Prediction of subsequent fragility fractures: application of machine learning.

BACKGROUND: Machine learning (ML) has shown exceptional promise in various domains of medical research. However, its application in predicting subsequent fragility fractures is still largely unknown. In this study, we aim to evaluate the predictive power of different ML algorithms in this area and identify key features associated with the risk of subsequent fragility fractures in osteoporotic patients. METHODS: We retrospectively analyzed data from patients presented with fragility fractures at our Fracture Liaison Service, categorizing them into index fragility fracture (n = 905) and subsequent fragility fracture groups (n = 195). We independently trained ML models using 27 features for both male and female cohorts. The algorithms tested include Random Forest, XGBoost, CatBoost, Logistic Regression, LightGBM, AdaBoost, Multi-Layer Perceptron, and Support Vector Machine. Model performance was evaluated through 10-fold cross-validation. RESULTS: The CatBoost model outperformed other models, achieving 87% accuracy and an AUC of 0.951 for females, and 93.4% accuracy with an AUC of 0.990 for males. The most significant predictors for females included age, serum C-reactive protein (CRP), 25(OH)D, creatinine, blood urea nitrogen (BUN), parathyroid hormone (PTH), femoral neck Z-score, menopause age, number of pregnancies, phosphorus, calcium, and body mass index (BMI); for males, the predictors were serum CRP, femoral neck T-score, PTH, hip T-score, BMI, BUN, creatinine, alkaline phosphatase, and spinal Z-score. CONCLUSION: ML models, especially CatBoost, offer a valuable approach for predicting subsequent fragility fractures in osteoporotic patients. These models hold the potential to enhance clinical decision-making by supporting the development of personalized preventative strategies.

Risk factors for subsequent fractures in hip fracture patients: a nested case-control study.

BACKGROUND: The risk factors for subsequent fractures following an initial hip fracture are not entirely understood. This study examined the clinical characteristics of hip fracture patients to identify potential risk factors associated with a higher risk of experiencing subsequent fractures. METHODS: We conducted a nested case-control study using data from the Chinese PLA General Hospital Hip Fracture Cohort between January 2008 and March 2022. The cases were individuals who experienced subsequent fractures following an initial hip fracture. Each case was matched with up to 2 controls who did not develop subsequent fractures. Important clinical factors were compared across groups, including traditional fracture risk factors and potential risk factors (e.g., comorbidities, falls risk, physical impairment, calcium or vitamin D use, and anti-osteoporosis medications). Conditional logistic regression analyses were used to evaluate the impact of these clinical features as potential risk factors for subsequent fractures. RESULTS: A total of 96 individuals who suffered from subsequent fractures were matched with 176 controls. The median time between the initial hip fracture and the subsequent fracture was 2.1 years. The overall proportion of patients receiving anti-osteoporosis treatment after initial hip fracture was 25.7%. In the multivariable regression analysis, living in a care facility (OR = 3.78, 95%CI: 1.53-9.34), longer hospital stays (OR = 1.05, 95%CI: 1.00-1.11), and falls after discharge (OR = 7.58, 95%CI: 3.37-17.04) were associated with higher odds of subsequent fractures. CONCLUSIONS: This study showed that living in a care facility, longer hospital stays, and falls after discharge may be independent risk factors for repeat fractures following an initial hip fracture. These findings could be used to identify and manage patients at high risk of subsequent fractures.

Impact of diabetes on the risk of subsequent fractures in 92,600 patients with an incident hip fracture: A Danish nationwide cohort study 2004-2018.

PURPOSE: We investigated the incidence rates of a subsequent hip fracture (HF) and other subsequent fractures than HF after first incident HF, comparing patients with and without diabetes. METHODS: Using Danish medical databases, we identified 92,600 incident HF patients in the period 2004-2018. Diabetes exposure was examined overall, by type of diabetes (T2D and T1D), and by presence of diabetes complications. We estimated cumulative incidence of subsequent HFs and fractures other than HF within two years of the incident HF. Using Cox regression, adjusted hazard ratios (aHRs) with 95 % confidence interval (CI) were calculated. RESULTS: Among incident HF patients, 11,469 (12 %) had diabetes, of whom 10,253 (89 %) had T2D and 1216 (11 %) had T1D. The 2-year incidence rates for a new subsequent HF were 4.8 % (95 % CI: 4.6-4.9) for patients without diabetes (reference group), 4.1 % (95 % CI: 3.8-4.6) for T2D, and 4.3 % (95 % CI: 3.3-5.6) for T1D. Corresponding aHRs were 1.01 (95 % CI 0.90-1.14) for T2D and 1.17 (95 % CI 0.87-1.58) for T1D. There was effect modification by sex, as women with T1D had an aHR of 1.52 (95 % CI: 1.09-2.11) for subsequent HF, and by specific diabetes complications (for example, patients with T2D and prior hypoglycemia had an aHR of 1.75 (95 % CI: 1.24-2.42) for subsequent HF, while patients with T1D and neuropathy had an aHR of 1.73 (95 %: 1.09-2.75), when compared with patients without diabetes). For fractures other than HF, the 2-year incidence rates were 7.3 % (95 % CI: 7.2-7.5) for patients without diabetes, 6.6 % (95 % CI: 6.1-7.1) for T2D, and 8.5 % (95 % CI: 7.0-10.1) for T1D, with corresponding aHRs of 1.01 (95 % CI 0.92-1.11) for T2D and 1.43 (95 % CI: 1.16-1.78) for T1D. T2D was only a risk factor for other subsequent fractures among HF patients of high age (age 86-89 years: aHR 1.22 (95 % CI 0.99-1.55), age 90+ years: aHR 1.37 (95 % CI 1.08-1.74)), whereas T1D was robustly associated with increased risk of fractures other than HF in all subgroups. CONCLUSION: Among HF patients, we found no strong overall association of T2D or T1D with increased risk of subsequent HF, but diabetes patients with prior hypoglycemic events or neuropathy were at increased risk. In contrast, patients with T1D had a clearly increased risk of subsequent fractures other than HF.

