Clinical Fracture Research Articles

Pre-treatment bone mineral density and the benefit of pharmacologic treatment on fracture risk and BMD change: analysis from the FNIH-ASBMR SABRE project.

Some osteoporosis drug trials have suggested that treatment is more effective in those with low BMD measured by DXA. This study used data from a large set of randomized controlled trials (RCTs) to determine whether the anti-fracture efficacy of treatments differs according to baseline BMD. We used individual patient data from 25 RCTs (103 086 subjects) of osteoporosis medications collected as part of the FNIH-ASBMR SABRE project. Participants were stratified into FN BMD T-score subgroups (≤-2.5, > -2.5). We used Cox proportional hazard regression to estimate treatment effect for clinical fracture outcomes and logistic regression for the radiographic vertebral fracture outcome. We also performed analyses based on BMD quintiles. Overall, 42% had a FN BMD T-score ≤ -2.5. Treatment with anti-osteoporosis drugs led to significant reductions in fractures in both T-score ≤ -2.5 and > -2.5 subgroups. Compared to those with FN BMD T-score > -2.5, the risk reduction for each fracture outcome was greater in those with T-score ≤ -2.5, but only the all-fracture outcome reached statistical significance (interaction P = .001). Results were similar when limited to bisphosphonate trials. In the quintile analysis, there was significant anti-fracture efficacy across all quintiles for vertebral fractures and with greater effects on fracture risk reduction for non-vertebral, all, and all clinical fractures in the lower BMD quintiles (all interaction P ≤ .03). In summary, anti-osteoporotic medications reduced the risk of fractures regardless of baseline BMD. Significant fracture risk reduction with treatment for 4 of the 5 fracture endpoints was seen in participants with T-scores above -2.5, though effects tended to be larger and more significant in those with baseline T-scores <-2.5.

Walking with unilateral ankle-foot unloading: a comparative biomechanical analysis of three assistive devices

BackgroundFoot and ankle unloading is essential in various clinical contexts, including ulcers, tendon ruptures, and fractures. Choosing the right assistive device is crucial for functionality and recovery. Yet, research on the impact of devices beyond crutches, particularly ankle-foot orthoses (AFOs) designed to unload the ankle and foot, is limited. This study investigates the effects of three types of devices—forearm crutches, knee crutch, and AFO—on biomechanical, metabolic, and subjective parameters during walking with unilateral ankle-foot unloading.MethodsTwenty healthy participants walked at a self-selected speed in four conditions: unassisted able-bodied gait, and using three unloading devices, namely forearm crutches, iWalk knee crutch, and ZeroG AFO. Comprehensive measurements, including motion capture, force plates, and metabolic system, were used to assess various spatiotemporal, kinematic, kinetic, and metabolic parameters. Additionally, participants provided subjective feedback through questionnaires. The conditions were compared using a within-subject crossover study design with repeated measures ANOVA.ResultsSignificant differences were found between the three devices and able-bodied gait. Among the devices, ZeroG exhibited significantly faster walking speed and lower metabolic cost. For the weight-bearing leg, ZeroG exhibited the shortest stance phase, lowest braking forces, and hip and knee angles most similar to normal gait. However, ankle plantarflexion after push-off using ZeroG was most different from normal gait. IWalk and crutches caused significantly larger center-of-mass mediolateral and vertical fluctuations, respectively. Participants rated the ZeroG as the most stable, but more participants complained it caused excessive pressure and pain. Crutches were rated with the highest perceived exertion and lowest comfort, whereas no significant differences between ZeroG and iWalk were found for these parameters.ConclusionsSignificant differences among the devices were identified across all measurements, aligning with previous studies for crutches and iWalk. ZeroG demonstrated favorable performance in most aspects, highlighting the potential of AFOs in enhancing gait rehabilitation when unloading is necessary. However, poor comfort and atypical sound-side ankle kinematics were evident with ZeroG. These findings can assist clinicians in making educated decisions about prescribing ankle-foot unloading devices and guide the design of improved devices that overcome the limitations of existing solutions.

Three-year effect of bisphosphonates on bone mineral density after denosumab withdrawal: observations from a real-world study.

