The impact of chronic obstructive pulmonary disease on bone strength.

Chronic obstructive pulmonary disease (COPD) is a lifestyle-related disease that develops in middle-aged and older adults, often due to smoking habits, and has been noted to cause bone fragility. COPD is a risk factor for osteoporosis and fragility fracture, and a high prevalence of osteoporosis and incidence of vertebral fractures have been shown in patients with COPD. Findings of lung tissue analysis in patients with COPD are primarily emphysema with a loss of alveolar septal walls, and the severity of pulmonary emphysema is negatively correlated with thoracic spine bone mineral density (BMD). On the other hand, epidemiological studies on COPD and fracture risk have reported a BMD-independent increase in fracture risk; however, verification in animal models and human bone biopsy samples has been slow, and the essential pathogenesis has not been elucidated. The detailed pathological/molecular mechanisms of musculoskeletal complications in patients with COPD are unknown, and basic research is needed to elucidate the mechanisms. This paper discusses the impacts of COPD on bone strength, focusing on findings in animal models in terms of bone microstructure, bone metabolic dynamics, and material properties.

Experimental study on the biomechanical stability of complex acetabular fractures in the quadrilateral area: application of a dynamic anterior titanium-plate screw system.

BACKGROUND AND OBJECTIVE: Complex acetabular fractures involving quadrilateral areas are more challenging to treat during surgery. To date, there has been no ideal internal fixation for these acetabular fractures. The purpose of this study was to evaluate the biomechanical stability of complex acetabular fractures using a dynamic anterior titanium-plate screw system of the quadrilateral area (DAPSQ) by simulating the standing and sitting positions of pelvic specimens. MATERIALS AND METHODS: Eight formal in-preserved cadaveric pelvises aged 30-50 years were selected as the research objects. First, one hip of the normal pelvises was randomly used as the control model (group B) for measurement, and then one hip of the pelvises was randomly selected to make the fracture model in the 8 intact pelvises as the experimental model (group A) for measurement. In group A, acetabular both-column fractures in the quadrilateral area were established, and the fractures were fixed by DAPSQ. The biomechanical testing machine was used to load (simulated physiological load) from 400 N to 700 N at a 1 mm/min speed for 30 s in the vertical direction when the specimens were measured at random in simulated standing or sitting positions in groups. The horizontal displacement and longitudinal displacement of the acetabular fractures in the quadrilateral area were measured in both the standing and sitting simulations. RESULTS: As the load increased, no dislocation or internal fixation breakage occurred during the measurements. In the standing position, the horizontal displacement of the quadrilateral area fractures in group A and group B appeared to be less than 1 mm with loads ranging from 400 N to 700 N, and there was no significant difference between group A and group B (p > 0.05). The longitudinal displacement appeared to be greater than 1 mm with a load of 700 mm in group A (700 N, 2 cases), and the difference was significant between group A and group B (p < 0.05). In the sitting position, the horizontal and longitudinal displacements of the quadrilateral areas were within 0.5 mm in group A and group B, and there was no significant difference between group A and group B (p > 0.05). CONCLUSION: For complex acetabular fractures in the quadrilateral area, DAPSQ fixation may provide early sitting stability, but it is inappropriate for patients to stand too early.

Postoperative recreational sports and subjective shoulder function: a comprehensive analysis following intramedullary stabilization of displaced midshaft clavicular fractures.

