Faculty Bibliography

Fractures of the talus are challenging to manage, with historically poor outcomes and a high rate of complications. The rare nature of this injury limits the number of studies available to guide treatment. Fortunately, a number of advancements have been made in the last decade. There is increased recognition regarding the importance of anatomic reconstruction of the osseous injury. Advanced imaging is used to assess the subtalar joint, where even slight displacement may predispose to arthritis. Increasing use of dual anteromedial and anterolateral approaches, along with plate fixation, has improved our ability to accurately restore the anatomy of the talus. Modification of the original Hawkins classification can both guide treatment and allow us to better predict which patients will develop avascular necrosis. Lastly, improved reconstructive techniques help address the most common complications after talus fracture, including arthritis, avascular necrosis, and malunion.

Mechanical loading is an important aspect of post-surgical fracture care. The timing of load application relative to the injury event may differentially regulate repair depending on the stage of healing. Here, we used a novel mechanobiological model of cortical defect repair that offers several advantages including its technical simplicity and spatially confined repair program, making effects of both physical and biological interventions more easily assessed. Using this model, we showed that daily loading (5N peak load, 2Hz, 60 cycles, 4 consecutive days) during hematoma consolidation and inflammation disrupted the injury site and activated cartilage formation on the periosteal surface adjacent to the defect. We also showed that daily loading during the matrix deposition phase enhanced both bone and cartilage formation at the defect site, while loading during the remodeling phase resulted in an enlarged woven bone regenerate. All loading regimens resulted in abundant cellular proliferation throughout the regenerate and fibrous tissue formation directly above the defect demonstrating that all phases of cortical defect healing are sensitive to physical stimulation. Stress was concentrated at the edges of the defect during exogenous loading, and finite element (FE)-modeled longitudinal strain (εzz) values along the anterior and posterior borders of the defect (~2200με) was an order of magnitude larger than strain values on the proximal and distal borders (~50-100με). It is concluded that loading during the early stages of repair may impede stabilization of the injury site important for early bone matrix deposition, whereas loading while matrix deposition and remodeling are ongoing may enhance stabilization through the formation of additional cartilage and bone.

The adult periosteum serves as a niche for skeletal stem cells, and its contribution to fracture healing and bone regeneration is well documented (Colnot 2009). All bones in the skeleton possess regenerative features and share a similar histological architecture, however, their embryonic origins are diverse: the appendicular skeleton develops from the mesoderm, while the craniofacial bones, except the parietal bones, are derived from the neural crest. With notable exceptions, the embryonic origin determines their differential expression of Hox genes, transcriptional factors that vary along the cranial-caudal axis to regulate the anterior-posterior positional patterning during development (Mallo et al. 2010). Previous studies have identified a superior regenerative potential of craniofacial osteoprogenitor cells (OPCs) to appendicular OPCs (Leucht et al. 2008). Here, we employed RNAseq analysis to interrogate OPCs from four distinct anatomic locations (Fig. 1A). We hypothesized that embryonic Hox gene expression is maintained into adulthood, provides a transcriptional signature that best differentiates between craniofacial and appendicular OPCs, and that Hox gene expression regulates adult OPC fate decisions. Hierarchical cluster analysis (Fig.1B.1), PCA (Fig.1B.2) and MA plot analysis (Fig.1B.3,4) revealed that OPCs negative for Hox gene expression contain 5390 differentially expressed genes compared to Hox-positive OPCs, showing for the first time that on a transcriptional level, OPCs from the craniofacial skeleton and the appendicular skeleton present two distinct cell populations. While the embryonic function of Hox genes is well characterized (Mallo et al. 2010), their role in adult cells is not clearly defined yet. Here, we used siRNA and antisense oligonucleotide (ASOs) to knockdown epigenetic regulators of Hox expression in adult periosteal OPCs in vitro and then assessed their differentiation potential. Hox knockdown in Hox-expressing tibial OPCs resulted in a more osteogenic and less adipogenic cell fate, demonstrating that Hox gene expression is crucial for adult OPC cell fate decisions (Fig 1C). This study provides evidence that embryonic Hox gene expression is maintained into adulthood, where one of its functions is to regulate OPC cell fate decisions. Epigenetic manipulation can be utilized to target and manipulate Hox gene expression, which may provide potential therapeutic opportunities with the goal to improve fracture healing. (Figure Presented)

