Cost-effectiveness analysis of the Geriatric Fracture Center (GFC) concept: a prospective multicentre cohort study.

INTRODUCTION: Geriatric Fracture Centers (GFCs) are dedicated treatment units where care is tailored towards elderly patients who have suffered fragility fractures. The primary objective of this economic analysis was to determine the cost-utility of GFCs compared with usual care centres. METHODS: The primary analysis was a cost-utility analysis that measured the cost per incremental quality-adjusted life-year gained from treatment of hip fracture in GFCs compared with treatment in usual care centres from the societal perspective over a 1-year time horizon. The secondary analysis was a cost-utility analysis from a societal perspective over a lifetime time horizon. We evaluated these outcomes using a cost-utility analysis using data from a large multicentre prospective cohort study comparing GFCs versus usual care centres that took place in Austria, Spain, the USA, the Netherlands, Thailand and Singapore. RESULTS: GFCs may be cost-effective in the long term, while providing a more comprehensive care plan. Patients in usual care centre group were slightly older and had fewer comorbidities. For the 1-year analysis, the costs per patient were slightly lower in the GFC group (-$646.42), while the quality-adjusted life-years were higher in the usual care centre group (+0.034). The incremental cost-effectiveness ratio was $18 863.34 (US$/quality-adjusted life-year). The lifetime horizon analysis found that the costs per patient were lower in the GFC group (-$7210.35), while the quality-adjusted life-years were higher in the usual care centre group (+0.02). The incremental cost-effectiveness ratio was $320 678.77 (US$/quality-adjusted life-year). CONCLUSIONS: This analysis found that GFCs were associated with lower costs compared with usual care centres. The cost-savings were greater when the lifetime time horizon was considered. This comprehensive cost-effectiveness analysis, using data from an international prospective cohort study, found that GFC may be cost-effective in the long term, while providing a more comprehensive care plan. A greater number of major adverse events were reported at GFC, nevertheless a lower mortality rate associated with these adverse events at GFC. Due to the minor utility benefits, which may be a result of greater adverse event detection within the GFC group and much greater costs of usual care centres, the GFC may be cost-effective due to the large cost-savings it demonstrated over the lifetime time horizon, while potentially identifying and treating adverse events more effectively. These findings suggest that the GFC may be a cost-effective option over the lifetime of a geriatric patient with hip fracture, although future research is needed to further validate these findings. LEVEL OF EVIDENCE: Economic, level 2. TRIAL REGISTRATION NUMBER: NCT02297581.

Risk factors and healthcare costs associated with long bone fracture non-union: a retrospective US claims database analysis.

BACKGROUND: Few contemporary US-based long bone non-union analyses have recently been published. Our study was designed to provide a current understanding of non-union risks and costs, from the payers' perspective. METHODS: The Merative™ MarketScan® Commercial Claims and Encounters database was used. Patients with surgically treated long bone (femur, tibia, or humerus) fractures in the inpatient setting, from Q4 2015 to most recent, were identified. Exclusion criteria included polytrauma and amputation at index. The primary outcome was a diagnosis of non-union in the 12 and 24 months post-index. Additional outcomes included concurrent infection, reoperation, and total healthcare costs. Age, gender, comorbidities, fracture characteristics, and severity were identified for all patients. Descriptive analyses were performed. Crude and adjusted rates of non-union (using Poisson regressions with log link) were calculated. Marginal incremental cost of care associated with non-union and infected non-union and reoperation were estimated using a generalized linear model with log link and gamma distribution. RESULTS: A total of 12,770, 13,504, and 4,805 patients with femoral, tibial, or humeral surgically treated fractures were identified, 74-89% were displaced, and 18-27% were comminuted. Two-year rates of non-union reached 8.5% (8.0%-9.1%), 9.1% (8.6%-9.7%), and 7.2% (6.4%-8.1%) in the femoral, tibial, and humeral fracture cohorts, respectively. Shaft fractures were at increased risk of non-union versus fractures in other sites (risk ratio (RR) in shaft fractures of the femur: 2.36 (1.81-3.04); tibia: 1.95 (1.47-2.57); humerus: 2.02 (1.42-2.87)). Fractures with severe soft tissue trauma (open vs. closed, Gustilo III vs. Gustilo I-II) were also at increased risk for non-union (RR for Gustilo III fracture (vs. closed) for femur: R = 1.96 (1.45-2.58), for tibia: 3.33 (2.85-3.87), RR for open (vs. closed) for humerus: 1.74 (1.30-2.32)). For all fractures, younger patients had a reduced risk of non-union compared to older patients. For tibial fractures, increasing comorbidity (Elixhauser Index 5 or greater) was associated with an increased risk of non-union. The two-year marginal cost of non-union ranged from $33K-$45K. Non-union reoperation added $16K-$34K in incremental costs. Concurrent infection further increased costs by $46K-$86K. CONCLUSIONS: Non-union affects 7-10% of surgically treated long bone fracture cases. Shaft and complex fractures were at increased risk for non-union.

