Epidemiological transition to mortality and refracture following an initial fracture
- Healthy Ageing Theme, Garvan Institute of Medical Research, Australia
- Swinburne University of Technology, Australia
- Faculty of Engineering and Information Technology, Hatinh University, Viet Nam
- St Vincent Clinical School, UNSW Sydney, Australia
- Fertility Department, Andrology and Fertility Hospital of Hanoi, Viet Nam
- School of Medicine Sydney, University of Notre Dame Australia, Australia
- School of Biomedical Engineering, University of Technology, Australia
Figures
Figure 1
Flowchart of recruitment and follow-up.
Figure 2
Predictors of transition to fracture/refracture (Panel A) and predictors of transition to death (Panel B): hazard ratio and 95% confidence interval from the multistate model, adjusting for age, femoral neck BMD, BMI, history of fall within 12 months, prior fracture, and other comorbidities (cardiovascular disease, cancer, type 2 diabetes, neuromuscular, rheumatoid arthritis, and chronic obstructive pulmonary disease).
Fx, fracture. FNBMD, femoral neck bone mineral density. COPD, chronic obstructive pulmonary disease. Symbol * indicates statistical significance at level of 5% (p<0.05).
Figure 3 with 2 supplements
Adjusted cumulative probability of mortality in women (left panel) and men (right panel) who had stayed in different states of bone health.
There were four potential bone heath states before transiting to state 5 (i.e., mortality): state 1: no fracture (green blue colour area) if the individual entered the study without any osteoporotic …
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Figure 3—source data 1
Adjusted cumulative probability of mortality in women and men, who had stayed in different states of bone health.
Risk was estimated for women and men with different BMD profiles (i.e.,−1.5 vs −2.5), at the event age of 70 and 80, having all other factors set to the population mean, that is, body massindex = 26.6 kg/m2, no history of fall at baseline, no prior fracture and no comorbidities.
- https://cdn.elifesciences.org/articles/61142/elife-61142-fig3-data1-v2.xlsx
Figure 3—figure supplement 1
Adjusted cumulative mortality probability in women (left panel) and men (right panel) by bone health state.
An individual could stay in a state (state 1 to state 4) before transiting to state 5 (i.e., mortality): state 1: no fracture (blue area) if an individual entered the study without any osteoporotic …
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Figure 3—figure supplement 1—source data 1
Adjusted cumulative mortality probability in women and men by bone health state.
Risk was estimated for women and men with different BMD profiles (i.e., T-score = 0, –1.5, and −2.5), at different event ages (60, 70, and 80), with all other factors being at the sample mean, that is, body massindex = 26.6 kg/m2 (equal to mean), no history of fall at baseline, no prior fracture and no comorbidities.
- https://cdn.elifesciences.org/articles/61142/elife-61142-fig3-figsupp1-data1-v2.xlsx
Figure 3—figure supplement 2
Assessment of goodness-of-fit of the analysis model for each of five heath states: alive and free of fracture, initial fracture, second fracture, third and further fracture, and death.
Grey curve shows the observed prevalence of each heath state while the expected values are shown in dashed black curve with 95% confident interval (dotted grey curves).
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Figure 3—figure supplement 2—source data 1
Assessment of goodness-of-fit of the analysis model: Observed and expected prevalences of each heath state.
- https://cdn.elifesciences.org/articles/61142/elife-61142-fig3-figsupp2-data1-v2.xlsx
Figure 4
Markovian model of transition between five heath states (e.g., alive without a fracture, initial fracture, second fracture, third and further fractures, and death).
The transition between state r to state s is 'governed' by the instantaneous risk of transition (i.e., intensity) qrs, where r and s represent each of the five health states. At a given time point, …
Tables
Table 1
Baseline characteristics and incident illnesses of 2046 women and 1205 men in the Dubbo Osteoporosis Epidemiology Study.
