Milbrandt, Todd A.

Background: Previous studies report elevated serum titanium (Ti) levels in children with spinal implants. To provide additional data on this topic, we sought to assess serum ion levels at multiple timepoints in pediatric patients with growing spine devices, spinal fusion instrumentation, and extremity implants placed for fracture treatment. We hypothesized that serum Ti, cobalt (Co), and chromium (Cr) levels would be elevated in pediatric patients with growing spine devices compared with patients with extremity implants. Methods: Pediatric patients undergoing any primary spine implant placement, those with spine implant revision or removal surgery and patients with other appendicular implant removal had serum Ti, Co, and Cr ion levels drawn at the time of surgery. Fifty-one patients (12 growing spine devices, 13 fusions, and 26 extremity implants) had one set of labs, 31 of whom had labs drawn both preoperatively and postoperatively. Biopsies obtained from tissue specimens at the time of implant revision were analyzed histologically for the presence of metal debris and macrophage activity. Results: Patients with growing spine implants had elevated serum Ti (3.3 vs. 1.9 ng/mL, P=0.01) and Cr levels (1.2 vs. 0.27 ng/mL, P=0.01) in comparison to patients with fusion rods or extremity implants. With respect to patients with extremity implants, patients with growing spine devices had elevated serum Ti (3.3 vs. 0.98 ng/mL, P=0.013), Co (0.63 vs. 0.26 ng/mL, P=0.017), and Cr levels (1.18 vs. 0.26 ng/mL, P=0.005). On matched pairs analysis, patients who had labs drawn before and after spine implantation had significant increase in serum Ti levels (0.57 vs. 3.3 ng/mL, P=0.02). Histology of tissue biopsies adjacent to growing spine implants showed presence of metal debris and increased macrophage activity compared with patients with extremity implants. Conclusion: Serum Ti, Co, and Cr levels are elevated in children with spinal implants compared with those with extremity implants, particularly in those with growing spine devices. However, the clinical significance of these findings remains to be determined. Level of Evidence: Level II—prospective comparative study.

Background: Anterior vertebral body tethering is an alternative to fusion surgery for the treatment of adolescent idiopathic scoliosis (AIS) that is purported to preserve spinal motion. There is limited information regarding the measurable motion that is maintained over the instrumented levels following thoracic anterior vertebral body tethering surgery in humans. The purpose of the present study was to assess radiographic spinal motion 1 year after anterior vertebral body tethering. Methods: As part of a prospective U.S. Food and Drug Administration investigational device exemption study, 32 patients were treated with thoracic anterior vertebral body tethering. At 1 year postoperatively, patients were evaluated with standing flexion-extension and side-bending radiographs in a microdose biplanar slot scanning imaging system. The angle subtended by the screws at the upper instrumented vertebra (UIV) and lower instrumented vertebra (LIV) was measured on left and right-bending radiographs to evaluate the coronal arc of motion and was compared with preoperative values over the same levels. At 1 year postoperatively, the sagittal Cobb angle was measured over the instrumented levels on flexion and extension radiographs. Results: Side-bending radiographs revealed that the mean angle subtended by the screws changed from 15° ± 8° on left-bending radiographs to 8° ± 6° on right-bending radiographs. The mean coronal arc of motion on bending was 7° ± 6°, with 20 (62.5%) of 32 patients having a coronal arc of motion of >5°. The mean preoperative coronal arc of motion over the instrumented segments was 30° ± 9°. On flexion-extension lateral radiographs made at 1 year postoperatively, the mean kyphotic angle over the instrumented segments was 33° ± 13° in flexion and 11° ± 14° in extension, for a mean postoperative arc of motion of 21° ± 12° between flexion and extension radiographs. Conclusions: At 1 year following thoracic anterior vertebral body tethering for the treatment of AIS, the thoracic spine showed a measurable range of coronal and sagittal plane motion over the instrumented levels without evidence of complete autofusion. Motion in the coronal plane decreased by 77% following anterior vertebral body tethering. These findings provide proof of concept that sagittal spinal motion is preserved after thoracic anterior vertebral body tethering, although the functional importance remains to be determined. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Purpose Tarsal coalitions are congenital fusions of two or more tarsal bones and can lead to foot pain and stiffness. Few studies examine the long-term reoperation rates following paediatric tarsal coalition surgery. Methods A population-based database, linking medical records at all medical centres to capture the entire medical history of the full population of a Midwest county, was used to identify tarsal coalitions in children between 1966 and 2018. Records were reviewed for clinical data, surgical records and followed up to identify any subsequent surgical interventions. Results A total of 58 patients (85 coalitions) were identified; 46 calcaneonavicular (CN) coalitions, 30 talocalcaneal (TC) coalitions and nine other coalitions (seven talonavicular, one naviculocuboid, one naviculocuneiform). In all, 46 coalitions were treated surgically (43 coalition resections, three arthrodeses) and 39 were treated nonoperatively. Patients treated surgically were less likely to report ongoing symptoms at final follow-up compared with patients managed nonoperatively (33% versus 67%; p = 0.0017). With a median 14.4 years (interquartile range 9.3 to 19.7) follow-up, there was an overall re-operation rate of 8.7% (4/46). Differences in reoperation rates by initial surgery (resection versus arthrodesis; p = 0.2936), coalition type (CN versus TC versus Other; p = 0.6487) or composition (osseous versus fibrocartilaginous; p = 0.29) did not reach statistical significance. Conclusion This is the first population-based study demonstrating the durability of surgical management of tarsal coalitions in a paediatric population. At final follow-up, patients treated surgically are less likely to report persistent symptoms compared with patients managed nonoperatively. Long-term reoperation rates appear to be low (8.7%). Level of evidence III