Grip strength cut-points from the Swiss DO-HEALTH population.

BACKGROUND: While grip strength (GS) is commonly assessed using a Dynamometer, the Martin Vigorimeter was proposed as an alternative method especially in older adults. However, its reference values for Swiss older adults are missing. We therefore aimed to derive sex- and age-specific GS cut-points for the dominant and non-dominant hand (DH; NDH) using the Martin Vigorimeter. Additionally, we aimed to identify clinically relevant weakness and assess convergent validity with key markers of physical function and sarcopenia in generally healthy Swiss older adults. METHODS: This cross-sectional analysis includes baseline data from Swiss participants enrolled in DO-HEALTH, a 3-year randomized controlled trial in community-dwelling adults age 70 + . For both DH and NDH, 4 different definitions of weakness to derive GS cut-points by sex and age category (≤ 75 vs. > 75 years) were used: i) GS below the median of the 1st quintile, ii) GS below the upper limit of the 1st quintile, iii) GS below 2-standard deviation (SD) of the sex- and age-specific mean in DO-HEALTH Swiss healthy agers (i.e. individuals without major chronic diseases, disabilities, cognitive impairment or mental health issues) and iv) GS below 2.5-SD of the sex- and age-specific mean in DO-HEALTH Swiss healthy agers. To assess the proposed cut-points' convergent validity, we assessed their association with gait speed, time to complete the 5 Times Sit-To-Stand (5TSTS) test, and present sarcopenia. RESULTS: In total, 976 participants had available GS at the DH (mean age 75.2, 62% women). According to the 4 weakness definitions, GS cut-points at the DH ranged from 29-42 and 25-39 kPa in younger and older women respectively, and from 51-69 and 31-50 kPa in younger and older men respectively. Overall, weakness prevalence ranged from 2.0% to 19.3%. Definitions of weakness using the median and the upper limit of the 1st GS quintile were most consistently associated with markers of physical performance. Weak participants were more likely to have lower gait speed, longer time to complete the 5TSTS, and sarcopenia, compared to participants without weakness. CONCLUSIONS: In generally healthy Swiss older adults, weakness defined by the median or the upper limit of the 1st GS quintile may serve as reference to identify clinically relevant weakness. Additional research is needed in less healthy populations in order to derive representative population-based cut-points. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01745263.

Comparing the volume of vascular intersection of two femoral neck fracture fixation implants using an In silico technique.

Femoral neck fracture displacement with subsequent vascular disruption is one of the factors that contribute to trauma-induced avascular necrosis of the femoral head. Iatrogenic damage of the intraosseous arterial system during fixation of femoral neck fracture is another possible cause of avascular necrosis that is less well understood. Recently, Zhao et al (2017) reconstructed 3D structures of intraosseous blood supply and identified the epiphyseal and inferior retinacular arterial system to be important structures for maintaining the femoral head blood supply after femoral neck fracture. The authors therefore recommended placing implants centrally to reduce iatrogenic vascular injuries. Our in vitro study compared the spatial footprint of a traditional dynamic hip screw with an antirotation screw versus a newly developed hip screw with an integrated antirotation screw on intraosseous vasculature. Methods: Three dimensional (3D) µCT angiograms of 9 cadaveric proximal femora were produced. Three segmented volumes-porous or cancellous bone, filled or cortical bone, and intraosseous vasculature-were converted to surface files. 3D in silico models of the fixation systems were sized and implanted in silico without visibility of the vascular maps. The volume of vasculature that overlapped with the devices was determined. The ratio of the vascular intersection to the comparator device was calculated, and the mean ratio was determined. A paired design, noninferiority test was used to compare the devices. Results: Results indicate both significant (P < 0.001) superiority and noninferiority of the hip screw with an integrated antirotation screw when compared with a dynamic hip screw and antirotation screw for the volume of vasculature that overlapped with each device in the femoral neck. Conclusions: Combining established methods of vascular visualization with newer methods enables an implant's impact on vascular intersection to be assessed in silico. This methodology suggests that when used for femoral neck fracture management, the new device intersects fewer blood vessels than the comparator. Comparative clinical studies are needed to investigate whether these findings correlate with the incidence of avascular necrosis and clinical outcomes.