Understanding the long-term impact of incident osteoporotic fractures on healthcare utilization and costs in Korean postmenopausal women.

This study provides long-term evidence that healthcare resource utilization and costs of care in women who experienced incident osteoporotic fractures remained higher than those in women without fractures over a span of 5 years. These findings emphasize the importance of early diagnostics and treatment for osteoporosis. PURPOSE: To evaluate healthcare resource utilization (HCRU) and costs of care over 5 years after the incident osteoporotic fractures (OF) in postmenopausal women. METHODS: We used data from the National Health Insurance Service databases 2011-2018. Women aged ≥ 50 years with incident OF (OF group) were matched to women without OF (non-OF group). HCRU (inpatient, outpatient, and emergency room [ER] visits) and costs of care (inpatient, outpatient, and ER visits) during the 5-year follow-up period were derived after propensity score matching (PSM). Additionally, we identified women with subsequent fractures within the first 2 years after the incident OF. RESULTS: After PSM, 47,238 OF and 134,813 non-OF women were identified. HCRU rates and costs of care were highest in the first year after OF and decreased substantially, but remained higher in the OF group during the entire follow-up period. The increase in cumulative HCRU rates over 5 years was highest in inpatient admissions with ER visits (138% higher in OF vs non-OF). The cumulative total costs over 5 years were 73% higher in the OF group than in the non-OF group, which was mostly driven by inpatient costs. Trends were similar for women with subsequent fractures, but they generally showed higher HCRU and costs than those in the total OF group. CONCLUSION: OF imposes a substantial and sustained economic burden on women, resulting in an approximately twofold increase in the cumulative cost over 5 years compared to women without fracture, which highlights the need for early diagnostics and treatment of osteoporosis.

Treatment Persistence and Medication Switch Associated With Subsequent Fractures After Osteoporotic Fractures.

CONTEXT: Despite prevalent anti-osteoporosis medication (AOM) switching in real-world osteoporosis management, few studies have evaluated the impact of persistent AOM treatment, allowing for AOM switching, on the risk of subsequent fracture. OBJECTIVE: We examined the association between persistence in AOM and subsequent fractures, allowing for medication switching among patients with osteoporotic fractures. METHODS: This retrospective cohort study used Taiwan National Health Insurance claims data to select patients who initiated AOM between 2013 and 2016. Treatment persistence was defined as use of any AOM on a given day of interest with a 45-day grace period. Medication switch was allowed for persistence if remaining on treatment. AOMs with long-lasting inhibition of bone resorption (zoledronate and denosumab) were categorized as high-potency; others as low-potency. Multivariate Cox models were used to evaluate risk of subsequent fractures ≥3 months after initiating AOM. RESULTS: A total of 119 473 patients were included (mean [SD] follow-up 46.4 [15.6] months), and 26.8% switched from the index AOM. Within 1 year, 52% remained persistent with AOM. Compared to patients with persistent AOM, those not persistent had higher risk of subsequent hip (adjusted hazard ratio [aHR] = 1.31; 95% CI, 1.21-1.42), vertebral (aHR = 1.17; 95% CI, 1.13-1.22), and radius fractures (aHR = 1.16; 95% CI, 1.08-1.25). Patients with persistent AOM who switched from high- to low-potency AOM had higher risk of subsequent vertebral fractures than those with persistent AOM and no potency switch (aHR = 1.28; 95% CI, 1.02-1.60). CONCLUSION: Patients with non-persistent AOM had higher risk of subsequent fractures than persistent users when allowing AOM switch. Switching AOM potency may influence the risk of subsequent vertebral fractures and warrants further investigation.

