A head-to-head comparison of EQ-5D-5L and SF-6D in Dutch patients with fractures visiting a Fracture Liaison Service.

AIMS: This study compared the psychometric properties of EQ-5D-5L and SF-6D to assess the interchangeability of both instruments in patients with a recent fracture presenting at a Fracture Liaison Service (FLS). MATERIALS AND METHODS: Data from a prospective observational study in a Dutch FLS clinic were used. Over 3 years, subjects were interviewed at several time points using EQ-5D-5L and SF-36. Floor and ceiling effects were evaluated. Agreement was evaluated by intra-class correlation coefficients and visualized in Bland-Altman plots. Spearman's rank correlation coefficients were applied to assess convergent validity. Mann-Whitney U test or Kruskal-Wallis H test as well as effect size (ES) were used to explore known-groups validity. Responsiveness was explored using standardized response mean (SRM) and ES. For each measurement property, hypotheses on direction and magnitude of effects were formulated. RESULTS: A total of 499 patients were included. EQ-5D-5L had a considerable ceiling effect in comparison to SF-6D (21 vs. 1.2%). Moderate agreement between the (UK and Dutch) EQ-5D-5L and SF-6D was identified with intra-class correlation coefficients of 0.625 and 0.654, respectively. Bland-Altman plots revealed proportional bias as the differences in utilities between two instruments were highly dependent on the health states. High correlation between instruments was found (UK: rho = 0.758; Dutch: rho = 0.763). EQ-5D-5L and SF-6D utilities showed high correlation with physical component score but low correlation with mental component score of SF-36. Both instruments showed moderate discrimination (ES > 0.5) for subgroup by baseline fracture type, and moderate responsiveness (SRM > 0.5) in patients that sustained a subsequent fracture. CONCLUSION: Both EQ-5D-5L and SF-6D appeared to be valid utility instruments in patients with fractures attending the FLS. However, they cannot be used interchangeably given only moderate agreement was identified, and differences in utilities and ceiling effect were revealed. Comparable construct validity and responsiveness were indicated, and neither instrument was found to be clearly superior.

The EQ-5D and SF-36 as generic multi-domain questionnaires are widely used to measure the health-related quality-of-life (HRQoL) in a sample of the persons who suffer from the diseases or the general population. Their responses could be converted to patients or societal Health State Utility Values (HSUVs) with the range of 0 ("death") to 1 ("full health"). A specific application of HSUV is to calculate quality-adjusted life years as the indicator of effectiveness to evaluate whether the cost of a new intervention is justified in terms of health gains through cost-utility analysis in health economics, the evidence can be further used to inform decision-making. However, different instruments differ in construct and valuation, potentially leading to different estimates for the person's same "health state", and healthcare decisions could be compromised when researchers or decision-makers are not aware of potential differences in HSUV. Therefore, it is important to gain insight into the specific psychometric properties of these instruments, and to understand whether instruments are interchangeable. Our study is based on data from a Dutch Fracture Liaison Service (FLS is a program for secondary fracture prevention), compared the psychometric properties and interchangeability of two instruments (EQ-5D-5L and SF-6D) in patients with a recent fracture presenting at the FLS, and suggested both instruments are valid in utility elicitation in our target population. However, they cannot be used interchangeably given only moderate agreement and differences in utilities. Neither instrument was found to be clearly superior given comparable construct and longitudinal validity, but different instruments values in different aspects of HRQoL assessment.

Effect of osteoporosis-related reduction in the mechanical properties of bone on the acetabular fracture during a sideways fall: A parametric finite element approach.

