predictor of first-incident hip fracture. The correlation between femoral neck and total hip BMD and the risk of hip fracture was stronger than that between spine BMD and the risk of hip fracture (Table 2). When all the
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Table 1 Characteristics of the study population. Variables
Patient group (N ¼ 50)
Control group (N ¼ 50)
Age (y)
79.6 ± 8.0 (51e91)
79.6 ± 5.2 (67e88)
29 (58.0) 14 (28.0) 7 (14.0) 52.5 ± 7.7 152.9 ± 5.8 22.5 ± 3.5 47.6 ± 5.6 4.5 ± 2.0 3 (6) 6 (12) 17 (14) 4 (8) 4 (8) 18 (36) 15 (30) 7 (14) 11 (22) 22 (44) 13 (26) 20 (40) 2 (4) 2 (4) 5 (10) 12 (24) 22 (44) 12 (24) 4 (8) 14 (28) 8 (16)
11 (22.0) 30 (60.0) 9 (18.0) 51.9 ± 8.5 149.8 ± 6.7 23.1 ± 3.3 50.2 ± 4.8 4.1 ± 1.7 4 (8) 8 (16) 17 (14) 3 (6) 8 (16) 12 (24) 29 (58) 4 (8) 5 (10) 33 (66) 8 (16) 13 (26) 4 (8) 0 5 (10) 20 (40) 25 (50) 23 (46) 0 15 (30) 9 (18)
37 (74) 10 (20) 3 (6)
32 (64) 15 (30) 3 (6)
Education level Unschooled Primary school Secondary or higher education Body weight (kg) Body height (cm) Body mass index (kg/m2) Age at menopause (y) Parity Bilateral oophorectomy prior to 45 y Estrogen therapy Prior history of fracture Parental history of fracture Prior history of hyperthyroidism Prior history of diabetes mellitus Chronic diseasesa Rheumatoid arthritis Prior history of stroke Prior history of cataracts or glaucoma Prior history of visual impairment Walking aids Current smoking 3 alcoholic beverages/d Coffee intake every day Calcium supplement Sun exposure >30 min/d Weight-bearing exercise 3 times/wk Steroid use 3 mo & 5 mg/d Psychological medicationb Diureticsc Bone mineral density T-scored 0.99 >0.99 0.3567 0.1856 0.0032 0.5246 0.1017 0.027 0.2196 0.1552 0.6777 0.4949 >0.99 0.0863 0.5478 0.0211 0.1175 0.8256 0.7901 0.0328
Data are presented as n (%), mean ± standard deviation, or mean ± standard deviation (range). DXA ¼ dual-energy X-ray absorptiometry. a Chronic diseases include coronary heart disease, renal disease, epilepsy, parkinsonism, and cancer. b Psychological medications include tranquilizers, and antianxiety and antipsychological medications. c Diuretics include thiazide diuretics and behyd. d T-score: measurement of bone mineral density in the hip and spine by DXA.
Table 2 Association of BMD with first-incident hip fracture. BMD site
Patient group (N ¼ 50)
Control group (N ¼ 50)
p
Lumbar spine Total hip Femoral neck
0.85 ± 0.16 0.63 ± 0.12 0.58 ± 0.12
0.87 ± 0.18 0.71 ± 0.16 0.63 ± 0.10
0.351 0.0104 0.0391
Data are presented as mean ± standard deviation. BMD ¼ bone mineral density.
Table 3 Multivariate adjusted odds ratios for the major risk factors of first-incident hip fractures. Variables
Adjusted OR
95% CI
p
Education level Total hip BMD Age at menopause Body height
2.875 1.998 1.171 1.139
1.295e6.381 1.227e3.252 1.031e1.331 1.041e1.227
0.0094 0.0054 0.0155 0.0048
BMD ¼ bone mineral density; CI ¼ confidence interval; OR ¼ odds ratio.