Frailty and risk of subsequent fracture among older adults presenting to hospital with a minimal trauma fracture.

We investigated frailty and refracture risk among older adults with a minimal trauma fracture. After adjusting for age, sex, and site of initial fracture, increasing frailty was associated with an increased risk subsequent fracture. These results indicate the need to routinely screen for frailty following an initial fracture among older adults. INTRODUCTION: Minimal trauma fractures are common among older adults, and frailty increases risk of an initial minimal trauma fracture. This study was undertaken to estimate the risk of subsequent fracture based on frailty status at the time of an initial fracture. METHODS: The study population was older adults presenting to hospital, aged 60 years or more, with a minimal trauma fracture. Frailty was estimated using a cumulative deficit approach. The risk of subsequent fracture based on increasing cumulative frailty deficit item group, adjusted for sex, age, and site of initial fracture, was estimated using Cox's proportional hazard model. RESULTS: Between January 2014 and December 2020, 12,115 older adults presented to hospital (8371 women [69%]), with an initial minimal trauma fracture. The average age was 80 years (SD 9.5). Subsequent fractures identified during the follow-up period occurred in 1137 (9.4%) of study participants. The incidence of subsequent fracture ranged from 25.0 per 1000 older adults (95% confidence interval (CI) 22.4 to 27.8) among the lowest frailty deficit group (1 deficit item) to 31.8 per 1000 (95% CI 28.0 to 35.8) among the highest frailty deficit group (4 to 12 deficit items). After adjusting for age, sex, and site of initial fracture, an increasing number of frailty deficit items was associated with increased risk subsequent fracture (p-value for trend = 0.008). CONCLUSION: Our results indicate that following an initial minimal trauma fracture, frailty independently increases the risk of a subsequent fracture. Therefore, it is important at the time of an initial fracture that older women and men are screened for the presence of frailty, and models of care are implemented to reduce the risk of subsequent fracture among this vulnerable group of older adults.

Five-year risk of fracture and subsequent fractures among adults with cerebral palsy.

Background: Epidemiologic evidence documenting the incidence of fracture and subsequent fractures among adults with cerebral palsy (CP) is lacking, which could inform fracture prevention efforts. The objective was to characterize the 5-year rate of initial and subsequent fragility fractures among adults with CP. Methods: This retrospective cohort study used Medicare claims from 01/01/2008-12/31/2019 from adults ≥18 years old with CP (n = 44,239) and elderly ≥65 years old without CP (n = 2,176,463) as a comparison. The incidence rate (IR), IR ratio (IRR), and site distribution were estimated for the initial and subsequent fragility fractures over 5-years by sex and age. Results: The IR of fragility fracture at any site over the 5-year follow-up was similar for 18-30-year-old men with CP (IR = 5.2; 95%CI = 4.4-5.9) and 30-34-year-old women with CP (IR = 6.3; 95%CI = 5.3-7.2) compared to the same sex youngest-old (65-74 years old) without CP (IRR = 1.09 and 0.94, respectively, both P > 0.05), and increased with older age for those with CP. The number of fragility fractures and IR of subsequent fragility fractures was similar for young men and middle-aged women with CP compared to elderly without CP, and increased with older age for those with CP. The proportion of fragility fracture at the tibia/fibula decreased while the vertebral column and multiple simultaneous sites (most involved hip/lower extremities) increased with older age. Conclusion: Young and middle-aged adults with CP had similar-to-worse initial and subsequent fragility fracture profiles compared to the general elderly population- a well characterized group for bone fragility. Findings emphasize the need for fracture prevention efforts at younger ages for CP, possibly by ~5 decades younger.

Osteoporosis Medications Prevent Subsequent Fracture in Frail Older Adults.

Frailty is common in older adults with fractures. Osteoporosis medications reduce subsequent fracture, but limited data exist on medication efficacy in frail individuals. Our objective was to determine whether medications reduce the risk of subsequent fracture in frail, older adults. A retrospective cohort of Medicare fee-for-service beneficiaries was conducted (2014-2016). We included adults aged ≥65 years who were hospitalized with fractures without osteoporosis treatment. Pre-fracture frailty was defined using claims-based frailty index (≥0.2 = frail). Exposure to any osteoporosis treatment (oral or intravenous bisphosphonates, denosumab, and teriparatide) was ascertained using Part B and D claims and categorized according to the cumulative duration of exposure: none, 1-90 days, and >90 days. Subsequent fractures were ascertained from Part A or B claims. Cause-specific hazard models with time-varying exposure were fit to examine the association between treatment and fracture outcomes, controlling for relevant covariates. Among 29,904 patients hospitalized with fractures, 15,345 (51.3%) were frail, and 2148 (7.2%) received osteoporosis treatment (median treatment duration 183.0 days). Patients who received treatment were younger (80.2 versus 82.2 years), female (86.5% versus 73.0%), and less frail (0.20 versus 0.22) than patients without treatment. During follow-up, 5079 (17.0%) patients experienced a subsequent fracture. Treatment with osteoporosis medications for >90 days compared with no treatment reduced the risk of fracture (hazard ratio [HR] = 0.82; 95% confidence interval [CI] 0.68-1.00) overall. Results were similar in frail (HR = 0.85; 95% CI 0.65-1.12) and non-frail (HR = 0.80; 95% CI 0.61-1.04) patients but not significant. In conclusion, osteoporosis treatment >90 days was associated with similar trends in reduced risk of subsequent fracture in frail and non-frail persons. Treatment rates were very low, particularly among the frail. When weighing treatment options in frail older adults with hospitalized fractures, clinicians should be aware that drug therapy does not appear to lose its efficacy. © 2022 American Society for Bone and Mineral Research (ASBMR).