INTRODUCTION: The operative management of tibial plateau fractures is challenging and post-operative complications do occur. The purpose of this study was three-fold. 1). To report complications and unplanned outcomes in patients who had sustained tibial plateau fractures and were operatively managed 2). To report predictors of these post-operative events 3). To report if differences in clinical outcomes exist in patients who sustained a post-operative event. METHODS: Over 11 years, all tibial plateau fractures were prospectively followed. Clinical outcomes were assessed using the validated Short Musculoskeletal Functional Assessment (SMFA) score. Demographics, initial injury characteristics, surgical details and post-operative events were prospectively recorded. Student's t-tests were used for continuous variables and chi-squared analysis was used for categorical variables. Binary logistic regression and multivariate linear regression were conducted for independent predictors of post-operative events and complications and functional outcomes, respectively. RESULTS: 275 patients with 279 tibial plateau fractures were included in our analysis. Ten patients (3.6%) sustained a deep infection. Six patients (2.2%) developed a superficial infection. One patient (0.4%) presented with early implant failure. Two patients (0.7%) developed a fracture nonunion. Eight patients (2.9%) developed a venous thromboembolism. Seventeen patients (6.2%) went on to re-operation for symptomatic implant removal. Nine patients (3.3%) underwent a lysis of adhesions procedure. Univariate analysis demonstrated bicondylar tibial plateau fractures (P<0.001), Moore fracture-dislocations (P=0.005), open fractures (P=0.022), and compartment syndrome (P=0.001) to be associated with post-operative complications and unplanned outcomes. Long-term functional outcomes were worse among patients who developed a post-operative complication or unplanned outcome (P=0.031). CONCLUSION: Orthopaedic trauma surgeons should be aware of complications and unplanned outcomes following operatively managed tibial plateau fractures, along with having the knowledge of factors that are associated with development of post-operative events.

PURPOSE: Whether racial differences are associated with function in the long term following surgical repair of lower extremity fractures has not been investigated. The purpose of this study is to compare how race affects function at 3, 6 and 12 months post-surgery following certain lower extremity fractures. METHODS: Four hundred and eighteen patients treated operatively for a lower extremity fracture (199 tibial plateau, 39 tibial shaft, and 180 rotational ankle fractures) were prospectively followed for 1 year. Race was stratified into four groups: Caucasian, African-American, Hispanic origin, and other. Long-term outcomes were evaluated using the short musculoskeletal function assessment (SMFA) and pain scores were assessed at 3, 6 months and 1 year. RESULTS: There were 223 (53.3%) Caucasians, 72 (17.2%) African-Americans, 53 (12.4%) Hispanics, and 71 (17.0%) patients from other ethnic groups, included in our study population. Minority patients (African-American, Hispanics, etc.) were more likely to be involved in high velocity mechanisms of injury and tended to have a greater percentage of open fractures. Although there were no differences in the rate of wound complications or reoperations, long-term functional outcomes were worse in minority patients as assessed by pain scores at 6 months and functional outcome scores at 3, 6 and 12 months. Multivariate analysis revealed that only African-American and Hispanic race continued to be independent predictors of worse functional outcomes at 12 months. CONCLUSIONS: Racial minorities and those on medicaid had poorer long-term function following fractures of the lower extremity. While minority patients were involved in more high velocity accidents, this was not an independent predictor of worse outcomes. These disparities may result from multifactorial socioeconomic factors, including socioeconomic status and education levels that were not controlled in our study. LEVEL OF EVIDENCE: Prognostic Level III.

