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Autologous bone grafts are considered the gold standard grafting material for the treatment of nonunion, but in very large bone defects, traditional autograft alone is insufficient to induce repair. Recombinant human bone morphogenetic protein 2 (rhBMP-2) can stimulate bone regeneration and enhance the healing efficacy of bone grafts. The delivery of rhBMP-2 may even enable engineered synthetic scaffolds to be used in place of autologous bone grafts for the treatment of critical size defects, eliminating risks associated with autologous tissue harvest. We here demonstrate that an osteoinductive scaffold, fabricated by combining a 3D printed rigid polymer/ceramic composite scaffold with an rhBMP-2-eluting collagen sponge can treat extremely large-scale segmental defects in a pilot feasibility study using a new sheep metatarsus fracture model stabilized with an intramedullary nail. Bone regeneration after 24 weeks was evaluated by micro-computed tomography, mechanical testing, and histological characterization. Load-bearing cortical bridging was achieved in all animals, with increased bone volume observed in sheep that received osteoinductive scaffolds compared to sheep that received an rhBMP-2-eluting collagen sponge alone.

Dynamization of fracture fixation constructs provides early rigidity for primary bone healing and late motion for secondary healing. A review of laboratory, animal, and clinical studies investigating the impact, and optimal timing, of dynamization is limited by lack of standardization across studies. However, in animal models, dynamization improves histologic and biomechanical properties compared with statically rigid or flexible controls. In animals, dynamization at 3 to 4 weeks showed improved histologic results. In clinical studies, it showed faster, stronger, and stiffer bone healing. Clinical success dynamizing external fixators and intramedullary nails suggests a role for late dynamization in other fixation types, such as bridge plating. [Orthopedics. 2020;43(3):e125-e133.]., (Copyright 2020, SLACK Incorporated.)

Fracture healing is a complex process of many coordinated biological pathways. This system can go awry resulting in nonunion, which leads to significant patient morbidity. The Hedgehog (Hh) signaling pathway is upregulated in fracture healing. We hypothesized that the Hh signaling pathway can be pharmacologically modulated to positively affect fracture healing. Diaphyseal femur fractures were created in elderly mice (18 months, C57BL/6 females), which have a blunted and delayed healing response compared to younger mice, and were stabilized with intramedullary pins. To activate the Hh pathway we targeted the receptor Smoothened using an agonist (Hh-Ag1.5 [Hh-Ag]) and compared this to a vehicle control. Expression of Hh target genes were significantly increased in the fracture callus of the agonist group compared to controls, indicating pathway activation. Expression of osteogenic and chondrogenic-related genes was greatly upregulated in fracture callus versus intact femora, although Hh agonist treatment did not consistently enhance this response. Blindly graded, radiographic callus healing scores were significantly higher in the Hh-Ag groups at post operative day (POD) 14, indicating earlier callus bridging. On microCT, Hh-Ag treatment led to greater callus volume (+40%) and bone volume (+25%) at POD21. By day 14, callus vascularity, as assessed by 3D microCT angiography vessel volume, was 85% greater in the Hh-Ag group. Finally, mechanical strength of the calluses in the Hh-Ag groups was significantly greater than in the control groups at POD21. In conclusion, systemic administration of a Hh agonist appears to improve the osseous and vascular healing responses in a mouse fracture healing-impaired model. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res., (© 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Fracture surgeons do a great job of managing bone issues, but they may overlook the associated soft tissue injuries that play a significant role in the final outcome after musculoskeletal injury. The soft tissue reconstruction ladder can help guide reconstructive procedures based on the least complex procedure that allows the best chance of fracture healing. Muscle injury, volume loss, and deconditioning occur with traumatic injury and during the recovery phase. Neuromuscular stimulation, nutrition, and strength training are potential ways to aid in recovery. Complex periarticular knee injuries have a high rate of associated soft tissue injuries that may affect outcome if associated with knee instability. Identifying and addressing these injuries can increase the likelihood of a good outcome. Articular cartilage loss can make articular reconstruction impossible. Large fresh osteoarticular allografts can be a reconstructive option. Addressing all the damaged structures involved with a fracture may be the next step in improving patient outcomes.