Introduction Sports-related outcomes and the role of recreational sports activities for shoulder function after intramedullary stabilization (IMS) of displaced midshaft clavicular fractures (DMCFs) in the general population are not well known. In this study, we aimed to determine the sport-related outcomes (return-to-sports [RTS] rate, type of sports, time until RTS, and intensity) and to explore the role of sports after IMS of DMCFs. Materials and Methods This single-center, retrospective, cohort study included patients who underwent IMS of DMCFs between 2009 and 2022 at a Level II trauma center in Germany, experienced no major complications, and had completed at least 1 year of follow-up. Propensity score matching was conducted to obtain a balanced sample of patients who did not engage (cases) and engaged (controls) in postoperative sports activities by adjusting for age and fracture complexity. Groups were compared to assess the impact of regular sports activities on subjective shoulder functioning at follow-up, as evaluated using the Disabilities of the Arm, Shoulder, and Hand and Oxford Shoulder Score (OSS) questionnaires, after controlling for the patient- (i.e., sex and smoking) and treatment- (i.e., surgery duration and physical therapy) factors. Results Among the 199 patients included, the RTS rate was 97.5%, and 160 patients practiced regular postoperative activity, mostly in the same sport and intensity. In the matched cohort (39 cases and 39 controls), practicing regular sports activities postoperatively was the only independent factor associated with a higher OSS in the multiple regression analysis (unstandardized regression coefficient = 2.40; Bias-corrected and accelerated 95% confidence interval [0.28, 4.69]). Conclusions The sport-related outcomes after IMS of DMCFs in our cohort were comparable to those achieved after plate osteosynthesis, and IMS reported in the literature. Recreational sports activities benefitted subjective shoulder function, thereby encouraging further research and potentially influencing management policies. Level of evidence Grade IV - a retrospective observational cohort study.

Dissecting the Genetics of Osteoporosis using Systems Approaches.

Osteoporosis is a condition characterized by low bone mineral density (BMD) and an increased risk of fracture. Traits contributing to osteoporotic fracture are highly heritable, indicating that a comprehensive understanding of bone requires a thorough understanding of the genetic basis of bone traits. Towards this goal, genome-wide association studies (GWASs) have identified over 500 loci associated with bone traits. However, few of the responsible genes have been identified, and little is known of how these genes work together to influence systems-level bone function. In this review, we describe how systems genetics approaches can be used to fill these knowledge gaps.

Apigenin promotes osteogenic differentiation of mesenchymal stem cells and accelerates bone fracture healing via activating Wnt/ß-catenin signaling.

Apigenin (API), a natural plant flavone, is abundantly found in common fruits and vegetables. As a bioactive flavonoid, API exhibits several activities including antiproliferation and anti-inflammation. A recent study showed that API could retard osteoporosis progress, indicating its role in the skeletal system. However, the detailed function and mechanism remain obscure. In the present study, API was found to promote osteogenic differentiation of mesenchymal stem cells (MSCs). And further investigation showed that API could enhance the expression of the critical transcription factor ß-catenin and several downstream target genes of Wnt signaling, thus activated Wnt/ß-catenin signaling. Using a rat femoral fracture model, API was found to improve new bone formation and accelerate fracture healing in vivo. In conclusion, our data demonstrated that API could promote osteogenesis in vitro and facilitate the fracture healing in vivo via activating Wnt/ß-catenin signaling, indicating that API may be a promising therapeutic candidate for bone fracture repair.NEW & NOTEWORTHY1) API promoted osteogenic differentiation of human MSCs in vitro; 2) API facilitated bone formation and accelerated fracture healing in vivo; 3) API stimulated Wnt/ß-catenin signaling during osteogenesis of human MSCs.

Relationships Between Level and Change in Sarcopenia and Other Body Composition Components and Adverse Health Outcomes: Findings from the Health, Aging, and Body Composition Study.

We investigated how baseline values and rates of decline in components of sarcopenia and other body composition parameters relate to adverse clinical outcomes using the Health, Aging, and Body Composition Study. 2689 participants aged 70-79 years were studied. Appendicular lean mass, whole body fat mass, and total hip BMD were ascertained using DXA; muscle strength by grip dynamometry; and muscle function by gait speed. Baseline values and 2-3 year conditional changes (independent of baseline) in each characteristic were examined as predictors of mortality, hospital admission, low trauma fracture, and recurrent falls in the subsequent 10-14 years using Cox regression (generalized estimating equations used for recurrent falls) with adjustment for sex, ethnicity, age, and potential confounders. Lower levels and greater declines in all parameters (excluding hip BMD level) were associated (p < 0.05) with increased rates of mortality; fully-adjusted hazard ratios per SD lower gait speed and grip strength were 1.27 (95% CI 1.19, 1.36) and 1.14 (1.07, 1.21), respectively. Risk factors of hospital admission included lower levels and greater declines in gait speed and grip strength, and greater declines in hip BMD. Lower levels and greater declines in fat mass and hip BMD were associated with low trauma fracture. Lower gait speed, higher fat mass, and both lower levels and greater declines in grip strength were related to recurrent falls. Lower baseline levels and greater declines in musculoskeletal parameters were related to adverse outcomes. Interventions to maximize peak levels in earlier life and reduce rates of age-related decline may reduce the burden of disease in this age group.

