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In a trial in patients with pelvic or acetabular fractures or extremity fractures that were treated operatively, aspirin thromboprophylaxis was noninferior to low-molecular-weight heparin in preventing death at 90 days.

Abstract Objective: To determine the effect of four monthly vitamin D supplementation on the rate of fractures in men and women aged 65 years and over living in the community. Design: Randomised double blind controlled trial of 100 000 IU oral vitamin D3 (cholecalciferol) supplementation or matching placebo every four months over five years. Setting and participants: 2686 people (2037 men and 649 women) aged 65-85 years living in the general community, recruited from the British doctors register and a general practice register in Suffolk. Main outcome measures: Fracture incidence and total mortality by cause. Results: After five years 268 men and women had incident fractures, of whom 147 had fractures in common osteoporotic sites (hip, wrist or forearm, or vertebrae). Relative risks in the vitamin D group compared with the placebo group were 0.78 (95% confidence interval 0.61 to 0.99, P=0.04) for any first fracture and 0.67 (0.48 to 0.93, P=0.02) for first hip, wrist or forearm, or vertebral fracture. 471 participants died. The relative risk for total mortality in the vitamin D group compared with the placebo group was 0.88 (0.74 to 1.06, P=0.18). Findings were consistent in men and women and in doctors and the general practice population. Conclusion: Four monthly supplementation with 100 000 IU oral vitamin D may prevent fractures without adverse effects in men and women living in the general community. What is already known in this topic Vitamin D and calcium supplements are effective in preventing fractures in elderly women Whether isolated vitamin D supplementation prevents fractures is not clear What this paper adds Four monthly oral supplementation with 100 000 IU vitamin D reduces fractures in men and women aged over 65 living in the general community Total fracture incidence was reduced by 22% and fractures in major osteoporotic sites by 33%

To examine the risk of mortality following all clinical fractures, we followed 6459 women age 55-81 years participating in the Fracture Intervention Trial for an average of 3.8 years. All fractures and deaths were confirmed by medical record or death certificate. Clinical fractures were fractures that came to medical attention. Fracture status was used as a time-dependent covariate in proportional hazards models. The 907 women who experienced a fracture were older, had lower bone mineral density and were more likely to report a positive fracture history. A total of 122 women died over the course of the study with 23 of these deaths occurring after a clinical fracture. The age-adjusted relative risk (95% confidence intervals) of dying following a clinical fracture was 2.15 (1.36, 3.42). This primarily reflected the higher mortality following a hip fracture, 6.68 (3.08, 14.52); and clinical vertebral fracture, 8.64 (4.45, 16.74). Results were similar after adjusting for treatment assignment, health status and specific common comorbidities. There was no increase in mortality following a forearm or other fracture (non-hip, non-wrist, nonvertebral fracture). In conclusion, clinical vertebral fractures and hip fractures are associated with a substantial increase in mortality among a group of relatively healthy older women.

Abstract Context Although bone mineral density (BMD) is strongly associated with fracture and postfracture mortality, the burden of fractures attributable to low BMD has not been investigated. Objectives We sought to estimate the population attributable fraction of fractures and fracture-related mortality that can be attributed to low BMD. Design and Setting This study is a part of an ongoing population-based prospective cohort study, the Dubbo Osteoporosis Epidemiology study. In total, 3700 participants aged ≥50 years participated in the study. Low-trauma fracture was ascertained by X-ray reports, and mortality was ascertained from the Birth, Death and Marriage Registry. Results Overall, 21% of women and 11% of men had osteoporotic BMD. In univariable analysis, 21% and 16% of total fractures in women and men, respectively, were attributable to osteoporosis. Osteoporosis combined with advancing age (>70 years) accounted for 34% and 35% of fractures in women and men, respectively. However, these two factors accounted for ∼60% of hip fractures. About 99% and 66% of postfracture mortality in women and men, respectively, were attributable to advancing age, osteoporosis, and fracture; however, most of the attributable proportion was accounted for by advancing age. Conclusions A substantial health care burden of fracture is on people aged <70 years or nonosteoporosis, suggesting that treatment of people with osteoporosis is unlikely to reduce a large number of fractures in the general population. In this population-based study, we found that whereas 35% of fractures were attributable to low BMD and advancing age, most postfracture mortality was attributable to advancing age.