Fracture healing recapitulates many aspects of developmental osteogenesis. The hedgehog (Hh) signaling pathway, essential to skeletal development, is upregulated during fracture healing, although its importance is unclear. Our goal was to assess the functional importance of Hh signaling in endochondral fracture healing. We created closed, transverse diaphyseal femur fractures in mice, stabilized with an intramedullary pin, and administered a systemic Hh inhibitor or vehicle. Because Hh pathway activation is mediated by the receptor Smoothened (Smo), we used the Smo antagonist GDC-0449 (GDC, 50mg/kg, twice daily) to target the pathway. First, in vehicle-treated 10-wk. female C57BL/6 mice we confirmed that Hh signaling was increased in fracture callus compared to intact bone, with >5-fold upregulation of target genes Ptch1 and Gli1. Additionally, using 10-wk. male and female Gli1 reporter mice, we saw a strong activation of the reporter in the osseous regions of the fracture callus 7-10days after fracture. GDC treatment significantly blunted these responses, indicating effective inhibition of fracture-induced Hh signaling in bone. Moreover, microCT analysis revealed that GDC treatment significantly reduced cancellous and cortical bone volume at non-fracture sites (tibial metaphysis and diaphysis), suggesting that the drug inhibited normal bone formation. GDC treatment had a modest effect on fracture healing, with evidence of delayed callus mineralization radiographically (significantly lower Goldberg score at day 14) and by microCT (reduced callus vBMD at 14days), and a delay in the recovery of torsional rotation to normal (elevated rotation-at-peak torque at 21days). On the other hand, GDC treatment did not inhibit qPCR or morphological measures of chondrogenesis or angiogenesis, and did not impair the recovery of failure torque (at day 14 or 21), a measure of biomechanical competence. In summary, GDC treatment inhibited Hh signaling, which delayed but did not prevent fracture healing in young mice. We conclude that Hh signaling is strongly induced after fracture and may play a role in early callus mineralization, although it does not appear to be required for eventual healing., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Scleraxis (Scx) is a known regulator of tendon development, and recent work has identified the role of Scx in bone modeling. However, the role of Scx in fracture healing has not yet been explored. This study was conducted to identify the role of Scx in cortical bone development and fracture healing. Scx green fluorescent protein-labeled (ScxGFP) reporter and Scx-knockout (Scx-mutant) mice were used to assess bone morphometry and the effects of fracture healing on Scx localization and gene expression, as well as callus healing response. Botulinum toxin (BTX) was used to investigate muscle unloading effects on callus shape. Scx-mutant long bones had structural and mechanical defects. Scx gene expression was elevated and bmp4 was decreased at 24 h after fracture. ScxGFP + cells were localized throughout the healing callus after fracture. Scx-mutant mice demonstrated disrupted callus healing and asymmetry. Asymmetry of Scx-mutant callus was not due to muscle unloading. Wild-type littermates (age matched) served as controls. This is the first study to explore the role of Scx in cortical bone mechanics and fracture healing. Deletion of Scx during development led to altered long bone properties and callus healing. This study also demonstrated that Scx may play a role in the periosteal response during fracture healing.-McKenzie, J. A., Buettmann, E., Abraham, A. C., Gardner, M. J., Silva, M. J., Killian, M. L. Loss of scleraxis in mice leads to geometric and structural changes in cortical bone, as well as asymmetry in fracture healing., (© FASEB.)

Stress modulation is the concept of manipulating bridge plate variables to provide a flexible fixation construct that allows callus formation through uneventful secondary bone healing. Obtaining absolute stability through the anatomic reduction of all fracture fragments comes at the expense of fracture biology, whereas intramedullary nailing, which is more advantageous for diaphyseal fractures of the lower extremity, is technically demanding and often may not be possible when stabilizing many metaphyseal fractures. Overly stiff plating constructs are associated with asymmetric callus formation, early implant failure, and fracture nonunion. Numerous surgeon-controlled variables can be manipulated to increase flexibility without sacrificing strength, including using longer plates with well-spaced screws, choosing titanium or stainless steel implants, and using locking or nonlocking screws. Axially dynamic emerging concepts, such as far cortical locking and near cortical overdrilling, provide further treatment options when bridge plating techniques are used.

