Association between Anti-Psychotic Drugs Use and Hip Fractures in Patients with Dementia: A Nationwide Population-Based Study

Background: People with dementia are a high-risk group for hip fractures. Although the increased risk of hip fractures associated with antipsychotic drugs (APD) is found in older populations, little is known about the risk for people with dementia living in Asia. We aimed to investigate the association between hip fractures and the characteristics of APD use in patients with dementia. Methods: A nested case-control analysis was conducted on a nationwide cohort in Taiwan. People with diagnoses of dementia during 2003–2012 were identified. Conditional logistic regression analysis was performed, and adjusted odds ratios (aORs) were calculated with a 95% confidence interval (CI) to estimate the risk of hip fractures. Results: APD use was associated with an increased risk of hip fractures in patients with dementia; current use or combined use of first and second generations of APDs had even higher risks. Regarding the duration of APD use, a U-shape curve of hip fracture risk was noted, and the risk peaked during 0–15 days and >215 days of exposure (aOR = 1.46, 95% CI 1.37–1.57; aOR = 1.47, 95% CI 1.37–1.58; respectively). Considering the doses of APDs, the hip fracture risk was significantly increased with all four levels of the cumulative doses and average daily doses and peaked in the group with the highest average daily dose. Conclusions: The findings suggest that caution must be taken when initiating APD use in patients with dementia, even in a small dose, and mixed types of APD prescriptions should be administered with care. Furthermore, frequent evaluation of the possibility of tapering or withdrawal of the medication is necessary, as the risk does not attenuate after long-term use.

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The association of fracture risk in atrial fibrillation patients and long-term anticoagulant therapy category: a systematic review and meta-analysis

PeerJ ◽

10.7717/peerj.10683 ◽

2021 ◽

Vol 9 ◽

pp. e10683

Author(s):

Jun Chen ◽

Lingchun Lyu ◽

Jiayi Shen ◽

Chunlai Zeng ◽

Cheng Chen ◽

...

Keyword(s):

Atrial Fibrillation ◽

Systematic Review ◽

Hip Fracture ◽

Fracture Risk ◽

Hip Fractures ◽

Observational Studies ◽

Meta Analysis ◽

Cochrane Library ◽

Hip Fracture Risk ◽

Significant Difference

Objective Our study aimed to assess the risk of all fractures and hip fractures in patients with atrial fibrillation (AF) who took non-vitamin K antagonist oral anticoagulants (NOACs) compared to warfarin. Methods We searched PubMed, Embase, and Cochrane Library and Clinical Trials.gov Website. Reviewed related researches up to January 31, 2020, to identify studies with more than 12 months of follow-up data. The protocol for this systematic review and meta-analysis has been registered in the International Prospective Register of Systematic Reviews (PROSPERO Number: CRD42020156893). Results We included five RCT studies, and five observational studies that contained a total of 326,846 patients in our meta-analysis. Our meta-analysis showed that patients taken NOACs had no significant all fracture risk (RR = 0.91, 95% CI [0.81–1.01]) and hip fracture risk (RR = 0.92, 95% CI [0.82–1.03]) compared with those taken warfarin. Subanalysis showed that the risk of all fractures and hip fractures treated by NOACs were significant lower compared with warfarin in observational studies compared with RCT studies. Also, a subanalysis across the duration of anticoagulation showed the NOACs users have lower all fracture risk than warfarin users when the duration of anticoagulation ≤2 years (RR = 0.89, 95% CI [0.80–0.99]). Further analysis, significant lower all fracture risk in the rivaroxaban therapy (RR = 0.81; 95% CI [0.76–0.86]) compared with warfarin but no statistical significance in hip fracture. There were no significant difference of all fracture risk and hip fracture risk in dabigatran, apixaban, and edoxaban therapy compared with warfarin. Conclusion The meta-analysis demonstrated that NOACs associated with a significantly lower all fracture risk compared with warfarin when the duration of anticoagulation more than 2 years. Rivaroxaban users had lower risk of all fracture than warfarin users in AF patients. But there was no evidence to verify apixaban, edoxaban, and dabigatranin could decrease all fracture and hip fracture risk compared with warfarin.