Data on long-term treatment regimens for preventing bone mineral density (BMD) loss that occurs after denosumab (Dmab) withdrawal are scarce. Our aim was to evaluate the long-term changes (12-36months) in BMD and bone turnover markers in a group of postmenopausal women who had been treated with Dmab and received subsequent treatment with bisphosphonates. Secondary objectives were to evaluate factors associated with BMD loss, to compare the BMD change in patients who received oral vs intravenous bisphosphonates, and to assess the frequency of fragility fractures after Dmab discontinuation. The clinical data of 54 patients, 26 of whom had clinical and DXA assessments at 36months, were analyzed. After 12months, the mean LS BMD had decreased by 2.8% (±5.0), FN BMD by 1.9% (±5.8), and TH BMD by 1.9% (±3.7). After 36months, LS BMD had decreased by 3.7% (±6.7), FN BMD by 2.5% (±7.1), and TH BMD by 3.6% (±5.2). C-terminal cross-linked telopeptide of type I collagen significantly increased during the first 12months after Dmab withdrawal but then decreased at 36months. BMD loss at 12months was higher in patients with more than 30months of Dmab treatment, but this difference was only statistically significant at FN (-3.3% vs -0.3%, P = .252 at LS, -3.3% vs 0.3%, P = .033 at FN, and -2.1% vs 0.9, P = .091 at TH). There were no statistically significant differences regarding the change in BMD at 12 and 36months between oral and intravenous treatment. Seven patients suffered incidental vertebral fractures (clinical vertebral fractures: n = 6, morphometric fractures: n = 1) three of which were multiple. None of these patients were treated following international or institutional guidelines or recommendations. In summary, our study suggests that bisphosphonates can help maintain BMD for 36months after Dmab discontinuation.

TBS correlates with bone density and microstructure at trabecular and cortical bone evaluated by HR-pQCT.

Trabecular bone score (TBS) estimates bone microstructure, which is directly measured by high-resolution peripheral quantitative computed tomography (HRpQCT). We evaluated the correlation between these methods and TBS influence on fracture risk assessed by FRAX. We evaluated 129 individuals (82 women, 43 postmenopausal) 20 to 82.3 years without prevalent clinical or non-clinical morphometric vertebral fractures, using DXA (spine and hip), HR-pQCT at distal radius (R) and tibia (T) and TBS which classifies bone microarchitecture as normal (TBS ≥ 1.350), partially degraded (1.200 < TBS < 1.350), or degraded (TBS ≤ 1.200). Spine and hip BMD and HR-pQCT parameters at cortical bone: area (T), density (R,T) thickness (T) and trabecular bone: density (R,T), number (T) and thickness (R) were significantly better in the 78 individuals with normal TBS (group 1) versus the 51 classified as partially degraded (n = 42) or degraded microarchitecture (n = 9) altogether (group 2). TBS values correlated with age (r = -0.55), positively with spine and hip BMD and all cortical and trabecular bone density and microstructure parameters evaluated, p < 0.05 all tests. Binary logistic regression defined age (p = 0.008) and cortical thickness (p = 0.018) as main influences on TBS, while ANCOVA demonstrated that HR-pQCT data corrected for age were not different between TBS groups 1 and 2. TBS adjustment increased FRAX risk for major osteoporotic fractures and hip fractures. We describe significant association between TBS and both trabecular and cortical bone parameters measured by HR-pQCT, consistent with TBS influence on fracture risk estimation by FRAX, including hip fractures, where cortical bone predominates.

Long-term therapy with bisphosphonates: review of clinical studies

The purpose of this scientific literature review was to examine clinical recommendations for the duration of bisphosphonate therapy in patients with osteoporosis who have experienced osteoporotic fractures if they remain at high risk after 3–5 years of taking them. An electronic search of electronic databases was conducted, as well as a hand search of journals. A total of 94 publications were examined. 17 publications were included in the review. We concluded that patients who stopped taking bisphosphonates had a 20–40% higher risk of new clinical fractures and nearly twice the risk of vertebral fractures compared with the treatment period, indicating that a drug holiday is recommended not for all patients receiving therapy. However, long-term therapy with alendronate and zoledronic acid has been shown to reduce the risk of fractures in women with osteoporosis. The persistent increase in spinal bone mineral density with long-term bisphosphonate use may explain the lower incidence of vertebral fractures in patients on therapy long-term compared with patients who discontinued therapy after 3 years.