Post-natal osteogenesis after mechanical trauma or stimulus occurs through either endochondral healing, intramembranous healing or lamellar bone formation. Bone morphogenetic protein 2 (BMP2) is up-regulated in each of these osteogenic processes and is expressed by a variety of cells including osteoblasts and vascular cells. It is known that genetic knockout of Bmp2 in all cells or in osteo-chondroprogenitor cells completely abrogates endochondral healing after full fracture. However, the importance of BMP2 from differentiated osteoblasts and endothelial cells is not known. Moreover, the importance of BMP2 in non-endochondral bone formation such as intramembranous healing or lamellar bone formation is not known. Using inducible and tissue-specific Cre-lox mediated targeting of Bmp2 in adult (10-24 week old) mice, we assessed the role of BMP2 expression globally, by osteoblasts, and by vascular endothelial cells in endochondral healing, intramembranous healing and lamellar bone formation. These three osteogenic processes were modeled using full femur fracture, ulnar stress fracture, and ulnar non-damaging cyclic loading, respectively. Our results confirmed the requirement of BMP2 for endochondral fracture healing, as mice in which Bmp2 was knocked out in all cells prior to fracture failed to form a callus. Targeted deletion of Bmp2 in osteoblasts (osterix-expressing) or vascular endothelial cells (vascular endothelial cadherin-expressing) did not impact fracture healing in any way. Regarding non-endochondral bone formation, we found that BMP2 is largely dispensable for intramembranous bone formation after stress fracture and also not required for lamellar bone formation induced by mechanical loading. Taken together our results indicate that osteoblasts and endothelial cells are not a critical source of BMP2 in endochondral fracture healing, and that non-endochondral bone formation in the adult mouse is not as critically dependent on BMP2., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: The purpose of this study was to determine if surgeons could reliably predict if patients with tibia fractures treated with intramedullary nails will proceed to nonunion based on their clinical scenario and radiographs at 3 months., Design: Blinded randomized questionnaire based on a retrospective cohort., Setting: University level 1 trauma center., Patients/participants: Fifty-six patients who underwent intramedullary fixation for tibia fractures with incomplete healing at 3 months., Methods: A questionnaire was applied to 56 consecutive patients treated between 2005 and 2009 with intramedullary fixation for tibia fractures who had incomplete healing at 3 months. Each case was developed into a vignette that included the 3-month radiographs and detailed clinical histories. The questionnaire was distributed to 3 fellowship-trained trauma surgeons who were asked to predict if the fracture would go onto nonunion., Main Outcome Measurements: Diagnostic accuracy of predicting nonunion in patients with incomplete healing of their tibia fracture at 3 months., Results: The combined overall diagnostic accuracy of all 3 surgeons was 74%. Sensitivity and specificity was 62% and 77%, respectively. Radiographic features and injury mechanism were the most commonly cited clinical information used to predict fracture healing. The average positive predictive value was 73%. In 9 patients with diabetes, the diagnostic accuracy was 88%., Conclusions: Clinical judgment at 3 months allows for correct prediction of eventual nonunion development in a majority of patients. We suggest that analysis of the entire clinical picture be used to predict fracture healing at 3 months. A protocol of waiting for 6 months before reoperation in all patients treated with intramedullary nailing for tibia fractures may subject patients to prolonged disability and discomfort., Level of Evidence: Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Acute traumatic pelvic instability mandates reduction and mechanical stabilization to maximize the chance of a good functional outcome. Posterior pelvic fixation is frequently inadequate to stabilize the pelvic ring in isolation. Fixation augmentation with anterior pelvic ring implants can take several forms, including plates, medullary screws, or external fixation. Based on a multitude of patient and injury factors, external fixation may be the definitive anterior pelvic implant of choice. However, many drawbacks exist with this treatment, most notably the high infection rates of the transcutaneous pins, impaired patient mobilization, and suboptimal mechanical properties. We present a technique of a subcutaneous anterior pelvic fixator as an alternative method of anterior pelvic ring reduction and stabilization that avoids many of the drawbacks of traditional anterior pelvic external fixation.

Background: The mechanisms underlying the interaction between the local mechanical environment and fracture healing are not known. We developed a mouse femoral fracture model with implants of different stiffness, and hypothesized that differential fracture healing would result., Methods: Femoral shaft fractures were created in 70 mice, and were treated with an intramedullary nail made of either tungsten (Young's modulus = 410 GPa) or aluminium (Young's modulus = 70 GPa). Mice were then sacrificed at 2 or 5 weeks. Fracture calluses were analyzed using standard microCT, histological, and biomechanical methods., Results: At 2 weeks, callus volume was significantly greater in the aluminium group than in the tungsten group (61.2 vs. 40.5 mm(3), p = 0.016), yet bone volume within the calluses was no different between the groups (13.2 vs. 12.3 mm(3)). Calluses from the tungsten group were stiffer on mechanical testing (18.7 vs. 9.7 N/mm, p = 0.01). The percent cartilage in the callus was 31.6% in the aluminium group and 22.9% in the tungsten group (p = 0.40). At 5 weeks, there were no differences between any of the healed femora., Conclusions: In this study, fracture implants of different stiffness led to different fracture healing in this mouse fracture model. Fractures treated with a stiffer implant had more advanced healing at 2 weeks, but still healed by callus formation. Although this concept has been well documented previously, this particular model could be a valuable research tool to study the healing consequences of altered fixation stiffness, which may provide insight into the pathogenesis and ideal treatment of fractures and non-unions.

