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Daniel G Whitney,1,2 Edward A Hurvitz,1 Michelle S Caird3 1Department of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor, MI, USA; 2Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, MI, USA; 3Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USACorrespondence: Daniel G Whitney University of Michigan, 325 E. Eisenhower Pkwy, Ann Arbor, MI, 48108, USATel +1 734-936-7175Email dgwhit@umich.eduPurpose: The efficacy of osteoporosis medication on reducing the risk of non-trauma fracture (NTFx) among adults with cerebral palsy (CP) has not been comprehensively investigated. There are many logistical and biological factors that may reduce this efficacy, and therefore requires attention. The purpose of this propensity score-matched, observational cohort study was to determine if osteoporosis medication was associated with NTFx risk attenuation among adults with CP and compared to adults without CP.Materials and Methods: Data from 07/01/2011 to 09/30/2015 were extracted from Optum Clinformatics® Data Mart. Claims identified adults (≥ 18 years), CP, osteoporosis medication, pre-index NTFx (6-months), and post-index NTFx (12-months). CP without osteoporosis medication (CPMeds-) and without CP with Meds (non-CPMeds+; reflects “background” population) served as controls and were matched (6:1 ratio) to adults with CP with Meds (CPMeds+; n=306). The Meds groups were further stratified by the initiation of their medication as new users or consistent users. Changes in the prevalence of NTFx from pre- to post-index periods were examined with risk ratios (RR) and the change was compared among groups using the ratio of the RR (RRR) via difference-in-difference analysis.Results: New users with CP had: a larger risk attenuation of any NTFx compared to CPMeds- (RRR=0.39; 95% CI=0.22– 0.71), which was consistent for vertebral column/hip and lower extremities; a larger risk attenuation for NTFx of the lower extremities compared to consistent users with CP (RRR=0.22; 95% CI=0.05– 0.93); and a similar risk attenuation of any NTFx compared to new users without CP (RRR=0.81; 95% CI=0.45– 1.43), which was consistent for vertebral column/hip and lower extremities.Conclusion: The findings suggest that osteoporosis medication is associated with clinically meaningful risk attenuation of NTFx, especially for new users with CP.Keywords: cerebral palsy, fracture, osteoporosis medication

Daniel G Whitney,1 Edward A Hurvitz,1 Jennifer M Ryan,2,3 Maureen J Devlin,4 Michelle S Caird,5 Zachary P French,1 Elie C Ellenberg,1 Mark D Peterson1 1Department of Physical Medicine and Rehabilitation, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA; 2Department of Epidemiology and Public Health Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland; 3Department of Clinical Sciences, Brunel University London, Uxbridge, UK; 4Department of Anthropology, University of Michigan, Ann Arbor, MI, USA; 5Department of Orthopedic Surgery, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA Purpose: Individuals with cerebral palsy (CP) are at increased risk for frailty and chronic disease due to factors experienced throughout the lifespan, such as excessive sedentary behaviors and malnutrition. However, little is known about noncommunicable diseases (NCDs) and multimorbidity profiles in young adults with CP. The study objective was to compare NCD and multimorbidity profiles between young adults with and without CP.Methods: A clinic-based sample of adults (18–30 years) with (n=452) and without (n=448) CP was examined at the University of Michigan Medical Center. The prevalence and predictors of 13 NCDs were evaluated, including existing diagnoses or historical record of musculoskeletal, cardiometabolic, and pulmonary morbidities. The level of motor impairment was determined by the Gross Motor Function Classification System (GMFCS) and stratified by less vs more severe motor impairment (GMFCS I–III vs IV–V). Logistic regression was used to determine the odds of NCD morbidity and multimorbidity in adults with CP compared to adults without CP, and for GMFCS IV–V compared to GMFCS I–III in those with CP, after adjusting for age, sex, body mass index, and smoking.Results: Adults with CP had a higher prevalence of osteopenia, osteoporosis, hypertension, myocardial infarction, hyperlipidemia, asthma, and multimorbidity compared to adults without CP, and higher odds of musculoskeletal (odds ratio [OR]: 6.97) and cardiometabolic morbidity (OR: 1.98), and multimorbidity (OR: 2.67). Adults with CP with GMFCS levels IV–V had a higher prevalence of osteopenia/osteoporosis, osteoarthritis, hypertension, other cardiovascular conditions, pulmonary embolism, and multimorbidity, and higher odds of musculoskeletal (OR: 3.41), cardiometabolic (OR: 2.05), pulmonary morbidity (OR: 1.42), and multimorbidity (OR: 3.45) compared to GMFCS I–III.Conclusion: Young adults with CP have a higher prevalence of chronic NCDs and multimorbidity compared to young adults without CP, which is pronounced in those with more severe motor impairment. These findings reiterate the importance of early screening for prevention of NCDs in CP. Keywords: cerebral palsy, noncommunicable disease, multimorbidity, osteoporosis, osteoarthritis, cardiovascular disease, diabetes, pulmonary disease