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.

Romosozumab followed by denosumab in Japanese women with high fracture risk in the FRAME trial.

INTRODUCTION: This post-hoc analysis of the FRAME study investigated the long-term efficacy and safety of romosozumab followed by denosumab in postmenopausal Japanese women with osteoporosis at high fracture risk. MATERIALS AND METHODS: Data from Japanese women with a high fracture risk participating in the international, randomised, double-blind, placebo-controlled, phase 3 FRAME study were analysed. High risk of fracture was defined as ≥ 1 fragility fracture with bone mineral density (BMD) ≤ - 2.5 standard deviations [SD], > 2 prevalent vertebral fractures, prevalent semiquantitative grade 3 vertebral fracture, or lumbar spine BMD < - 3.3 SD. Endpoints included incidence of new vertebral fracture at 12, 24 and 36 months and percentage change from baseline in BMD at the lumbar spine, total hip and femoral neck. RESULTS: 187 Japanese subjects at high risk of fracture were enrolled in FRAME. Incidence of new vertebral fractures was lower with romosozumab/denosumab vs. placebo/denosumab at 12, 24 and 36 months (relative risk reduction at all timepoints: 84%; p = 0.056). BMD increases at 12, 24 and 36 months were greater in subjects receiving romosozumab/denosumab than placebo/denosumab (lumbar spine: 16.3%, 21.5% and 23.2% vs 0.4%, 8.1% and 10.4%; total hip: 4.9%, 7.9% and 8.9% vs 0.4%, 2.8% and 4.1%; femoral neck: 4.8%, 7.6% and 8.1% vs 0.3%, 3.3% and 3.7%, respectively; all p < 0.001 vs placebo/denosumab). Adverse events were generally balanced between groups. CONCLUSION: Romosozumab/denosumab in Japanese subjects at high risk of fracture resulted in significant BMD gains and numerically lower vertebral fracture rate vs. placebo/denosumab at all timepoints measured.

Efficacy of once-weekly teriparatide in patients with glucocorticoid-induced osteoporosis: the TOWER-GO study.

INTRODUCTION: Bisphosphonates are the standard treatment for glucocorticoid-induced osteoporosis (GIOP) with teriparatide being another option. While daily teriparatide has been shown to be effective in increasing bone mineral density (BMD), the efficacy of once-weekly teriparatide (56.5 µg) has not yet been evaluated. The TOWER-GO study, a 72-week, multicenter, open-label, randomized controlled trial, was conducted in patients with GIOP to compare the effects of once-weekly teriparatide and once-weekly alendronate 35 mg on BMD. MATERIALS AND METHODS: Patients (N = 180) with GIOP for whom drug treatment was indicated according to the 2004 guidelines in Japan were randomized to receive once-weekly teriparatide (n = 89) or once-weekly alendronate (n = 91). The primary endpoint was the non-inferiority of percentage change in lumbar spine BMD at final follow-up. The secondary endpoints were the percentage change in BMD from baseline, incidence of bone fractures, and changes in bone turnover markers. RESULTS: While the non-inferiority of teriparatide to alendronate was not confirmed, BMD increased significantly from baseline with teriparatide and alendronate by 5.09% and 4.04%, respectively (both p < 0.05), at 72 weeks. The incidence of vertebral and non-vertebral fractures was similar in both groups. Bone formation markers increased in the teriparatide group and decreased in the alendronate group. CONCLUSIONS: The non-inferiority of once-weekly teriparatide versus once-weekly alendronate in BMD change at 72 weeks was not shown, but the increase in bone formation markers over time and the increase of BMD in GIOP patients treated with once-weekly teriparatide were confirmed.