Surrogate markers in assessment of bisphosphonate effectiveness in osteoporosis treatment (bone mineral density, bone turnover markers)

A review of the literature which summarizes our knowledge on the use of surrogate markers of the osteoporosis treatment effectiveness when on bisphosphonate (BP) therapy. Bone mineral density (BMD) and markers of bone turnover, which have been shown to be associated with the clinical fracture end point, have been used as surrogate criteria for the effectiveness of treatment of osteoporosis in randomized controlled trials. When prescribing BP for the treatment of osteoporosis, BMD measurement every 12 months by dual-energy x-ray absorptiometry (DXA) is the well-described surrogate marker of BP efficacy. At the same time, stabilization of BMD is also a criterion for the treatment effectiveness since changes in BMD determined only 16% of the anti-fracture effectiveness of BP. Markers of bone remodeling can be used as surrogate markers after 3 (bone resorption) or 6 (bone formation) months from the start of BP therapy. A decrease of 30% or more is considered to be prognostically effective for both antifracture and BMD gain. There is a direct relationship between the degree of bone remodeling markers decrease and the antifracture effectiveness of BP therapy. The decrease in markers persists throughout the entire period of therapy and, accordingly, they can be used as surrogate markers of effectiveness and adherence to BP therapy throughout the entire treatment period. However, the presence of pathological fractures is a key clinical manifestation of osteoporosis and should be considered first in every decision making compared to any surrogate marker.Thus, when prescribing BP treatment, surrogate markers of changes in BMD and/or markers of bone remodeling can be used to monitor the effectiveness of treatment throughout the entire period of treatment and patients’ monitoring.

Validity of Major Osteoporotic Fracture Diagnoses in the Danish National Patient Registry.

To evaluate the validity of diagnosis codes for Major Osteoporotic Fracture (MOF) in the Danish National Patient Registry (NPR) and secondly to evaluate whether the fracture was incident/acute using register-based definitions including date criteria and procedural codes. We identified a random sample of 2400 records with a diagnosis code for a MOF in the NPR with dates in the year of 2018. Diagnoses were coded with the 10th revision of the International Classification of Diseases (ICD-10). The sample included 2375 unique fracture patients from the Region of Southern Denmark. Medical records were retrieved for the study population and reviewed by an algorithmic search function and medical doctors to verify the MOF diagnoses. Register-based definitions of incident/acute MOF was evaluated in NPR data by applying date criteria and procedural codes. The PPV for MOF diagnoses overall was 0.99 (95% CI: 0.98;0.99) and PPV=0.99 for the four individual fracture sites, respectively. Further, analyses of incident/acute fractures applying date criteria, procedural codes and using patients' first contact in the NPR resulted in PPV=0.88 (95% CI: 0.84;0.91) for hip fractures, PPV=0.78 (95% CI: 0.74;0.83) for humerus fractures, PPV=0.78 (95% CI: 0.73;0.83) for clinical vertebral fractures and PPV=0.87 (95% CI: 0.83;0.90) for wrist fractures. ICD-10 coded MOF diagnoses are valid in the NPR. Furthermore, a set of register-based criteria can be applied to qualify if the MOF fracture was incident/acute. Thus, the NPR is a valuable and reliable data source for epidemiological research on osteoporotic fractures.

283 Association of Clinical Factors and Incident Vertebral Fracture in Persons with ESRD secondary to Vasculitis

283 Association of Clinical Factors and Incident Vertebral Fracture in Persons with ESRD secondary to Vasculitis

Decomposing and simplifying the Fracture Risk Assessment Tool-a module from the Taiwan-specific calculator.