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Does thyroid function influence fracture risk? Prospective data from the HUNT2 study, Norway

Acta Endocrinologica ◽

10.1530/eje-13-0546 ◽

2013 ◽

Vol 169 (6) ◽

pp. 845-852 ◽

Cited By ~ 24

Author(s):

Anders Svare ◽

Tom Ivar Lund Nilsen ◽

Bjørn Olav Åsvold ◽

Siri Forsmo ◽

Berit Schei ◽

...

Keyword(s):

Hip Fracture ◽

Fracture Risk ◽

Reference Group ◽

Positive Association ◽

Population Based ◽

Health Study ◽

Thyroid Peroxidase ◽

Forearm Fractures ◽

Hip Fracture Risk ◽

Increased Risk

ObjectiveTo prospectively study the relation between TSH and risk of hip and forearm fractures.DesignA population-based cohort study.MethodsIn a substudy of the second survey of the Nord Trøndelag Health Study, Norway (HUNT2, 1995–97), linked with a hospital-based fracture registry, we investigated the relation between baseline TSH and risk of hip and/or forearm fractures.PopulationA total of 16 610 women and 8595 men aged 40 years or more, without previous self-reported thyroid disease and hip or forearm fractures.ResultsDuring 12.5 years follow-up, a total of 1870 women and 342 men experienced hip or forearm fractures. Overall, there was no relation between baseline TSH and fracture risk. However, there was weak evidence that women with TSH <0.5 and >3.5 mU/l had a slightly increased risk of hip fractures (hazard ratio (HR) 1.30, 95% CI 0.97–1.94 and HR 1.19, 95% CI 0.93–1.52) compared with the reference group with TSH of 1.5–2.4 mU/l. Supplementary analyses showed higher hip fracture risk in women with TSH >4.0 mU/l and negative thyroid peroxidase antibodies (TPOAb) compared with the reference group (HR 1.75, 95% CI 1.24–2.46).ConclusionWe found no statistically significant relation between baseline TSH and subsequent fracture risk, but the data suggest a weak positive association with hip fracture risk among women with both low and high TSH. The latter association was confined to women with negative TPOAb status.

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Hip Fracture Risk among Hemodialysis-Dependent Patients Prescribed Opioids and Gabapentinoids

Journal of the American Society of Nephrology ◽

10.1681/asn.2019090904 ◽

2020 ◽

Vol 31 (6) ◽

pp. 1325-1334 ◽

Cited By ~ 1

Author(s):

Chandan Vangala ◽

Jingbo Niu ◽

Maria E. Montez-Rath ◽

Jingyin Yan ◽

Sankar D. Navaneethan ◽

...

Keyword(s):