Altered bone structure and function contribute to the high rates of fractures in dialysis patients compared to the general population. Fracture events may increase the risk of subsequent adverse clinical outcomes. Here we assessed the incidence of post-fracture morbidity and mortality in an international cohort of 34,579 in-center hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS). We estimated country-specific rates of fractures requiring a hospital admission and associated length of stay in the hospital. Incidence rates of death and of a composite event of death/rehospitalization were estimated for 1 year after fracture. Overall, 3% of participants experienced a fracture. Fracture incidence varied across countries, from 12 events/1000 patient-years (PY) in Japan to 45/1000 PY in Belgium. In all countries, fracture rates were higher in the hemodialysis group compared to those reported for the general population. Median length of stay ranged from 7 to 37 days in the United States and Japan, respectively. In most countries, postfracture mortality rates exceeded 500/1000 PY and death/rehospitalization rates exceeded 1500/1000 PY. Fracture patients had higher unadjusted rates of death (3.7-fold) and death/rehospitalization (4.0-fold) compared to the overall DOPPS population. Mortality and hospitalization rates were highest in the first month after the fracture and declined thereafter. Thus, the high frequency of fractures and increased adverse outcomes following a fracture pose a significant health burden for dialysis patients. Fracture prevention strategies should be identified and applied broadly in nephrology practices.

Key Points Hip and vertebral osteoporotic fractures are associated with considerable immediate and long-term increased risk of death The fracture event itself is responsible for part of this increased mortality risk; however, other factors such as age, sex, comorbidities and poor prefracture health status are also involved The majority of incident osteoporotic fractures are nonhip, nonvertebral fractures Evidence of mortality risk in nonhip, nonvertebral fractures is lacking, but evidence of an increased mortality risk with some fractures, such as those in the pelvis and humerus, does exist Medical treatment with bisphosphonates has been associated with a decreased risk of mortality in patients with osteoporotic fractures in some observational studies and in one randomized controlled trial Decreased cardiovascular-related mortality could be one of the potential mechanisms for the decreased risk of mortality with bisphosphonate therapy; however, further studies are required to clarify this point The rate of osteoporotic fractures seems to be stabilizing, but is still associated with considerable disability, costs and an increased risk of mortality. This Review summarizes the evidence regarding osteoporosis-related fractures and their link with mortality and examines data on the effects of treating osteoporosis on mortality in patients with this condition. The rates of incident osteoporotic fractures seem to be stabilizing; however, fragility fractures are still associated with considerable disability, costs and an increased risk of mortality, which is particularly the case for fractures of the hip and vertebra. Mortality is usually highest during the first year after fracture; however, a notably increased mortality risk might persist for several years after the event. In addition to its efficacy in the prevention of new and recurrent osteoporotic fractures, medical treatment has been associated with improved survival after osteoporotic fractures. Observational studies and randomized controlled clinical trials have reported increased survival in patients with a fracture who are treated with bisphosphonates. Rates of medical treatment in patients with osteoporosis remain low, and although the rationale for the putative increase in survival is unclear, this emerging evidence might help further justify the use of medical treatment after fracture. However, further work is needed before medical therapy for mortality prevention in patients with osteoporotic fractures is accepted.