The risk factors for subsequent fractures after distal radius fracture.

INTRODUCTION: The purpose of this study was to evaluate the risk factors for subsequent fractures after distal radius fracture (DRF). MATERIALS AND METHODS: We retrospectively reviewed 705 patients with DRF who performed dual-energy X-ray absorptiometry within six months before or after the DRF and followed more than 12 months. We identified patients with subsequent fractures and multivariate logistic regression analyses were conducted with demographic information, underlying disease status, and bone fragility parameters at the time of DRF to evaluate the risk factors for subsequent fractures. RESULTS: Subsequent fractures occurred in 56 patients (7.9% of 705 patients) with 65 fractures at a mean time of 33.5 months after DRF. In multivariate logistic regression analysis, older age (OR 1.032; 95% CI, 1.001-1.064, p = 0.044), diabetes mellitus (DM) (OR 2.663; 95% CI, 1.429-4.963, p = 0.002) and previous fracture history (OR 1.917; 95% CI, 1.019-3.607, p = 0.043), and low total hip BMD (OR 1.410; 95% CI, 1.083-1.836, p = 0.011) were significant risk factors for the occurrence of subsequent fractures. CONCLUSION: This study demonstrated that older age, DM, previous fracture history and low hip BMD are the risk factors for subsequent fractures after DRF. Active glycemic control would have a role in patients with DM and a more aggressive treat-to-target approach may be necessary for patients with low BMDs to prevent subsequent fractures after DRF.

Real-world evaluation of osteoporotic fractures using the Japan Medical Data Vision database.

In Japanese patients who experienced an osteoporotic fracture, 10.8% and 18.6% had a subsequent fracture within 1 and 2 years of follow-up, respectively. Although the burden of hip and vertebral fractures has been reported widely, we found that patients with non-hip non-vertebral (NHNV) fractures had a 26% higher risk of subsequent fracture than patients with hip fractures; therefore, NHNV fractures should also be considered an important risk factor for subsequent fracture. INTRODUCTION: To investigate imminent risk and odds of subsequent osteoporotic fractures and associated risk factors in patients who experienced an initial osteoporotic fracture. METHODS: Patients aged ≥ 50 years with ≥ 1 osteoporotic fracture were analyzed from Japan's Medical Data Vision (MDV) database of claims from acute-care hospitals (January 2012-January 2017). Multivariable models were constructed to explore the impact of key comorbidities and medications on the subsequent fracture risk: Cox proportional hazards model for time to subsequent fracture and logistic regression models for odds of subsequent fracture within 1 and 2 years from index fracture. RESULTS: In total, 32,926 patients were eligible with a median follow-up duration of 12.3 months. The percentage of patients experiencing subsequent fractures was 14.1% across the study duration, and 10.8% and 18.6% in patients with 1 and 2 years of follow-up, respectively. In the Cox proportional hazards model, patients with vertebral or NHNV index fractures had a higher subsequent fracture risk than patients with a hip index fracture (adjusted hazard ratio [aHR] 1.11 and 1.26, respectively); subsequent fracture risk was lower in males than females (aHR 0.89). Patients with baseline claims for tranquilizers and glucocorticoids had a higher subsequent fracture risk than those without (aHR 1.14 and 1.08, respectively). Additionally, baseline claims for anti-Parkinson's medications, alcoholism, and stage 4/5 chronic kidney disease were significantly associated with higher odds of subsequent fracture in the logistic regression models. CONCLUSION: Several clinical and demographic factors were associated with a higher risk and odds of subsequent fracture. This may help to identify patients who should be prioritized for osteoporosis treatment.

Muscle Strength and Physical Performance Are Associated With Risk of Postfracture Mortality But Not Subsequent Fracture in Men.