Hip Fracture ◽

Fracture Risk ◽

Conditional Logistic Regression ◽

Opioid Analgesics ◽

The United States ◽

Opioid Use ◽

Short Term ◽

Part D ◽

Hip Fracture Risk ◽

Short Term Exposure

BackgroundDespite opioids’ known association with hip fracture risk in the general population, they are commonly prescribed to patients with ESKD. Whether use of opioids or gabapentinoids (also used to treat pain in patients with ESKD) contributes to hip fracture risk in patients with ESKD on hemodialysis remains unknown.MethodsIn a case-control study nested within the US Renal Data System, we identified all hip fracture events recorded among patients dependent on hemodialysis from January 2009 through September 2015. Eligible cases were risk-set matched on index date with ten eligible controls. We required >1 year of Medicare Parts A and B coverage and >3 years of part D coverage to study cumulative longer-term exposure. To examine new, short-term exposure, we selected individuals with >18 months of Part D coverage and no prior opioid or gabapentinoid use between 18 and 7 months before index. We used conditional logistic regression to estimate unadjusted and multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (95% CI).ResultsFor the longer-term analyses, we identified 4912 first-time hip fracture cases and 49,120 controls. Opioid use was associated with increased hip fracture risk (adjusted OR, 1.39; 95% CI, 1.26 to 1.53). Subgroups of low, moderate, and high use yielded adjusted ORs of 1.33 (95% CI, 1.20 to 1.47), 1.53 (95% CI, 1.36 to 1.72), and 1.66 (95% CI, 1.45 to 1.90), respectively. The association with hip fractures was also elevated with new, short-term use (adjusted OR, 1.38; 95% CI, 1.25 to 1.52). There were no associations between gabapentinoid use and hip fracture.ConclusionsAmong patients dependent on hemodialysis in the United States, both short-term and longer-term use of opioid analgesics were associated with hip fracture events.

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Ratio of Urine Albumin to Creatinine Attenuates the Association of Dementia With Hip Fracture Risk

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2014-2409 ◽

2014 ◽

Vol 99 (11) ◽

pp. 4116-4123 ◽

Cited By ~ 8

Author(s):

Petra Bůžková ◽

Joshua I. Barzilay ◽

Howard A. Fink ◽

John A. Robbins ◽

Jane A. Cauley ◽

...

Keyword(s):

Cognitive Impairment ◽

Hip Fracture ◽

Fracture Risk ◽

Cardiovascular Health ◽

Brain Magnetic Resonance Imaging ◽

Microvascular Disease ◽

Cognitive Testing ◽

Lacunar Infarcts ◽

Hip Fracture Risk ◽

People With Dementia

Context: Microvascular disease is a leading cause of cognitive impairment. Approximately 50% of people with a hip fracture have cognitive impairment. Objective: We tested the hypothesis that microvascular diseases of the brain (lacunar infarcts and white matter disease [WMD]), kidney (albuminuria [≥ 30 mg/g creatinine] and albumin creatinine ratio [ACR]), and eye (retinal vascular disorders) attenuate the association of cognitive impairment with hip fracture risk. Setting: The Cardiovascular Health Cognition Study. Patients: Three thousand, one-hundred six participants (mean age, ∼79 y; 8.84 y median follow-up) with cognitive testing. Subsets received ACR testing (n=2389), brain magnetic resonance imaging scans (n = 2094), and retinal photography (n = 1098). Main Outcome Measure: Incident hip fracture. Results: There were 488 participants (16%) with mild cognitive impairment (MCI) and 564 (18%) with dementia. There were 337 incident hip fractures, of which 19% occurred in participants with MCI and 26% in participants with dementia. Adjusted hazard ratios (HR) and 95% confidence interval for hip fracture in participants with MCI were 2.45 (1.67–3.61) and for dementia 2.35 (1.57–3.52). With doubling of ACR, the HR for fracture was attenuated in participants with dementia compared with participants with normal cognition [interaction HR 0.70 (0.55–0.91)]. No such effect was found in participants with MCI. Albuminuria, lacunar infarcts, WMD, and retinal vascular disease (RVD) did not modify the association of dementia or MCI with hip fracture risk. Conclusions: ACR attenuates part of the risk of hip fracture in people with dementia, suggesting that these disorders share a common pathogenesis.

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TNF Receptors Predict Hip Fracture Risk in the WHI Study and Fatty Acid Intake Does Not Modify This Association

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2015-1662 ◽

2015 ◽

Vol 100 (9) ◽

pp. 3380-3387 ◽

Cited By ~ 11

Author(s):

Steven W. Ing ◽

Tonya S. Orchard ◽

Bo Lu ◽

Michael J. LaMonte ◽

Kamil E. Barbour ◽

...

