meta-analysis of risk factors for the second hip fracture (shf) in elderly patients

$: Meta-analysis of risk factors for the second hip fracture (SHF) in elderly patients$
Archives of Gerontology and Geriatrics xxx (2014) xxx–xxx

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AGG-2967; No. of Pages 6

Review

Meta-analysis of risk factors for the second hip fracture (SHF)in elderly patients

Yanbin Zhu a,b, Wei Chen a,b, Tao Sun a,b, Qi Zhang a,b, Jiaxiang Cheng a,b, Yingze Zhang a,b,*a Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, PR Chinab Key Laboratory of Biomechanics of Hebei Province, Shijiazhuang, Hebei 050051, PR China

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000

2. Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000

2.1. Literature search . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000

2.2. Data extraction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000

2.3. Quality of included studies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000

2.4. Meta-analyses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000

3. Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000

3.1. Literature search results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000

3.2. Methodological quality assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000

3.3. Pooled analysis of risk factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000

4. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000

Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 000

A R T I C L E I N F O

Article history:

Received 2 December 2013

Received in revised form 24 February 2014

Accepted 27 February 2014

Available online xxx

Keywords:

Second hip fracture

Elderly patients

Risk factor

Meta-analysis

A B S T R A C T

This study aims to quantitatively summarize the risk factors for the incidence of SHF. A meta-analysis

was performed with the data obtained from 22 relevant papers published in Pubmed, Embase and

Cochrane central database (all through January 2014) following strict selection. The pooled odds ratios

(ORs) or standardized mean difference (SMD) with 95% confidence intervals (CIs) were calculated for

potential risk factors associated with SHF. Our meta-analysis indicated the significant risk factors for SHF

were female (OR, 1.46; 95%CI, 1.29–1.66), living in institutions (OR, 2.23; 95%CI, 1.29–3.83), osteoporosis

(Singh index (SI) 1–3) (OR, 10.02; 95%CI, 5.41–18.57), low vision (OR, 2.09; 95%CI, 1.06–4.12), dementia

(OR, 1.89; 95%CI, 1.47–2.43), Parkinson (OR, 2.90; 95%CI, 1.41–5.95), cardiac diseases (OR, 1.32; 95%CI,

1.02–1.70) and respiratory disease (OR, 1.97; 95%CI, 1.16–3.32). Related strategies must be implemented

on those involved with above-mentioned medical conditions to effectively prevent a SHF.

� 2014 Elsevier Ireland Ltd. All rights reserved.

Contents lists available at ScienceDirect

Archives of Gerontology and Geriatrics

jo ur n al ho mep ag e: www .e lsev ier . c om / lo cate /ar c hg er

1. Introduction

Hip fracture is the most common fracture in elderly patientsand accounts for 20% of all the fractures in this population (Zhang,

* Corresponding author at: Department of Orthopaedics, The Third Hospital,

Hebei Medical University, No. 139 Ziqiang Road, Shijiazhuang 050051, PR China.

Tel.: +86 311 88603682; fax: +86 311 87023626.

E-mail addresses: [email protected], [email protected] (Y. Zhang).

Please cite this article in press as: Zhu, Y., et al., Meta-analysis of risk

Gerontol. Geriatr. (2014), http://dx.doi.org/10.1016/j.archger.2014.0

http://dx.doi.org/10.1016/j.archger.2014.02.012

0167-4943/� 2014 Elsevier Ireland Ltd. All rights reserved.

2012). Consequently, patients involved with hip fractures sufferedfunctional deterioration, limited mobility and increased morbidity,especially at the first year post operation (Fredman et al., 2005;Penrod et al., 2007; Vestergaard, Rejnmark, & Mosekilde, 2007).Furthermore, among the survivors of a first hip fracture, the age-standardized risk of a SHF was 2.5 times higher in women and 4.6times higher in men compared to the risk of a first hip fracture(Omsland et al., 2012). And worse still, patients had a greatermortality and more decreased dependence in their daily activitiesafter SHF (Pearse, Redfern, Sinha, & A, 2004; Sawalha & Parker,

factors for the second hip fracture (SHF) in elderly patients. Arch.2.012


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mailto:[email protected]


http://www.sciencedirect.com/science/journal/01674943

www.elsevier.com/locate/archger


Initi all y selec ted and

identi fied sea rch (242)

Exclud ed after sc ree ning for

abstract and reduplicati ve

publication(74)

References se lec ted for full

text retrieval (168)

Includ ed stud ies (22)

Non Engli sh stud ies (29 )

Non origina l stud ies e.g. lett ers, etc. (13)

Irrelevant popu lation and ou tcomes (63 )!Insuff icient qu antit ati ve data (37)

Unquali fied methodo log ical ass ess ment 4

Fig. 1. Flow diagram of literature searching.