predictor variables were put into a stepwise regression, level of education [p ¼ 0.0094, 95% confidence interval (CI) 1.295e6.381], BMD of total hip (p ¼ 0.0054, 95% CI 1.227e3.252), age at menopause (p ¼ 0.0155, 95% CI 1.031e1.331), and body height (p ¼ 0.0048, 95% CI 1.041e1.227) were the only significant factors found affect first-incident hip fracture. Once adjustments were made for these four factors, no other variables were statistically significant (p > 0.05) (Table 3). Discussion It is generally accepted that the incidence of hip fracture increases exponentially with advancing age. This study further confirms that most hip fractures occur in older postmenopausal women. However, there is a substantial worldwide variation in hip
fracture incidence rates [8,9], which may be related to the different potential risk factors in various regions. The present study demonstrated that aside from weight-bearing exercise less than three times per week, risk factors considered to be the main determinants of first-incident hip fracture in Taiwanese postmenopausal women included lower level of education, poor BMD especially at the total hip, younger age at menopause, and body height. The correlation between education and either bone mass or risk of fracture remains controversial. Shaw [10] found no significant associations between BMD and education in a cross-sectional study of healthy volunteers in Taiwan. Ho et al [11] demonstrated that a higher level of education is independently associated with better BMD and a lower prevalence of osteoporosis among
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postmenopausal Chinese women. However, a recent analysis demonstrated that a low socioeconomic status is associated with an increased incidence of hip fracture [12,13]. Colon-Emeric et al [14] observed a positive association between educational levels and risk of hip fracture among ambulatory non-Hispanic white men. In the present study, we demonstrated that lower levels of education were related to not only low bone mass, but also increased hip fracture risk. It is well established that decreased BMD is associated with an increased risk for fracture. In a large meta-analysis of prospective cohort studies, the relative risk for hip fracture was assumed to be 2.6 per one standard deviation > decrease in bone density [15]. The present study also demonstrated that low BMD is one of the major risk factors for first-incident hip fracture. However, after further analysis of the BMD of other skeletal sites, low hip bone density was shown to be a stronger predictor of hip fracture. It was also confirmed that site-specific measurements of BMD at the hip are better predictors of hip fracture than measurements at other skeletal sites [15e18]. Therefore, dual-energy X-ray absorptiometry should be used to evaluate BMD of not only spine, but also hip, especially for aged patients. Bone density is known to decrease rapidly in the period immediately after menopause and slows down thereafter [19]. Although early menopause is generally considered to be a risk factor for osteoporosis and fracture later in life, it is uncertain whether early menopause influences the risk of first-incident hip fracture or not. Besides Huo et al's [20] study, which assessed the relationship between reproductive factors and risk of hip fracture in postmenopausal Chinese women, other previous studies generally have not found younger age at menopause to significantly affect hip fracture risk [21e23]. Banks et al [24] suggested that age is by far the main determinant of hip fracture incidence and for women of a given age, their age at menopause had a weak additional effect at most. The present study showed that a woman's age at menopause was indeed related to hip fracture risk. However, due to the limited study sample size, postmenopausal women who underwent a bilateral oophorectomy prior to the age of 45 years and those who underwent previous or current estrogen therapy did not reveal any significant hip fracture risk. Taller women have a longer hip-axis length (the distance from the greater trochanter to the inner pelvic brim), which has been associated with a greater risk of hip fracture [25]. The present study confirmed that taller women have a greater risk of hip fracture, perhaps because they are prone to falling. Fall risk increases with aging, and about 90% of hip fractures result from a simple fall from a standing height or less [26]. However, increased height is not a definite causative factor of hip fracture due to the variation in a person's habits, activity, coordination, and movement. Although there are some currently recognized fall risk factors, such as thyroid dysfunction, diabetes, arthritis, psychological and diuretic medication use, and a prior history of fracture, there is very limited research on the relationship between socioeconomic