Keyword(s):

Hip Fracture ◽

Confidence Interval ◽

Fracture Risk ◽

Odds Ratio ◽

Linear Trend ◽

Conditional Logistic Regression ◽

Cytokine Gene Expression ◽

Soluble Receptors ◽

Pufa Intake ◽

Hip Fracture Risk

Context: Chronic inflammation may increase the risk of fracture, and omega-3 polyunsaturated fatty acids (PUFAs) may reduce fracture risk via down-regulation of inflammatory cytokine gene expression and other mechanisms. Objective: We investigated associations between baseline samples of inflammatory markers, TNFα soluble receptors 1 and 2 (TNFα-sR1 and -sR2), and incident hip fracture. These associations were then tested for effect modification by dietary PUFA intake estimated by a baseline food frequency questionnaire. Design and Setting: A nested case-control study was conducted among participants of the Women's Health Initiative Observational Study (ages, 50–79 y). Multivariable conditional logistic regression models were constructed to account for the paired design. Participants: This study sampled 400 pairs of hip fracture cases and controls without incident hip fracture, matched on age, year of enrollment, and menopausal hormone use. Main Outcome Measures: Odds ratio of hip fracture by quartile of TNF soluble receptors. Results: The odds ratio of hip fracture comparing the highest to lowest quartiles was 2.24 (95% confidence interval, 1.05–4.79; P for linear trend, .048) for TNFα-sR1 and 2.83 (95% confidence interval, 1.34–5.99; P for linear trend, .011) for TNFα-sR2, adjusted for FRAX hip fracture score, nutritional variables, and selected factors impacting inflammation; there was a gradient of risk by increasing quartile in TNFα-sR1. PUFA intake did not modify these associations. Conclusions: Women with the highest levels of TNFα-sR1 and TNFα-sR2 had a greater than 2-fold increased hip fracture risk, independent of other fracture risk factors. These associations did not differ by high vs low PUFA intake.

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Femoral Neck Shaft Angle in Men with Fragility Fractures

Journal of Osteoporosis ◽

10.4061/2011/903726 ◽

2011 ◽

Vol 2011 ◽

pp. 1-7 ◽

Cited By ~ 10

Author(s):

S. P. Tuck ◽

D. J. Rawlings ◽

A. C. Scane ◽

I. Pande ◽

G. D. Summers ◽

...

Keyword(s):

Hip Fracture ◽

Femoral Neck ◽

Fracture Risk ◽

Hip Fractures ◽

Distal Forearm ◽

Neck Shaft Angle ◽

Hip Fracture Risk ◽

Significant Difference ◽

Shaft Angle ◽

Combined Data

Introduction. Femoral neck shaft angle (NSA) has been reported to be an independent predictor of hip fracture risk in men. We aimed to assess the role of NSA in UK men.Methods. The NSA was measured manually from the DXA scan printout in men with hip (62, 31 femoral neck and 31 trochanteric), symptomatic vertebral (91), and distal forearm (67) fractures and 389 age-matched control subjects. Age, height, weight, and BMD (g/cm2: lumbar spine, femoral neck, and total femur) measurements were performed.Results. There was no significant difference in mean NSA between men with femoral neck and trochanteric hip fractures, so all further analyses of hip fractures utilised the combined data. There was no difference in NSA between those with hip fractures and those without (either using the combined data or analysing trochanteric and femoral neck shaft fractures separately), nor between fracture subjects as a whole and controls. Mean NSA was smaller in those with vertebral fractures (129.2°versus 131°:P=0.001), but larger in those with distal forearm fractures (129.8°versus 128.5°:P=0.01).Conclusions. The conflicting results suggest that femoral NSA is not an important determinant of hip fracture risk in UK men.

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The Association between Home Healthcare and Burdensome Transitions at the End-of-Life in People with Dementia: A 12-Year Nationwide Population-Based Cohort Study

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17249255 ◽

2020 ◽

Vol 17 (24) ◽

pp. 9255

Author(s):

Ping-Jen Chen ◽

Chung-Han Ho ◽

Jung-Yu Liao ◽

Lisanne Smits ◽

Chao A. Hsiung ◽

...