The Fracture Risk Assessment Tool (FRAX®) is a widely utilized country-specific calculator for identifying individuals with high fracture risk; its score is calculated from 12 variables, but its formulation is not publicly disclosed. We aimed to decompose and simplify the FRAX® by utilizing a nationwide community survey database as a reference module for creating a local assessment tool for osteoporotic fracture community screening in any country. Participants (n = 16384; predominantly women (75%); mean age = 64.8years) were enrolled from the Taiwan OsteoPorosis Survey, a nationwide cross-sectional community survey collected from 2008 to 2011. We identified 11 clinical risk factors from the health questionnaires. BMD was assessed via dual-energy X-ray absorptiometry in a mobile DXA vehicle, and 10-year fracture risk scores, including major osteoporotic fracture (MOF) and hip fracture (HF) risk scores, were calculated using the FRAX®. The mean femoral neck BMD was 0.7 ± 0.1g/cm2, the T-score was -1.9 ± 1.2, the MOF was 8.9 ± 7.1%, and the HF was 3.2 ± 4.7%. Following FRAX® decomposition with multiple linear regression, the adjusted R2 values were 0.9206 for MOF and 0.9376 for HF when BMD was included and 0.9538 for MOF and 0.9554 for HF when BMD was excluded. The FRAX® demonstrated better prediction for women and younger individuals than for men and elderly individuals after sex and age stratification analysis. Excluding femoral neck BMD, age, sex, and previous fractures emerged as 3 primary clinical risk factors for simplified FRAX® according to the decision tree analysis in this study population. The adjusted R2 values for the simplified country-specific FRAX® incorporating 3 premier clinical risk factors were 0.8210 for MOF and 0.8528 for HF. After decomposition, the newly simplified module provides a straightforward formulation for estimating 10-year fracture risk, even without femoral neck BMD, making it suitable for community or clinical osteoporotic fracture risk screening.

The "Can Do, Do Do" Framework Applied to Assess the Association between Physical Capacity, Physical Activity and Prospective Falls, Subsequent Fractures, and Mortality in Patients Visiting the Fracture Liaison Service.

The "can do, do do" framework combines measures of poor and normal physical capacity (PC, measured by a 6 min walking test, can do/can't do) and physical activity (PA, measured by accelerometer, do do/don't do) into four domains and is able to categorize patient subgroups with distinct clinical characteristics, including fall and fracture risk factors. This study aims to explore the association between domain categorization and prospective fall, fracture, and mortality outcomes. This 6-year prospective study included patients visiting a Fracture Liaison Service with a recent fracture. Outcomes were first fall (at 3 years of follow-up, measured by fall diaries), first subsequent fracture, and mortality (at 6 years). Cumulative incidences of all three outcomes were calculated. The association between domain categorization and time to the three outcomes was assessed by uni- and multivariate Cox proportional hazard analysis with the "can do, do do" group as reference. The physical performance of 400 patients with a recent fracture was assessed (mean age: 64 years; 70.8% female), of whom 61.5%, 20.3%, and 4.9% sustained a first fall, sustained a subsequent fracture, or had died. Domain categorization using the "can do, do do" framework was not associated with time to first fall, subsequent fracture, or mortality in the multivariate Cox regression analysis for all groups. "Can't do, don't do" group: hazard ratio [HR] for first fall: 0.75 (95% confidence interval [CI]: 0.45-1.23), first fracture HR: 0.58 (95% CI: 0.24-1.41), and mortality HR: 1.19 (95% CI: 0.54-6.95). Categorizing patients into a two-dimensional framework seems inadequate to study complex, multifactorial outcomes. A personalized approach based on known fall and fracture risk factors might be preferable.

Association of serum sodium levels with fractures and mortality in patients undergoing maintenance hemodialysis.

Hyponatremia is implicated in pathological bone resorption and has been identified as a risk factor for bone fracture in the general population. However, there are limited data on the association between serum sodium levels and fracture risk in patients undergoing hemodialysis (HD). We analyzed a historical cohort of 2220 maintenance HD patients to examine the association between serum sodium levels and the risk of fracture and mortality. We also examined the association between serum sodium levels and osteoporosis, based on metacarpal bone mineral density, in a subcohort of 455 patients with available data. In addition, we examined the association between serum sodium levels and bone turnover markers in a separate cross-sectional cohort of 654 maintenance HD patients. During a median follow-up of 5.4years, 712 patients died, 113 experienced clinical fractures, and 64 experienced asymptomatic vertebral fractures. Lower serum sodium levels were associated with an increased risk of mortality (HR 1.06 per 1mEq/L decrease; 95% CI 1.03-1.09) but not with the risk of clinical fracture (HR 1.04 per 1mEq/L decrease; 95% CI 0.97-1.11). A similar lack of association was observed for asymptomatic vertebral fracture and any fracture. Serum sodium levels were also not associated with osteoporosis in a subcohort with available data (n = 455) or with bone alkaline phosphatase or tartrate-resistant acid phosphatase-5b in a separate cross-sectional cohort. Serum sodium levels were associated with mortality but not with fracture risk, osteoporosis, or bone turnover markers in maintenance HD patients.