Muscle strength and physical performance are associated with incident fractures and mortality. However, their role in the risk of subsequent fracture and postfracture mortality is not clear. We assessed the association between muscle strength (grip strength) and performance (gait speed and chair stands time) and the risk of subsequent fracture and mortality in 830 men with low-trauma index fracture, who participated in the Osteoporotic Fractures in Men (MrOS) USA Study and had their index measurements assessed within 5 years prior to the index fracture. The annual decline in muscle strength and performance following index fracture, estimated using linear mixed-effects regression, was also examined in relation to mortality. The associations were assessed using Cox proportional hazards models adjusted for age, femoral neck bone mineral density (FN BMD), prior fractures, falls, body mass index (BMI), index fracture site, lifestyle factors, and comorbidities. Over a median follow-up of 3.7 (interquartile range [IQR], 1.3-8.1) years from index fracture to subsequent fracture, 201 (24%) men had a subsequent fracture and over 5.1 (IQR, 1.8-9.6) years to death, and 536 (65%) men died. Index measurements were not associated with subsequent fracture (hazard ratios [HRs] ranging from 0.97 to 1.07). However, they were associated with postfracture mortality. HR (95% confidence interval [CI]) per 1 standard deviation (1-SD) decrement in grip strength: HR 1.12 (95% CI, 1.01-1.25) and gait speed: HR 1.14 (95% CI, 1.02-1.27), and 1-SD increment in chair stands time: HR 1.08 (95% CI, 0.97-1.21). Greater annual declines in these measurements were associated with higher mortality risk, independent of the index values and other covariates. HR (95% CI) per 1-SD annual decrement in change in grip strength: HR 1.15 (95% CI, 1.01-1.33) and in gait speed: HR 1.38 (95% CI, 1.13-1.68), and 1-SD annual increment in chair stands time: HR 1.28 (95% CI, 1.07-1.54). Men who were unable to complete one or multiple tests had greater risk of postfracture mortality (24%-109%) compared to those performed all tests. It remains to be seen whether improvement in these modifiable factors can reduce postfracture mortality. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Incidence of different types of subsequent fractures and related mortality in Taiwan.

Hip fracture is the most common type of fracture to occur within 2 years after an initial fracture. Mortality risk increases when a subsequent fracture occurs. The occurrence of subsequent fracture is significantly higher in patients with hip fractures than others. Prevention of subsequent fracture is of paramount important. PURPOSE: Osteoporotic fracture significantly increases risk of subsequent fracture. In this retrospective cohort study, we used the Taiwan National Health Insurance Database (NHIRD) to analyze data on fractures in a group at high risk of osteoporosis. We aimed to distinguish differences in subsequent fracture types and their relationship with mortality. METHODS: We enrolled patients aged ≥ 50 years old who were diagnosed with an initial fracture classified as hip, vertebral, upper end of the humerus, or wrist. Data from 2 years of follow-up were analyzed. Risks of subsequent fracture events and mortality were calculated by Kaplan-Meier estimation and assessed with Cox proportional hazards models. RESULTS: We included 375,836 patients from the 2011-2015 NHIRD. Patients with initial hip fracture had the highest incidence of subsequent fracture at both 1- and 2-year follow-up (7.0% and 10.9%). Subsequent fractures occurred mainly at the hip. Conversely, other patients had a higher proportion of subsequent vertebral fracture. Patients with subsequent fracture classified as hip, vertebral, and upper end of the humerus had significantly higher cumulative mortality rates than that of patients who had no subsequent fracture, with adjusted hazard ratios of 1.64 (95% CI = 1.57-1.71, p < 0.01), 1.06 (95% CI = 1.00-1.12, p = 0.04), 1.31 (95% CI = 1.17-1.46, p < 0.01), respectively. CONCLUSION: Patients who experienced an initial hip fracture are at greatest risk of subsequent fracture, most commonly the hip. Occurrence of subsequent fractures was associated with an increased mortality risk. Thus, there is a need for early intervention following initial hip fractures.

Outcomes post fragility fracture among members of an integrated healthcare organization.

This study highlights an unmet need in osteoporosis management, suggesting that beyond bone mineral density and fracture history, gender, fracture type, and age should be considered for fracture risk assessment. Following fragility fracture, men, patients with a spine or hip fracture, and those aged ≥ 65 have a higher disease burden. INTRODUCTION: The objective of this study was to characterize osteoporosis-related fracture incidence and identify predictors of subsequent fractures and mortality. METHODS: This retrospective cohort study, conducted within Kaiser Permanente Southern California, included patients aged ≥ 50 years with qualifying fractures from 1/1/2007 to 12/31/2016, identified from diagnosis/procedure codes. Rates for fracture incidence, mortality, and resource utilization in the year post-fracture are reported. Associations between index fracture types and demographic/clinical characteristics, and mortality, subsequent fracture, and rehospitalization outcomes were estimated. RESULTS: Of 63,755 eligible patients, 66.7% were ≥ 65 years and 69.1% female. Index fractures included nonhip/nonspine (64.4%), hip (25.3%), and spine (10.3%). Age-adjusted subsequent fracture rate/100 person-years was higher for those with an index spine (14.5) versus hip fracture (6.3). Hospitalization rate/100 person-years was highest for patients ≥ 65 (31.8) and for spine fractures (43.5). Men (vs women) had higher age-adjusted rates of hospitalization (19.4; 17.7), emergency room visits (73.8; 66.3), and use of rehabilitation services (31.7; 27.2). The 30-day age-adjusted mortality rate/100 person-years was 46.7, 32.4, and 15.5 for spine, hip, and nonspine/nonhip fractures. The 1-year age-adjusted mortality rate/100 person-years was 14.7 for spine and 15.6 for hip fractures. In multivariable analyses, spine and hip fractures (vs nonhip/nonspine fractures) were significant predictors of 1-year mortality, all-cause and osteoporosis-related hospitalization, and nursing home use (all P-values < 0.0001). CONCLUSION: Morbidity is high in the year following a fragility fracture and men, patients with a spine or hip fracture, and those aged ≥ 65 have a greater disease burden.