Keyword(s):

Cohort Study ◽

End Of Life ◽

Conditional Logistic Regression ◽

National Level ◽

Population Data ◽

Home Healthcare ◽

Control Analysis ◽

People With Dementia ◽

Increased Risk ◽

The Impact

Background: For people with dementia, burdensome transitions may indicate poorer-quality end-of-life care. Little is known regarding the association between home healthcare (HHC) and these burdensome transitions. We aimed to investigate the impact of HHC on transitions and hospital/intensive care unit (ICU) utilisation nearing the end-of-life for people with dementia at a national level. Methods: A nested case-control analysis was applied in a retrospective cohort study using a nationwide electronic records database. We included people with new dementia diagnoses who died during 2002–2013 in whole population data from the universal healthcare system in Taiwan. Burdensome transitions were defined as multiple hospitalisations in the last 90 days (early transitions, ET) or any hospitalisation or emergency room visit in the last three days of life (late transitions, LT). People with (cases) and without (controls) burdensome transitions were matched on a ratio of 1:2. We performed conditional logistic regression with stratified analyses to estimate the adjusted odds ratio (OR) and 95% confidence interval (CI) of the risks of transitions. Results: Among 150,125 people with new dementia diagnoses, 61,399 died during follow-up, and 31.1% had burdensome transitions (50% were early and 50% late). People with ET had the highest frequency of admissions and longer stays in hospital/ICU during their last year of life, while people with LT had fewer hospital/ICU utilisation than people without end-of-life transitions. Receiving HHC was associated with an increased risk of ET (OR = 1.14, 95 % CI: 1.08–1.21) but a decreased risk of LT (OR = 0.89, 95 % CI 0.83–0.94). In the people receiving HHC, however, those who received longer duration (e.g., OR = 0.50, 95 % CI: 0.42–0.60, >365 versus ≤30 days) or more frequent HHC or HHC delivered closer to the time of death were associated with a remarkably lower risk of ET. Conclusions: HHC has differential effects on early and late transitions. Characteristics of HHC such as better continuity or interdisciplinary coordination may reduce the risk of transitions at the end-of-life. We need further studies to understand the longitudinal effects of HHC and its synergy with palliative care, as well as the key components of HHC that achieve better end-of-life outcomes.

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Biomechanical Computed Tomography Captures Older Men at High Risk of Hip Fracture Despite Low Fracture Risk Calculation by FRAX

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.493 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A242-A243

Author(s):

Polly Fu ◽

Janet Chiang ◽

Tony M Keaveny ◽

Daniel D Bikle

Keyword(s):