Background: Tarsal coalitions are an important reason for foot pain in children. Early estimates placed the prevalence at up to 2%, while more recent data suggest that it is as high as 11% to 13%. To our knowledge, there have been no population-based studies to determine the true incidence of symptomatic tarsal coalitions in a pediatric population. Methods: A population-based database was used to identify all new diagnoses of symptomatic tarsal coalitions in children 18 years old or younger between 1966 and 2018. Patient records were reviewed for clinical data, and comparisons were made between the types and characteristics of the coalitions identified to determine differences in the affected populations. The annual age-specific, sex-specific, and type-specific incidence rates were estimated. Results: During the study period, 58 patients with a total of 79 symptomatic tarsal coalitions were identified (annual incidence = 3.5 per 100,000 children). There were 43 calcaneonavicular (CN) coalitions (annual incidence = 1.9 per 100,000 children), 27 talocalcaneal (TC) coalitions (annual incidence = 1.2 per 100,000 children), as well as 9 other coalitions (7 talonavicular, 1 naviculocuboid, and 1 naviculocuneiform) (annual incidence = 0.4 per 100,000 children). The overall incidence peaked between the ages of 10 and 14 years for both boys and girls (8.1 per 100,000 and 7.4 per 100,000 children, respectively). Statistical differences were identified between the types of tarsal coalitions. TC coalitions present at an older age relative to CN and other coalitions (mean,13.9, 12.7, and 11.4 years, respectively; p = 0.02). While CN and TC coalitions were similar in composition (23% and 30%, respectively, were osseous as opposed to fibrocartilaginous), other coalitions were more likely to be osseous (78%) (p = 0.0035). Other coalitions were also less likely to require surgery than CN and TC coalitions (11%, 74%, and 56%, respectively; p = 0.0015). Conclusions: This population-based study demonstrates differences in the clinical presentation of tarsal coalitions and provides an estimate of the true incidence of symptomatic tarsal coalitions in a pediatric population.