Influence of age on the efficacy of pharmacologic treatments on fracture risk reduction and increases in BMD: RCT results from the FNIH-ASBMR-SABRE project.

There is a common belief that antiosteoporosis medications are less effective in older adults. This study used data from randomized controlled trials (RCTs) to determine whether the anti-fracture efficacy of treatments and their effects on BMD differ in people ≥70 compared to those <70yr. We used individual patient data from 23 RCTs of osteoporosis medications collected as part of the FNIH-ASBMR SABRE project. We assessed the following fractures: radiographic vertebral, non-vertebral, hip, all clinical, and all fractures. We used Cox proportional hazard regression to estimate treatment effect for clinical fracture outcomes, logistic regression for the radiographic vertebral fracture outcome, and linear regression to estimate treatment effect on 24-mo change in hip and spine BMD in each age subgroup. The analysis included 123 164 (99% female) participants; 43% being ≥70yr. Treatment with anti-osteoporosis drugs significantly and similarly reduced fractures in both subgroups (eg, odds ratio [OR] = 0.47 and 0.51 for vertebral fractures in those below and above 70yr, interaction P = .19; hazard ratio [HR] for all fractures: 0.72 vs 0.70, interaction P = .20). Results were similar when limited to bisphosphonate trials with the exception of hip fracture risk reduction which was somewhat greater in those <70 (HR = 0.44) vs ≥70 (HR = 0.79) yr (interaction P = .02). Allocation to anti-osteoporotic drugs resulted in significantly greater increases in hip and spine BMD at 24mo in those ≥70 compared to those <70yr. In summary, anti-osteoporotic medications similarly reduced the risk of fractures regardless of age, and the few small differences in fracture risk reduction by age were of uncertain clinical significance.

Long-term treatment with bisphosphonates in clinical practice: advantages, main problems and risks

Bisphosphonates are the main class of drugs for treatment osteoporosis (OP) and other diseases with increased bone resorption, as bisphosphonates are very effective in reducing risk of fracture. The problem of maintaining the effectiveness and possible loss of effect of bisphosphonates, as well as their safety during long-term use, remains actual Long-them therapy with bisphosphonates and it’s effects has been discussed over the past 20 years, as the risk of osteoporotic fracture may stay hight in patients with presence of irreducible risk factors (continous use of glucocorticoids etc.) despite ongoing antiosteoporotic therapy. Real clinical practice demonstrates very low patient adherence to treatment with bisphosphonates. However, observational studies have showed that treatment with bisphosphonates for more than 10 years without initiating a drug holiday can be effective for patients at high risk of fracture. Moreover, the longer therapy with bisphosphonates is continued and the later the“drug holiday”is initiated, the lower the risks of fractures of the proximal femur and clinical vertebral fractures. However, the duration of continuous bisphosphonate therapy for each patient remains at the decision of the physician and is determined individually in each case, based on the risk-benefit ratio, taking into account the patient’s risk factors for fractures and comorbid diseases.

Bone-Modifying Agents in Patients With High-Risk Metastatic Castration-Sensitive Prostate Cancer Treated With Abiraterone Acetate

