Faculty Bibliography

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: 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.

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: 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.

OBJECTIVES: To identify the association between social and moderate alcohol consumption and functional outcomes after surgical management of orthopaedic fractures. DESIGN: Prospective cohort study. SETTING: Level 1 trauma center. PATIENTS/PARTICIPANTS: Seven hundred eighty-four patients who were operatively treated for an isolated orthopaedic fracture were prospectively followed. Patients were categorized into groups according to self-reported drinking frequencies based on NIAAA guidelines. MAIN OUTCOME MEASUREMENTS: SMFA scores at baseline, 3, 6, and 12 months postoperatively; postoperative complications; and subsequent operations. RESULTS: There were 367 (46.8%) abstinent, 327 (41.7%) social, 52 (6.6%) moderate, and 38 (4.8%) heavy drinkers. Mean SMFA scores of social and moderate drinkers were significantly lower than those of abstinent patients at 3-, 6-, and 12-month follow-ups, denoting better functional outcomes (social: 24.3 vs. 30.5, P = 0.001; 14.8 vs. 21.5, P < 0.005; and 10.1 vs. 18.8, P < 0.005); (moderate: 18.3 vs. 30.5, P = 0.001; 9.7 vs. 21.5, P = 0.001; and 5.4 vs. 18.8, P < 0.005). Multiple linear regression revealed that social drinking and baseline SMFA scores were the only statistically significant independent predictors of lower SMFA scores at 12 months after surgery. CONCLUSIONS: Social to moderate drinking may have a protective effect on functional outcomes at 3, 6, and 12 months after surgery. Social drinking may also have a protective effect on postoperative complications and reoperation rates. Further studies should be performed to fully appreciate the clinical effect of social and moderate drinking after operative treatment of orthopaedic fractures. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

OBJECTIVE: The purpose of this study was to determine whether the finding of failed fracture implants in association with lower extremity long bone fracture nonunion portends worse clinical or functional outcome following surgical nonunion repair. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Academic Medical Center. PATIENTS: One hundred eighty-one patients who presented to our institution over a 10-year period and underwent surgical repair of a lower extremity fracture nonunion. INTERVENTION: Surgical repair of lower extremity fracture nonunion. MAIN OUTCOME MEASUREMENTS: Time to union, postoperative complications, VAS pain scores, and Short Musculoskeletal Function Assessment (SMFA) scores following lower extremity nonunion repair. Data was analyzed to assess for differences in postoperative outcomes based on the integrity of fracture implants at the time of nonunion diagnosis. Implant integrity was defined using 3 groups: broken implants (BI), implants intact (II), and no implants (NI). RESULTS: There was no significant difference in time to union following surgery between the BI, II, or NI groups (mean 8.1 months vs 7.6 months vs 6.2 months, respectively). Fourteen patients (7.7%) failed to heal, including 5 BI patients, 7 II patients, and 2 NI patients. One tibial nonunion patient in each of the 3 groups underwent amputation for persistent nonunion following multiple failed revision attempts at a mean of 4.8 years after initial injury. There was no difference in postoperative pain scores, the rate of postoperative complications, or functional outcome scores identified between the 3 groups. CONCLUSION: The finding of failed fracture implants at the time of lower extremity long bone nonunion diagnosis does not portend worse clinical or functional outcome following surgical nonunion repair. Patients who present with failed fracture implants at the time of nonunion diagnosis can anticipate similar time to union, complication rates, and functional outcomes when compared to patients who present with intact implants or those with history of nonoperative management. LEVEL OF EVIDENCE: Prognostic Level IV.

Chronic use of selective serotonin re-uptake inhibitors (SSRI) for the treatment of depression has been linked to osteoporosis. In this study, we investigated the effect of chronic SSRI use on fracture healing in two murine models of bone regeneration. First, we performed a comprehensive analysis of endochondral bone healing in a femur fracture model. C57/BL6 mice treated with fluoxetine, the most commonly prescribed SSRI, developed a normal cartilaginous soft-callus at 14 days after fracture and demonstrated a significantly smaller and biomechanically weaker bony hard-callus at 28 days. In order to further dissect the mechanism that resulted in a smaller bony regenerate, we used an intramembranous model of bone healing and revealed that fluoxetine treatment resulted in a significantly smaller bony callus at 7 and 14 days post-injury. In order to test whether the smaller bony regenerate following fluoxetine treatment was caused by an inhibition of osteogenic differentiation and/or mineralization, we employed in vitro experiments, which established that fluoxetine treatment decreases osteogenic differentiation and mineralization and that this effect is serotonin-independent. Finally, in a translational approach, we tested whether cessation of the medication would result in restoration of the regenerative potential. However, histologic and microCT analysis revealed non-union formation in these animals with fibrous tissue interposition within the callus. In conclusion, fluoxetine exerts a direct, inhibitory effect on osteoblast differentiation and mineralization, shown in two disparate murine models of bone repair. Discontinuation of the drug did not result in restoration of the healing potential, but rather led to complete arrest of the repair process. Besides the well-established effect of SSRIs on bone homeostasis, our study provides strong evidence that fluoxetine use negatively impacts fracture healing