1. Epidemiology and Global Health

‘Skeletal Age’ for mapping the impact of fracture on mortality

  1. Thach Tran  Is a corresponding author
  2. Thao Ho-Le
  3. Dana Bliuc
  4. Bo Abrahamsen
  5. Louise Hansen
  6. Peter Vestergaard
  7. Jacqueline R Center
  8. Tuan V Nguyen  Is a corresponding author
  1. School of Biomedical Engineering, University of Technology Sydney, Australia
  2. Garvan Institute of Medical Research, Australia
  3. Faculty of Medicine, UNSW Sydney, Australia
  4. Department of Medicine, Holbæk Hospital, Denmark
  5. Department of Clinical Research, Odense Patient Data Explorative Network, University of Southern Denmark, Denmark
  6. Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences University of Oxford, United Kingdom
  7. Kontraktenheden, North Denmark Region, Denmark
  8. Department of Clinical Medicine, Aalborg University, Denmark
  9. Department of Endocrinology, Aalborg University Hospital, Denmark
  10. Steno Diabetes Center North Jutland, Denmark
  11. School of Medicine Sydney, University of Notre Dame Australia, Australia
  12. School of Population Health, UNSW Medicine, UNSW Sydney, Australia
https://doi.org/10.7554/eLife.83888
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Cite this article
  1. Thach Tran
  2. Thao Ho-Le
  3. Dana Bliuc
  4. Bo Abrahamsen
  5. Louise Hansen
  6. Peter Vestergaard
  7. Jacqueline R Center
  8. Tuan V Nguyen
(2023)
‘Skeletal Age’ for mapping the impact of fracture on mortality
eLife 12:e83888.
https://doi.org/10.7554/eLife.83888
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4 figures, 3 tables and 5 additional files

Figures

Figure 1
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Flowchart of recruitment and follow-up.
Figure 2
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Schematic representation of time-dependent analysis.
Figure 3
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Association between specific fracture and mortality risk, adjusted for age and severity of comorbidities*: hazard ratio and 95% confidence interval (CI).

Legend * severity of comorbidities is assessed using the Charlson Comorbidity Index. Hazard ratio and the corresponding 95% confidence interval were estimated from a multivariable-adjusted Cox's proportional hazards regression.

Figure 4
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Skeletal age by specific fracture site and chronological age at fracture.