PURPOSE: The incidence of acetabular fractures due to low-energy falls is increasing among the geriatric population. Studies have shown that several biomechanical factors such as body configuration, impact velocity, and trochanteric soft-tissue thickness contribute to the severity and type of acetabular fracture. The effect of reduction in apparent density and elastic modulus of bone as well as other bone mechanical properties due to osteoporosis on low-energy acetabular fractures has not been investigated. METHODS: The current comprehensive finite element study aimed to study the effect of reduction in bone mechanical properties (trabecular, cortical, and trabecular + cortical) on the risk and type of acetabular fracture. Also, the effect of reduction in the mechanical properties of bone on the load-transferring mechanism within the pelvic girdle was examined. RESULTS: We observed that while the reduction in the mechanical properties of trabecular bone considerably affects the severity and area of trabecular bone failure, reduction in mechanical properties of cortical bone moderately influences both cortical and trabecular bone failure. The results also indicated that by reducing bone mechanical properties, the type of acetabular fracture turns from elementary to associated, which requires a more extensive intervention and rehabilitation period. Finally, we observed that the cortical bone plays a substantial role in load transfer, and by increasing reduction in the mechanical properties of cortical bone, a greater share of load is transmitted toward the pubic symphysis. CONCLUSION: This study increases our understanding of the effect of osteoporosis progression on the incidence of low-energy acetabular fractures. The osteoporosis-related reduction in the mechanical properties of cortical bone appears to affect both the cortical and trabecular bones. Also, during the extreme reduction in the mechanical properties of bone, the acetabular fracture type will be more complicated. Finally, during the final stages of osteoporosis (high reduction in mechanical properties of bone) a smaller share of impact load is transferred by impact-side hemipelvis to the sacrum, therefore, an osteoporotic pelvis might mitigate the risk of sacral fracture.

Biomechanical duality of fracture healing captured using virtual mechanical testing and validated in ovine bones.

Bone fractures commonly repair by forming a bridging structure called callus, which begins as soft tissue and gradually ossifies to restore rigidity to the bone. Virtual mechanical testing is a promising technique for image-based assessment of structural bone healing in both preclinical and clinical settings, but its accuracy depends on the validity of the material model used to assign tissue mechanical properties. The goal of this study was to develop a constitutive model for callus that captures the heterogeneity and biomechanical duality of the callus, which contains both soft tissue and woven bone. To achieve this, a large-scale optimization analysis was performed on 2363 variations of 3D finite element models derived from computed tomography (CT) scans of 33 osteotomized sheep under normal and delayed healing conditions. A piecewise material model was identified that produced high absolute agreement between virtual and physical tests by differentiating between soft and hard callus based on radiodensity. The results showed that the structural integrity of a healing long bone is conferred by an internal architecture of mineralized hard callus that is supported by interstitial soft tissue. These findings suggest that with appropriate material modeling, virtual mechanical testing is a reliable surrogate for physical biomechanical testing.

Functional outcome of 103 fractures of the proximal fifth metatarsal bone.

BACKGROUND: Metatarsal fractures are common skeletal injuries of the lower extremity in adults. The majority involves the proximal fifth metatarsal bone. In the current literature, there still exists controversy regarding treatment recommendations for the different fracture entities. METHODS: All patients suffering from single fractures to the proximal fifth metatarsal bone between 2003 and 2015 were enrolled in this retrospective analysis. Only patients with a minimum follow-up of 12 months were included. The fractures were classified according to Lawrence and Botte (L&B). Data were collected via patient registry, radiographs and a standardized questionnaire (Foot and Ankle Outcome Score = FOAS). For outcome analysis, the nonparametric Mann-Whitney U test was performed and Spearman's rank correlation coefficient calculated. RESULTS: In total, the functional outcomes of 103 patients suffering from fractures to the proximal fifth metatarsal bone were analyzed. L&B type I fractures (n = 13) had a FAOS score of 91 ± 23, L&B type II (n = 67) presented a score of 91 ± 15 and L&B type III (n = 23) a score of 93 ± 11. Surgically treated patients with an L&B type II fracture had no statistically significant better functional outcome in comparison to conservative management (p = 0.89). Operatively treated L&B type III fractures tended to have a better functional score (p = 0.16). The follow-up time was 58 (min: 15; max: 164) months. CONCLUSIONS: Overall, the functional outcome following fractures to the proximal fifth metatarsal bone is satisfactory. Conservatively treated L&B type II fractures showed an equivalent functional outcome compared to surgical management. Patients with an L&B type III fracture mainly were treated surgically, but difference in FAOS score did not reach level of significance.