Precision of bone mechanoregulation assessment in humans using longitudinal high-resolution peripheral quantitative computed tomography in vivo.

Local mechanical stimuli in the bone microenvironment are essential for the homeostasis and adaptation of the skeleton, with evidence suggesting that disruption of the mechanically-driven bone remodelling process may lead to bone loss. Longitudinal clinical studies have shown the combined use of high-resolution peripheral quantitative computed tomography (HR-pQCT) and micro-finite element analysis can be used to measure load-driven bone remodelling in vivo; however, quantitative markers of bone mechanoregulation and the precision of these analyses methods have not been validated in human subjects. Therefore, this study utilised participants from two cohorts. A same-day cohort (n = 33) was used to develop a filtering strategy to minimise false detections of bone remodelling sites caused by noise and motion artefacts present in HR-pQCT scans. A longitudinal cohort (n = 19) was used to develop bone imaging markers of trabecular bone mechanoregulation and characterise the precision for detecting longitudinal changes in subjects. Specifically, we described local load-driven formation and resorption sites independently using patient-specific odds ratios (OR) and 99 % confidence intervals. Conditional probability curves were computed to link the mechanical environment to the remodelling events detected on the bone surface. To quantify overall mechanoregulation, we calculated a correct classification rate measuring the fraction of remodelling events correctly identified by the mechanical signal. Precision was calculated as root-mean-squared averages of the coefficient of variation (RMS-SD) of repeated measurements using scan-rescan pairs at baseline combined with a one-year follow-up scan. We found no significant mean difference (p < 0.01) between scan-rescan conditional probabilities. RMS-SD was 10.5 % for resorption odds, 6.3 % for formation odds, and 1.3 % for correct classification rates. Bone was most likely to be formed in high-strain and resorbed in low-strain regions for all participants, indicating a consistent, regulated response to mechanical stimuli. For each percent increase in strain, the likelihood of bone resorption decreased by 2.0 ± 0.2 %, and the likelihood of bone formation increased by 1.9 ± 0.2 %, totalling 38.3 ± 1.1 % of strain-driven remodelling events across the entire trabecular compartment. This work provides novel robust bone mechanoregulation markers and their precision for designing future clinical studies.

In Vitro Testing and Clinical Handling of a Novel Implant Positioning Technology for Proximal Humeral Plating.

BACKGROUND AND OBJECTIVES: Fractures of the proximal humerus are common, particularly in elderly populations. Anatomical locking plates target stabilization with a multitude of screws spanning into the humeral head. Sound implant placement and screw length determination are key for a successful clinical outcome but are difficult to obtain from planar X-rays. A novel implant positioning technology for proximal humerus plating (Xin1) outputs screw lengths suggestions and plate position based on hole projections in conventional X-ray images. This study investigated the performance of a prototype Xin1 system in a postmortem (in vitro) experiment as well as in a clinical handling test. MATERIALS AND METHODS: For in vitro testing, twelve shoulders from six anatomical specimens were randomized into two groups to compare the Xin1 technique to the conventional operation in terms of surgical precision, procedure time and X-ray exposure. For the clinical trial, 11 patients undergoing plating of the proximal humerus were included. The aim was to investigate clinical handling of the Xin1 marker clip and to retrospectively evaluate the system performance in a real-life fracture situation. Image pairs before and after insertion of the proximal screws were retrospectively processed to investigate the influence of potential bone fragment shifts on the system output. RESULTS: In the postmortem experiment, the use of the system significantly improved the surgical precision (52% error reduction), procedure time (38% shorter) and radiation exposure (64% less X-rays). Clinical handling demonstrated seamless embedding of the marker clip into existing clinical workflows without adverse events reported. Retrospective X-ray analysis on six eligible patients revealed differences in the calculated screw lengths of ≤2 mm before and after screw insertion for five patients. In one patient, the screw lengths differed up to 8 mm, which might indicate displacement of the head fragment. CONCLUSIONS: Results suggest a strong potential of the Xin1 assistance technology to enhance the surgical procedure and patient outcomes in the rising incidence of osteoporotic humeral fractures. Robust performance in a real-life fracture situation was observed. In-depth validation of the system is, however, needed before placing it into clinical practice.