Skeletal development is controlled by epigenetic mechanisms that regulate chromatin compaction and suppress access to gene regulatory sequences. Post‐translational modifications in the N‐termini of histone 3 (H3), including tri‐methylated H3 lysine 9 (H3K9Me3) or lysine 27 (H3K27Me3) represent repressive chromatin marks that are recognized by a family of heterochromatin‐associated Chromobox (Cbx) proteins (i.e., Cbx1 to Cbx8). We show using RNA‐seq analysis that each of these Cbx isoforms is actively expressed in bone and osteoblasts with variable expression of distinct members (between 1 and 100 reads per million). The most prominently expressed Cbx member is Cbx3, which encodes a member of the heterochromatin protein 1 (HP1) family that interacts with H3K9me3. Cbx3 is known to be important for normal development while promoting neurogenesis, as well as renal and smooth muscle development. Therefore, we postulated that CBx3 may perform a similar role in osteoblastogenesis. We tested this hypothesis by both transient and stable knock‐down of Cbx3 by respectively siRNA or shRNA. RNA interference in MC3T3 osteoblasts effectively decreases Cbx3 mRNA levels by 2 to 5 fold, while increasing expression of bone‐related markers by RT‐qPCR (e.g., Alpl/alkaline phosphatase, Ibsp/bone sialoprotein, Bglap/osteocalcin, and Col1a1/Collagen Type I α1 chain). In addition, Cbx3 depletion increases mineral deposition as measured by Alizarin Red staining. Thus, Cbx3 normally appears to suppress osteoblastic differentiation, unlike its essential function in the neuronal differentiation. Because Cbx3 recognizes H3K9me3, we examined whether Cbx3 controls the levels of this histone mark. Loss of Cbx3 did not affect total H3K9me3 levels unless Cbx1 and Cbx5 were simultaneously depleted by siRNA. We propose that Cbx3 may suppress osteoblastogenesis by controlling select loci with H3K9me3 marks.

Background: Annual rankings by US News and World Report are a widely utilized metric by both health care leaders and patients. One longstanding measure is time to treatment of femur shaft fractures. Hospitals able to provide at least 80% of pediatric patients with an operating room start time within 18 hours of admission to the emergency department score better as part of the overall pediatric orthopaedic ranking. Therefore, it is important to determine whether the 18-hour treatment time for pediatric femur shaft fractures is a clinically meaningful metric. Methods: A retrospective review of clinical outcomes of 174 pediatric patients (aged below 16 y) with isolated femur shaft fractures (Injury Severity Score=9) was conducted from 1997 to 2017 at a single level I pediatric trauma center. The 2 comparison groups were patients receiving fracture reduction within 18 hours of emergency department admission (N=87) or >18 hours (N=87). Results: Patient, injury, and surgical characteristics were similar between the 2 groups. Both groups had a similar mean age (treatment <18 h=7.5 y; treatment >18 h=8.1 y). Patients who received treatment within 18 hours were more often immobilized postoperatively (70.1% vs. 53.5%; P=0.0362) and had a shorter median hospital length of stay (2 vs. 3 d; P=0.0047). There were no statistically significant differences in any outcomes including surgical site infection, time to weight-bearing (treatment <18 h mean=48.1 d vs. 52.5 d), time to complete radiographic fracture healing (treatment <18 h mean=258.9 d vs. 232.0 d), decreased range of motion, genu varus/valgus, limb length discrepancy, loss of reduction, or persistent pain. Conclusions: Treatment of pediatric femur shaft fractures within 18 hours does not impact clinical outcomes. National quality measures should therefore use evidence-based metrics to help improve the standard of care. Level of Evidence: Therapeutic level III.

Background: The National Health and Nutritional Examination Survey III, 2009 reported that 48% of adolescents in the United States are vitamin D insufficient/deficient. Nutritional and environmental factors are implicated. The purpose of this study was to measure the prevalence of vitamin D insufficiency in orthopaedic patients and typical children and identify risk factors to aid in screening. Methods: This prospective study recruited 138 patients and 30 typical children ages 2 to <18 yr. Those with known problems with abnormal vitamin D metabolism or diminished ability to play outside were excluded. Height, weight, and serum 25-OH vitamin D levels were measured. Questionnaires assessed skin type, sunscreen use, diet, and physical activity. Results: Statistical analysis failed to detect any differences between patients and controls. Therefore, they were combined for statistical analysis (N=168). The mean age was 11.9±4.2 yr. The mean vitamin D level was 26.5±7.8 ng/mL, which was deficient (<20 ng/mL, n=33) or insufficient (≥21 to <30 ng/mL, n=84) for 71% of participants. Children with sufficient vitamin D levels were younger than those with insufficient/deficient levels (P=0.02). Multivariate analysis showed that vitamin D levels were negatively affected in ethnic minority groups, those with higher body mass index, those with Medicaid or no insurance status, and those with outside playtime of less than 20 min/day (P=0.0006, P=0.001, P=0.0004, P=0.0005, respectively). Conclusions: Vitamin D insufficiency in 71% of our population is much greater than that being reported. The high rate of vitamin D insufficiency suggests that routine screening may be necessary to prevent long-term effects on bone growth and fragility. Characteristics of those at highest risk are ethnic minority, older age, obesity, time spent outdoors of less than 20 min per day, and no private health insurance. Level of Evidence: Level II.