| Women | Men | P-value | |
|---|---|---|---|
| Number of participants | 2046 | 1205 | |
| BMI (kg/m2) | 26.5 (5.1) | 26.8 (3.9) | 0.035 |
| FNBMD (g/cm2) | 0.81 (0.14) | 0.92 (0.15) | <0.001 |
| FNBMD T-score | −1.62 (–1.15) | −0.99 (–1.22) | <0.001 |
| Osteoporosis (n; %) | 458 (22.4) | 111 (9.2) | <0.001 |
| History of falls (n; %) | 776 (37.9) | 317 (26.3) | <0.001 |
| Prior fracture since age 50 (n; %) | 357 (17.5) | 139 (11.5) | <0.001 |
| Cardiovascular disease (n; %) | 632 (30.9) | 470 (39.0) | <0.001 |
| Bone-unrelated cancer (n; %) | 174 (8.5) | 108 (9.0) | 0.654 |
| Neurological disease (n; %) | 142 (6.9) | 69 (5.7) | 0.175 |
| Rheumatoid arthritis (n; %) | 84 (4.1) | 25 (2.1) | 0.002 |
| Respiratory disease (n; %) | 221 (10.8) | 141 (11.7) | 0.431 |
| Type 2 diabetes (n; %) | 219 (10.7) | 158 (13.1) | 0.038 |
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Notes: Values shown are mean and standard deviation (in brackets), unless otherwise specified. P-values were derived from t-test for continuous variables and from chi-squared test for binary variables. FNBMD, femoral neck bone mineral density.
Table 2
Instantaneous risk of transition between states of bone health for women and men.
| Transitional state | Women: risk (95% CI) | Men: risk (95% CI) | Hazard ratio for men vs women (95% CI) |
|---|---|---|---|
| No Fx → Initial Fx | 2.7 (2.4–3.0) | 1.7 (1.4–2.0) | 0.63 (0.53–0.75) |
| Initial Fx → Second Fx | 4.8 (3.8–6.3) | 4.1 (2.8–5.9) | 0.85 (0.61–1.19) |
| Second Fx → Third+ Fx | 6.3 (3.7–10.9) | 13.3 (6.7–26.1) | 2.11 (1.13–3.95) |
| No Fx → Death | 1.8 (1.5–2.0) | 3.2 (2.8–3.7) | 1.81 (1.55–2.10) |
| Initial Fx → Death | 2.1 (1.5–2.9) | 5.0 (3.5–7.4) | 2.40 (1.79–3.21) |
| Second Fx → Death | 2.2 (1.1–4.4) | 16.5 (8.8–32.9) | 7.52 (4.33–13.07) |
| Third+ Fx → Death | 12.9 (5.8–28.9) | 33.9 (11.8–86.2) | 2.62 (1.17–5.87) |
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Note: ‘Fx’, fracture. CI, confidence interval. BMD, bone mineral density. BMI, body mass index. See Data Analysis for the definition of ‘instantaneous risk’ (hazard). Risk was estimated for a ‘typical’ man or woman having average BMD, characterized by mean values of predictors as follows: age at event = 70 years, femoral neck bone mineral density T-score = −1.5 (equal to mean), BMI = 26.6 kg/m2 (equal to mean), no history of falls, no prior fracture, no comorbidities. Hazard ratio and 95% confidence interval were derived from the multistate model, adjusting for age, femoral neck BMD, BMI, history of a fall within 12 months, prior fracture, and other comorbidities (cardiovascular disease, cancer, type 2 diabetes, neuromuscular, rheumatoid arthritis, and chronic obstructive pulmonary disease). Bold-face values indicate a statistically significant difference between men and women. In each cell, values are percentage of risk and 95% confident interval (in the brackets).
Table 3
Sojourn time (in years) of women/men with different bone health*.
| Transition | T-score = 0 | T-score = −1.5 | T-score = −2.5 |
|---|---|---|---|
| Women | |||
| No Fx. | 32.1 (28.2–36.6) | 22.4 (20.4–24.6) | 16.9 (15.2–18.7) |
| Initial Fx. | 21.9 (16.7–28.8) | 14.5 (11.8–17.7) | 10.1 (8.8–13.4) |
| Second Fx. | 18.5 (10.1–34.0) | 11.8 (7.6–18.1) | 8.7 (5.7–13.1) |
| Third+ Fx. | 5.2 (1.7–15.9) | 7.7 (3.4–17.7) | 10.0 (4.7–21.5) |
| Men | |||
| No Fx. | 25.5 (22.5–28.9) | 20.4 (18.3–22.8) | 16.9 (14.8–19.3) |
| Initial Fx. | 15.5 (11.5–20.9) | 11.0 (8.5–14.3) | 08.7 (6.6–11.4) |
| Second Fx. | 5.4 (3.0–9.9) | 3.3 (2.2–5.4) | 2.4 (1.5–3.9) |
| Third+ Fx. | 2.0 (0.6–7.2) | 3.0 (1.1–8.2) | 3.8 (1.5–9.9) |
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*Time was estimated for women or men with different BMD profiles (i.e., 0, –1.5 vs −2.5), at the age of 70, with BMI of 26.6 kg/m2 (equal to mean), with no history of falls, no prior fracture and no comorbidities. Sojourn time is defined as the predicted time an individual stays in one state before moving to the next state. Fx, fracture. In each cell, values are number of years and 95% confident interval (in the brackets).