Objectives: A healed, yet shortened, femoral neck has historically been deemed a success in fracture treatment. This, however, comes at the price of diminished physical function and quality of life. We analyzed the outcomes of our treatment algorithm, which attempts to minimize postoperative shortening of femoral neck fractures and determined which preoperative factors were associated with femoral neck shortening and failure of surgical fixation., Level of Evidence: This is level IV retrospective study., Materials: Fifty-four patients underwent open reduction and internal fixation for acute femoral neck fracture with nonsliding constructs. The collapse of the femoral neck in the horizontal (X), vertical (Y), and along the resultant along the (Z) vector (X+Y=Z) was measured on anteroposterior radiographs corrected for leg rotation. The migration of the superior-most screw tip in all axes was measured. Age, gender, Garden grade, and Pauwel's angle were analyzed for their association with shortening or failure of surgical fixation., Results: The average age of the patients was 78.1 years. There were 23 Garden I, 2 Garden II, 14 Garden III, and 15 Garden IV fractures. Fifty-one (94%) healed successfully without complications. The minimum follow-up was 9 months (average, 17.6 months; range, 9-30 months). Surgical fixation failed in two patients, and one patient developed avascular necrosis. The average displacement of the femoral head and the screw tip was 1.23, 0.86, 1.98 mm and 0.7 mm, 0.9 mm, and 1.7 mm in the X, Y, and Z (resultant) vectors, respectively., Discussion: With careful consideration to reduction, we fixed femoral neck fractures with nonsliding constructs, resulting in a high union rate with very minimal shortening of the femoral neck.

Fracture repair is influenced by the mechanical environment, particularly when cyclic loads are applied across the fracture site. However, the specific mechanical loading parameters that accelerate fracture healing are unknown. Intact bone adaptation studies show enhanced bone formation with pauses inserted between loading cycles. We hypothesized pause-inserted noninvasive external loading to mouse tibial fractures would lead to accelerated healing. Eighty mice underwent tibial osteotomies with intramedullary stabilization and were divided into four loading protocol groups: (1) repetitive loading (100 cycles, 1 Hz); (2) pause/time-equivalent (10 cycles, 0.1 Hz); (3) pause/cycle-equivalent (100 cycles, 0.1 Hz); and (4) no load control. Loading was applied daily for 2 weeks. Healing was assessed using histology, biomechanical bending tests, and microcomputed tomography. The pause-inserted, cycle-equivalent group had a greater percentage of osteoid present in the callus cross-sectional area compared with no-load controls, indicating more advanced early healing. The pause-inserted, cycle-equivalent group had a failure moment and stiffness that were 37% and 31% higher than the controls, respectively. All three loaded groups had smaller overall mineralized callus volumes than the control group, also indicating more advanced healing. At an early stage of fracture healing, pause-inserted loading led to more histologically advanced healing.

The mechanical environment at a fracture site can influence the course of healing. Intermittent parathyroid hormone (PTH) has been shown to accelerate fracture healing. Intact bone models show that mechanical loading and PTH have a synergistic beneficial effect on osteogenesis. We hypothesized that PTH and mechanical loading would have a similar synergistic effect on fracture healing. Eighty mice underwent surgical osteotomy and intramedullary nailing of the tibia. The mice were divided into four groups: one underwent daily loading, one received daily subcutaneous PTH injections (30 microg/kg/day), one received both loading and PTH, and a control group received sham loading and vehicle injection. Daily loading was applied to the ends of the tibia with an external loading device for 2 weeks. Fracture healing was assessed by microcomputed tomography, histology, and biomechanical testing. The group with both loading and PTH had increased osteoblast and osteoclast activity and was the only group with a significantly larger callus mineral density and bone volume fraction. The PTH only group had significantly more osteoid in the callus compared to the control group, indicating enhanced early osteoblast activity. This group also had a significantly higher bone mineral content and total bone volume compared to controls. The group that received loading as the only intervention had significantly greater osteoclast activity versus controls. The contribution of loading and PTH administration to the fracture healing cascade indicates a synergistic effect. This finding may be of potential clinical utility when weight bearing is utilized to stimulate lower extremity fracture healing., ((c) 2007 Orthopaedic Research Society.)