Background: Historically, total hip arthroplasty (THA) performed in patients ≤20 years old has been associated with poor survivorship because of bearing-surface wear with conventional polyethylene, acetabular loosening with cemented sockets, and liner fracture in ceramic-on-ceramic (CoC) THA. For this population, there is a paucity of data regarding outcomes of THAs performed with use of modern implants and bearing surfaces. The purpose of the present study was to examine the mid- to long-term outcomes of modern THA in patients ≤20 years old. Methods: Utilizing a single-institution, prospectively collected total joint registry, we retrospectively identified 91 primary THAs performed in 78 patients ≤20 years old from 1998 to 2016. The average patient age was 17 years (range, 11 to 20 years), and the average body mass index was 26 kg/m 2 (range, 16 to 49 kg/m 2 ). Forty-eight THAs (53%) were performed in male patients, and 47 (52%) were performed on the right hip. Bearing surfaces included CoC (53 THAs, 58%), metal-on-highly cross-linked polyethylene (MoP; 28 THAs, 31%), and ceramic-on-highly cross-linked polyethylene (CoP; 10 THAs, 11%). Outcome measures included reoperations, revisions, complications, clinical outcome scores, and bearing-surface wear. Results: At an average follow-up of 8 years (range, 2 to 18 years), the average modified Harris hip score was 92 (range, 54 to 100), and 95% of patients reported feeling “much better” following the surgical procedure. Survivorship at 2, 5, and 10 years postoperatively was 96.7%, 96.7%, and 95.0% for reoperation; 98.9%, 98.9%, and 97.2% for revision; and 91.2%, 91.2%, and 89.5% for complications, respectively. The most common complications were instability (3 THAs, 3%), aseptic acetabular loosening (2 THAs, 2%), and postoperative foot drop (2 THAs, 2%). Linear articular wear averaged 0.019 mm/yr. There were no correlations between age, sex, body mass index, bearing surface, femoral head size, use of cement, or operative time and survivorship from complications, reoperations, or revisions. There were no differences in linear wear among CoC, CoP, and MoP bearing surfaces. Conclusions: In patients ≤20 years old, THAs performed with use of modern implants exhibit excellent clinical outcome scores and survivorship at mid- to long-term follow-up. CoC, CoP, and MoP bearing surfaces have similar survivorship, clinical outcomes, and bearing-surface wear in this population. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Purpose The aim of this study is to review the management of all paediatric humerus diaphyseal fractures treated at a single institution over a 20-year period. Methods Retrospective review from between 1996 and 2016 identified 96 humerus shaft fractures in paediatric patients (0 to 17 years). After excluding those deceased from inciting trauma, pathological and perinatal fractures, 80 patients remained for analysis. Data collected included age, fracture type, displacement, nerve palsy, treatment, complications and time to union. Radiographs were reviewed at the time of injury and at latest follow-up. Results Of 80 paediatric humeral diaphyseal fractures, 65 (81%) were treated with immobilization. In all, 15 (19%) fractures were treated with surgical stabilization. Most common indications were fracture displacement, open fractures and to improve mobilization in patients with multiple injuries. Fractures were stabilized with a plate (eight), flexible nails (five), external fixation (one) and percutaneous pinning (one). The operative group, compared with the nonoperative group, was older, had more high-energy mechanisms, more open fractures and increased fracture displacement. All patients in the nonoperative and operative groups went on to union with minimal complications. A nerve palsy was present in five patients (6%)with three of the five involving the radial nerve (4%). All nerve palsies were observed and had full neurological recovery. Conclusion Over a 20-year period nonoperative management of paediatric humerus shaft fractures was successful in the majority of patients. Operative stabilization, when rarely indicated, had a low complication rate and improved radiographic alignment. All nerve injuries fully recovered without surgical intervention. Level of evidence IV