Long-term risk of subsequent major osteoporotic fracture and hip fracture in men and women: a population-based observational study with a 25-year follow-up.

The risk of subsequent major osteoporotic and hip fracture following an initial fracture was increased in both sexes over 25 years, with modest time-dependent attenuation. This risk was highest in men, underscoring the importance of targeted treatment strategies particularly in this under-treated population. INTRODUCTION: The risk of subsequent fractures is increased following an index fracture, and declines over time. We aimed to determine whether this risk was sustained over 25 years and evolved similarly in men and women. METHODS: Using population-based databases, we performed a matched cohort study in 16,876 men and 39,230 women ≥ 50 years who sustained an index fracture during 1989-2006. Rates of subsequent major osteoporotic fractures (MOF) and hip fractures until 2016 were compared to rates for matched controls (n = 160,983). Age- and sex-stratified cumulative incidences to 25 years were estimated in the presence of competing mortality. Hazard ratios (HRs) with 95% confidence intervals (CI) for subsequent fractures were estimated for each on the first 15 years of follow-up with a final category ≥ 15 years, adjusted for comorbidities. RESULTS: Risk for MOF and hip fractures remained elevated up to 25 years in both sexes. The cumulative incidence of fractures was higher in cases vs controls in both sexes and across all age categories except in those > 90 years. Crude rate ratios for subsequent MOF were 2.5 (95% CI 2.3-2.7) in men and 1.6 (95% CI 1.6-1.7) in women and were higher in the younger age groups. Adjusted HRs (aHRs) for subsequent MOF were higher in men than in women in the first year (men aHR 2.6, 95% CI 2.1-3.3; women aHR 1.6, 95% CI 1.4-1.7). CONCLUSIONS: The risk of subsequent fractures following an initial fracture was increased over 25 years and the magnitude of risk was initially greater in men than in women.

The impact of fracture liaison services on subsequent fractures and mortality: a systematic literature review and meta-analysis.

This systematic review and meta-analysis suggests that fracture liaison service (FLS) is associated with a significantly lower probability of subsequent fractures and mortality although the latter was only found in studies comparing outcomes before and after the introduction of an FLS. INTRODUCTION: To systematically review and evaluate the impact of fracture liaison services (FLSs) on subsequent fractures and mortality using meta-analysis. METHODS: A literature search was performed within PubMed and Embase to identify original articles published between January 1, 2010, and April 30, 2020, reporting the effect of FLSs on subsequent fractures and/or mortality. Only studies comparing FLS to no-FLS were included. A meta-analysis using random-effects models was conducted. The quality of studies was appraised after combining and modifying criteria of existing quality assessment tools. RESULTS: The search retrieved 955 published studies, of which 16 studies fulfilled the inclusion criteria. Twelve studies compared outcomes before (pre-FLS) and after (post-FLS) FLS implementation, two studies compared outcomes between hospitals with and without FLS, and two other studies performed both comparisons. In total, 18 comparisons of FLS and no-FLS care were reported. Follow-up time varied from 6 months to 4 years. Sixteen comparisons reported on subsequent fractures and 12 on mortality. The quality assessment revealed methodological issues in several criteria. Excluding studies with very high selection bias, the meta-analysis of nine comparisons (in eight papers) revealed that the FLS care was associated with a significantly lower probability of subsequent fractures (odds ratio: 0.70, 95% CI: 0.52-0.93, P=0.01). In studies with a follow-up > 2 years, a significantly lower probability of subsequent fractures was captured for FLS care (odds ratio: 0.57, 95% CI: 0.34-0.94, P=0.03), while in studies ≤ 2 years, there was no difference in the odds of subsequent fractures. No significant difference in the odds of mortality was observed (odds ratio: 0.73, 95% CI: 0.49-1.09, P=0.12) in the meta-analysis of eight comparisons (in seven papers). However, a significantly lower probability of mortality was identified in the six pre-post FLS comparisons (odds ratio: 0.65, 95% CI: 0.44-0.95, P=0.03), but not in studies comparing hospitals with and without FLS. No difference was observed in mortality stratified by follow-up time. CONCLUSION: This systematic review and meta-analysis suggests that FLS care is associated with a significantly lower probability of subsequent fractures and mortality although the latter was only found in studies comparing outcomes before and after the introduction of an FLS. The quality assessment revealed that some important methodological issues were unmet in the currently available studies. Recommendations to guide researchers to design high-quality studies for evaluation of FLS outcomes in the future were provided.