Objectives: The purpose of this study was to determine what factors influence the maintenance of fracture reduction after locked plating of proximal humerus fractures, and particularly the role of medial column support., Setting: University medical center., Intervention: Thirty-five patients who underwent locked plating for a proximal humerus fracture were followed up until healing. For the initial and final radiographs, 2 lines were drawn perpendicular to the shaft of the plate, one at the top of the plate and one at the top of the humeral head, and the distance between them was measured as an indicator of loss of reduction. Medial support was considered to be present if the medial cortex was anatomically reduced, if the proximal fragment was impacted laterally in the distal shaft fragment, or if an oblique locking screw was positioned inferomedially in the proximal humeral head fragment., Main Outcome Measurements: Multivariate linear regressions were performed to determine the effects that age, sex, fracture type, cement augmentation, and medial support had on loss of reduction., Results: The presence of medial support had a significant effect on the magnitude of subsequent reduction loss (P < 0.001). Age, sex, fracture type, or cement augmentation had no effect on maintenance of reduction. Eighteen patients were determined to have adequate mechanical medial support (+MS group), and the remaining 17 patients did not have medial support (-MS group). In the +MS group, the average loss of humeral head height was 1.2 mm, and 1 case of articular screw penetration occurred that required removal. In the -MS group (without an appropriately placed inferomedial oblique screw and either nonanatomic humeral head malreduction with lateral displacement of the shaft or medial comminution), loss of humeral height averaged 5.8 mm (P < 0.001). There were 5 cases in this group in which screw penetration of the articular surface occurred (P = 0.02), 2 of which required reoperation for removal. All fractures in both groups healed without delay, and none required revision to arthroplasty., Conclusions: Achieving mechanical support of the inferomedial region of the proximal humerus seems to be important for maintaining fracture reduction. Locked plates in general do not appear to be a panacea for these fractures and are unable to support the humeral head alone from a lateral tension-band position. However, there are several factors that are in the surgeon's control that may improve the mechanical environment. Achieving an anatomic or slightly impacted stable reduction, as well as meticulously placing a superiorly directed oblique locked screw in the inferomedial region of the proximal fragment, may achieve more stable medial column support and allow for better maintenance of reduction.

Abundant evidence exists that fracture healing can be influenced by mechanical loading. However, the specific loading parameters that are osteogenic remain unknown. We hypothesized that the bone healing response in mouse tibial osteotomies would be different with a short delay before loading compared to immediate load application, as well as with higher and lower load magnitudes applied. Eighty 12-week-old mice underwent osteotomy of the left tibia followed by intramedullary nailing. Mice were divided into six groups based on days delayed until application of load (0 days or 4 days) and amplitude of cyclic load (0.5N, 1N, or 2N). Loading regimens were applied at 1 Hz for 100 cycles per day, 5 days per week for 2 weeks, using an external device that applied axial compression to the tibia. Bone healing was assessed by both microcomputed tomography (CT) and four-point bend testing. A short delay followed by cyclic application of a relatively low load led to improved fracture healing, as determined by increased callus strength, but this enhancement disappeared as load amplitudes increased. Load initiation immediately following fracture inhibited healing, regardless of the magnitude of load applied. MicroCT measurements of calluses in the early healing stage did not predict the mechanical strength of the fractures. These findings confirm that controlled, noninvasive cyclic loading can improve the strength of healing callus. However, application of load immediately after fracture appears to be detrimental to healing. Load magnitude also plays a critical role, and must be taken into account in future studies and clinical applications. As the loading parameters necessary to enhance fracture healing become refined, external compression may be used as a potent stimulus for treating fractures with decreased biological capacity.

Fracture healing is highly dependent on an early inflammatory response in which prostaglandin production by cyclo-oxygenases (COX) plays a crucial role. Current patient analgesia regimens favor opioids over Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) since the latter have been implicated in delayed fracture healing. While animal studies broadly support a deleterious role of NSAID treatment to bone-regenerative processes, data for human fracture healing remains contradictory. In this study, we prospectively isolated mouse and human skeletal stem cells (SSCs) from fractures and compared the effect of various NSAIDs on their function. We found that osteochondrogenic differentiation of COX2-expressing mouse SSCs was impaired by NSAID treatment. In contrast, human SSCs (hSSC) downregulated COX2 expression during differentiation and showed impaired osteogenic capacity if COX2 was lentivirally overexpressed. Accordingly, short- and long-term treatment of hSSCs with non-selective and selective COX2 inhibitors did not affect colony forming ability, chondrogenic, and osteogenic differentiation potential in vitro. When hSSCs were transplanted ectopically into NSG mice treated with Indomethacin, graft mineralization was unaltered compared to vehicle injected mice. Thus, our results might contribute to understanding species-specific differences in NSAID sensitivity during fracture healing and support emerging clinical data which conflicts with other earlier observations that NSAID administration for post-operative analgesia for treatment of bone fractures are unsafe for patients.