Background: Distinguishing septic arthritis from transient synovitis of the hip in children can be challenging. Authors of recent retrospective studies have used presenting factors to establish algorithms for predicting septic arthritis of the hip in children. This study differs from previous work in three ways: data were collected prospectively, C-reactive protein levels were recorded, and the focus was on children in whom the findings were so suspicious for septic arthritis that hip aspiration was performed.Methods: Over four years, we prospectively collected data on every child (a total of fifty-three) who underwent hip aspiration because of a suspicion of septic arthritis at our institution. Diagnoses of confirmed septic arthritis, presumed septic arthritis, and transient synovitis were determined on the basis of the results of Gram staining, culture, and a cell count of the hip aspirate. Presenting factors and laboratory values were recorded. To evaluate the strength of predictors, we performed univariate and multivariate analysis on data from forty-eight patients who met the inclusion criteria.Results: Univariate analysis showed that fever, the C-reactive protein level, and the erythrocyte sedimentation rate were strongly associated with the final diagnosis (p < 0.05). On multivariate analysis, the C-reactive protein level and erythrocyte sedimentation rate were found to be significant predictors. However, the erythrocyte sedimentation rate was not independent of the C-reactive protein level on backward elimination, and the C-reactive protein level was the only risk factor that was strongly associated with the outcome at a 5% significance level. Patients with five predictive factors had a 98% chance of having septic arthritis, those with four factors had a 93% chance, and those with three factors had an 83% chance.Conclusions: This prospective study of children who presented with findings that were highly suspicious for septic arthritis of the hip builds on the work of previous authors. We found fever (an oral temperature >38.5 degrees C) was the best predictor of septic arthritis followed by an elevated C-reactive protein level, an elevated erythrocyte sedimentation rate, refusal to bear weight, and an elevated serum white blood-cell count. In our study group, a C-reactive protein level of >2.0 mg/dL (>20 mg/L) was a strong independent risk factor and a valuable tool for assessing and diagnosing children suspected of having septic arthritis of the hip. [ABSTRACT FROM AUTHOR]

STUDY DESIGN: In this retrospective study, 20 spastic quadriplegic cerebral palsy (CP) patients with baclofen pumps, who underwent spinal fusion and instrumentation for neuromuscular scoliosis, were matched for weight, age, and type of fusion with patients without pumps. OBJECTIVE: The objective of this study is to determine the rate of complications, adverse outcomes, and curve correction after spinal fusion in patients with CP and baclofen pumps compared with similar patients without pumps. SUMMARY OF BACKGROUND DATA: CP patients treated with continuous intrathecal baclofen (ITB) can develop neuromuscular scoliosis and may require spinal fusion with instrumentation. ITB pumps may increase complications with this procedure. METHODS: Medical records were examined, and preoperative risks, intraoperative complications, postoperative complications, and pump-specific complications were documented. Cobb angles were measured throughout the treatment to determine surgical correction. RESULTS: Pump patients more frequently required reoperation (9 vs. 4, P = 0.039) and rehospitalization (8 vs. 2, P = 0.008). There was a trend toward more wound infections in pump patients (5 vs. 0, P = 0.063). Nine pump patients (45%) had a pump-related complication; 5 of these patients required pump removal or revision. Complications included durotomy, tubing problems, and deep spinal infection. Average surgical correction in pump patients was 42% (81 degrees -48 degrees ) versus 50% (81 degrees -39 degrees ) in nonpump patients, with no significant difference between pairs (P = 0.11). CONCLUSION: CP patients with baclofen pumps who underwent spinal fusion had more complications compared with similar patients without pumps. There was no significant difference in surgical correction between matched pairs. Physicians and families should be aware of the increased risks of reoperation and rehospitalization after spinal fusion in the presence of baclofen pumps. [ABSTRACT FROM AUTHOR]