Prospective randomized multicenter noninferiority clinical trial evaluating the use of TFN-advancedTM proximal femoral nailing system (TFNA) for the treatment of proximal femur fracture in a Chinese population.

PURPOSE: To evaluate whether the 24-weeks postoperative fracture union rate for the investigational TFNA intramedullary nail was non-inferior compared to the control product PFNA-II. METHODS: The study was a prospective, randomized, single-blind, noninferiority dual-arm study drawing from 9 trauma centers across China, between November 2018 and September 2020, with follow-up measurements at 24 weeks after internal fixation. The full analysis data set (FAS [Intent-to-Treat]) was analyzed and is summarized here. The primary outcome was fracture union rate, a composite score combining clinical and radiographic assessment. Secondary endpoints comprised (a) clinical outcomes including (1) SF-12, (2) Harris Hip, and (3) EQ-5D Scores, (b) radiographic incidence of complications such as loosening or cut-out requiring revision, (c) revision rates, (d) reoperation rates, and (e) adverse events, including 24-weeks revision and reoperation rates. RESULTS: Both TFNA and PFNA-II group fracture healing rates were 100% at 24 weeks; TFNA was therefore shown to be non-inferior to PFNA-II. With baseline data matched in all parameters except age in both the TFNA and PFNA-II groups, comparisons of union rates, SF-12, Harris Hip, and EQ-5D Scores yielded p values > 0.05 indicating no significant difference between the two groups, further supporting the noninferiority of TFNA. In both groups, revision and re-operation rates were 0, and the incidences of serious adverse events were 19.4% and 17.4%, respectively. CONCLUSION: In terms of fracture union rate at 24 weeks, the DePuy Synthes Trochanteric Fixation Nail Advanced (TFNA) was not inferior to the marketed Proximal Femoral Nail Antirotation (PFNA-II) device produced by the same manufacturer. Secondary and safety outcomes showed no significant differences between the two groups. REGISTRATION: Registration was completed at ClinicalTrials.gov NCT03635320.

Clinical observation of diminished bone quality and quantity through longitudinal HR-pQCT-derived remodeling and mechanoregulation.

High resolution peripheral quantitative computed tomography (HR-pQCT) provides methods for quantifying volumetric bone mineral density and microarchitecture necessary for early diagnosis of bone disease. When combined with a longitudinal imaging protocol and finite element analysis, HR-pQCT can be used to assess bone formation and resorption (i.e., remodeling) and the relationship between this remodeling and mechanical loading (i.e., mechanoregulation) at the tissue level. Herein, 25 patients with a contralateral distal radius fracture were imaged with HR-pQCT at baseline and 9-12 months follow-up: 16 patients were prescribed vitamin D3 with/without calcium supplement based on a blood biomarker measures of bone metabolism and dual-energy X-ray absorptiometry image-based measures of normative bone quantity which indicated diminishing (n = 9) or poor (n = 7) bone quantity and 9 were not. To evaluate the sensitivity of this imaging protocol to microstructural changes, HR-pQCT images were registered for quantification of bone remodeling and image-based micro-finite element analysis was then used to predict local bone strains and derive rules for mechanoregulation. Remodeling volume fractions were predicted by both average values of trabecular and cortical thickness and bone mineral density (R2 > 0.8), whereas mechanoregulation was affected by dominance of the arm and group classification (p < 0.05). Overall, longitudinal, extended HR-pQCT analysis enabled the identification of changes in bone quantity and quality too subtle for traditional measures.

Prevalence of healthy aging among community dwelling adults age 70 and older from five European countries.