The association between the use of bone-modifying agents (BMAs) and the outcomes among patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with abiraterone acetate plus prednisone (AAP) remains unclear. To investigate the association between BMA use and the outcomes of patients with mCSPC receiving AAP. In this cohort study, a post hoc analysis of individual participant data from the LATITUDE trial was performed. The LATITUDE trial, a phase 3 randomized clinical trial, aimed to assess the efficacy of AAP and androgen deprivation therapy (ADT) vs dual-placebo and ADT in patients with high-risk mCSPC (data cutoff, August 15, 2018). Eligible patients had newly diagnosed prostate cancer with metastases and at least 2 of 3 high-risk factors (Gleason score ≥8, presence of ≥3 lesions on bone scan, or presence of measurable visceral metastasis). The trial was conducted at 235 sites in 34 countries. Data for the present study were evaluated from July 18 to September 23, 2023. Use of BMAs was defined as the administration of bisphosphonates and denosumab within 90 days before and after randomization. The primary outcomes were time to skeletal-related events (SREs) and overall survival (OS). An SRE was defined as a clinical or pathological fracture, spinal cord compression, palliative radiation to bone, or surgery involving bone. Differences in these outcomes were examined using the restricted mean survival time from inverse probability of treatment weighting-adjusted Kaplan-Meier curves, estimated until the last event was observed (longest time observed, 63.9 months). Treatment × covariate interactions were analyzed using weighted Cox proportional hazards regression models for the total cohort. In the total cohort of 1199 patients (956 [79.7%] younger than 75 years), 597 (49.8%) received AAP and ADT, including 474 (79.4%) younger than 75 years and 384 (64.3%) with more than 10 bone metastases (AAP cohort); 602 (50.2%) were treated with dual placebo and ADT, including 482 (80.1%) younger than 75 years and 377 (62.6%) with more than 10 bone metastases (ADT cohort). In the AAP cohort, 132 patients (22.1%) received BMAs, while in the ADT cohort, 131 (21.8%) did. Zoledronic acid was the most frequently administered BMA in both the AAP (93 [70.5%]) and the ADT (88 [67.2%]) cohorts. During the median follow-up of 51.8 (IQR, 47.2-57.0) months in the AAP cohort, BMA use was associated with a longer time to SRE (difference, 7.8 [95% CI, 4.2-11.3] months) but not with OS (difference, 1.6 [95% CI, -2.5 to 5.8] months). In the ADT cohort, BMA use was associated with both time to SRE (difference, 9.3 [95% CI, 5.2-13.3] months) and OS (difference, 5.5 [95% CI, 3.2-9.8] months). No evidence was found that the outcomes of BMA varied by AAP or ADT (hazard ratio for time to SRE, 0.99 [95% CI, 0.48-2.08]; P = .99 for interaction; hazard ratio for OS, 1.31 [95% CI, 0.88-1.96]; P = .18 for interaction). The findings of this cohort study suggest that use of BMAs was associated with a longer time to SRE in patients with high-risk mCSPC treated with ADT, with or without AAP, suggesting that BMA use might provide benefits to this population.

Patient-specific finite element analysis for assessing hip fracture risk in aging populations

The femur is one of the most important bone in the human body, as it supports the body’s weight and helps with movement. The aging global population presents a significant challenge, leading to an increasing demand for artificial joints, particularly in knee and hip replacements, which are among the most prevalent surgical procedures worldwide. This study focuses on hip fractures, a common consequence of osteoporotic fractures in the elderly population. To accurately predict individual bone properties and assess fracture risk, patient-specific finite element models (FEM) were developed using CT data from healthy male individuals. The study employed ANSYS 2023 R2 software to estimate fracture loads under simulated single stance loading conditions, considering strain-based failure criteria. The FEM bone models underwent meticulous reconstruction, incorporating geometrical and mechanical properties crucial for fracture risk assessment. Results revealed an underestimation of the ultimate bearing capacity of bones, indicating potential fractures even during routine activities. The study explored variations in bone density, failure loads, and density/load ratios among different specimens, emphasizing the complexity of bone strength determination. Discussion of findings highlighted discrepancies between simulation results and previous studies, suggesting the need for optimization in modelling approaches. The strain-based yield criterion proved accurate in predicting fracture initiation but required adjustments for better load predictions. The study underscores the importance of refining density-elasticity relationships, investigating boundary conditions, and optimizing models through in vitro testing for enhanced clinical applicability in assessing hip fracture risk. In conclusion, this research contributes valuable insights into developing patient-specific FEM bone models for clinical hip fracture risk assessment, emphasizing the need for further refinement and optimization for accurate predictions and enhanced clinical utility.

The Relationship Between Intra-articular Fracture Energy and a Patient's Inflammatory Response.