Background: Opioid overprescribing can lead to nonmedical opioid use. In a previous prospective study (STUDY), we showed that a standardized protocol involving preoperative education and reduced opioid prescription quantity decreased opioid use in idiopathic scoliosis patients following posterior spinal fusion (PSF). A potential limitation was the Hawthorne effect, where participant behavior changes due to observation. At STUDY conclusion, we continued the reduced opioid prescriptions but discontinued the formal preoperative education. This retrospective study (post-STUDY) assessed if opioid refill requests increased outside of a study setting., Methods: Post-STUDY included patients aged 10 to 17 years who underwent PSF for idiopathic scoliosis between January 2022 and December 2023 and were discharged with a prescription of ≤30 oxycodone doses. Patients were excluded if they had previous spine surgery or were discharged with an opioid other than oxycodone. Demographics, perioperative variables, and opioid refill requests were compared with the data from STUDY, in which patients were aware their opioid use would be tracked. Patient-reported outcomes were collected via Scoliosis Research Society-22r (SRS-22r) surveys., Results: The post-STUDY cohort included 67 patients (69% female). The average age at the time of PSF was 13.9 years (range, 11 to 17 y). The mean number of levels fused was slightly higher (10.9 vs. 10.0, P=0.04), and intraoperative estimated blood loss was lower (211 vs. 303 mL, P<0.01) compared with the STUDY cohort. Demographics, preoperative major curve magnitude, surgery duration, and length of hospital stay were similar. The percentage of patients who requested and received opioid refills between the post-STUDY and STUDY cohorts was also similar [6/67 (9%) vs. 3/49 (6%), P=0.30]. SRS-22r showed improvements in self-image, satisfaction, and mean total score from preoperative to postoperative., Conclusions: Reduced opioid prescriptions did not result in increased opioid refill requests in adolescents undergoing PSF for idiopathic scoliosis outside of a study setting. While formal preoperative discussions about postoperative pain control are important, other factors likely influence opioid use. Further research should explore characteristics that predispose patients to require higher amounts of postoperative opioids., Level of Evidence: Level III-therapeutic., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

We evaluated the potential of sclerostin antibody (SclAb) therapy to enhance osseointegration of dental and orthopaedic implants in a mouse model (Brtl/+) mimicking moderate to severe Osteogenesis Imperfecta (OI). To address the challenges in achieving stable implant integration in compromised bone conditions, our aim was to determine the effectiveness of sclerostin antibody (SclAb) at improving bone-to-implant contact and implant fixation strength. Utilizing a combination of micro-computed tomography, mechanical push-in testing, immunohistochemistry, and Western blot analysis, we observed that SclAb treatment significantly enhances bone volume fraction (BV/TV) and bone-implant contact (BIC) in Brtl/+ mice, suggesting a normalization of bone structure toward WT levels. Despite variations in implant survival rates between the maxilla and tibia, SclAb treatment consistently improved implant stability and resistance to mechanical forces, highlighting its potential to overcome the inherent challenges of OI in dental and orthopaedic implant integration. These results suggest that SclAb could be a valuable therapeutic approach for enhancing implant success in compromised bone conditions., Competing Interests: Declaration of competing interest KMK is a consultant for NextCure, Inc. The remaining authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Children with cerebral palsy (CP) have a high risk of fracture; yet, little is known about their post-fracture health outcomes. A fracture is an unplanned event in contrast to surgeries or procedures where there is a pre-operative period to optimize body composition and health and planned post-operative follow-up care. Fractures may be associated with significant outcomes due to the unplannable nature and reactionary care. The objective of this study was to determine if fractures were associated with an increased rate of short-term adverse health outcomes among children with CP, and if these associations were dependent on age., Methods: This retrospective cohort study used commercial claims from 01/01/2001-12/31/2018. The primary cohort was children 2-18 years old with CP and an incident fracture (CP + Fx). Comparison cohorts were propensity score matched 1:1 to CP + Fx on demographic and health-related indicators: CP without fractures (CPw/oFx); without CP with (w/oCP + Fx) or without (w/oCPw/oFx) a fracture. The incidence rate (IR) and IR ratios (IRR) of 30-day and 31-90-day pneumonia and 90-day emergency department (ED) visit were estimated. Cox regression tested for effect modification by age and sex., Results: The CP + Fx cohort (n = 1670) had higher IRs of 30-day pneumonia (IRR range, 1.53-4.54) and 90-day ED visit (IRR range, 1.45-2.37) (all P < 0.05), and higher IRs of 31-90-day pneumonia but this did not reach statistical significance (IRR, 1.41 to 2.32, all P > 0.05). Notably, there was evidence of effect modification by age. The rate of 30-day pneumonia became more problematic for CP + Fx with older age relative to comparison cohorts and for 90-day ED visit compared to CPw/oFx. The rate of 90-day ED visit for CP + Fx was more problematic at younger ages compared to w/oCP + Fx., Conclusions: Fractures among children with CP were associated with an increased rate of short-term pneumonia