Pelvic ring injuries in the elderly often occur after low-energy accidents. They may result in prolonged immobilization, complications and an intense rehabilitation process. The aim of this study was to assess mortality, physical functioning and quality of life (QoL) in elderly patients with pelvic ring injuries. A cross-sectional study was performed including all elderly patients (≥ 65 years) admitted for a pelvic ring injury between 2007-2016. Mortality and survival were evaluated and patient reported outcome measures (PROMs) were used to assess physical functioning (SMFA) and QoL (EQ-5D). These were compared to age-matched normative data from the general Dutch population. A total of 153 patients, with a mean age of 79 years (SD 8) at the time of injury, were included in this study. The mortality rate was 20% at 30 days, 27% at 1 year and 41% at 3 years of follow-up. All six patients with a type C fracture died within 30 days. Analyses of the 153 patients showed that increasing age, fracture type C and Injury Severity Score (ISS) were all independent risk factors for mortality. Eventually, after excluding patients that died (N = 78) or were unable to contact (N = 2), 73 patients were eligible for follow-up, of which 53 patients (73%) responded. Mean Short Musculoskeletal Function Assessment (SMFA) scores were respectively 67.4 (function index), 65.2 (bother index), 66.5 (lower extremity), 60.4 (activities of daily living) and 68.2 (emotion). Mean EuroQuol-5D (EQ-5D) score was 0.72. Overall, physical functioning and quality of life were significantly decreased in comparison with normative data from the general population. Elderly people who sustain a pelvic ring injury should be considered as a fragile population with substantial mortality rates. The patients who survived demonstrated a substantially lower level of physical functioning and quality of life in comparison with their age-matched peers from the general population. IV, therapeutic study.

Multiple myeloma (MM) is known to compromise bone integrity, leading to an increased risk of fractures, which compromise the quality of life and increase mortality rates. This study investigated the incidence of fractures in MM patients and explored the association between fractures after MM diagnosis and mortality using the Korean National Health Insurance Service database. Fracture incidence was compared between MM patients (n = 9365) and 1:1 matched control group from general population. MM patients demonstrated a significantly higher cumulative incidence of fractures, and vertebral and hip fractures presented a particularly elevated hazard ratio (1.36 [95% CI 1.18–1.55] and 1.47 [95% CI 1.10–1.97], respectively). Furthermore, the presence of fracture within the first year of MM diagnosis were associated with increased mortality (any fracture—HR 1.37 [95% CI 1.19–1.58]; vertebral fractures—HR 1.39 [95% CI 1.19–1.63]; hip fractures—HR 2.46 [95% CI 1.52–3.99]; upper limb fractures—HR 1.94 [95% CI 1.32–2.87]). These results showed an increased risk of fracture and a correlation between fractures and increased mortality in MM patients, with hip fractures notably doubling the mortality risk. These findings underscore the importance of monitoring and managing bone health in MM patients to improve survival outcomes.