Y. Zhu et al. / Archives of Gerontology and Geriatrics xxx (2014) xxx–xxx2

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2012). About 31.6% (Sawalha & Parker, 2012) died at the first yearafter the operation, 78.3% would have to survive with the aid ofwalking tools, and most would never recover to their pre-operativelevel (Galois, Dausse, Mainard, & Delagoutte, 2001). Besides thepersonal influence to patients, a heavy economic and social burdenshould be also considered, a proximally financial cost of over16,000 dollar per patient for unilateral hip fracture and at leastdoubled for bilateral hip fracture (Van Balen et al., 2001), still notincluding postoperative care cost after discharge. Therefore, it isvital to identify risk factors to prevent the occurrence of SHF inthose sustaining initial hip fractures.

Many risk factors have been identified for the SHF, includingadvanced age (Angthong, Suntharapa, & Harnroongroj, 2004;Souder et al., 2012; Vochteloo et al., 2012), female (Gaumetou,Zilber, & Hernigou, 2011; Rodaro, Pasqualini, Iona, & Di Benedetto,2004), osteoporosis (Angthong et al., 2004; Yamanashi et al., 2004),dementia (Mitani, Shimizu, Abo, Hiroshi, & Youichi, 2010; Saxena &Shankar, 2000; Yamanashi et al., 2004), Parkinson’s disease(Saxena & Shankar, 2000; Yamanashi et al., 2004), respiratorydisease (Mitani et al., 2010) and lower vision (Angthong et al.,2004; Saxena & Shankar, 2000). However, these studies had somelimitations such as a small sample size and the inclusion of a singleor very few potential risk factors. In addition, some of the resultsobtained were controversial. For example, female and advancedage were both considered risk factors for SHF in some studies(Rodaro et al., 2004), however, were neither significant in otherstudy (Mitani et al., 2010). Mary et al. (Egan, Jaglal, Byrne, Jennie, &Paul, 2008) made a systematic review of studies on SHF in 2006with a qualitative description rather than a quantitative meta-analysis on the potential risks. Recently, Jesper et al. (Ryg,Rejnmark, Overgaard, Kim, & Peter, 2009) have conducted anationwide population-based cohort study of 169, 145 cases toinvestigate the risks for SHF. Although with a greatest number ofcases by far, the study had some certain limitations such as themisclassification of infections, periprosthetic fracture, alloplasticsurgery and removal of osteosynthesis as SHF. Therefore, it wasdifficult for them to get the precise information with regard to therisk factors for SHF.

To achieve a reliable and comprehensive conclusion, a meta-analysis was performed using data obtained from previous studiesto evaluate the risk factors for SHF in elderly patients with initialhip fractures, and subsequently reduce the occurrence of SHF.

2. Methods

2.1. Literature search

A computerized search was performed on Medline, Embase, andCochrane central database (all through January 2014) for thestudies exploring risk factors for SHF. The main key words were asfollows: ‘‘factor’’ or ‘‘predictor’’ or ‘‘risk’’ AND ‘‘subsequent’’ or‘‘second’’ or ‘‘contralateral’’ or ‘‘recurrent’’ or ‘‘bilateral’’ or ‘‘non-simultaneous’’ AND ‘‘proximal femur’’ or ‘‘hip’’ or ‘‘intertrochan-teric’’ or ‘‘femoral neck’’ AND ‘‘fracture’’. Also, a manual search ofreferences in the identified articles and systematic reviews wasperformed for possible inclusion.

Two reviewers independently evaluated the titles and abstractsof the identified papers. Only full-text articles published in Englishwere included in this meta-analysis. The inclusion criteria were asfollows: (1) only subsequent fracture at hip (including ipsilateraland contralateral hip), were considered SHF. (2) A case–controlstudies was performed to explore risk factors for SHF, controls andcases were defined based on the number of fractures (unilateral orSHF). (3) Sufficient data was published for estimating an OR or SMDwith 95%CI.



2.2. Data extraction

All the data were carefully extracted from all eligible studiesindependently by the two reviewers, Chen and Sun. The followingvariables were extracted from each study: first author’s name,publication year, country, significant risk factors, definitions andnumbers of case and control groups, numbers of citations for eachpotential risk factors for SHF. Any disagreement was settled bydiscussion and a consensus was reached for all data.