Fragility fracture identifies patients at imminent risk for subsequent fracture: real-world retrospective database study in Ontario, Canada.

BACKGROUND: The secondary fracture prevention gap in the osteoporosis field has been previously described as a 'crisis'. Closing this gap is increasingly important in the context of accumulating evidence showing that an incident fragility fracture is associated with an increased risk of subsequent fracture within 1-2 years, known as imminent fracture risk. The objective of this study was to use health services data to characterize the time between index fragility fractures occurring at different osteoporotic sites and subsequent fractures. METHODS: This retrospective observational study used de-identified health services data from the publicly funded healthcare system in Ontario, the largest province of Canada. Patients aged > 65 with an index fragility fracture occurring between 2011 and 2015 were identified from the ICES Data Repository using International Classification of Diseases (ICD)-10 codes. We examined median time to subsequent fragility fractures for osteoporotic fracture sites until the end of follow-up (2017). BMD assessment and use of osteoporosis therapies following index fracture were also characterized. RESULTS: Among 115,776 patients with an index fragility fracture, 17.8% incurred a second fragility fracture. Median time between index and second fracture occurring at any site was 555 days (interquartile range: 236-955). For each index fracture site examined, median time from index to second fracture was < 2 years. The proportion of patients with BMD assessment was 10.3% ≤1 year prior to and 16.4% ≤1 year post index fracture. The proportion of patients receiving osteoporosis therapy was 29.8% ≤1 year prior, 34.6% ≤1 year post, and 25.9% > 3 years post index fracture. CONCLUSIONS: This cohort of Canadian patients aged > 65 years who experienced a fragility fracture at any site are at imminent risk of experiencing subsequent fracture within the next 2 years and should be proactively assessed and treated.

Risk factors for subsequent vertebral fracture after acute osteoporotic vertebral fractures.

PURPOSE: To investigate the incidence and characteristics of subsequent vertebral fracture after osteoporotic vertebral fractures (OVFs) and identify risk factors for subsequent vertebral fractures. METHODS: This post-hoc analysis from a prospective randomized multicenter trial included 225 patients with a 48-week follow-up period. Differences between the subsequent and non-subsequent fracture groups were analyzed. RESULTS: Of the 225 patients, 15 (6.7%) had a subsequent fracture during the 48-week follow-up. The annual incidence of subsequent vertebral fracture after fresh OVFs in women aged 65-85 years was 68.8 per 1000 person-years. Most patients (73.3%) experienced subsequent vertebral fractures within 6 months. At 48 weeks, European Quality of Life-5 Dimensions, the Japanese Orthopedic Association Back Pain Evaluation Questionnaire pain-related disorder, walking ability, social life function, and lumbar function scores were significantly lower, while the visual analog scale (VAS) for low back pain was higher in patients with subsequent fracture. Cox proportional hazards analysis showed that a VAS score ≥ 70 at 0 weeks was an independent predictor of subsequent vertebral fracture. After adjustment for history of previous fracture, there was a ~ 67% reduction in the risk of subsequent vertebral fracture at the rigid-brace treatment. CONCLUSION: Women with a fresh OVF were at higher risk for subsequent vertebral fracture within the next year. Severe low back pain and use of soft braces were associated with higher risk of subsequent vertebral fractures. Therefore, when treating patients after OVFs with these risk factors, more attention may be needed for the occurrence of subsequent vertebral fractures. LEVEL OF EVIDENCE: III.

Comparing three machine learning approaches to design a risk assessment tool for future fractures: predicting a subsequent major osteoporotic fracture in fracture patients with osteopenia and osteoporosis.