and ED visit, which was more problematic with older age., Competing Interests: Declaration of competing interest All authors declare there is no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Craniofacial and dentoalveolar abnormalities are present in all types of osteogenesis imperfecta (OI). Mouse models of the disorder are critical to understand these abnormalities and underlying OI pathogenesis. Previous studies on severely affected OI mice report a broad spectrum of craniofacial phenotypes, exhibiting some similarities to the human disorder. The Brtl/+ and G610c/+ are moderately severe and mild-type IV OI, respectively. Little is known about the aging effects on the craniofacial bones of these models and their homology to human OI. This study aimed to analyze the Brtl/+ and G610c/+ craniofacial morphometries during aging to establish suitability for further OI craniofacial bone intervention studies. We performed morphological measurements on the micro-CT-scanned heads of 3-wk-old, 3-mo-old, and 6-mo-old female Brtl/+ and G610c/+ mice. We observed that Brtl/+ skulls are shorter in length than WT ( P  < .05), whereas G610c/+ skulls are similar in length to their WT counterparts. The Brtl/+ mice exhibit alveolar bone with a porotic-like appearance that is not observed in G610c/+. As they age, Brtl/+ mice show severe bone resorption in both the maxilla and mandible ( P  < .05). By contrast, G610c/+ mice experience mandibular resorption consistently across all ages, but maxillary resorption is only evident at 6 mo ( P  < .05). Western blot shows high osteoclastic activities in the Brtl/+ maxilla. Both models exhibit delayed pre-functional eruptions of the third molars ( P  < .05), which are similar to those observed in some bisphosphonate-treated OI subjects. Our study shows that the Brtl/+ and G610c/+ mice display clear features found in type IV OI patients; both show age-related changes in the craniofacial growth phenotype. Therefore, understanding the craniofacial features of these models and how they age will allow us to select the most accurate mouse model, mouse age, and bone structure for the specific craniofacial bone treatment of differing OI groups., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Background: Elevated serum titanium levels have been found in patients with early onset scoliosis (EOS) treated with traditional growing rods (TGR), magnetically controlled growing rods (MCGR), and vertical expandable prosthetic titanium rib (VEPTR). No studies have investigated whether serum titanium remains persistently elevated and if titanium is excreted. Our purpose was to compare serum titanium levels in patients with EOS with growth-friendly instrumentation to age-matched controls and evaluate urine titanium and serial serum titanium levels in patients with EOS., Methods: This was a prospective case-control study. Patients with EOS with TGR, MCGR, or VEPTR underwent urine titanium and serial serum titanium collection at a minimum 6-month interval. Control patients did not have a history of metal implant insertion and underwent serum titanium collection before fracture fixation., Results: Twenty patients with EOS (6 TGR, 8 MCGR, and 6 VEPTR) and 12 controls were analyzed. The control group had no detectable serum titanium (0 ng/mL), whereas the patients with EOS had a median serum titanium of 4.0 ng/mL ( P < 0.001). Analysis of variance showed significantly higher median serum titanium levels in the MCGR and VEPTR groups than the TGR group at time point 1 (5.5 vs 6.0 vs 2.0 ng/mL, P = 0.01) and time point 2 (6.5 vs 7.5 vs 2.0 ng/mL, P < 0.001). Binary comparisons showed a significant difference in serum titanium level between TGR and MCGR (time point 1: P = 0.026, time point 2: P = 0.011) and TGR and VEPTR (time point 1: P = 0.035, time point 2: P = 0.003). However, there was no difference between MCGR and VEPTR (time point 1: P = 0.399, time point 2: P = 0.492) even though the VEPTR group had a longer duration of follow-up ( P = 0.001) and a greater number of lengthenings per patient at the first serum collection ( P = 0.016). No patients with EOS had detectable urine titanium., Conclusions: Patients with EOS treated with titanium alloy growth-friendly instrumentation had elevated serum titanium levels compared with age-matched controls that persisted over time with no evidence of renal excretion. Additional studies are necessary to assess for local and systemic accumulation of titanium and the significance of long-term exposure to titanium in growing children., Level of Evidence: Level III, therapeutic., Competing Interests: Y.L. has received research grants from the Scoliosis Research Society, has received consulting fees from Medtronic, has received support for travel from Zimmer-Biomet, and is the Chair of the Scoliosis Research Society’s Outcomes and Benchmarking Committee. The remaining authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Bone development is a highly orchestrated process that establishes the structural basis of bone strength during growth and functionality across the lifespan. This developmental process is generally robust in establishing mechanical function, being adaptable