BACKGROUND: To compare the prevalence of healthy aging among adults age 70 and older from 5 European countries recruited for the DO-HEALTH clinical trial. Participants were selected for absence of prior major health events. METHODS: Cross-sectional analysis of DO-HEALTH baseline data. All 2,157 participants (mean age 74.9, SD 4.4; 61.7% women) were included and 2,123 had data for all domains of the healthy aging status (HA) definition. HA was assessed based on the Nurses` Health Study (NHS) definition requiring four domains: no major chronic diseases, no disabilities, no cognitive impairment (Montreal Cognitive Assessment, MoCA ≥25), no mental health limitation (GDS-5 <2, and no diagnosis of depression). Association between HA and age, BMI, gender, and physical function (sit-to-stand, gait speed, grip strength) was assessed by multivariate logistic regression analyses adjusting for center. RESULTS: Overall, 41.8% of DO-HEALTH participants were healthy agers with significant variability by country: Austria (Innsbruck) 58.3%, Switzerland (Zurich, Basel, Geneva) 51.2%, Germany (Berlin) 37.6%, France (Toulouse) 36.7% and Portugal (Coimbra) 8.8% (p <0.0001). Differences in prevalence by country persisted after adjustment for age. In the multivariate model, younger age (OR = 0.95, 95% CI 0.93 to 0.98), female gender (OR = 1.36, 95% CI 1.03 to 1.81), lower BMI (OR = 0.94, 95% CI 0.91 to 0.96), faster gait speed (OR = 4.70, 95% CI 2.68 to 8.25) and faster performance in sit-to-stand test (OR = 0.90, 95% CI 0.87 to 0.93) were independently and significantly associated with HA. CONCLUSIONS: Despite the same inclusion and exclusion criteria preselecting relatively healthy adults age 70 years and older, HA prevalence in DO-HEALTH varied significantly between countries and was highest in participants from Austria and Switzerland, lowest in participants from Portugal. Independent of country, younger age, female gender, lower BMI and better physical function were associated with HA. TRIAL REGISTRATION: DO-HEALTH was registered under the protocol NCT01745263 at the International Trials Registry ( clinicaltrials.gov ), and under the protocol number 2012-001249-41 at the Registration at the European Community Clinical Trial System (EudraCT).

Effects of vitamin D, omega-3 fatty acids, and a simple home strength exercise program on fall prevention: the DO-HEALTH randomized clinical trial.

BACKGROUND: The roles of vitamin D, omega-3 fatty acids, and home exercise on fall prevention among generally healthy and active older adults are unclear. OBJECTIVES: We tested the effects of daily supplemental vitamin D, daily supplemental marine omega-3s fatty acids, and a simple home exercise program (SHEP), alone or in combination, on the incidences of total and injurious falls among generally healthy older adults. METHODS: We performed a 2 × 2 × 2 factorial-design randomized controlled trial among 2157 community-dwelling adults aged 70 years and older, who had no major health events in the 5 years prior to enrolment, recruited from Switzerland, Germany, Austria, France, and Portugal between December 2012 and November 2014. Participants were randomly assigned to supplementation with 2000 international units/day of vitamin D3 and/or 1 g/day of marine omega-3s, and/or a SHEP compared with placebo and/or control exercise over 3 years. The primary endpoint for the present fall analysis was the incidence rate of total falls. Falls were recorded prospectively throughout the trial. Since there were no interactions between treatments, the main effects are reported based on a modified intent-to-treat analysis. RESULTS: Of 2157 randomized participants, 1900 (88%) completed the study. The mean age was 74.9 years, 61.7% were women, 40.7% had a serum 25-hydroxyvitamin D concentration < 20 ng/ml, and 83% were at least moderately physically active. In total, 3333 falls were recorded over a median follow-up of 2.99 years. Overall, vitamin D and the SHEP had no benefit on total falls, whilst supplementation with omega-3s compared to no omega-3 supplementation reduced total falls by 10% (incidence rate ratio = 0.90; 95% CI, 0.81-1.00; P = 0.04). CONCLUSIONS: Among generally healthy, active, and vitamin D-replete older adults, omega-3 supplementation may have a modest benefit on the incidence of total falls, whilst a daily high dose of vitamin D or a SHEP had no benefit.

Simplified Mechanical Tests Can Simulate Physiological Mechanics of a Fixation Construct for Periprosthetic Femoral Fractures.

Plate fractures after fixation of a Vancouver Type B1 periprosthetic femoral fracture (PFF) are difficult to treat and could lead to severe disability. However, due to the lack of direct measurement of in vivo performance of the PFF fixation construct, it is unknown whether current standard mechanical tests or previous experimental and computational studies have appropriately reproduced the in vivo mechanics of the plate. To provide a basis for the evaluation and development of appropriate mechanical tests for assessment of plate fracture risk, this study applied loads of common activities of daily living (ADLs) to implanted femur finite element (FE) models with PFF fixation constructs with an existing or a healed PFF. Based on FE simulated plate mechanics, the standard four-point-bend test adequately matched the stress state and the resultant bending moment in the plate as compared with femur models with an existing PFF. In addition, the newly developed constrained three-point-bend tests were able to reproduce plate stresses in models with a healed PFF. Furthermore, a combined bending and compression cadaveric test was appropriate for risk assessment including both plate fracture and screw loosening after the complete healing of PFF. The result of this study provides the means for combined experimental and computational preclinical evaluation of PFF fixation constructs.