factors and fall risk, and the relationship between such demographic variables and the effectiveness of interventions. In the present study, the control group had a higher prevalence of chronic diseases in postmenopausal women and a prior history of cataracts or glaucoma. However, in addition to the limited study sample size, because the control group also had a higher average education level, increased level of exercise, and higher BMD, further evaluation is needed to determine whether the absence of hip fracture in this group is due to their knowledge regarding how to prevent falling and subsequent hip fracture or other factors. A meta-analysis of randomized controlled trials in older adults reported that a combination of weight-bearing exercise and progressive resistance training was the most effective method for
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preserving BMD and preventing bone loss at clinically relevant sites such as the hip and spine [27]. The present study also showed that women performing weight-bearing exercise less than three times per week had a higher incidence of hip fracture. A number of lifestyle risk factors are believed to affect BMD, such as smoking, alcohol, and coffee consumption. In this study, fewer postmenopausal women in both groups had these habits, which can be attributed to the culture difference between Taiwan and Western countries. Although this study was small and had a limited ability to account for potential confounding factors, such as rheumatoid arthritis and stroke, it is the first study to evaluate the risk factors affecting first-incident hip fracture in Taiwanese postmenopausal women. Among the four significant risk factors noted in the present study, lower level of education and total hip BMD should be classified as the two major risk factors. While total hip BMD is the strongest predictor of hip fractures, increasing awareness on osteoporosis prevention by educating people about good lifestyle habits and how to maintain BMD is prioritized for preventing the firstincident hip fracture in Taiwanese women. Conflicts of interest The authors declare that they have no conflicts of interest relevant to this article. Acknowledgments This study was supported by the Medical Research Center (Chang Gung Memorial Hospital) and a research grant from the Wang Zhan Yang Charitable Trust. References [1] Chie WC, Yang RS, Liu JP, Tsai KS. High incidence rate of hip fracture in Taiwan-estimated from a nationwide health insurance database. Osteoporos Int 2004;15:998e1002. [2] Shao CJ, Hsieh YH, Tsai CH, Lai KA. A nationwide seven-year trend of hip fractures in the elderly population of Taiwan. Bone 2009;44:125e9. n A, McCloskey EV, Johansson H, Wahl DA, Cooper C, IOF [3] Kanis JA, Ode Working Group on Epidemiology and Quality of Life. A systematic review of hip fracture incidence and probability of fracture worldwide. Osteoporos Int 2012;23:2239e56. [4] Wong CW, Yeh CB, Chou MC, Chang HC. Epidemiology and medical costs of patients with hip fracture at a medical center in Central Taiwan. J Emerg Med Taiwan 2008;10:81e6. [5] Colon-Emeric C, Kuchibhatla M, Pieper C, Hawkes W, Fredman L, Magaziner J, et al. The contribution of hip fracture to subsequent fracture: data from two longitudinal studies. Osteoporos Int 2003;14:879e83. [6] Cummings SR, Nevitt MC, Browner WS, Stone K, Fox KM, Ensrud KE, et al. Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group. N Engl J Med 1995;332:767e73. [7] Taylor BC, Schreiner PJ, Stone KL, Fink HA, Cummings SR, Nevitt MC, et al. Long-term prediction of incident hip fracture risk in elderly white women: study of osteoporotic fractures. J Am Geriatr Soc 2004;52:1479e86. [8] Kanis JA, Johnell O, De Laet C, Jonsson B, Oden A, Ogelsby AK. International variations in hip fracture probabilities: implications for risk assessment. J Bone Miner Res 2002;17:1237e44. [9] Dhanwal DK, Dennison EM, Harvey NC, Cooper C. Epidemiology of hip fracture: worldwide geographic variation. Indian J Orthop 2011;45:15e22. [10] Shaw CK. An epidemiologic study of osteoporosis in Taiwan. Ann Epidemiol 1993;3:264e71. [11] Ho SC, Chen YM, Woo JL. Educational level and osteoporosis risk in postmenopausal Chinese women. Am J Epidemiol 2005;161:680e90. [12] Quah C, Boulton C, Moran C. The influence of socioeconomic status on the incidence, outcome and mortality of fractures of the hip. J Bone Joint Surg Br 2011;93:801e5. [13] Guilley E, Herrmann F, Rapin CH, Hoffmeyer P, Rizzoli R, Chevalley T. Socioeconomic and living conditions are determinants of hip fracture incidence and age occurrence among community-dwelling elderly. Osteoporos Int 2011;22: 647e53. [14] Colon-Emeric C, Biggs D, Schenck A, Lyles KW. Risk factors for hip fracture in skilled nursing facilities: who should be evaluated? Osteoporos Int 2003;14: 484e9.
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