Tables

Key resources table
Reagent type (species) or resourceDesignationSource or referenceIdentifiersAdditional information
Software, algorithmR Project for Statistical ComputingR Project for Statistical ComputingRRID:SCR_001905
Software, algorithmStata Statistical SoftwareA Software resource for statistical analysis and presentation of graphicsRRID:SCR_012763
Table 1
Characteristics of the study population at baseline stratified by gender, fracture, and mortality status.
CharacteristicNon-fracture groupFracture group
AliveDeadAliveDead
Men
Number of individuals466,936231,50754,35541,017
Age at baseline159.8 (7.7)71.1 (10.4)61.3 (8.9)72.4 (10.4)
Age at fracture168.2 (9.9)77.8 (10.5)
Comorbidities*
Charlson comorbidity index20 (0, 0)0 (0, 1)0 (0, 1)1 (0, 2)
 0404,415 (86.7%)140,293 (60.6%)32,287 (59.4%)12,592 (30.7%)
 1–256,701 (12.1%)70,841 (30.6%)17,557 (32.3%)19,073 (46.5%)
 3–43,328 (0.7%)9,260 (4.0%)2,881 (5.3%)5,209 (12.7%)
 5+2,492 (0.5%)1,112 (4.8%)1,631 (3.0%)4,143 (10.1%)
Specific comorbidities3
Myocardial infarction18,734 (4.0%)22,225 (9.6%)5,055 (9.3%)6,071 (14.8%)
Congestive heart failure12,814 (2.7%)26,623 (11.5%)5,109 (9.4%)8,655 (21.1%)
Stroke21,792 (4.7%)31,253 (13.5%)9,458 (17.4%)11,567 (28.2%)
Peripheral vascular disease10,912 (2.3%)18,058 (7.8%)4,240 (7.8%)5,660 (13.8%)
Arrhythmias10,835 (2.3%)18,289 (7.9%)4,892 (9.0%)5,747 (18.4%)
Hypertension14,340 (3.1%)15,279 (6.6%)7,718 (14.2%)7,875 (19.2%)
Diabetes mellitus with no chronic complications19,805 (4.2%)21,067 (9.1%)6,305 (11.6%)6,317 (15.4%)
Diabetes mellitus with chronic complications6,120 (1.3%)8,103 (3.5%)2,446 (4.5%)2,748 (6.7%)
Renal disease4,290 (0.9%)8,797 (3.8%)2,120 (3.9%)3,609 (8.8%)
Cancer26,126 (5.6%)43,523 (18.8%)8,914 (16.4%)11,813 (28.8%)
Metastatic tumors1,894 (0.4%)9,492 (4.1%)1,033 (1.9%)3,035 (7.4%)
Dementia2,869 (0.6%)7,640 (3.3%)2,663 (4.9%)6,071 (14.8%)
Chronic lung disease16,600 (3.6%)25,697 (11.1%)6,740 (12.4%)8,696 (21.2%)
Rheumatologic4,881 (1.1%)4,630 (2.0%)1,685 (3.1%)1,600 (3.9%)
Mild liver disease2,647 (0.6%)3,704 (1.6%)1,468 (2.7%)1,805 (4.4%)
Moderate/severe liver disease589 (0.1%)1,389 (0.6%)435 (0.8%)779 (1.9%)
Hemiplegia661 (0.1%)927 (0.4%)461 (0.9%)480 (0.9%)
HIV/AIDS108 (0.02%)81 (0.03%)37 (0.07%)23 (0.06%)
Women
Number of individuals465,559195,467130,77181,727
Age at baseline160.5 (8.3)74.0 (11.1)63.9 (9.7)76.3 (9.9)
Age at fracture170.9 (10.2)81.3 (9.6)
Comorbidities*
Charlson comorbidity index20 (0, 0)0 (0, 1)0 (0, 1)1 (0, 2)
 0400,005 (85.9%)121,776 (62.3%)81,574 (62.4%)32,093 (39.3%)
 1–259,923 (12.9%)57,663 (29.5%)41,114 (31.4%)35,866 (44.0%)
 3–42,975 (0.6%)6,255 (3.2%)5,196 (4.0%)7,960 (9.8%)
 5+2,656 (0.6%)9,773 (5.0%)2,887 (2.2%)5,695 (7.0%)
Specific comorbidities3
Myocardial infarction7,164 (1.5%)10,946 (5.6%)6,109 (4.7%)7,562 (9.3%)
Congestive heart failure7,307 (1.6%)18,374 (9.4%)8,056 (6.2%)13,615 (16.7%)
Stroke16,329 (3.5%)22,870 (11.7%)17,143 (13.1%)19,247 (23.6%)
Peripheral vascular disease6,517 (1.4%)10,555 (5.4%)6,196 (4.7%)7,309 (9.0%)
Arrhythmias7,671 (1.7%)13,096 (6.7%)7,947 (6.1%)11,440 (14.0%)
Hypertension12,910 (2.8%)12,510 (6.4%)17,970 (13.7%)15,727 (19.3%)
Diabetes mellitus with no chronic complications14,151 (3.0%)14,074 (7.2%)9,960 (7.6%)9,214 (11.3%)
Diabetes mellitus with chronic complications3,367 (0.7%)4,496 (2.3%)2,969 (2.3%)3,126 (3.8%)
Renal disease2,386 (0.5%)4,300 (2.2%)2,697 (2.1%)3,561 (4.4%)
Cancer30,913 (6.6%)34,989 (17.9%)20,246 (15.5%)18,785 (23.0%)
Metastatic tumors2,302 (0.5%)8,796 (4.5%)2,221 (1.7%)4,632 (5.7%)
Dementia3,035 (0.7%)7,428 (3.8%)7,169 (5.5%)13,136 (16.1%)
Chronic lung disease18,759 (4.0%)20,915 (10.7%)15,065 (11.5%)14,018 (17.2%)
Rheumatologic10,392 (2.2%)7,037 (3.6%)7,482 (5.7%)5,256 (6.4%)
Mild liver disease2,599 (0.6%)2,346 (1.2%)2,165 (1.7%)1,802 (2.2%)
Moderate/severe liver disease296 (0.1%)782 (0.4%)422 (0.3%)643 (0.8%)
Hemiplegia524 (0.1%)573 (0.3%)577 (0.4%)475 (0.6%)
HIV/AIDS14 (0.0%)9 (0.0%)12 (0.01%)4 (0.0%)

  1. Notes: 1: mean (SD); 2: median (IQR); 3: number (%). *: at baseline for individuals without fracture or at fracture time for fracture patients. Comorbidities included not only chronic diseases that require hospitalization, but also those documented as either secondary diagnoses or at outpatient or emergency visits.