Four machine learning models were developed and compared to predict the risk of a future major osteoporotic fracture (MOF), defined as hip, wrist, spine and humerus fractures, in patients with a prior fracture. We developed a user-friendly tool for risk calculation of subsequent MOF in osteopenia patients, using the best performing model. INTRODUCTION: Major osteoporotic fractures (MOFs), defined as hip, wrist, spine and humerus fractures, can have serious consequences regarding morbidity and mortality. Machine learning provides new opportunities for fracture prediction and may aid in targeting preventive interventions to patients at risk of MOF. The primary objective is to develop and compare several models, capable of predicting the risk of MOF as a function of time in patients seen at the fracture and osteoporosis outpatient clinic (FO-clinic) after sustaining a fracture. METHODS: Patients aged > 50 years visiting an FO-clinic were included in this retrospective study. We compared discriminative ability (concordance index) for predicting the risk on MOF with a Cox regression, random survival forests (RSF) and an artificial neural network (ANN)-DeepSurv model. Missing data was imputed using multiple imputations by chained equations (MICE) or RSF's imputation function. Analyses were performed for the total cohort and a subset of osteopenia patients without vertebral fracture. RESULTS: A total of 7578 patients were included, 805 (11%) patients sustained a subsequent MOF. The highest concordance-index in the total dataset was 0.697 (0.664-0.730) for Cox regression; no significant difference was determined between the models. In the osteopenia subset, Cox regression outperformed RSF (p = 0.043 and p = 0.023) and ANN-DeepSurv (p = 0.043) with a c-index of 0.625 (0.562-0.689). Cox regression was used to develop a MOF risk calculator on this subset. CONCLUSION: We show that predicting the risk of MOF in patients who already sustained a fracture can be done with adequate discriminative performance. We developed a user-friendly tool for risk calculation of subsequent MOF in patients with osteopenia.

Association between mortality risk and the number, location, and sequence of subsequent fractures in the elderly.

The mortality risk showed a positive correlation as the number of subsequent fractures increased. Hip fracture showed the greatest association with mortality risk, followed by vertebral fracture. For the combination of hip and vertebral fracture, a hip fracture after a vertebral fracture showed the highest mortality risk. INTRODUCTION: It is unclear whether subsequent fractures or a certain location and sequence of subsequent fractures are associated with mortality risk in the elderly. We aimed to investigate the relationship between subsequent fractures and mortality risk. METHODS: Using the Korean National Health Insurance Research Database, we analyzed the cohort data of 24,756 patients aged > 60 years who sustained fractures between 2002 and 2013. Cox regression was used to assess the mortality risk associated with the number, locations, and sequences of subsequent fractures. RESULTS: Mortality hazard ratios (HRs) for women and men were shown to be associated with the number of subsequent fractures (one, 1.63 (95% confidence interval [CI], 1.48-1.80) and 1.42 (95% CI, 1.28-1.58); two, 1.75 (95% CI, 1.47-2.08) and 2.03 (95% CI, 1.69-2.43); three or more, 2.46(95% CI, 1.92-3.15) and 1.92 (95% CI, 1.34-2.74), respectively). For women, the mortality risk was high when hip (HR, 2.49; 95% CI, 1.80-3.44) or vertebral (HR, 1.40; 95% CI, 1.03-1.90) fracture occurred as a second fracture. Compared with a single hip fracture, there was a high mortality risk in the group with hip fracture after the first vertebral fracture (HR, 2.90; 95% CI, 1.86-4.54), followed by vertebral fracture after the first hip fracture (HR, 1.90; 95% CI, 1.12-3.22). CONCLUSION: The mortality risk showed a positive correlation as the number of subsequent fractures increased. Hip fracture showed the greatest association with mortality risk, followed by vertebral fracture. For the combination of hip and vertebral fracture, a hip fracture after a vertebral fracture showed the highest mortality risk.

Risk factors for subsequent vertebral fractures following a previous hip fracture.

INTRODUCTION: The purpose of our study was to evaluate the incidence and to identify risk factors of subsequent vertebral fractures after hip fractures, and to determine whether the subsequent vertebral fracture increases the mortality rate of elderly hip fracture patients. MATERIALS AND METHODS: From January 2009 to July 2016, 1,554 patients were diagnosed as having a hip fracture and were treated surgically at our institution. Among them, 1121 patients age > 50 years at the time of injury and were followed up for 1 year or longer after the hip fracture surgery. In these patients, radiographs of the hip and spine were taken at each follow-up. We reviewed medical records and radiographs of these patients. Among the 1121 patients, 107 patients (9.5%) had subsequent vertebral fractures after the hip fracture during entire follow-up periods. RESULTS: In multivariable analysis, previous history of vertebral fracture [odds ratio (OR), 2.62; p < 0.001], medication possession rate (MPR) of osteoporosis treatment < 80% (OR, 1.92; p = 0.014), and a lower lumbar bone mineral density (BMD) (OR, 2.58; p = 0.001) appeared as risk factors for subsequent vertebral fractures. CONCLUSION: However, the subsequent vertebral fractures did not affect the mortality after the hip fractures. Age ≥ 70 years [hazard ration (HR) 2.70; p = .039], body mass index < 18.5 kg/m2 (HR, 2.57; p =0 .048), and Charlson comorbidity index ≥ 2 (HR, 2.04; p =0.036) were risk factors of the death. Timely management is warranted to prevent subsequent vertebral fractures in hip fracture patients with risk factors.