HA-g-CS Implant and Moderate-intensity Exercise Stimulate Subchondral Bone Remodeling and Promote Repair of Osteochondral Defects in Mice.

Background: Substantial evidence shows that crosstalk between cartilage and subchondral bone may play an important role in cartilage repair. Animal models have shown that hydroxyapatite-grafted-chitosan implant (HA-g-CS) and moderate-intensity exercise promote regeneration of osteochondral defects. However, no in vivo studies have demonstrated that these two factors may have a synergistic activity to facilitate subchondral bone remodeling in mice, thus supporting bone-cartilage repair. Questions: This study was to clarify whether HA-g-CS and moderate-intensity exercise might have a synergistic effect on facilitating (1) regeneration of osteochondral defects and (2) subchondral bone remodeling in a mouse model of osteochondral defects. Methods: Mouse models of osteochondral defects were created and divided into four groups. BC Group was subjected to no treatment, HC Group to HA-g-CS implantation into osteochondral defects, ME group to moderate-intensity treadmill running exercise, and HC+ME group to both HA-g-CS implantation and moderate-intensity exercise until sacrifice. Extent of subchondral bone remodeling at the injury site and subsequent cartilage repair were assessed at 4 weeks after surgery. Results: Compared with BC group, HC, ME and HC+ME groups showed more cartilage repair and thicker articular cartilage layers and HC+ME group acquired the best results. The extent of cartilage repair was correlated positively to bone formation activity at the injured site as verified by microCT and correlation analysis. Histology and immunofluorescence staining confirmed that bone remodeling activity was increased in HC and ME groups, and especially in HC+ME group. This bone formation process was accompanied by an increase in osteogenesis and chondrogenesis factors at the injury site which promoted cartilage repair. Conclusions: In a mouse model of osteochondral repair, HA-g-CS implant and moderate-intensity exercise may have a synergistic effect on improving osteochondral repair potentially through promotion of subchondral bone remodeling and generation of osteogenesis and chondrogenesis factors. Clinical Relevance: Combination of HA-g-CS implantation and moderate-intensity exercise may be considered potentially in clinic to promote osteochondral defect repair. Also, cartilage and subchondral bone forms a functional unit in an articular joint and subchondral bone may regulate cartilage repair by secreting growth factors in its remodeling process. However, a deeper insight into the exact role of HA-g-CS implantation and moderate-intensity exercise in promoting osteochondral repair in other animal models should be explored before they can be applied in clinic in the future.

Congenital Metabolic Bone Disorders as a Cause of Bone Fragility.

Bone fragility is a pathological condition caused by altered homeostasis of the mineralized bone mass with deterioration of the microarchitecture of the bone tissue, which results in a reduction of bone strength and an increased risk of fracture, even in the absence of high-impact trauma. The most common cause of bone fragility is primary osteoporosis in the elderly. However, bone fragility can manifest at any age, within the context of a wide spectrum of congenital rare bone metabolic diseases in which the inherited genetic defect alters correct bone modeling and remodeling at different points and aspects of bone synthesis and/or bone resorption, leading to defective bone tissue highly prone to long bone bowing, stress fractures and pseudofractures, and/or fragility fractures. To date, over 100 different Mendelian-inherited metabolic bone disorders have been identified and included in the OMIM database, associated with germinal heterozygote, compound heterozygote, or homozygote mutations, affecting over 80 different genes involved in the regulation of bone and mineral metabolism. This manuscript reviews clinical bone phenotypes, and the associated bone fragility in rare congenital metabolic bone disorders, following a disease taxonomic classification based on deranged bone metabolic activity.

Effect of Bone-Marrow-Derived Mesenchymal Stem Cells on the Healing of Bone Fractures.