Hip Fracture ◽

Fracture Risk ◽

Bone Strength ◽

Older Men ◽

Ct Scans ◽

Hip Fracture Risk ◽

T Score ◽

Increased Risk ◽

Fragile Bone ◽

Fracture Risks

Abstract Background: Biomechanical computed tomography (BCT) can be applied to hip-containing CT scans to estimate femoral bone strength using finite-element analysis and to measure DXA-equivalent femoral neck (FN) BMD. Current guidelines recommend osteoporosis pharmacotherapy initiation in men with BMD T-score ≤ -2.5 or T-score between -1.0 and -2.5 with 10-year hip fracture risk ≥ 3% by FRAX.1 Estimated femoral strength by BCT is associated with incident hip fractures in men, independent of BMD,2 and can be used in conjunction with clinical risk factors for consideration of therapy initiation per the International Society of Clinical Dosimetry.3 Aim: To determine how many men are at increased risk of fractures with fragile bone strength (≤ 3500N) despite normal-to-low BMD (T-score > -2.5) and low 10-year hip fracture risk (< 3%). Methods: 625 men age ≥ 65 with hip-containing CT scans were randomly selected for BCT analysis out of 4209 scans performed from 2017 to 2019 at a single academic hospital. Scans were excluded if an intact femur was not imaged. BCT was performed for 557 men after accounting for un-processable scans. Electronic health records were retrospectively reviewed by investigators blinded to BCT results. 10-year hip fracture risks were calculated by FRAX based on available clinical data and FN BMD T-score from BCT. Chi-squared and t-test were used to investigate differences in clinical parameters between men with and without fragile bone strength. Results: The mean age was 77 (± 7.6 years), and 69% of men were white. Out of 102 men (18.3%) who met criteria for fragile bone strength by BCT, 42 (7.5%) had low FN BMD (T-score between -1.0 and -2.5) and 2 (0.4%) had normal FN BMD (T-score ≥ -1.0). The percentage of men with fragile bone strength and discrepant BMD increased with age (5.4% in age 65–74; 8.2% in age 75–84; 13.0% in age ≥ 85). The average 10-year hip fracture risk by FRAX of men with fragile bone strength was 6.5% (± 4.0%). However, 13 out of 44 men with normal-to-low BMD had 10-year hip fracture risks < 3% despite fragile bone strength presence and did not meet recommendation for osteoporosis pharmacotherapy. Examining men with normal-to-low BMD (n=493), those with fragile bone strength tended to be older, have lower BMI, and of Hispanic ethnicity compared to those with normal-to-low bone strength (p<0.05). Conclusions: Our study showed that fragile bone strength is present in older men with normal-to-low BMD, and that inclusion of 10-year hip fracture risk by FRAX may capture some, but not all, men at increased risk of hip fractures. Skeletal fragility measured by BCT may serve as additional data to assist with clinical decision making for men with osteoporosis, though further prospective research is needed. Reference: 1. Watts et al, J Clin Endocrinol Metab. 2012 Jun;97(6):1802–22. 2. Adams et al, J Bone Miner Res 2018 Jul;33(7):1291–1301. 3. Shuhart et al, J Clin Densitom. 2019 Oct-Dec;22(4):453–471.

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Coffee consumption and hip fracture risk: a meta-analysis

Journal of Nutritional Science ◽

10.1017/jns.2013.13 ◽

2013 ◽

Vol 2 ◽

Cited By ~ 3

Author(s):

Xin-li Li ◽

Jiu-hong Xu

Keyword(s):

Hip Fracture ◽

Fracture Risk ◽

Random Effects ◽

Meta Analysis ◽

Coffee Consumption ◽

Hip Fracture Risk ◽

Pubmed Database ◽

Increased Risk ◽

Subgroup Analyses

AbstractTo investigate the effect of coffee consumption on hip fracture risk, a meta-analysis was conducted. The PubMed database was screened for all published studies about coffee consumption and hip fracture through to November 2011. Reviews, PubMed option ‘related articles’ and references of retrieved papers were also searched for potentially relevant papers. Only studies that contained OR with 95 % CI for the association between coffee consumption and hip fracture risk were included. The summary risk estimates were calculated by fixed- and random-effects models. Subgroup analyses were carried out stratified by study designs and participant characteristics, respectively. A total of six prospective cohort studies and six case–control studies were included in the final analysis. The pooled OR displayed increased risk of hip fracture by 29·7 % (95 % CI 0·960, 1·751; P = 0·09) for the highest compared with the lowest coffee consumption by the random-effects model (P for heterogeneity = 0·000; I2 = 84·0 %), but the result had no statistical significance. Subgroup analyses showed that coffee consumption significantly increased hip fracture risk by 54·7 % (95 % CI 1·152, 2·077; P = 0·004) among women, by 40·1 % (95 % CI 1·015, 1·935; P = 0·040) for elderly participants aged over 70 years, and by 68·3 % for Northern Americans (95 % CI 1·492, 1·899; P = 0·000). Other subgroup analyses according to data published before the year 2000 showed a positive association between coffee and hip fracture risk, and follow-up duration also positively affected hip fracture risk, especially when the follow-up length was less than 13 years. Although our meta-analysis has provided insufficient evidence that coffee consumption significantly increases hip fracture risk, coffee intake may increase hip fracture risk among women, elderly participants and Northern Americans. No dose–response pattern was observed.

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