Table 4
Five-year probability of transition between states of bone health for women and men.
| Women | |||||
|---|---|---|---|---|---|
| From | To | ||||
| No fracture | 1st fracture | 2nd fracture | 3rd fracture | Death | |
| No fracture | 80.0 (78.2–81.4) | 10.1 (9.1–11.3) | 1.2 (0.9–1.5) | 0.1 (0.1–0.2) | 8.6 (7.6–9.7) |
| 1st fracture | 70.8 (65.3–75.4) | 16.5 (12.9–20.6) | 2.4 (1.4–3.9) | 10.4 (7.9–14.0) | |
| 2nd fracture | 65.3 (51.4–75.5) | 18.5 (10.2–28.9) | 16.2 (10.0–26.4) | ||
| 3rd fracture | 52.4 (22.9–75.0) | 47.6 (25.0–77.1) | |||
| Men | |||||
| From | To | ||||
| No fracture | 1st fracture | 2nd fracture | 3rd fracture | Death | |
| No fracture | 78.3 (76.1–80.3) | 6.0 (5.0–7.0) | 0.4 (0.3–0.6) | 0.1 (0.0–0.2) | 15.3 (13.6–17.2) |
| 1st fracture | 63.5 (54.9–70.2) | 8.1 (4.9–12.1) | 2.1 (0.8–4.3) | 26.3 (20.0–34.3) | |
| 2nd fracture | 22.4 (8.4–38.4) | 13.6 (3.7–29.7) | 64.0 (44.5–82.5) | ||
| 3rd fracture | 18.4 (0.8–53.8) | 81.6 (46.2–99.2) | |||
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Note: Risk was estimated for a ‘typical’ man or woman having a risk profile characterized by mean values of predictors as follows: age at event = 70 years, femoral neck bone mineral density T-score of −1.5, BMI = 26.6 kg/m2, no history of falls, no prior fracture, no comorbidities. In each cell, values are percentage of risk and 95% confident interval (in the brackets).
Key resources table
| Reagent type (species) or resource | Designation | Source or reference | Identifiers | Additional information |
|---|---|---|---|---|
| Software, algorithm | R Project for Statistical Computing | R Project for Statistical Computing | RRID:SCR_001905 | |
| Software, algorithm | Algorithm SAS program | Statistical Analysis System | RRID:SCR_008567 |
Author response table 1
| Event age (years) | |||||
|---|---|---|---|---|---|
| 60-69 | 70-79 | ≥80 | Total | ||
| Baseline age (years) | 60-69 | 158 | 209 | 68 | 435 |
| 70-79 | - | 115 | 171 | 286 | |
| ≥80 | - | - | 95 | 95 | |
| Total | 158 | 324 | 334 | 816 |
Author response table 2
| Fracture type | Women | Men | Total |
|---|---|---|---|
| Hip fracture | 87 | 29 | 116 |
| Vertebral fracture | 240 | 80 | 320 |
| Non-hip non-vertebral fracture | 305 | 75 | 380 |
| Total | 632 | 184 | 816 |
Additional files
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Supplementary file 1
Age at study entry, initial fracture, second fracture, third fracture, and death in women and men.
Values shown are mean and standard deviation (in brackets).
- https://cdn.elifesciences.org/articles/61142/elife-61142-supp1-v2.docx
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Supplementary file 2
Transition between health states during the study period: actual number of individuals and probability for 2046 women and 1205 men.
Data shown are the number of individuals (percentage in brackets). The sign ‘–’ in a state indicates that the transition to the state is shown in the next row.
- https://cdn.elifesciences.org/articles/61142/elife-61142-supp2-v2.docx
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Supplementary file 3
Five-year probability of transition between states of bone health for women and men with femoral neck BMD T-score of 0 (normal) and −2.5 (osteoporosis).
Risk was estimated for a man or woman characterized as follows: age = 70 years, BMI = 26.6 kg/m2 (equal to mean), no history of falls, no prior fracture, no comorbidities. Bold values indicate transition probability for initial and subsequent fractures significantly different between an individual with a BMD T-score of 0 (normal) and one with a BMD T-score of −2.5 (osteoporosis). In each cell, values are percentages of risks for T-score = 0 and T-score = −2.5, separated by a slash sign.
- https://cdn.elifesciences.org/articles/61142/elife-61142-supp3-v2.docx
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Transparent reporting form
- https://cdn.elifesciences.org/articles/61142/elife-61142-transrepform-v2.docx