2.3. Quality of included studies

The quality of the included studies was evaluated using theNewcastle–Ottawa Scale (Stang, 2004): based on the three mainitems: the selection of the study groups (0–4 points), thecomparability of the groups (0–2 points) and the determinationof either the exposure or the outcome of interest (0–3 points), witha perfect score of 9.

2.4. Meta-analyses

For each risk factor, we extracted the adjusted OR or relativerisk (RR), with its 95%CI. When the adjusted OR or the RR was notobtained, we computed a crude OR and pooled across studies toassess the associations between different variables and the risk ofSHFs with a P < 0.05 indicating significant difference. Heteroge-neity between the studies was tested by Q-test statistics withsignificance set at P < 0.10 (Lau, Ioannidis, & Schmid, 1997). The I2

statistics were used as a second measure of heterogeneity, with I2

more than 50% indicating inconsistency. A random effects modelwas used to calculate pooled ORs or SMDs in the case of significantheterogeneity (P < 0.10 or I2 > 50%); otherwise, a fixed-effectsmodel was used (Wei, Yang, Luo, Qin, & Kong, 2013). The meta-analysis of risk factors was summarized graphically using a forestplot. Publication bias was assessed by Begg test and graphed by afunnel plot, a P < 0.10 was considered significant. Furthermore, weestimated pooled ORs including only studies presenting multivar-iate ORs. All analyses were performed using the software Stata 11.0(Stata Corporation, College Station, TX).

3. Results

3.1. Literature search results

A total of 242 initially selected references were retrieved, ofwhich 22 studies altogether including 2154 cases and 24,859controls were identified eligible (Fig. 1). The basic characteristics ofincluded studies and participants are summarized in Table 1. Dataon 19 potential risk factors for SHF were abstracted from theincluded studies, and number of citations for each risk factor werepresented in Table 2.



Table 1The basic characteristics of these 22 included studies and participants.

First author Publication

year

Country Control Case Total Age (years) Significant factors

Saxena 2000 UK 530 53 583 No data Alzheimer’s disease, cerebrovascular accident, blindness, syncope and collapsea

Chayanin 2009 Thailand 97 28 125 �60 Hypotrophic change, eye diseases and neurological diseasesb

Sawalha 2012 UK 4708 633 5341 �60 Institutionalized, female, older, lower mobility and mental test scoresa

Chiu 1992 China HK 1479 35 1514 �57 Neurological diseases, osteomalacia changea

Yamanashi 2005 Japan 669 45 714 �65 Dementia and Parkinsonsc

Fukushima 2006 Japan 741 94 835 �60 Dementiaa

Gaumetou 2011 France 215 26 241 �60 Femalea

Anne 2012 Netherlands 1060 169 1229 �50 Advanced agea

Sugao 2010 Japan 335 49 384 �50 Dementia and respiratory diseased

Rodaro 2004 Italy 2771 210 2981 �50 Advanced age and sedentary womena

Dretakis 1998 Greece 1579 106 1685 �50 Recurrent fallsa

Christopher 2012 USA 1089 88 1177 Mean, 80.0 Older age, internal fixation, diabetes and bisphosphonatesa

Lee 2012 Korea 483 34 517 �56 Bisphosphonates for osteoporosisa

Dinah 2002 UK 164 22 186 Mean, 83.0 Femalea

Lawrence 2010 UK 4746 280 5026 �55 Agea

Lee 2013 Korea 755 71 826 �50 Hematologic disease, renal disease, compliant use of bisphosphonatesd

Chapurlat 2003 USA 579 53 632 �65 BMD, taking Tums, walking for exercise, weight, estrogenb

Lonnroos 2007 Finland 467 34 501 �60 Treatment of first hip fractured

Hagino 2012 Japan 2251 77 2328 �65 Body weightc

Chang 2013 Korea 141 47 188 �65 Respiratory diseases, visual impairments, postoperative delirium,

rehabilitation and ambulatory statusc

Kim 2012 Korea 377 38 415 �60 Residency, fracture type, falls, cognitive impairment and diabetes mellitusd

Sarah 2007 USA 410 71 481 Mean, 81 Older age and functional statusd

a Univariate t-test or Chi-square test.b Multivariate analyses (not specific).c Multivariate logistic regression analyses.d Multivariate cox regression analyses.