This study was performed to evaluate the effectiveness of mesenchymal stem cells (MSCs) on bone healing and to assess the role of various chemical stimulants and mediators in healing. Forty female mice were randomly assigned to 4 groups (10 mice each) after the induction of fixed fractures: group I: received fixation only; group II: received phosphate-buffered saline (PBS); group III: received intralesion MSCs (IL-MSCs); and group IV: received intraperitoneal MSCs (IP-MSCs). Serum alkaline phosphatase (ALP) levels and the expression of the osteocalcin (OCN), bone morphogenetic protein-2 (BMP-2), and stromal-derived factor-1 (SDF-1) genes were measured. ALP reached baseline level only in IL-MSCs, whereas OCN reached baseline level in MSCs recipients (IL-MSCs and IP-MSCs). BMP-2 significantly increased in MSCs recipients 3 weeks postfracture and increased in all groups 8 weeks postfracture with significant increases in MSC recipients than the fixation and PBS groups. The highest BMP-2 expression was reached in IL-MSC group. MSCs either locally or systemically improves or accelerates the healing of bone fractures with better results obtained after local injection, as shown by biochemical, radiological, and histological findings. MSCs are effective candidates for bone regeneration.

Automated bone mineral density prediction and fracture risk assessment using plain radiographs via deep learning.

Dual-energy X-ray absorptiometry (DXA) is underutilized to measure bone mineral density (BMD) and evaluate fracture risk. We present an automated tool to identify fractures, predict BMD, and evaluate fracture risk using plain radiographs. The tool performance is evaluated on 5164 and 18175 patients with pelvis/lumbar spine radiographs and Hologic DXA. The model is well calibrated with minimal bias in the hip (slope = 0.982, calibration-in-the-large = -0.003) and the lumbar spine BMD (slope = 0.978, calibration-in-the-large = 0.003). The area under the precision-recall curve and accuracy are 0.89 and 91.7% for hip osteoporosis, 0.89 and 86.2% for spine osteoporosis, 0.83 and 95.0% for high 10-year major fracture risk, and 0.96 and 90.0% for high hip fracture risk. The tool classifies 5206 (84.8%) patients with 95% positive or negative predictive value for osteoporosis, compared to 3008 DXA conducted at the same study period. This automated tool may help identify high-risk patients for osteoporosis.

The endothelium-bone axis in development, homeostasis and bone and joint disease.

Blood vessels form a versatile transport network that is best known for its critical roles in processes such as tissue oxygenation, metabolism and immune surveillance. The vasculature also provides local, often organ-specific, molecular signals that control the behaviour of other cell types in their vicinity during development, homeostasis and regeneration, and also in disease processes. In the skeletal system, the local vasculature is actively involved in both bone formation and resorption. In addition, blood vessels participate in inflammatory processes and contribute to the pathogenesis of diseases that affect the joints, such as rheumatoid arthritis and osteoarthritis. This Review summarizes the current understanding of the architecture, angiogenic growth and functional properties of the bone vasculature. The effects of ageing and pathological conditions, including arthritis and osteoporosis, are also discussed.

Clinical efficacy of closed reduction and percutaneous parallel K-wire interlocking fixation of first metacarpal base fracture.

BACKGROUND: This study aimed to explore the clinical efficacy of treating a first metacarpal base fracture by closed reduction and percutaneous parallel K-wire interlocking fixation between the first and second metacarpals. METHODS: Twenty patients treated by the abovementioned modified technique (modified technique group) and ten patients treated by the traditional percutaneous K-wire fixation technique (traditional technique group) from October 2015 to November 2019 at our institution were retrospectively reviewed. The patients' average age was 38 years (range, 16-61 years). The mean follow-up period was 13 months (range, 10-18 months). At the final follow-up, the functional recovery of the injured hand was assessed and compared between the modified and traditional technique groups. In addition, the functional recovery of the injured hand was compared with that of the uninjured hand within the modified technique group. RESULTS: All patients recovered well, with no cases of infection or nonunion. Compared with the traditional technique group, the modified technique group had a shorter operative time, lower postoperative visual analogue scale pain score, better effective range of motion score of the first carpometacarpal joint (Kapandji score), and had almost no need for auxiliary plaster fixation, enabling functional exercise to be started earlier. Within the modified technique group, the mean hand grip strength, pinch strength, and Kapandji score on the injured side did not significantly differ to the values on the uninjured side in both the extra-articular and intra-articular fracture subgroups. While the abduction and flexion-extension arcs of the thumb on the injured hand were significantly smaller than those on the uninjured hand in both the extra-articular and intra-articular fracture subgroups, the patients felt clinically well with respect to daily activities and strength. CONCLUSION: The percutaneous parallel K-wire and interlocking fixation technique is simple, effective, and economical for first metacarpal base fractures.