Delayed union or nonunion are relatively rare complications after fracture surgery, but when they do occur, they can result in substantial morbidity for the patient. In many cases, the etiology of impaired fracture healing is uncertain and attempts to determine the molecular basis for delayed union and nonunion formation have been limited. Prospectively isolating skeletal stem cells (SSCs) from fracture tissue samples at the time of surgical intervention represent a feasible methodology to determine a patient's biologic risk for compromised fracture healing. This report details a case in which functional in vitro readouts of SSCs derived from human fracture tissue at time of injury predicted a poor fracture healing outcome. This case suggests that it may be feasible to stratify a patient's fracture healing capacity and predict compromised fracture healing by prospectively isolating and analyzing SSCs during the index fracture surgery. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Fracture healing is highly dependent on an early inflammatory response in which prostaglandin production by cyclo-oxygenases (COX) plays a crucial role. Current patient analgesia regimens favor opioids over Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) since the latter have been implicated in delayed fracture healing. While animal studies broadly support a deleterious role of NSAID treatment to bone-regenerative processes, data for human fracture healing remains contradictory. In this study, we prospectively isolated mouse and human skeletal stem cells (SSCs) from fractures and compared the effect of various NSAIDs on their function. We found that osteochondrogenic differentiation of COX2-expressing mouse SSCs was impaired by NSAID treatment. In contrast, human SSCs (hSSC) downregulated COX2 expression during differentiation and showed impaired osteogenic capacity if COX2 was lentivirally overexpressed. Accordingly, short- and long-term treatment of hSSCs with non-selective and selective COX2 inhibitors did not affect colony forming ability, chondrogenic, and osteogenic differentiation potential in vitro. When hSSCs were transplanted ectopically into NSG mice treated with Indomethacin, graft mineralization was unaltered compared to vehicle injected mice. Thus, our results might contribute to understanding species-specific differences in NSAID sensitivity during fracture healing and support emerging clinical data which conflicts with other earlier observations that NSAID administration for post-operative analgesia for treatment of bone fractures are unsafe for patients. [ABSTRACT FROM AUTHOR]

Purpose: The primary aim of this study was to compare clinical outcomes in patients with associated both column (ABC) acetabular fractures with fracture of the posterior wall (PW), in which the PW underwent reduction and fragment-specific fixation versus those that were treated with column fixation alone. Secondary aims were to assess PW fracture incidence and morphology, as well as to compare radiographic outcomes including fracture healing and interval displacement of the PW in those that did and did not undergo fragment-specific fixation of the PW. Methods: This was a retrospective series of ABC acetabular fractures treated at a single Level I trauma center. Separate fractures of the PW were identified, and associated features were assessed. Associated both column fractures that underwent reduction and fragment-specific fixation of the PW where then compared to ABC fractures with PW involvement that underwent column reconstruction alone. Radiographic and clinical outcomes were compared. Results: Fractures of the PW occurred in 55.7% of ABC fractures and were associated with central displacement of the femoral head. The majority of PW fractures were large and involved the acetabular roof. All PW fractures healed without displacement by 3 months, regardless of whether or not reduction and stabilization was performed. Mid-term outcomes at 1-year were similar regardless of whether or not the PW was reduced and stabilized, with regards to Tönnis grade, Merle d'Aubigné-Postel score, and conversion to total hip arthroplasty. Conclusion: Reduction and fragment-specific fixation of the PW component of ABC acetabular fractures did not improve outcomes in this small comparative study. Posterior wall fractures associated with ABC patterns are frequently large-sized fragments that involve the acetabular roof and are rendered stable after reconstruction of the columns. [ABSTRACT FROM AUTHOR]

Purpose: This study examined the outcomes and complications after treatment of unstable distal clavicle fractures with hook or locking plate fixation. Methods: A retrospective search was performed of all acute distal clavicle fractures treated with open reduction and internal fixation from 2009 to 2019 at a Level I trauma center. Patients were separated into hook and locking plate fixation groups. Rates of union, complications, and reoperation, were extracted. QuickDASH (Disabilities of Arm, Shoulder, and Hand) scores were determined. Results: Thirty-one patients met the inclusion criteria and were included in the study. Of these, 12 patients were treated with hook plates and 19 were treated with locking plates. All fractures healed without loss of reduction, regardless of implant selection. There were no immediate or long-term complications in either group. 83% of hook plate patients underwent planned implant removal, while 37% of locking plate patients requested implant removal secondary to irritation. QuickDASH scores were comparable and excellent in both groups. Conclusions: Hook and locking plate fixation for Neer type-II and type-V distal clavicle fractures have comparably high rates of union. Hook plates were removed routinely per protocol, while locking plates were removed only if symptomatic and occurred significantly less often. [ABSTRACT FROM AUTHOR]

Case: A 57-year-old male carpenter sustained a 2-part displaced proximal humerus fracture of his nondominant arm with varus angulation after a fall down the stairs. Fifteen days postinjury, the patient underwent direct reduction and surgical fixation with an intramedullary cage implant via a deltoid split approach. Nine days postsurgery, the patient presented to the emergency department after another fall with failed fixation. Two weeks after index surgery, he was revised to a reverse total shoulder arthroplasty via a deltopectoral approach and healed both incisions uneventfully. Conclusion: A deltopectoral approach performed acutely after a deltoid split approach for fracture can heal uneventfully. [ABSTRACT FROM AUTHOR]