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.

Pilot randomized trial of pre-hospital advanced therapies for the control of hemorrhage (PATCH) using pelvic binders.

BACKGROUND: Pelvic fractures represent a small percent of all skeletal injuries but are associated with significant morbidity and mortality secondary to hemodynamic instability from bleeding bone surfaces and disrupted pelvic vasculature. Stabilization of the pelvis prior to arrival at a treatment facility may mitigate the hemodynamic consequences of pelvic ring injuries and improve morbidity and mortality. Whether pelvic compression devices such as pelvic binders or sheets can be safely applied in the prehospital setting has not been well-studied. This study aims to evaluate the safety of applying a pelvic binder to at-risk patients in the field after scalable training and the feasibility of conducting a randomized trial evaluating this practice in the prehospital setting. METHODS: A pilot study (prospective randomized trial design) was conducted in the pre-hospital environment in an urban area surrounding a level-one trauma center. Pre-hospital emergency medical (EMS) personnel were trained to identify patients at high-risk for pelvic fracture and properly apply a commercial pelvic binder. Adult patients with a high-energy mechanism, suspected pelvic fracture, and "Priority 1" criteria were prospectively identified by paramedics and randomized to pelvic binder placement or usual care. Medical records were reviewed for safety outcomes. Secondary outcomes were parameters of efficacy including interventions needed to control hemorrhage (such as angioembolization and surgical control of bleeding) and mortality. RESULTS: Forty-three patients were randomized to treatment (binder: N=20; nonbinder: N=23). No complications of binder placement were identified. Eight patients (40%) had binders placed correctly at the level of the greater trochanter. Two binders (10%) were placed too proximally and 10 (50%) binders were not visualized on x-ray. Two binder group patients and three nonbinder group patients required angioembolization. None required surgical control of pelvic bleeding. Two nonbinder group patients and one binder group patient were readmitted within 30 days and one nonbinder group patient died within 30 days. CONCLUSION: Identification of pelvic fractures in the field remains a challenge. However, a scalable training model for appropriate binder placement was successful without secondary injury to patients. The model for conducting prospective, randomized trials in the prehospital setting was successful.

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.

Is Social Deprivation Associated with PROMIS Outcomes After Upper Extremity Fractures in Children?