Nomogram for Predicting Deep Venous Thrombosis in Lower Extremity Fractures.

Deep venous thrombosis (DVT) is a common complication in patients with lower extremity fractures, causing delays in recovery short-term and possible impacts on quality of life long-term. Early prediction and prevention of thrombosis can effectively reduce patient pain while improving outcomes. Although research on the risk factors for thrombosis is prevalent, there is a stark lack of clinical predictive models for DVT occurrence specifically in patients with lower limb fractures. In this study, we aim to propose a new thrombus prediction model for lower extremity fracture patients. Data from 3300 patients with lower limb fractures were collected from Wuhan Union Hospital and Hebei Third Hospital, China. Patients who met our inclusion criteria were divided into a thrombosis and a nonthrombosis group. A multivariate logistic regression analysis was carried out to identify predictors with obvious effects, and the corresponding formulas were used to establish the model. Model performance was evaluated using a discrimination and correction curve. 2662 patients were included in the regression analysis, with 1666 in the thrombosis group and 996 in the nonthrombosis group. Predictive factors included age, Body Mass Index (BMI), fracture-fixation types, energy of impact at the time of injury, blood transfusion during hospitalization, and use of anticoagulant drugs. The discriminative ability of the model was verified using the C-statistic (0.676). For the convenience of clinical use, a score table and nomogram were compiled. Data from two centers were used to establish a novel thrombus prediction model specific for patients with lower limb fractures, with verified predictive ability.

Fracture biomechanics influence local and systemic immune responses in a murine fracture-related infection model.

Biomechanical stability plays an important role in fracture healing, with unstable fixation being associated with healing disturbances. A lack of stability is also considered a risk factor for fracture-related infection (FRI), although confirmatory studies and an understanding of the underlying mechanisms are lacking. In the present study, we investigate whether biomechanical (in)stability can lead to altered immune responses in mice under sterile or experimentally inoculated conditions. In non-inoculated C57BL/6 mice, instability resulted in an early increase of inflammatory markers such as granulocyte-colony stimulating factor (G-CSF), keratinocyte chemoattractant (KC) and interleukin (IL)-6 within the bone. When inoculated with Staphylococcus epidermidis, instability resulted in a further significant increase in G-CSF, IL-6 and KC in bone tissue. Staphylococcus aureus infection led to rapid osteolysis and instability in all animals and was not further studied. Gene expression measurements also showed significant upregulation in CCL2 and G-CSF in these mice. IL-17A was found to be upregulated in all S. epidermidis infected mice, with higher systemic IL-17A cell responses in mice that cleared the infection, which was found to be produced by CD4+ and γδ+ T cells in the bone marrow. IL-17A knock-out (KO) mice displayed a trend of delayed clearance of infection (P=0.22, Fisher's exact test) and an increase in interferon (IFN)-γ production. Biomechanical instability leads to a more pronounced local inflammatory response, which is exaggerated by bacterial infection. This study provides insights into long-held beliefs that biomechanics are crucial not only for fracture healing, but also for control of infection.

Comparison of clinical and radiological results of fixation methods with retrograde intramedullary Kirschner wire and plate-screw in extra-articular metacarpal fractures.