Fragility fractures have a limited capacity to regenerate, and impaired fracture healing is a leading cause of morbidity in the elderly. The recent identification of a highly purified bona fide human skeletal stem cell (hSSC) and its committed downstream progenitor cell populations provides an opportunity for understanding the mechanism of age‐related compromised fracture healing from the stem cell perspective. In this study, we tested whether hSSCs isolated from geriatric fractures demonstrate intrinsic functional defects that drive impaired healing. Using flow cytometry, we analyzed and isolated hSSCs from callus tissue of five different skeletal sites (n = 61) of patients ranging from 13 to 94 years of age for functional and molecular studies. We observed that fracture‐activated amplification of hSSC populations was comparable at all ages. However, functional analysis of isolated stem cells revealed that advanced age significantly correlated with reduced osteochondrogenic potential but was not associated with decreased in vitro clonogenicity. hSSCs derived from women displayed an exacerbated functional decline with age relative to those of aged men. Transcriptomic comparisons revealed downregulation of skeletogenic pathways such as WNT and upregulation of senescence‐related pathways in young versus older hSSCs. Strikingly, loss of Sirtuin1 expression played a major role in hSSC dysfunction but re‐activation by trans‐resveratrol or a small molecule compound restored in vitro differentiation potential. These are the first findings that characterize age‐related defects in purified hSSCs from geriatric fractures. Our results provide a foundation for future investigations into the mechanism and reversibility of skeletal stem cell aging in humans. [ABSTRACT FROM AUTHOR]

Purpose: Precontoured plates used to stabilize lateral tibial plateau (LTP) fractures are limited in their ability to raft particular areas of the reconstructed articular surface. These implants also do not fit every individual's bony anatomy and can lead to soft tissue irritation. The purpose of this study was to evaluate fragment specific plate fixation of LTP fractures using generic small and mini fragment constructs.Methods: This was a retrospective case series of LTP fractures treated with small fragment tubular and/or mini fragment plate constructs at a single Level I trauma center. Postoperative complications were recorded. Final radiographs were analyzed to determine union and interval subsidence of the articular surface and/or loss of reduction.Results: All 19 LTP fractures healed without loss of reduction or implant failure. There was minimal interval subsidence of the LTP in all patients. There were no complications or reoperations for symptomatic implant removal within the given follow-up period.Conclusion: Fragment specific fixation of LTP fractures using small and mini fragment plates creates a lower profile construct that reliably maintains fracture reduction to union. [ABSTRACT FROM AUTHOR]

Objectives: 1) To determine the effect of single versus dual plate metaphyseal fixation for pilon fractures on callus formation and reoperation rates, 2) to determine the effect of biomechanically matched versus unmatched fixation, and 3) to determine whether patient or surgical factors were independent predictors of bridging callus formation or need for reoperation.Design: Retrospective comparative study.Setting: Single level one trauma center.Patients: Fifty patients with AO/OTA type C2 or C3 pilon fractures treated with plate fixation.Intervention: Internal fixation with a plate and screw construct, with comparisons made between patients with single versus dual plate fixation, and patients treated with biomechanically matched or unmatched fixation.Main Outcome Measurements: Modified RUST (mRUST) scores at three and six months and reoperation rate.Results: At six months, mean mRUST scores were significantly lower in patients treated with dual metaphyseal plates compared to a single plate (8.7 vs 10.4, p=0.046) There were 15 open fractures; eight were treated with supplemental fixation, while seven were treated with single-column fixation. Open fracture (OR 51.05, p=0.008) was a risk factor for reoperation. Screw density between 0.4 and 0.5 was a protective factor against reoperation (OR 0.03, p=0.026). Biomechanically unmatched fixation did not affect mRUST scores or reoperation rates.Conclusions: Pilon fractures treated with a single plate had more callus formation six months after surgery compared to those treated with dual plate fixation, and there was no difference in reoperation rates. Screw density between 0.4-0.5 was protective against reoperation. These data may serve as the basis of future work to determine the ideal fixation construct for the frequently comminuted metaphysis in pilon fractures. Further work is necessary to determine whether callus formation in these injuries is desirable.Level Of Evidence: Three. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate the safety and efficacy of using lower profile 2.4/2.4 mm and 2.0/2.4 mm dual mini-fragment plate constructs for fixation of diaphyseal clavicle fractures.Methods: This was a retrospective case series of all displaced diaphyseal clavicle fractures treated with 2.4/2.4 and 2.0/2.4 dual mini-fragment plate constructs at a single level-one trauma center. Postoperative complications and fracture healing rates were recorded. A subset of patients with long-term follow up was used to determine the rate of reoperation for symptomatic implant removal.Results: All 36 identified fractures healed without loss of reduction or implant failure. There was one superficial infection and no deep infections or cases of wound dehiscence. Twenty patients from the entire cohort had longer-term follow up available to assess the reoperation rate for symptomatic implant removal. Two patients (10%) underwent symptomatic implant removal, and one patient with retained implants was planning on future removal due to soft-tissue irritation; this combined to a projected reoperation rate of 15% for symptomatic implant removal.Conclusion: Dual mini-fragment plating of diaphyseal clavicle fractures, using 2.4/2.4 mm and 2.0/2.4 mm plate combinations, creates a lower profile construct that reliably maintains fracture reduction to healing, and has a low rate of reoperation for symptomatic implant removal. [ABSTRACT FROM AUTHOR]