BACKGROUND: We previously found that social deprivation was associated with worse perceived function and pain among children presenting with upper extremity fractures. We performed the current study to determine whether this differential in outcome scores would resolve after children received orthopaedic treatment for their fractures. This was needed to understand whether acute pain and impaired function were magnified by worse social deprivation or whether social deprivation was associated with differences in health perception even after injury resolution. QUESTIONS/PURPOSES: Comparing patients from the least socially deprived national quartile and those from the most deprived quartile, we asked: (1) Are there differences in age, gender, race, or fracture location among children with upper extremity fractures? (2) After controlling for relevant confounding variables, is worse social deprivation associated with worse self-reported Patient-Reported Outcomes Measurement Information System (PROMIS) scores before and after the treatment of pediatric upper extremity fractures? (3) Is social deprivation associated with PROMIS score improvements as a result of fracture treatment? METHODS: In this this retrospective, comparative study, we considered data from 1131 pediatric patients (aged 8 to 17 years) treated nonoperatively at a single tertiary academic medical center for isolated upper extremity fractures between June 2016 and June 2017. We used the Area Deprivation Index to define the patient's social deprivation by national quartiles to analyze those in the most- and least-deprived quartiles. After excluding patients with missing zip codes (n = 181), 18% (172 of 950) lived in the most socially deprived national quartile, while 31% (295 of 950) lived in the least socially deprived quartile. Among these 467 patients in the most- and least-deprived quartiles, 28% (129 of 467) were excluded for lack of follow-up and 9% (41 of 467) were excluded for incomplete PROMIS scores. The remaining 297 patients were analyzed (107 most-deprived quartile, 190 least-deprived quartile) longitudinally in the current study; they included 237 from our initial cross-sectional investigation that only considered reported health at presentation (60 patients added and 292 removed from the 529 patients in the original study, based on updated Area Deprivation Index quartiles). The primary outcomes were the self-completed pediatric PROMIS Upper Extremity Function, Pain Interference, and secondarily PROMIS Peer Relationships computer-adaptive tests. In each PROMIS assessment, higher scores indicated more of that domain (such as, higher function scores indicate better function but a higher pain score indicates more pain), and clinically relevant differences were approximately 3 points. Bivariate analysis compared patient age, gender, race, fracture type, and PROMIS scores between the most- and least-deprived groups. A multivariable linear regression analysis was used to determine factors associated with the final PROMIS scores. RESULTS: Between the two quartiles, the only demographic and injury characteristic difference was race, with Black children being overrepresented in the most-deprived group (most deprived: white 53% [57 of 107], Black 45% [48 of 107], other 2% [2 of 107]; least deprived: white 92% [174 of 190], Black 4% [7 of 190), other 5% [9 of 190]; p < 0.001). At presentation, accounting for patient gender, race, and fracture location, the most socially deprived quartile remained independently associated with the initial PROMIS Upper Extremity (ß 5.8 [95% CI 3.2 to 8.4]; p < 0.001) scores. After accounting for patient gender, race, and number of days in care, we found that the social deprivation quartile remained independently associated with the final PROMIS Upper Extremity (ß 4.9 [95% CI 2.3 to 7.6]; p < 0.001) and Pain Interference scores (ß -4.4 [95% CI -2.3 to -6.6]; p < 0.001). Social deprivation quartile was not associated with any differential in treatment impact on change in PROMIS Upper Extremity function (8 ± 13 versus 8 ± 12; mean difference 0.4 [95% CI -3.4 to 2.6]; p = 0.79) or Pain Interference scores (8 ± 9 versus 6 ± 12; mean difference 1.1 [95% CI -1.4 to 3.5]; p = 0.39) from presentation to the conclusion of treatment. CONCLUSION: Delivering upper extremity fracture care produces substantial improvement in pain and function that is consistent regardless of a child's degree of social deprivation. However, as social deprivation is associated with worse perceived health at treatment initiation and conclusion, prospective interventional trials are needed to determine how orthopaedic surgeons can act to reduce the health disparities in children associated with social deprivation. As fractures prompt interaction with our health care system, the orthopaedic community may be well placed to identify children who could benefit from enrollment in proven community health initiatives or to advocate for multidisciplinary care coordinators such as social workers in fracture clinics. LEVEL OF EVIDENCE: Level III, therapeutic study.

Minimal Pain Decrease Between 2 and 4 Weeks After Nonoperative Management of a Displaced Midshaft Clavicle Fracture Is Associated with a High Risk of Symptomatic Nonunion.