OBJECTIVES: In this study, we aimed to compare clinical and radiographic outcomes of retrograde intramedullary Kirschner-wire (K-wire) fixation with those of plate-screw (PS) fixation. PATIENTS AND METHODS: A total of 98 metacarpal shaft fractures in 75 patients (65 males, 10 females; mean age: 31.2±10.9 years; range, 16 to 65 years) were included between January 2011 and December 2017. The total joint active range of motion (AROM) and grip strength of the healthy and broken hands were evaluated. The Visual Analog Scale (VAS) and Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) scores were recorded. We compared surgery duration, number of fluoroscopy images, and cost-effectiveness for each technique. RESULTS: The overall mean follow-up was 21.9 (range, 12 to 56) months. At the last follow-up, total joint AROM (p=0.072), VAS score (p=0.298), QuickDASH score (p=0.132), and hand grip strength (p=0.947) were similar between the groups. Radiological union occurred in the PS and K-wire groups in a mean of 5.84 (range, 3 to 8) and 4.46 (range, 3 to 20) weeks, respectively (p=0.173). A significant difference was found in surgery duration (p=0.021) and number of fluoroscopy images (p<0.05) between the PS and K-wire groups. Two wound complications were observed in the PS group and one with K-wires. CONCLUSION: Retrograde intramedullary K-wire fixation has certain advantages such as being less invasive and more accessible with shorter operation time, compared to PS fixation. Similar radiological and clinical scores can be obtained in patients undergoing retrograde intramedullary K-wire fixation or PS fixation.

Advanced glycation endproducts and bone quality: practical implications for people with type 2 diabetes.

PURPOSE OF REVIEW: Individuals with type 2 diabetes (T2D) are at increased risk of fracture, often despite normal bone density. This observation suggests deficits in bone quality in the setting of abnormal glucose homeostasis. The goal of this article is to review recent developments in our understanding of how advanced glycation end products (AGEs) are incorporated into the skeleton with resultant deleterious effects on bone health and structural integrity in patients with T2D. RECENT FINDINGS: The adverse effects of skeletal AGE accumulation on bone remodeling and the ability of the bone to deform and absorb energy prior to fracture have been demonstrated both at the bench as well as in small human studies; however, questions remain as to how these findings might be better explored in large, population-based investigations. SUMMARY: Hyperglycemia drives systemic, circulating AGE formation with subsequent accumulation in the bone tissue. In those with T2D, studies suggest that AGEs diminish fracture resistance, though larger clinical studies are needed to better define the direct role of longstanding AGE accumulation on bone strength in humans as well as to motivate potential interventions to reverse or disrupt skeletal AGE deposition with the goal of fracture prevention.

Military Service Members with Major Lower Extremity Fractures Return to Running with a Passive-dynamic Ankle-foot Orthosis: Comparison with a Normative Population.