Y. Zhu et al. / Archives of Gerontology and Geriatrics xxx (2014) xxx–xxx 3

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3.2. Methodological quality assessment

The outcome of quality assessment for included studies was asfollows: four studies scored 9 (Dinah, 2002; Gaumetou et al., 2011;Hagino et al., 2012; Lawrence, Wenn, & Boulton, 2010), eightstudies (Angthong et al., 2004; Chapurlat, Bauer, Nevitt, Stone, &Cummings, 2003; Lee, Ha, Yoon, & Koo, 2013; Mitani et al., 2010;Rodaro et al., 2004; Sawalha & Parker, 2012; Saxena & Shankar,2000; Yamanashi et al., 2004) scored 8; seven studies (Berry,Samelson, Hannan, Robert, & Mei Lu Adrienne, 2007; Chang et al.,2013; Dretakis, Dretakis, Papakitsou, P, & Steriopoulos, 1998;Fukushima, Sudo, & Uchida, 2006; Lee, Lee, & Cho, 2012; Souderet al., 2012; Vochteloo et al., 2012) scored 7; three studies (Chiu,

Table 2Detailed data on 19 potential risk factors for the SHF and the outcome of meta-analys

Potential risk No. of studies Pooled OR or SMD

Female 15 1.46

Age 9 0.08

BMI 4 �0.10

Institutionalized 4 2.23

Dementia 7 1.89

Low vision 4 2.09

Cardiac disease 7 1.32

Diabetes mellitus 7 1.35

Hypertension 5 0.97

Parkinson 2 2.90

Respiratory disease 6 1.97

Neurological diseases 8 1.17

Fracture type (femoral neck) 9 1.06

Surgical type (osteosynthesis) 3 0.75

Cognitive impairment 3 2.01

Osteoarthritis 3 1.47

Osteoporosis (SI 1–3) 2 10.02

Alcoholism 2 1.93

Cancer 2 0.71

Abbreviations: LL, lower limit; UL, upper limit.a Fixed-effects model was performed.b Fandom-effects model was performed.c I2 statistic was defined as the proportion of heterogeneity not due to chance or ra



Pun, Luk, & Chow, 1992; Kim et al., 2012; Vochteloo et al., 2012)scored 6.

3.3. Pooled analysis of risk factors

A meta-analysis of combinable data was conducted to analyzethe risk factors for SHF, and the main results were summarized inTable 2. The combined ORs ranged from 1.32 to 10.02. Significantheterogeneity was observed among studies, when evaluating thepotential risk factors including age, living in institutions, lowvision, diabetes mellitus, respiratory disease, neurological dis-eases, fracture type, cognitive impairment and osteoarthritis. Onthe basis of the combined ORs and 95%CI, the significant risk

es.

LL 95%CI UL 95%CI P value Q-test (P) I2 (%)c

1.29 1.66 <0.001a 0.303 13.4

�0.11 0.27 0.415b <0.001 84.6

�0.29 0.08 0.144a 0.282 44.6

1.29 3.83 0.004b 0.011 73.2

1.47 2.43 <0.001a 0.483 0

1.06 4.12 0.034b 0.038 64.3

1.02 1.70 0.032a 0.591 0

0.91 2.00 0.132b 0.042 54

0.74 1.26 0.806a 0.364 7.4

1.41 5.95 0.004 0.702 0

1.16 3.32 0.011b 0.075 50.0

0.90 1.52 0.244b 0.032 54.4

0.82 1.35 0.672b 0.007 61.8

0.43 1.31 0.311b 0.078 60.7

0.93 4.37 0.077b 0.072 62.0

0.50 4.26 0.483b 0.03 71.5

5.41 18.57 <0.001a 0.182 43.9

0.61 6.18 0.266a 0.550 0

0.32 1.57 0.400a 0.463 0

ndom error.




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factors were female (OR, 1.46; 95%CI, 1.29–1.66), living ininstitutions (OR, 2.23; 95%CI, 1.29–3.83), osteoporosis (SI 1–3)(OR, 10.02; 95%CI, 5.41–18.57), low vision (OR, 2.09; 95%CI, 1.06–4.12), dementia (OR, 1.89; 95%CI, 1.47–2.43), Parkinson (OR, 2.90;95%CI, 1.41–5.95), cardiac diseases (OR, 1.32; 95%CI, 1.02–1.70)and respiratory disease (OR, 1.97; 95%CI, 1.16–3.32). No significantdifference was found in admission age between patients with theunilateral hip fracture and the first hip fracture of SHF groups(SMD, 0.08; 95%CI, �0.11 to 0.27, P = 0.415). The outcome ofanalysis for female, dementia, cardiac diseases and respiratorydisease, as significant risks were presented by forest plots (Fig. 2)and others, were presented in Table 2. Fracture types, BMI,alcoholism, surgical types, cognitive impairment, osteoarthritis,cancer, diabetes mellitus, hypertension and neurological diseaseswere identified not as the risk factors for SHF (P > 0.05). Funnelplot and Begg’ test showed that no significant publication bias wasfound in the studies concerning the risk of gender (P = 0.767)(Fig. 3).