to many genetic and environmental factors. However, not all factors can be fully accommodated, leading to abnormal bone development and lower bone strength. This can give rise to early-onset bone fragility that negatively impacts bone strength across the lifespan. Current guidelines for assessing bone strength include measuring bone mineral density, but this does not capture the structural details responsible for whole bone strength in abnormally developing bones that would be needed to inform clinicians on how and when to treat to improve bone strength. The clinical consequence of not operationalizing how altered bone development informs decision making includes under-detection and missed opportunities for early intervention, as well as a false positive diagnosis of fragility with possible resultant clinical actions that may actually harm the growing skeleton. In this Perspective, we emphasize the need for a multi-trait, integrative approach to better understand the structural basis of bone growth for pediatric conditions with abnormal bone development. We provide evidence to showcase how this approach might reveal multiple, unique ways in which bone fragility develops across and within an array of pediatric conditions that are associated with abnormal bone development. This Perspective advocates for the development of new translational research aimed at informing better ways to optimize bone growth, prevent fragility fractures, and monitor and treat bone fragility based on the child's skeletal needs., Competing Interests: Declaration of competing interest There are no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Children with bone fragility often exhibit elevated bone marrow lipid levels, which may affect mesenchymal stem cell (MSC) differentiation potential and ultimately bone strength via cell-autonomous and/or non-cell-autonomous factors. Here, we use standard co-culture techniques to study biological effects of bone marrow cell-derived secretome on MSC. Bone marrow was collected during routine orthopedic surgery, and the entire marrow cell preparation, with or without red blood cell (RBC) reduction, was plated at three different densities. Conditioned medium (secretome) was collected after 1, 3, and 7 days. ST2 cells, a murine MSC line, were then cultured in the secretomes. Exposure to the secretomes was associated with reductions of up to 62% in MSC MTT outcomes that depended on the duration of secretome development, as well as marrow cell plating density. Reduced MTT values were not associated with diminished cell number and viability assessed using Trypan Blue exclusion. Expression of pyruvate dehydrogenase kinase 4 was modestly elevated, and β-actin levels were transiently reduced in ST2 cells exposed to secretome formulations that had elicited maximal reductions in MTT outcomes. The findings from this study can inform the design of future experimental studies to examine contributions of cell-autonomous and non-cell-autonomous factors in the bone marrow to MSC differentiation potential, bone formation, and skeletal growth. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.)

Background: Parental leave impacts family engagement, bonding, stress, and happiness. Because parental leave benefits are important to all surgeons regardless of sex, understanding parental leave practices in pediatric orthopaedic surgery is critical to promote equity within the profession and supporting balance in work and family life. The aim of this study was to survey pediatric orthopaedic surgeons about their knowledge of parental leave policies, attitudes towards parental leave, and their individual experiences taking leave., Methods: A 34-question anonymous survey was distributed to the Pediatric Orthopaedic Society of North America membership. Eligible respondents were attending pediatric orthopaedic surgeons practicing in the United States or Canada. The survey gathered information about employer parental leave policies, perceptions about and experiences with parental leave while practicing as a surgeon, and demographic information about respondents., Results: A total of 77 responses were completed and used for analysis. Most respondents were men (59.7%), <50 years old (67.5%), married (90.9%), and in urban communities (75.3%). A large majority were practicing in the United States (97.4%). Most respondents were unfamiliar with employer parental leave policies (maternity: 53.3%; paternity: 67.5%; and adoption: 85.7%). Those familiar with policies reported that employers offered 7 to 12 weeks for maternity leave (45.7%) and <1 week for paternity leave (50%) and adoption leave (45.5%). Most respondents believed 7 to 12 weeks should be offered for maternity leave (66.2%), 1 to 6 weeks for paternity leave (54.6%), and 7 to 12 weeks for adoption leave (46.8%). Many respondents reported taking 1 to 6 weeks of parental leave as a surgeon (53.3%) and that their colleagues were supportive of their parental leave (40.3%)., Conclusions: Most pediatric orthopaedic surgeons were unfamiliar with parental leave benefits provided by employers. Respondents who were familiar with these policies believed that more parental leave should