BACKGROUND: Lower extremity fractures represent a high percentage of reported injuries in the United States military and can devastate a service member's career. A passive dynamic ankle-foot orthosis (PD-AFO) with a specialized rehabilitation program was initially designed to treat military service members after complex battlefield lower extremity injuries, returning a select group of motivated individuals back to running. For high-demand users of the PD-AFO, the spatiotemporal gait parameters, agility, and quality of life is not fully understood with respect to uninjured runners. QUESTIONS/PURPOSES: Do patients who sustained a lower extremity fracture using a PD-AFO with a specialized rehabilitation program differ from uninjured service members acting as controls, as measured by (1) time-distance and biomechanical parameters associated with running, (2) agility testing (using the Comprehensive High-level Activity Mobility Predictor performance test and Four Square Step Test), and (3) the Short Musculoskeletal Function Assessment score. METHODS: We conducted a retrospective data analysis of a longitudinally collected data registry of patients using a PD-AFO from 2015 to 2017 at a single institution. The specific study cohort were patients with a unilateral lower extremity fracture who used the PD-AFO for running. Patients had to be fit with a PD-AFO, have completed rehabilitation, and have undergone a three-dimensional (3-D) running analysis at a self-selected speed at the completion of the program. Of the 90 patients who used the PD-AFO for various reasons, 10 male service members with lower extremity fractures who used a PD-AFO for running (median [range] age 29 years [22 to 41], height 1.8 meters [1.7 to 1.9], weight 91.6 kg [70 to 112]) were compared with 15 uninjured male runners in the military (median age 33 years [21 to 42], height 1.8 meters [1.7 to 1.9], weight 81.6 kg [71.2 to 98.9]). The uninjured runners were active-duty service members who voluntarily participated in a gait analysis at their own self-selected running speeds; to meet eligibility for inclusion as an uninjured control, the members had to be fit for full duty without any medical restrictions, and they had to be able to run 5 miles. The controls were then matched to the study group by age, weight, and height. The primary study outcome variables were the running time-distance parameters and frontal and sagittal plane kinematics of the trunk and pelvis during running. The Four Square Step Test, Comprehensive High-level Activity Mobility Predictor scores, and Short Musculoskeletal Function Assessment scores were analyzed for all groups as secondary outcomes. Nonparametric analyses were performed to determine differences between the two groups at p < 0.05. RESULTS: For the primary outcome, patients with a PD-AFO exhibited no differences compared with uninjured runners in median (range) running velocity (3.9 meters/second [3.4 to 4.2] versus 4.1 meters/second [3.1 to 4.8], median difference 0.2; p = 0.69), cadence (179 steps/minute [169 to 186] versus 173 steps/minute [159 to 191], median difference 5.8; p = 0.43), stride length (2.6 meters [2.4 to 2.9] versus 2.8 meters [2.3 to 3.3], median difference 0.2; p = 0.23), or sagittal plane parameters such as peak pelvic tilt (24° [15° to 33°] versus 22° [14° to 28°], median difference 1.6°; p = 0.43) and trunk forward flexion (16.2° [7.3° to 23°) versus 15.4° [4.2° to 21°), median difference 0.8°; p > 0.99) with the numbers available. For the secondary outcomes, runners with a PD-AFO performed worse in Comprehensive High-level Activity Mobility Predictor performance testing than uninjured runners did, with their four scores demonstrating a median (range) single-limb stance of 35 seconds (32 to 58) versus 60 seconds (60 to 60) (median difference 25 seconds; p < 0.001), t-test result of 15 seconds (13 to 20) versus 13 seconds (10 to 14) (median difference 2 seconds; p < 0.001), and Illinois Agility Test result of 22 seconds (20 to 25) versus 18 seconds (16 to 20) (median difference 4; p < 0.001). Edgren side step test result of 20 meters (16 to 26) versus 24 meters (16 to 29) (median difference 4 meters; p = 0.11) and the Four Square Step Test of 5.5 seconds (4.1 to 7.2) versus 4.2 seconds (3.1 to 7.3) (median difference 1.3 seconds; p = 0.39) were not different between the groups with an effect size of 0.83 and 0.75, respectively. CONCLUSION: The results of our study demonstrate that service members run with discernible differences in high-level mobility and demonstrate inferior self-reported patient functioning while having no differences in speed and biomechanics compared with their noninjured counterparts with the sample size available. This study is an early report on functional gains of highly motivated service members with major lower extremity injuries who use a PD-AFO and formalized therapy program to run. LEVEL OF EVIDENCE: Level III, therapeutic study.

Reverse dynamisation: a modern perspective on Stephan Perren's strain theory.

The present review acknowledges the tremendous impact of Stephan Perren's strain theory, considered with respect to the earlier contributions of Roux and Pauwels. Then, it provides further insight by examining how the concept of reverse dynamisation extended Perren's theory within a modern context. A key factor of this more contemporary theory is that it introduces variable mechanical conditions at different time points during bone healing, opening the possibility of manipulating biology through mechanics to achieve the desired clinical outcome. The discussion focusses on the current state of the art and the most recent advances made towards optimising and accelerating bone regeneration, by actively controlling the mechanical environment as healing progresses. Reverse dynamisation utilises a very specific mechanical manipulation regimen, with conditions initially flexible to encourage and expedite early callus formation. Once callus has formed, the mechanical conditions are intentionally modified to create a rigid environment under which the soft callus is quickly converted to hard callus, bridging the fracture site and leading to a more rapid union. The relevant literature, principally animal studies, was surveyed to provide ample evidence in support of the effectiveness of reverse dynamisation. By providing a modern perspective on Stephan Perren's strain theory, reverse dynamisation perhaps holds the key to tipping the balance in favour of a more rapid and reliable union when treating acute fractures, osteotomies, non-unions and other circumstances where it is necessary to regenerate bone.