Prior studies have demonstrated elevated inflammatory cytokine concentrations in the synovial fluid of articular fracture patients postinjury. Similarly, CT-based fracture energy measurements have been correlated with posttraumatic osteoarthritis risk after pilon fracture. The purpose of this study was to determine the associations between synovial fluid cytokine levels, fracture energy, and overall trauma to the body in articular fracture patients. Acute tibial plateau, tibial plafond, and rotational ankle fracture patients were prospectively enrolled from December 2011 through January 1, 2019. Synovial fluid concentrations of interleukin-1 beta, interleukin-1 receptor antagonist, IL-6, IL-8, IL-10, matrix metallopeptidase-1, MMP-3, and MMP-13 were quantified. Patient CT scans were used to calculate fracture energy. The Injury Severity Score (ISS) was used to relate cytokine levels to whole-body injury severity. Spearman rho correlation coefficients were calculated to assess the relationship between injury severity metrics and synovial fluid cytokine, chemokine, and matrix metallopeptidase concentrations. Eighty-seven patients were enrolled with 42 had a tibial plateau fractures (OTA/AO 41B1-2, 41B2-14, 41B3-3, 41C1-3, 41C2-4, 41C3-16), 24 patients had a tibial plafond fracture (OTA/AO 43B1-2, 43B2-4, 43B3-5, 43C1-2, 43C2-3, 43C3-8), and 21 had a rotational ankle fracture (OTA/AO 44B1-3, 44B2-3, 44B3-6, 44C1-4, 44C2-5). Fracture energy significantly differed between fracture patterns, with ankle fractures involving substantially less fracture energy (median = 2.92 J) than plafond (10.85 J, P < 0.001) and plateau fractures (13.05 J, P < 0.001). After adjustment for multiple comparisons, MMP-3 was significantly correlated with transformed fracture energy (r = 0.41, 95% confidence interval [CI], 0.22-0.58, P < 0.001), while IL-1β was significantly correlated with the Injury Severity Score (Spearman ρ = 0.31, 95% CI, 0.08-0.49, P = 0.004). Synovial fluid MMP-3 concentration was significantly correlated with CT-quantified fracture energy in intra-articular fracture patients. Given that in clinical practice fracture energy tends to correlate with posttraumatic osteoarthritis risk, MMP-3 may warrant further investigation for its role in posttraumatic osteoarthritis development after articular fracture. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Risks of incident major osteoporotic fractures following SARS-CoV-2 infection among older individuals: a population-based cohort study in Hong Kong.

Population-based epidemiological studies on post-acute phase coronavirus 2019 (COVID-19)-related fractures in older adults are lacking. This study aims to examine the risk of incident major osteoporotic fractures following SARS-CoV-2 infection among individuals aged ≥50, compared to individuals without COVID-19. It was a retrospective, propensity-score matched, population-based cohort study of COVID-19 patients and non-COVID individuals identified from the electronic database of the Hong Kong Hospital Authority from January 2020 to March 2022. The primary outcome was a composite of major osteoporotic fractures (hip, clinical vertebral, and upper limb). COVID-19 patients were 1:1 matched to controls using propensity-score according to age, sex, vaccination status, medical comorbidities and baseline medications. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. A total of 429 459 COVID-19 patients were included, 1:1 matched to non-COVID individuals. Upon median follow-up of 11months, COVID-19 patients had higher risks of major osteoporotic fractures (5.08 vs 3.95 per 1000 persons; HR 1.22 95%CI [1.15-1.31]), hip fractures (2.71 vs 1.94; 1.33 [1.22-1.46]), clinical vertebral fractures (0.42 vs 0.31; 1.29 [1.03-1.62]), and falls (13.83 vs 10.36; 1.28 [1.23-1.33]). Subgroup analyses revealed no significant interaction. In acute (within 30days) and post-acute phases (beyond 30days) following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we consistently observed a significant increase in fractures and falls risks. Our study demonstrated increased risk of major osteoporotic fractures after SARS-CoV-2 infection in both acute and post-acute phases in older adults, partly due to increased fall risk. Clinicians should be aware of musculoskeletal health of COVID-19 survivors.

Patient Characteristics Associated With Using Transcatheter Left Atrial Appendage Occlusion Versus Oral Anticoagulants for Atrial Fibrillation.