Angular stable locking in a novel intramedullary nail improves construct stability in a distal tibia fracture model.

INTRODUCTION: Intramedullary nails are frequently used for treatment of unstable distal tibia fractures. However, insufficient fixation of the distal fragment could result in delayed healing, malunion or nonunion. Recently, a novel concept for angular stable nailing was developed that maintains the principle of relative stability and introduces improvements expected to reduce nail toggling, screw migration and secondary loss of reduction. The aim of this study was to investigate the biomechanical competence of the novel angular stable intramedullary nail concept for treatment of unstable distal tibia fractures, compared to a conventional nail locking in a human cadaveric model under dynamic loading. MATERIALS AND METHODS: Ten pairs of fresh-frozen human cadaveric tibiae with a simulated AO/OTA 42-A3.1 fracture were assigned to 2 groups for reamed intramedullary nailing using either a conventional (non-angular stable) Expert Tibia Nail (ETN) with 3 distal screws or the novel Tibia Nail Advanced (TNA) system with 2 distal angular stable locking low-profile retaining screws. The specimens were biomechanically tested under conditions including initial quasi-static loading, followed by progressively increasing combined cyclic axial and torsional loading in internal rotation until failure of the bone-implant construct. Both tests were monitored by means of motion tracking. RESULTS: Initial nail toggling of the distal tibia fragment in varus and flexion under axial loading was lower for TNA compared to ETN, being significant in flexion, P = 0.91 and P = 0.03. After 5000 cycles, interfragmentary movements in terms of varus, flexion, internal rotation, axial displacement, and shear displacement at the fracture site were all lower for TNA compared to ETN, with flexion and shear displacement being significant, P = 0.14, P = 0.04, P = 0.25, P = 0.11 and P = 0.04, respectively. Cycles to failure until both interfragmentary 5° varus and 5° flexion were significantly higher for TNA compared to ETN, P = 0.04. CONCLUSION: From a biomechanical perspective, the novel angular stable intramedullary nail concept provides increased construct stability and maintains it over time while reducing the number of required locking screws without impeding the flexibility of the nail itself and resists better towards loss of reduction under dynamic loading, compared to conventional locking in intramedullary nailed unstable distal tibia fractures.

Bone Mechanoregulation Allows Subject-Specific Load Estimation Based on Time-Lapsed Micro-CT and HR-pQCT in Vivo.

Patients at high risk of fracture due to metabolic diseases frequently undergo long-term antiresorptive therapy. However, in some patients, treatment is unsuccessful in preventing fractures or causes severe adverse health outcomes. Understanding load-driven bone remodelling, i.e., mechanoregulation, is critical to understand which patients are at risk for progressive bone degeneration and may enable better patient selection or adaptive therapeutic intervention strategies. Bone microarchitecture assessment using high-resolution peripheral quantitative computed tomography (HR-pQCT) combined with computed mechanical loads has successfully been used to investigate bone mechanoregulation at the trabecular level. To obtain the required mechanical loads that induce local variances in mechanical strain and cause bone remodelling, estimation of physiological loading is essential. Current models homogenise strain patterns throughout the bone to estimate load distribution in vivo, assuming that the bone structure is in biomechanical homoeostasis. Yet, this assumption may be flawed for investigating alterations in bone mechanoregulation. By further utilising available spatiotemporal information of time-lapsed bone imaging studies, we developed a mechanoregulation-based load estimation (MR) algorithm. MR calculates organ-scale loads by scaling and superimposing a set of predefined independent unit loads to optimise measured bone formation in high-, quiescence in medium-, and resorption in low-strain regions. We benchmarked our algorithm against a previously published load history (LH) algorithm using synthetic data, micro-CT images of murine vertebrae under defined experimental in vivo loadings, and HR-pQCT images from seven patients. Our algorithm consistently outperformed LH in all three datasets. In silico-generated time evolutions of distal radius geometries (n = 5) indicated significantly higher sensitivity, specificity, and accuracy for MR than LH (p < 0.01). This increased performance led to substantially better discrimination between physiological and extra-physiological loading in mice (n = 8). Moreover, a significantly (p < 0.01) higher association between remodelling events and computed local mechanical signals was found using MR [correct classification rate (CCR) = 0.42] than LH (CCR = 0.38) to estimate human distal radius loading. Future applications of MR may enable clinicians to link subtle changes in bone strength to changes in day-to-day loading, identifying weak spots in the bone microstructure for local intervention and personalised treatment approaches.