Impact of serum magnesium and bone mineral density on systemic fractures in chronic hemodialysis patients.

INTRODUCTION: Bone mineral density (BMD) measured with dual-energy X-ray absorptiometry (DXA) can be used to predict fractures, but its clinical utility has not been fully established in chronic kidney disease (CKD) patients. Magnesium is an essential trace element. Although magnesium is associated with the risk of fractures in non-CKD populations, the relationship is unknown in CKD patients. METHODS: BMD and serum magnesium levels were measured in 358 stable outpatients undergoing maintenance hemodialysis therapy. The primary outcome was fragility fracture. Patients were divided into groups according to the median level of magnesium and the normal threshold value of lumbar spine BMD. RESULTS: During the median follow-up period of 36 months, 36 (10.0%) fractures occurred. The cumulative incidence rates of fractures were 17.6% and 5.2% [adjusted hazard ratio (aHR) 2.31, 95% confidence interval (CI) 1.03-5.17, P = 0.030] in the lower (<2.6 mg/dL) and higher (≥2.6 mg/dL) magnesium (Mg) groups, respectively, and 21.2% and 7.3% (aHR 2.59, 95% CI 1.09-6.16, P = 0.027) in the low- and high-BMD groups, respectively. The lower-Mg and low-BMD group had a 9.21-fold higher risk of fractures (95% CI; 2.35-47.00; P = 0.0010) than the higher-Mg and high-BMD group. Furthermore, adding both magnesium levels and lumbar spine BMD levels to the established risk factors significantly improved the prediction of fractures (C-index: 0.784 to 0.830, p = 0.041). DISCUSSION/CONCLUSIONS: The combination of serum magnesium and lumbar spine BMD can be used for fracture risk stratification and synergistically improves the prediction of fractures in CKD patients.

Direct contribution of skeletal muscle mesenchymal progenitors to bone repair.

Bone regenerates by activation of tissue resident stem/progenitor cells, formation of a fibrous callus followed by deposition of cartilage and bone matrices. Here, we show that mesenchymal progenitors residing in skeletal muscle adjacent to bone mediate the initial fibrotic response to bone injury and also participate in cartilage and bone formation. Combined lineage and single-cell RNA sequencing analyses reveal that skeletal muscle mesenchymal progenitors adopt a fibrogenic fate before they engage in chondrogenesis after fracture. In polytrauma, where bone and skeletal muscle are injured, skeletal muscle mesenchymal progenitors exhibit altered fibrogenesis and chondrogenesis. This leads to impaired bone healing, which is due to accumulation of fibrotic tissue originating from skeletal muscle and can be corrected by the anti-fibrotic agent Imatinib. These results elucidate the central role of skeletal muscle in bone regeneration and provide evidence that skeletal muscle can be targeted to prevent persistent callus fibrosis and improve bone healing after musculoskeletal trauma.

Relaxation capacity of cartilage is a critical factor in rate- and integrity-dependent fracture.

Articular cartilage heals poorly but experiences mechanically induced damage across a broad range of loading rates and matrix integrity. Because loading rates and matrix integrity affect cartilage mechanical responses due to poroviscoelastic relaxation mechanisms, their effects on cartilage failure are important for assessing and preventing failure. This paper investigated rate- and integrity-dependent crack nucleation in cartilage from pre- to post-relaxation timescales. Rate-dependent crack nucleation and relaxation responses were obtained as a function of matrix integrity through microindentation. Total work for crack nucleation increased with decreased matrix integrity, and with decreased loading rates. Critical energy release rate of intact cartilage was estimated as 2.39 ± 1.39 to 2.48 ± 1.26 kJ m-2 in a pre-relaxation timescale. These findings showed that crack nucleation is delayed when cartilage can accommodate localized loading through poroviscoelastic relaxation mechanisms before fracture at a given loading rate and integrity state.