BACKGROUND: The main long-term benefit of operative treatment of displaced midshaft clavicular fractures is the reduction in nonunion risk, and as this risk is generally low, the ideal approach would be to operate only patients at high risk of nonunion. However, most current surgical decision models use baseline variables to estimate the nonunion risk, and the value of these models remains unclear. Pain in the early weeks after fracture could be potentially be an indirect measurement of fracture healing, and so it is a potential proxy variable that could lead to simpler prediction models. QUESTIONS/PURPOSES: (1) Is pain a possible proxy variable for the development of symptomatic nonunion after nonoperative treatment of midshaft clavicular fractures? (2) How reliable is the model we created that uses pain as a proxy variable for symptomatic nonunion of nonoperatively treated clavicle fractures? METHODS: In this secondary retrospective analysis of an earlier randomized trial, we studied prospectively collected data from 64 nonoperatively treated patients aged 18 years to 60 years. In the original randomized trial, we compared operative and nonoperative treatment of displaced midshaft clavicular fractures. In all, 150 patients were included in the study, of whom 71 received nonoperative treatment. Patients were predominantly males (75%, 48 of 64) with a mean age of 38 ± SD 12 years; most fractures were comminuted and shortened more than 1 cm. All 71 patients who were nonoperatively treated were potentially eligible for this secondary analysis; of those, 11% (8 of 71) were lost to follow-up, leaving 63 patients from the nonoperative treatment arm and one patient from the operative treatment arm (who declined surgical treatment after randomization but was followed in this group according to the intention-to-treat principle) for analysis here. Nonunion was defined as lack of callus formation, persistent fracture lines and/or sclerotic edges of the bones at the fracture site on plain radiographs at 6 months follow-up. Nonunions were regarded as symptomatic if pain, tenderness, and local crepitation were present at the fracture site. Seventeen percent (11 of 64) of patients had symptomatic nonunions. After investigating differences in early pain scores between the union and nonunion groups, we defined the VASratio as the VAS pain score at 4 weeks divided by the VAS pain score at 2 weeks. Week 2 VAS pain score was chosen as baseline after visual inspection of a linear mixed model that showed increased divergence in pain scores between union and nonunion group at 2 weeks after fracture. Week 4 was chosen as the cutoff because we wanted a reasonable time frame for the detection of pain reduction and did not want to delay surgical treatment more than necessary. Odds ratios for various risk factors were calculated using logistic regression analyses. We used a receiver operating characteristic curve analysis to identify cutoff values for the VASratio. RESULTS: An increase in absolute pain score at 4 weeks after fracture (odds ratio 1.8 per 1 point increase [95% confidence interval 1.1 to 3.4]) was associated with an increased risk of nonunion 6 months after fracture. Likewise, we found that an increasing VASratio (OR 1.02 per 0.01 point increase [95% CI 1.002 to 1.06]) was also associated with nonunion. Receiver operating curve analysis found that the best cutoff value of VASratio was about 0.6. Patients with a VASratio above 0.6 had a relative risk of developing nonunion of 18 (95% CI 2 to 130) compared with patients with a VASratio below 0.6. Sparse-data bias could be present, as is evident from this wide confidence interval, though even at the low end of the confidence interval, the relative risk was 2, which may still improve surgical decision-making. CONCLUSION: A pain score that exhibits no or minimal change from 2 to 4 weeks after nonoperative treatment of a displaced midshaft fracture of the clavicle is associated with a high risk that symptomatic nonunion will develop. Patients with no or minimal change in pain in the early weeks may be candidates for surgery to reduce the risk of symptomatic nonunion. As this was a retrospective study, with a risk of sparse-data bias, the predictive value of the VASratio needs to be further investigated in large prospective studies before clinical use. LEVEL OF EVIDENCE: Level III, diagnostic study.

Adequate union rates for the treatment of acute proximal fifth metatarsal fractures.

PURPOSE: To compare the bone healing, clinical, and return to daily activity outcomes after either surgical or conservative management of acute zone 1, 2, and 3 fifth metatarsal fractures. METHODS: A literature search was performed to identify studies published from the earliest record to January 2019 using EMBASE (Ovid), MEDLINE via PubMed, CINAHL, and Web of Science. All articles assessing clinical outcomes of acute proximal fifth metatarsal fractures were included. Bone healing and clinical outcomes were thereafter calculated using a simplified pooling method. RESULTS: Thirty-two articles comprising of a total of 1,239 fractures were included, of which one was a randomized controlled trial, seven were prospective studies, and 24 were retrospective studies. 627 zone 1 fractures demonstrated union rates of 93.2% following conservative treatment and 95.1% following surgical treatment. Conservatively managed zone 1 fractures were displaced 49.5% of the time, compared to a rate of 92.8% for the surgically treated cases. For Jones' (zone 2) fractures, bone healing outcomes of conservative versus surgical treatment showed union rates of 77.4% versus 96.3%, refracture rates of 2.4% versus 2.1%, and mean time to union of 11.0 weeks versus 9.4 weeks, respectively. Only ten proximal diaphyseal (zone 3) fractures were reported, with a mean return to work of 8.2 weeks. CONCLUSION: Acute zone 1 fractures are preferably treated conservatively as similar union rates were found after both conservative and surgical management. In contradistinction, acute zone 2 fractures demonstrate higher union rates and faster time to union when treated surgically. The outcomes of acute zone 3 fractures are rarely reported in the literature, so treatment recommendations remain unclear. Further research of proximal fifth metatarsal fractures is warranted to provide more definitive conclusions, but current findings can aid surgeons during the shared clinical decision making process. LEVEL OF EVIDENCE: IV.