The detailed results of pooled ORs computed for only for studiespresenting multivariate analysis are presented in SupplementaryTable 1. The results revealed that the exclusion of the more biasedcrude ORs did not affect the statistical significance of theassociations among the most potential risk factors includinggender, dementia, cardiac disease, hypertension, Parkinson,respiratory disease, neurological diseases; hence, the meta-analytic associations reported in this review for these risk factorsdemonstrate robust to the extent. In terms of the risk factors forlow vision (OR, 2.31; 95%CI, 0.86–6.22 for the multivariatesubgroup) and cognitive impairment (OR, 1.59; 95%CI, 1.05–2.41

Fig. 2. Forest plots of the meta-analysis of female (A), osteoporosis (SI 1–3) (B), low vision

the SHFs after initial hip fractures. The width of the horizontal line represents the 95%CI

study. The diamond represents the pooled OR and 95%CI.



for the multivariate subgroup), the results were revealed to beinconsistent with those obtained from the crude ORs, however,significant heterogeneity was detected for low vision (P = 0.02) butnot for cognitive impairment (P = 0.733).

See Supplementary Table 1 as supplementary file. Supplemen-tary material related to this article can be found, in the onlineversion, at http://dx.doi.org/10.1016/j.archger.2014.02.012.

4. Discussion

SHF after the initial hip fracture is not rare in elderly patientsand the incidence of SHF was 2.3–13.8% (Chiu et al., 1992; Dinah,2002; Finsen & Benum, 1986; Gaumetou et al., 2011; Schroder &Petersen, 1993; Vochteloo et al., 2012; Yamanashi et al., 2004),almost 80% occurred in the three years after IHF (Dretakis et al.,1998; Mitani et al., 2010; Sawalha & Parker, 2012). The presentsystematic review and meta-analysis revealed multiple risk factorsassociated with SHF in IHF elderly patients. Statistically significantassociations were identified for female, osteoporosis (SI 1–3), lowvision, dementia, cardiac diseases and respiration diseases. Nosignificant difference was found in admission age among patientswith the unilateral hip fracture and the first hip fracture of SHFgroups, therefore, older age was not a negative factor for SHF and itwas not advisable to screen for patients at risk of SHF relying solelyon the age at which the initial hip fracture occurred.

Living in institutions after IHF was analyzed (Lonnroos,Kautiainen, Karppi, H, & Kiviranta, 2007; Mitani et al., 2010;Sawalha & Parker, 2012), but its potential role as a risk factor forSHF was inclusive. It is probably that significant differences in

(C), dementia (D), cardiac diseases (E) and respiratory disease (F) as risk factors for

of the individual studies, and the square proportional represents the weight of each




Fig. 2. (Continued ).

Y. Zhu et al. / Archives of Gerontology and Geriatrics xxx (2014) xxx–xxx 5

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methodology, including sample sizes and a broad range ofinstitutions examined, contributed to significant heterogeneityin the analytical results. Clinically, many factors (including familydynamics and chronic pathological conditions) could influence theneed for IHF patients to be admitted to these institutions.Furthermore, living in institutions was a significant risk for notregaining pre-fracture level of mobility and resulted in worsefunctional outcome, as reported by Dharmarajan (2001) andBeaupre et al. (2007). Therefore, whether living in institutions as anindependent factor influencing SHF needed to be further prospec-tively investigated. In this review, due to the significantheterogeneity after sensitive and subgroup analysis, pooled resultwas unreliable. Likewise, significant heterogeneity was found forstudies of recurrent falls, indicating not a proper quantitative riskassessment.