Formation Dominates Resorption With Increasing Mineralized Density and Time Postfracture in Cortical but Not Trabecular Bone: A Longitudinal HRpQCT Imaging Study in the Distal Radius.

Clinical evaluation of fracture healing is often limited to an assessment of fracture bridging from radiographic images, without consideration for other aspects of bone quality. However, recent advances in HRpQCT offer methods to accurately monitor microstructural bone remodeling throughout the healing process. In this study, local bone formation and resorption were investigated during the first year post fracture in both the fractured (n = 22) and contralateral (n = 19) radii of 34 conservatively treated patients (24 female, 10 male) who presented with a unilateral radius fracture at the Innsbruck University Hospital, Austria. HRpQCT images and clinical metrics were acquired at six time points for each patient. The standard HRpQCT image acquisition was captured for all radii, with additional distal and proximal image acquisitions for the fractured radii. Measured radial bone densities were isolated with a voxel-based mask and images were rigidly registered to images from the previous imaging session using a pyramid-based approach. From the registered images, bone formation and resorption volume fractions were quantified for multiple density-based thresholds and compared between the fractured and contralateral radius and relative to demographics, bone morphometrics, and fracture metrics using regression. Compared with the contralateral radius, both bone formation and resorption were significantly increased in the fractured radius throughout the study for nearly all evaluated thresholds. Higher density cortical bone formation continually increased throughout the duration of the study and was significantly greater than resorption during late-stage healing in both the fractured and intact regions of the radius. With the small and diverse study population, only weak relationships between fracture remodeling and patient-specific parameters were unveiled. However this study provides methods for the analysis of local bone remodeling during fracture healing and highlights relevant considerations for future studies, specifically that remodeling postfracture is likely to continue beyond 12-months postfracture. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Geriatric fracture centre vs usual care after proximal femur fracture in older patients: what are the benefits? Results of a large international prospective multicentre study.

OBJECTIVE: The aim of this study was to determine the effect of treatment in geriatric fracture centres (GFC) on the incidence of major adverse events (MAEs) in patients with hip fractures compared with usual care centres (UCC). Secondary objectives included hospital-workflow and mobility-related outcomes. DESIGN: Cohort study recruiting patients between June 2015 and January 2017. Follow-up was 1 year. SETTING: International (six countries, three continents) multicentre study. PARTICIPANTS: 281 patients aged ≥70 with operatively treated proximal femur fractures. INTERVENTIONS: Treatment in UCCs (n=139) or GFCs (n=142), that is, interdisciplinary treatment including regular geriatric consultation and daily physiotherapy. OUTCOME MEASURES: Primary outcome was occurrence of prespecified MAEs, including delirium. Secondary outcomes included any other adverse events, time to surgery, time in acute ward, 1-year mortality, mobility, and quality of life. RESULTS: Patients treated in GFCs (n=142) had a mean age of 81.9 (SD, 6.6) years versus 83.9 (SD 6.9) years in patients (n=139) treated in UCCs (p=0.013) and a higher mean Charlson Comorbidity Index of 2.0 (SD, 2.1) versus 1.2 (SD, 1.5) in UCCs (p=0.001). More patients in GFCs (28.2%) experienced an MAE during the first year after surgery compared with UCCs (7.9%) with an OR of 4.56 (95% CI 2.23 to 9.34, p<0.001). Analysing individual MAEs, this was significant for pneumonia (GFC: 9.2%; UCC: 2.9%; OR, 3.40 (95% CI 1.08 to 10.70), p=0.027) and delirium (GFC: 11.3%; UCC: 2.2%, OR, 5.76 (95% CI 1.64 to 20.23), p=0.002). CONCLUSIONS: Contrary to our study hypothesis, the rate of MAEs was higher in GFCs than in UCCs. Delirium was revealed as a main contributor. Most likely, this was based on improved detection rather than a truly elevated incidence, which we interpret as positive effect of geriatric comanagement. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT02297581.

Automated segmentation of fractured distal radii by 3D geodesic active contouring of in vivo HR-pQCT images.