Long-term Functional Outcomes and Complications in Operative Versus Nonoperative Treatment for Displaced Midshaft Clavicle Fractures in Adolescents: A Retrospective Comparative Study.

INTRODUCTION: Traditionally, midshaft clavicular fractures in adolescents are treated nonoperatively. In later years, a trend toward operative treatment can be observed. Documentation of the benefit of surgery in this group is scarce. The purpose of this study is to evaluate the long-term patient reported functional outcomes and complications for patients treated operatively and nonoperatively for displaced midshaft clavicular fractures. Using the same outcomes we also compared the operative methods. METHODS: One hundred nine adolescents aged 12 to 18 years sustaining displaced midshaft clavicular fractures in the period 2010 to 2016 were identified in our computerized files. Sixty-one were treated nonoperatively, 48 operatively (22 plate and 26 intramedullary nail). Their radiographs and patient journals were examined for fracture classification, wound infection, sensory affection, surgery duration, hardware removal, and nonunion (n=109). Long-term function, pain, and satisfaction were measured with Quick Disability of Arm, Shoulder, and Hand (QuickDASH), Oxford Shoulder Score and Visual Analogue Scale (n=87). RESULTS: Operative treatment: We could find no difference in functional score outcomes. The main outcome QuickDASH was excellent in both groups (median 0 nail vs. 2.26 plate). Surgery duration was shorter with intramedullary nail. We found 2 infections and 2 sensory affections in the plate group, and 1 infection and 1 sensory affection in the intramedullary nail group. There were 2 refractures in the nail group. Operative versus nonoperative treatment: there were no differences in functional outcomes between the operative and nonoperative groups. For the main outcome QuickDASH both groups scored excellently (median 1.12 operative vs. 0 nonoperative). The nonoperative group was more satisfied with the cosmetic result. There was 1 nonunion in the nonoperative group that later was operated. CONCLUSIONS: Adolescents aged 12 to 18 years with displaced midshaft clavicular fractures show good long-term functional results after plate fixation, intramedullary nail, and nonoperative treatment. No additional benefit is demonstrated for surgery in our material. Nonoperatively treated patients are more satisfied with the cosmetic results. Little difference is seen between the operative methods in our study. We conclude that surgery should rarely be the choice of treatment for displaced midshaft clavicular fractures in adolescents. LEVEL OF EVIDENCE: Level III study-retrospective comparative study.

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.

The Progress of Stem Cell Technology for Skeletal Regeneration.

Skeletal disorders, such as osteoarthritis and bone fractures, are among the major conditions that can compromise the quality of daily life of elderly individuals. To treat them, regenerative therapies using skeletal cells have been an attractive choice for patients with unmet clinical needs. Currently, there are two major strategies to prepare the cell sources. The first is to use induced pluripotent stem cells (iPSCs) or embryonic stem cells (ESCs), which can recapitulate the skeletal developmental process and differentiate into various skeletal cells. Skeletal tissues are derived from three distinct origins: the neural crest, paraxial mesoderm, and lateral plate mesoderm. Thus, various protocols have been proposed to recapitulate the sequential process of skeletal development. The second strategy is to extract stem cells from skeletal tissues. In addition to mesenchymal stem/stromal cells (MSCs), multiple cell types have been identified as alternative cell sources. These cells have distinct multipotent properties allowing them to differentiate into skeletal cells and various potential applications for skeletal regeneration. In this review, we summarize state-of-the-art research in stem cell differentiation based on the understanding of embryogenic skeletal development and stem cells existing in skeletal tissues. We then discuss the potential applications of these cell types for regenerative medicine.