Table 2
Incidence of mortality following specific fracture sites stratified by gender.
FractureNumberAge at fracture (years)Number of deathsFollow-up time (person-years)Rate* of mortality (95% CI)
Men
No fracture698,44363.6** (10.2)231,5079,049,1942.6% (2.5, 2.6)
Any fracture95,37272.3 (11.2)41,017626,7336.5% (6.5, 6.6)
Hip fracture25,70679.5 (9.7)16,890107,78915.7% (15.4, 15.9)
Femur1,91074.5 (10.8)99710,4689.5% (8.9, 10.1)
Pelvis1,30577.0 (10.9)7516,46511.6% (10.8, 12.5)
Vertebrae6,92472.7 (10.5)3,12541,7467.5% (7.2, 7.7)
Humerus10,12672.6 (10.7)4,82762,3507.7% (7.5, 8.0)
Rib6,86769.7 (10.4)2,35050,1864.7% (4.5, 4.9)
Clavicle5,20168.2 (10.5)1,63639,7314.1% (3.9, 4.3)
Lower leg6,29667.0 (9.5)1,79652,9153.4% (3.2, 3.6)
Forearm15,26869.4 (10.2)4,675120,7193.9% (3.8, 4.0)
Knee1,38270.2 (10.1)44710,8864.1% (3.7, 4.5)
Ankle1,08467.6 (9.8)2759,0813.0% (2.7, 3.4)
Hand8,30967.7 (10.1)2,17870,2633.1% (3.0, 3.2)
Foot4,99465.3 (9.7)1,07044,1362.4% (2.3, 2.6)
Women
No fracture661,02664.5** (11.1)195,4678,723,8632.2% (2.2, 2.3)
Any fracture212,49874.9 (11.2)81,7271,506,9405.4% (5.4, 5.5)
Hip fracture51,66982.1 (9.2)31,816259,08712.3% (12.1, 12.4)
Femur3,52978.9 (10.9)1,92119,3229.9% (9.5, 10.4)
Pelvis4,92081.2 (10.0)2,89326,76110.8% (10.4, 11.2)
Vertebrae9,73276.6 (10.6)4,65860,2957.7% (7.5, 7.9)
Humerus28,29874.4 (10.5)10,330202,6625.1% (5.0, 5.2)
Rib3,15374.1 (11.9)1,21822,2855.5% (5.2, 5.8)
Clavicle4,48072.7 (11.5)1,57731,7555.0% (4.7, 5.2)
Lower leg11,46070.1 (10.8)3,13094,3083.3% (3.2, 3.4)
Forearm68,33372.0 (10.3)18,470559,4063.3% (3.2, 3.3)
Knee2,60471.3 (9.7)62921,0853.0% (2.8, 3.2)
Ankle1,93670.0 (10.6)49915,7263.2% (2.9, 3.5)
Hand12,48969.6 (10.2)2681108,1122.5% (2.4, 2.6)
Foot9,91667.8 (9.6)190486,1362.2% (2.1, 2.3)

  1. Notes: *: rates were calculated as number of deaths/100 person-years; **: age at baseline (years).

Additional files

Supplementary file 1

List of ICD-10 codes used to define specific fractures and comorbidities.

https://cdn.elifesciences.org/articles/83888/elife-83888-supp1-v1.docx
Supplementary file 2

Skeletal age by specific fracture site and chronological age at fracture.

https://cdn.elifesciences.org/articles/83888/elife-83888-supp2-v1.docx
Supplementary file 3

Skeletal age for a 60-year-old individual who sustained a fracture at a specific bone.

https://cdn.elifesciences.org/articles/83888/elife-83888-supp3-v1.docx
Supplementary file 4

R codes used to construct skeletal age for individual fracture sites associated with increased mortality risk.

https://cdn.elifesciences.org/articles/83888/elife-83888-supp4-v1.docx
MDAR checklist
https://cdn.elifesciences.org/articles/83888/elife-83888-mdarchecklist1-v1.docx

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  1. Thach Tran
  2. Thao Ho-Le
  3. Dana Bliuc
  4. Bo Abrahamsen
  5. Louise Hansen
  6. Peter Vestergaard
  7. Jacqueline R Center
  8. Tuan V Nguyen
(2023)
‘Skeletal Age’ for mapping the impact of fracture on mortality
eLife 12:e83888.
https://doi.org/10.7554/eLife.83888