Background The purpose of this study was to design and validate a novel stiffness-measuring device using locked plating of distal femur fractures as a model. Methods All patients underwent a laterally-based approach, with a bridging locked construct after indirect reduction. A custom and calibrated intraoperative stiffness device was applied and the stiffness of the construct was blindly recorded. Fourteen of twenty-seven patients enrolled with distal femur fractures (AO/OTA 33A and 33C) completed the study. Correlations between stiffness and callus formation, working length, working length/plate length ratio, number of distal locking screws, and fracture pattern were explored. Findings Callus and modified radiographic union scale in tibias scores as a linear function of stiffness did not correlate (R2 = 0.06 and 0.07, respectively). Construct working length and working length to plate length ratio did not correlate to stiffness (R2 = 0.18 and 0.16 respectively). A combined delayed and nonunion rate was 14%. Lower extremity measure scores were not statistically different when comparing delayed and nonunion with healed fractures. Interpretation The lack of correlation may have been due to the mechanical properties of the plate itself and its large contribution to the overall stiffness of the construct. To our knowledge, clinically relevant stiffness has not been described and this study may provide some estimates. This methodology and these preliminary findings may lay the groundwork for further investigations into this prevalent clinical problem. Other parameters not investigated may play a key role such as body mass index and bone mineral density. Level of evidence Diagnostic/Prognostic Level II. [ABSTRACT FROM AUTHOR]

Type 1 diabetes (T1DM) impairs bone formation and fracture healing in humans. Akita mice carry a mutation in one allele of the insulin-2 (Ins2) gene, which leads to pancreatic beta cell dysfunction and hyperglycemia by 5–6 weeks age. We hypothesized that T1DM in Akita mice is associated with decreased bone mass, weaker bones, and impaired fracture healing. Ins2 ± (Akita) and wildtype (WT) males were subjected to femur fracture at 18-weeks age and healing assessed 3–21 days post-fracture. Non-fractured left femurs were assessed for morphology (microCT) and strength (bending or torsion) at 19–21 weeks age. Fractured right femurs were assessed for callus mechanics (torsion), morphology and composition (microCT and histology) and gene expression (qPCR). Both Akita and WT mice gained weight from 3 to 18 weeks age, but Akita mice weighed less starting at 5 weeks (−5.2%, p < 0.05). At 18–20 weeks age Akita mice had reduced serum osteocalcin (−30%), cortical bone area (−16%), and thickness (−17%) compared to WT, as well as reduced cancellous BV/TV (−39%), trabecular thickness (−23%) and vBMD (−31%). Mechanical testing of non-fractured femurs showed decreased structural (stiffness, ultimate load) and material (ultimate stress) properties of Akita bones. At 14 and 21 days post fracture Akita mice had a significantly smaller callus than WT mice (~30%), with less cartilage and bone area. Assessment of torsional strength showed a weaker callus in Akita mice with lower stiffness (−42%), maximum torque (−44%) and work to fracture (−44%). In summary, cortical and cancellous bone mass were reduced in Akita mice, with lower bone mechanical properties. Fracture healing in Akita mice was impaired by T1DM, with a smaller, weaker fracture callus due to decreased cartilage and bone formation. In conclusion, the Akita mouse mimics some of the skeletal features of T1DM in humans, including osteopenia and impaired fracture healing, and may be useful to test interventions. • Bone structure and fracture healing in diabetic, male Akita mice at 18–21 weeks • Akita mice have low cortical and cancellous bone mass with low serum osteocalcin. • Fracture healing is impaired with smaller callus and reduced mechanical properties. • Akita mice are a useful model to study skeletal complications associated with T1DM. [ABSTRACT FROM AUTHOR]