Ecto-5'-nucleotidase (CD73) generates adenosine, an osteoblast activator and key regulator of skeletal growth. It is unknown, however, if CD73 regulates osteogenic differentiation during fracture healing in adulthood, and in particular how CD73 activity regulates intramembranous bone repair in the elderly. Monocortical tibial defects were created in 46-52-week-old wild type (WT) and CD73 knock-out mice (CD73-/-) mice. Injury repair was analyzed at post-operative days 5, 7, 14 and 21 by micro-computed tomography (micro-CT), histomorphometry, proliferating cell nuclear antigen (PCNA) immunostaining, alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) histochemistry. Middle-aged CD73 knock-out mice exhibited delayed bone regeneration and significantly reduced bone matrix deposition detected by histomorphometry and micro-CT. Cell proliferation, ALP activity and osteoclast number were reduced in the CD73-/- mice, suggesting a combined defect in bone formation and resorption due the absence of CD73 activity in this model of intramembranous bone repair. Results from this study demonstrate that osteoblast activation through CD73 activity is essential during bone repair in aging mice, and it may present a drugable target for future biomimetic therapeutic approaches that aim at enhancing bone formation in the elderly patients.

PURPOSE: Fracture nonunion is a common problem for today's orthopaedic surgeon. However, many techniques are currently available for the treatment of long-bone nonunion. This video demonstrates the use of iliac crest bone graft and plate stabilization in the setting of a hypertrophic femoral nonunion. METHODS: Treatment of femoral nonunion after intramedullary nail fixation using compression plating and bone grafting is a reliable technique for reducing pain, improving function, and achieving radiographic union. Furthermore, the use of autologous bone graft, in particular iliac crest bone graft, has provided reliable clinical results. RESULTS: In this video, we present the case of a hypertrophic femoral nonunion treated with supplemental bone grafting in addition to plate and screw fixation. CONCLUSIONS: Although femoral nonunions are a relatively rare occurrence, they can be reasonably treated using stabilization and supplemental bone grafting. Iliac crest bone graft provides for excellent results when used for treatment of a fracture nonunion.

BACKGROUND: The number of hip fractures is rising as life expectancy increases. As such, the number of centenarians sustaining these fractures is also increasing. The purpose of this study was to determine whether patients who are >/=100 years old and sustain a hip fracture fare worse in the hospital than those who are younger. METHODS: Using a large database, the New York Statewide Planning and Research Cooperative System (SPARCS), we identified patients who were >/=65 years old and had been treated for a hip fracture over a 12-year period. Data on demographics, comorbidities, and treatment were collected. Three cohorts were established: patients who were 65 to 80 years old, 81 to 99 years old, and >/=100 years old (centenarians). Outcome measures included hospital length of stay, estimated total costs, and in-hospital mortality rates. RESULTS: A total of 168,087 patients with a hip fracture were identified, and 1,150 (0.7%) of them had sustained the fracture when they were >/=100 years old. Centenarians incurred costs and had lengths of stay that were similar to those of younger patients. Despite the similarities, centenarians were found to have a significantly higher in-hospital mortality rate than the younger populations (7.4% compared with 4.4% for those 81 to 99 years old and 2.6% for those 65 to 80 years old; p < 0.01). Male sex and an increasing number of medical comorbidities were found to predict in-hospital mortality for centenarians sustaining extracapsular hip fractures. No significant predictors of in-hospital mortality were identified for centenarians who sustained femoral neck fractures. An increased time to surgery did not influence the odds of in-hospital mortality. CONCLUSIONS: Centenarians had increased in-hospital mortality, but the remaining short-term outcomes were comparable with those for the younger cohorts with similar fracture patterns. For this extremely elderly population, time to surgery does not appear to affect short-term mortality rates, suggesting a potential benefit to preoperative optimization. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.