The effect of preperitoneal pelvic packing for hemodynamically unstable patients with pelvic fractures.

PURPOSE: Hemodynamically unstable patients with pelvic fractures still represent a challenge to trauma surgeons and have a very high mortality. This study was designed to explore the effect of the interventions of direct preperitoneal pelvic packing for the hemodynamically unstable pelvic fractures. METHODS: This retrospective study enrolled 67 cases of severe pelvic fractures with unstable hemodynamics from October 2011 to December 2019. All patients presented in our emergency center and received preperitoneal pelvic packing were included in this study. The indication was persistent systolic blood pressure ≤90 mmHg during initial resuscitation and after transfusion of two units of red blood cells. Patients with hemodynamic stability who need no preperitoneal pelvic packing to control bleeding were excluded. Their demographic characteristics, clinical features, laboratory results, therapeutic interventions, adverse events, and prognostic outcomes were collected from digital information system of electronic medical records. Statistics were described as mean ± standard deviation or medium and analyzed using pair sample t-test or Mann-Whitney U-test. RESULTS: The patients' average age was 41.6 years, ranging from 10 to 88 years. Among them, 45 cases were male (67.2%) and 22 cases were female (32.8%). Significant difference was found regarding the systolic blood pressure (mmHg) in the emergency department (78.4 ± 13.9) and after preperitoneal pelvic packing in the surgery intensive care unit (100.1 ± 17.6) (p < 0.05). Simultaneously, the arterial base deficit (mmol/L) were significantly lower in the surgery intensive care unit (median -6, interquartile range -8 to -2) than in the emergency department (median -10, interquartile range -14 to -8) (p < 0.05). After preperitoneal pelvic packing, 15 patients (22.4%) underwent pelvic angiography for persistent hypotension or suspected ongoing haemorrhage. The overall mortality rate was 29.5% (20 of 67). CONCLUSIONS: Preperitoneal pelvic packing, as a useful surgical technique, is less invasive and can be very efficient in early intra-pelvic bleed control.

Intravenous Mannitol reduces intracompartmental pressure following tibia fractures: A randomized controlled trial.

PURPOSE: Impending compartment syndrome is a common event following closed tibia fractures, which can progress to sinister compartment syndrome. Fasciotomy is the only definitive treatment available, though it has its own drawbacks and complications. Medical management at present consists of limb elevation and adequate hydration. This study aims at determining whether intravenous administration of Mannitol reduced the intracompartmental pressure in patients with closed tibial fractures. METHODS: This is a double blinded, randomized control trial done in a single tertiary care center in India. Forty-five patients were recruited between February 2012 and October 2012. Forty patients who presented to the emergency department with isolated, closed, high velocity, and proximal 2/3 tibia fractures were included in this study. Patients with contraindication to Mannitol were excluded. They were allocated into 2 groups by the investigator using computer generated randomization. The pressure in the anterior compartment of the leg was measured with a handheld Stryker pressure monitor. Then either 20% Mannitol or 0.9% normal saline as given intravenously in a blinded manner, based on the randomization. The intracompartmental pressure was measured at 0, 1 and 3 h after the infusion. The participant, investigator and statistician were masked to the group assessment. RESULTS: There was no difference in intracompartmental pressures at 1 or 3 h, between the groups. However, in patients with the baseline of compartmental pressures ≥30 mmHg, Mannitol showed a marked reduction in pressure of 8.5 mmHg at 1 h compared to almost no change in pressure in the saline group. There were no adverse events with the use of Mannitol. CONCLUSIONS: This preliminary study appears to show that Mannitol is useful in the management of the increased compartment pressure. The limitations of this study were that it only involved a small group of patients and the baseline pressures in both the groups were not comparable. More studies are required before the use of Mannitol as a standard of care in the management of compartment syndrome can be established.