This review also extends previous work by showing that cardiacdisease is a strongly significant (P = 0.032) factor associated withthe occurrence of SHF, which benefited directly from pooledsamples of individual studies. As a matter of fact, the negativeimpact of cardiac diseases is complex. Firstly, this can be explainedby the common pathophysiological mechanisms that cardiacdiseases and hip fracture share, including calcification regulatoryhormones, sex steroids, oxidative stress and chronic inflammation(McFarlane et al., 2004; Sennerby et al., 2009). Secondly, this maybe partly due to the greater propensity for falls in those withcardiac diseases, because balance disturbances might occur due tosudden myocardial ischemia and the adverse effect of multiplemedications (Hartikainen, Lonnroos, & Louhivuori, 2007). Furtherstudies are required to elucidate the mechanism whereby cardiacdisease influenced the SHF. Undoubtedly, effective strategies for

Begg 's funnel plo t wit h pseudo 95 % confid ence limits

lo

g[v

ar2

]

s.e. of: lo g[var2]

0 .2 .4 .6 .8

-1

0

1

2

Fig. 3. Begg’s funnel plot for publication bias (with 95% pseudoconfidence limits) of

the case–control studies that investigated female and risk factor for the SHF

(P = 0.767).



management and secondary prevention of hip fracture amongpatients with initial hip fracture must be developed, for instancethrough implementing routine home visits for medications byphysiotherapists to help prevent falls.

It is notable that, the majority of above-motioned risk factors(gender, low vision, dementia, cardiac diseases and respirationdiseases) could not be modified, however, these factors should bekept in mind to prepare prevention strategy or reminder with theaim to reduce the risk of SHF for patients with such factors. Theosteoporosis as a significant risk factor was potentially amenable.As reported by Bischoff et al. (Bischoff-Ferrari et al., 2009), avitamin D high dose of 700–800 IU/d could significantly reduce theRR of the hip fracture. Likewise, the compliant use of bipho-sphonates have been identified to reduce 60% of the occurrence ofSHF (4.2% vs. 10.9%) (Lee et al., 2013).

Lower bone mineral density have been undoubtedly regardedas the most important factors associated with SHF, althoughrelevant studies were not pooled and calculated in present studydue to the inconsistent quantitative criteria (mean or count) andmeasurement in different sites (calcaneus, total hip or vertebra) foreach study. Likewise, American Society of Anesthesiologists (ASA)physical status score were not pooled for the non-uniformquantitative criteria. Because we could not obtain the originalraw data, it was impossible to perform a meta-analysis of BMD orASA. In addition, there were other risk factors that could not becombined because studies were reported in fewer studies. Forexample, hematologic disease (Lee et al., 2013), renal disease (Leeet al., 2013) and smoking (Souder et al., 2012) were reported inonly a single study.

This meta-analysis has some limitations. Firstly, a weaknessexists in the analyses that not all the ORs on the potential riskfactors for the meta-analysis are adjusted because a lot of reportscould only provide the univariate rather than multivariatestatistics; likewise, some studies might choose not to report theinsignificant results or results of no interest, potentially resultingin a considerable amounts of missing data. Hence, our overall effectestimates may be an over-estimate but the multivariate subgroupanalysis was performed and the corresponding pooled results arereliable. Secondly, all the included studies were case–controlstudies with unavoidable recall and interviewer biases, whichmight affect the associations between the risk and SHF. Thirdly, themeasurements of various risk factors differed much from eachother, either by standard grading forms or by patient-reportedquestionnaires. Similarly, follow-up periods ranged widely fromseveral months to more than 10 years. Therefore, a significantheterogeneity was unavoidable in this review. Finally, all thesubjects in 22 papers were Asian, European and US; therefore, ourconclusions might not extrapolate to African and Australasianpopulations.




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Despite these limitations, some advantages should be men-tioned. First and the most important, cardiac disease as a risk factorwas identified, which might contribute to complementingprevention strategies for patients involved. Secondly, a compre-hensive search strategy based on computer-assisted and manualsearching avoided any eligible study to omission. Finally, nopublications bias was found, suggesting a robust result.

In summary, the present meta-analysis suggests that females,living in institutions, osteoporosis (SI 1–3) low vision, dementia,Parkinson, respiration diseases and cardiac diseases were signifi-cant risk factors for SHF. Furthermore, cardiac disease as thesignificantly increased risk for SHF was firstly reported and relatedprevention strategies should be formulated.

Conflict of interest

All the authors declare that they have no conflict of interestwith any organization that sponsored the research.

Acknowledgements

We are grateful to S.L. and Z.W. of the Department ofOrthopedics, and to X.C. and G.W. of the Department of Statisticsand Applications for their kind assistance.

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meta-analysis of risk factors for the second hip fracture (shf) in elderly patients

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