Radius fractures are among the most common fracture types; however, there is limited consensus on the standard of care. A better understanding of the fracture healing process could help to shape future treatment protocols and thus improve functional outcomes of patients. High-resolution peripheral quantitative computed tomography (HR-pQCT) allows monitoring and evaluation of the radius on the micro-structural level, which is crucial to our understanding of fracture healing. However, current radius fracture studies using HR-pQCT are limited by the lack of automated contouring routines, hence only including small number of patients due to the prohibitively time-consuming task of manually contouring HR-pQCT images. In the present study, a new method to automatically contour images of distal radius fractures based on 3D morphological geodesic active contours (3D-GAC) is presented. Contours of 60 HR-pQCT images of fractured and conservatively treated radii spanning the healing process up to one year post-fracture are compared to the current gold standard, hand-drawn 2D contours, to assess the accuracy of the algorithm. Furthermore, robustness was established by applying the algorithm to HR-pQCT images of intact radii of 73 patients and comparing the resulting morphometric indices to the gold standard patient evaluation including a threshold- and dilation-based contouring approach. Reproducibility was evaluated using repeat scans of intact radii of 19 patients. The new 3D-GAC approach offers contours within inter-operator variability for images of fractured distal radii (mean Dice score of 0.992 ± 0.005 versus median operator Dice score of 0.992 ± 0.006). The generated contours for images of intact radii yielded morphometric indices within the in vivo reproducibility limits compared to the current gold standard. Additionally, the 3D-GAC approach shows an improved robustness against failure (n = 5) when dealing with cortical interruptions, fracture fragments, etc. compared with the automatic, default manufacturer pipeline (n = 40). Using the 3D-GAC approach assures consistent results, while reducing the need for time-consuming hand-contouring.

Development of axial compression and combined axial compression and torque loading configurations to reproduce strain in the implanted femur during activities of daily living.

Femoral strain is indicative of the potential for bone remodeling (strain energy density, SED) and periprosthetic femoral fracture (magnitude of principal strains) after total hip arthroplasty (THA). Previous modeling studies have evaluated femoral strains in THA-implanted femurs under gait loads including both physiological hip contact force and femoral muscle forces. However, experimental replication of the complex muscle forces during activities of daily living (ADLs) is difficult for in vitro assessment of femoral implant or fixation hardware. Alternatively, cadaveric tests using simplified loading configurations have been developed to assess post-THA bone mechanics, although no current studies have demonstrated simplified loading configurations used in mechanical tests may simulate the physiological femoral strains under ADL loads. Using an optimization approach integrated with finite element analysis, this study developed axial compression and combined axial compression and torque testing configurations for three common ADLs (gait, stair-descent and sit-to-stand) via matching the SED profile of the femur in THA-implanted models of three specimens. The optimized simplified-loading models showed good agreement in predicting bone remodeling stimuli (post-THA change in SED per unit mass) and fatigue regions as compared with the ADL-loading models, as well as other modeling and clinical studies. The optimized simplified test configurations can provide a physiological-loading based pre-clinical platform for the evaluation of implant/fixation devices of the femur.

The AO trauma CPP bone infection registry: Epidemiology and outcomes of Staphylococcus aureus bone infection.

Bone infection represents a serious complication of orthopedic surgery and Staphylococcus aureus is the most common pathogen. To improve the understanding of host-pathogen interaction, we developed a biospecimen registry (AO Trauma CPP Bone Infection Registry) to collect clinical data, bacterial isolates, and serum from patients with S. aureus bone infection. A prospective multinational registry with a 12-month follow-up was created to include adult patients (18 years or older) with culture-confirmed S. aureus infection in long bones after fracture fixation or arthroplasty. Baseline patient attributes and details on infections and treatments were recorded. Blood and serum samples were obtained at baseline, 6, and 12 months. Patient-reported outcomes were collected at 1, 6, and 12 months. Clinical outcomes were recorded. Two hundred and ninety-two patients with fracture-related infection (n = 157, 53.8%), prosthetic joint infection (n = 86, 29.5%), and osteomyelitis (n = 49, 16.8%) were enrolled. Methicillin-resistant S. aureus was detected in 82 patients (28.4%), with the highest proportion found among patients from North American sites (n = 39, 48.8%) and the lowest from Central European sites (n = 18, 12.2%). Patient outcomes improved at 6 and 12 months in comparison to baseline. The SF-36 physical component summary mean (95% confidence interval) score, however, did not reach 50 at 12 months. The cure rate at the end of the study period was 62.1%. Although patients improved with treatment, less than two-thirds were cured in 1 year. At 12-month follow-up, patient-reported outcome scores were worse for patients with methicillin-resistant S. aureus infections.