Transcatheter left atrial appendage occlusion (LAAO) is an alternative to oral anticoagulants (OACs) for stroke prevention in patients with atrial fibrillation, but the predictors of LAAO use in routine care are unclear. We aimed to assess the utilization trends of LAAO and compare the change in characteristics of LAAO users versus OACs since its marketing. Using the US Medicare claims database (March 15, 2015, to December 31, 2020), we identified patients with atrial fibrillation, ≥65 years, and CHA2DS2-VASc score ≥2 (men) or ≥3 (women), with either first implantation of an LAAO device or initiation of OACs, including apixaban, dabigatran, rivaroxaban, edoxaban, or warfarin. Patient characteristics, measured 365 days before the first LAAO or OAC use date, were compared using logistic regression. There were 30 058 LAAO recipients (mean age, 77.74 years; female, 42.1%) and 792 600 OAC initiators (mean age, 78.48; female, 53.3%). In 2020, patients had higher odds of initiating LAAO use than in 2015 (0.52 versus 9.32%; adjusted odds ratio [aOR], 13.64 [95% CI, 12.56-14.81]). Old age (ie, >85 versus 65-75 years; aOR, 0.84 [95% CI, 0.80-0.88]), female sex (aOR, 0.74 [95% CI, 0.71-0.76]), Black race (aOR, 0.63 [95% CI, 0.58-0.68]) versus White race, and Medicaid eligibility (aOR, 0.61 [95% CI, 0.58-0.64]) were associated with lower odds of receiving LAAO. Among clinical characteristics, frailty, cancer, fractures, and venous thromboembolism were associated with lower odds of LAAO use, while history of intracranial and extracranial bleeding, coagulopathy, and falls were associated with higher odds of receiving LAAO. Among patients with atrial fibrillation receiving stroke-preventive therapy, LAAO use increased rapidly from 2015 to 2020 and was positively associated with the risk factors for OAC complications but negatively associated with old age, advanced frailty, and cancer. Black race and female sex were associated with a lower likelihood of receiving LAAO.

Does early administration of denosumab delay bone healing after intertrochanteric femoral fractures?

IntroductionHip fractures are commonly associated with osteoporosis and pose a risk for secondary fractures. Although the administration of anti-osteoporotic drugs is recommended after fractures to mitigate this risk, the potential effect of strong anti-resorptive drugs (e.g., denosumab) on fracture healing processes have not been extensively studied. This prospective study aimed to evaluate the feasibility of early denosumab administration after femoral intertrochanteric fracture surgery and to compare its effect on fracture healing to that of bisphosphonate-treated patients. Materials and MethodsPatients who underwent surgery for intertrochanteric femoral fragility fractures between November 2018 and November 2020 were prospectively examined. Patients were randomized into two groups (denosumab [DSM] and ibandronate [IBN] groups) using a simple randomization procedure. Physical findings, plain radiographs, and computed tomography (CT) were used to evaluate fracture healing at 3 months postoperatively. ResultsPhysical findings showed no significant differences between the two groups in pain on loading, tenderness at fracture site, or walking ability. There were inter-rater differences in radiological fracture healing rate: plain radiographs, 57.5% to 81.8% in the DSM group and 51.5% to 90.9% in the IBN group; CT, 51.5% to 72.7% in the DSM group and 45.4% to 81.8% in the IBN group. Although there were variations, there were no significant differences in the fracture healing rate between groups on plain radiographs or CT among all three raters. ConclusionsEarly administration of denosumab after intertrochanteric femoral fracture surgery did not delay radiological or clinical fracture healing times when compared with ibandronate administration.

Clinical Indicators of Bone Deterioration in Alcoholic Liver Cirrhosis and Chronic Alcohol Abuse: Looking beyond Bone Fracture Occurrence.

Although previous studies indicated that chronic alcohol abuse (CAA) and alcoholic liver cirrhosis (ALC) are associated with increased bone fragility, understanding bone fragility determinants is still modest in these individuals. We used a comprehensive individualized clinical fracture risk assessment approach (vertebral osteodensitometry, femoral osteodensitometry and geometry, and serum bone turnover biomarkers) to compare adult male patients with ALC who have not previously had femoral or vertebral fractures (n = 39), patients with CAA (without liver cirrhosis, n = 78) who have not previously had femoral or vertebral fractures and healthy age- and sex-matched controls (n = 43). Our data suggested that intertrochanteric bone mineral density was significantly lower in ALC and CAA patients than in controls. Also, the trabecular bone score was considerably lower in ALC patients compared with CAA and control individuals. The most significant inter-group differences in femoral geometry were noted on the femoral shaft. Patients with ALC and CAA have a higher 10-year risk of major osteoporotic fractures compared to the controls. Analysis of bone turnover biomarkers showed increased osteoprotegerin and beta-C-terminal telopeptide serum concentrations and decreased insulin growth factor-1 concentrations in patients with ALC compared to CAA and control groups. Our data revealed that bone alterations are present in patients with ALC and CAA even if they did not sustain a nontraumatic bone fracture, but it is also indicative that current bone-assessing clinical methods are not entirely reliable. Thus, future studies should focus on developing a reliable integrative clinical tool that can be used to accurately predict and prevent bone fracture occurrences in patients with ALC and CAA.