Background Survival estimation guides surgical decision-making in metastatic bone disease. Traditionally, classic scoring systems, such as the Bauer score, provide survival estimates based on a summary score of prognostic factors. Identification of new factors might improve the accuracy of these models. Additionally, the use of different algorithms—nomograms or boosting algorithms—could further improve accuracy of prognostication relative to classic scoring systems. A nomogram is an extension of a classic scoring system and generates a more-individualized survival probability based on a patient’s set of characteristics using a figure. Boosting is a method that automatically trains to classify outcomes by applying classifiers (variables) in a sequential way and subsequently combines them. A boosting algorithm provides survival probabilities based on every possible combination of variables. Questions/purposes We wished to (1) assess factors independently associated with decreased survival in patients with metastatic long bone fractures and (2) compare the accuracy of a classic scoring system, nomogram, and boosting algorithms in predicting 30-, 90-, and 365-day survival. Methods We included all 927 patients in our retrospective study who underwent surgery for a metastatic long bone fracture at two institutions between January 1999 and December 2013. We included only the first procedure if patients underwent multiple surgical procedures or had more than one fracture. Median followup was 8 months (interquartile range, 3-25 months); 369 of 412 (90%) patients who where alive at 1 year were still in followup. Multivariable Cox regression analysis was used to identify clinical and laboratory factors independently associated with decreased survival. We created a classic scoring system, nomogram, and boosting algorithms based on identified variables. Accuracy of the algorithms was assessed using area under the curve analysis through fivefold cross validation. Results The following factors were associated with a decreased likelihood of survival after surgical treatment of a metastatic long bone fracture, after controlling for relevant confounding variables: older age (hazard ratio [HR], 1.0; 95% CI, 1.0–1.0; p < 0.001), additional comorbidity (HR, 1.2; 95% CI, 1.0–1.4; p = 0.034), BMI less than 18.5 kg/m 2 (HR, 2.0; 95% CI, 1.2–3.5; p = 0.011), tumor type with poor prognosis (HR, 1.8; 95% CI, 1.6–2.2; p < 0.001), multiple bone metastases (HR, 1.3; 95% CI, 1.1–1.6; p = 0.008), visceral metastases (HR, 1.6; 95% CI, 1.4–1.9; p < 0.001), and lower hemoglobin level (HR, 0.91; 95% CI, 0.87–0.96; p < 0.001). The survival estimates by the nomogram were moderately accurate for predicting 30-day (area under the curve [AUC], 0.72), 90-day (AUC, 0.75), and 365-day (AUC, 0.73) survival and remained stable after correcting for optimism through fivefold cross validation. Boosting algorithms were better predictors of survival on the training datasets, but decreased to a performance level comparable to the nomogram when applied on testing datasets for 30-day (AUC, 0.69), 90-day (AUC, 0.75), and 365-day (AUC, 0.72) survival prediction. Performance of the classic scoring system was lowest for all prediction periods. Conclusions Comorbidity status and BMI are newly identified factors associated with decreased survival and should be taken into account when estimating survival. Performance of the boosting algorithms and nomogram were comparable on the testing datasets. However, the nomogram is easier to apply and therefore more useful to aid surgical decision making in clinical practice. Level of Evidence Level III, prognostic study.

Entropy, characterized by increased disorder throughout biological systems, can be quantified by homeostatic dysregulation (HD). One potential measure of HD is the dispersion of points from a normal value, approximated at the individual level by Mahalanobis distance (DM). We hypothesized that greater HD in electrocardiogram (ECG) would also reflect greater HD in the musculoskeletal system which, in turn, would be associated with age and manifest as an increased risk of fracture independently of age, bone mineral density (BMD), and history of fracture. We further hypothesized that greater ECG‐HD would be associated with increased risk of all‐cause mortality. A cohort of 7738 individuals aged 40 years or older who underwent a screening 12‐lead ECG between 2007 and 2018 was analyzed (mean age 63.5 years; 59.5% women; 5.5 years follow‐up). ECG‐HD was calculated as the natural log‐transformed DM of five ECG measurements (ventricular rate, QRS duration, corrected QT interval, R axis, and T axis) referenced to young individuals (age 19–29). ECG‐HD increased with age (r = 0.28). Each standard deviation increment in ECG‐HD was associated with a 48% higher unadjusted fracture risk (HR 1.48, 95% CI 1.37–1.58) and remained significant after adjustment for clinical risk factors, ECG diagnoses, and femoral neck BMD (aHR 1.28, 95% CI 1.15–1.42). ECG‐HD was also associated with vertebral, nonvertebral, and hip fractures, and with mortality (aHR 1.44, 95% CI 1.18–1.74). ECG‐HD, a measurement of entropy in the cardiac system, was associated with fracture risk and mortality in adults, independent of clinical risk factors, BMD, and ECG diagnoses. Electrocardiogram‐based homeostatic dysregulation (ECG‐HD), a marker of cardiac conduction entropy, increases with age. Higher ECG‐HD is associated with a greater risk of aging outcomes including fractures and all‐cause mortality, independent of clinical risk factors, bone density, and ECG diagnoses.