be provided, especially for men who may feel social pressure to take less time for leave. Although respondents reported that their work environments were supportive, this study identified opportunities for improvement to support surgeons who wish to balance parental experiences with work responsibilities., Level of Evidence: Level V., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Rehabilitation may mitigate the high mortality rates and health declines post-fracture for adults with cerebral palsy, but this is understudied. The objectives were to characterize the post-fracture rehabilitation pathways and identify their association with 1-year survival among adults with cerebral palsy., Methods: A retrospective cohort study of adults with cerebral palsy with a fragility fracture with continuous health plan enrollment ≥1-year prior to and ≥1 day after their fracture date was performed using a random 20% Medicare fee-for-service dataset. Participants were categorized as a home discharge or inpatient rehabilitation admission post-fracture. For the home discharge cohort, weekly exposure to outpatient physical/occupational therapy (PT/OT) was examined up to 6-month post-fracture. Cox regression examined the association between time-varying PT/OTuse within 6-month post-fracture and mortality from 30 days to 1-year post-fracture before and after adjusting for confounders (e.g. medical complexity)., Results: Of 3598 adults with cerebral palsy with an incident fragility fracture, 74% were discharged home without inpatient rehabilitation; they were younger, but more medically complex compared to the 26% admitted to inpatient rehabilitation. Among the home discharge cohort (n = 2662), 43.1% initiated PT/OTwithin 6-month post-fracture, and cumulative PT/OTexposure post-fracture was associated with improved survival; for example, per 3 weeks of PT/OTexposure, the adjusted mortality rate was 40% lower (95% confidence interval (CI) = 0.41-0.89)., Conclusions: Most adults with cerebral palsy with a fragility fracture were discharged home rather than to inpatient rehabilitation, and only 43.1% of that group initiated outpatient PT/OTwithin 6 months post-fracture. Receiving outpatient PT/OTwas associated with improved 1-year survival.

Physical and/or occupational therapy (PT/OT) may improve post-fracture health and survival among adults with cerebral palsy (CP), but this has not been studied in the inpatient setting. The objective was to quantify the association between acute inpatient and outpatient PT/OT use with 1-year mortality among adults with CP. This was a retrospective cohort study of adults with CP with an incident fragility fracture admitted to an acute care or rehabilitation facility using a random 20% Medicare fee-for-service dataset. Acute care/rehabilitation PT/OT was measured as the average PT/OT cost/day for the length of stay (LOS). Weekly exposure to outpatient PT/OT was examined up to 6 months post-fracture. Cox regression examined the adjusted association between the interaction of acute care/rehabilitation average PT/OT cost/day and LOS with 1-year mortality. A separate Cox model added time-varying outpatient PT/OT. Of 649 adults with CP, average PT/OT cost/day was associated with lower mortality rate for LOS < 17 days (HR range = 0.78−0.93), and increased mortality rate for LOS > 27 days (HR ≥ 1.08) (all, p < 0.05). After acute care/rehabilitation, 44.5% initiated outpatient PT/OT, which was associated with lower mortality rate (HR = 0.52; 95% CI = 0.27−1.01). Post-fracture inpatient and outpatient PT/OT were associated with improved 1-year survival among adults with CP admitted to acute care/rehabilitation facilities.

Background: Most opioids prescribed postoperatively are unused. Leftover opioids are a major source of nonmedical opioid use among adolescents. Postoperative opioid use has also been associated with prescription quantity. Our purpose was to evaluate the effect of preoperative patient education and implementation of evidence-based prescribing guidelines on opioid use and pain level after posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS)., Methods: AIS patients aged 10 to 17 years undergoing PSF were prospectively enrolled [postintervention cohort (POST-INT)]. Previous data on 77 patients showed median consumption of 29 doses of oxycodone after PSF [preintervention cohort (PRE-INT)]. All eligible patients during the study period were discharged with 30 doses of oxycodone and standard nonopioid analgesics. Only study participants received education on postoperative pain control. Demographics, radiographic/surgical data, pain level, and patient-reported outcomes were collected. Requests for opioid refills were documented., Results: Forty-nine patients were enrolled. POST-INT was divided into low (L, ≤8 doses), average (AVE, 9-25), and high (H, >25) opioid use groups. Demographics, radiographic/surgical data, pain level, and patient-reported outcomes were similar between the groups. However, there was a difference in days of oxycodone use, doses consumed in the first week, and leftover doses ( P <0.001). Comparison to the PRE-INT L (≤16 doses), AVE (17 to 42), and high (H, >42) use groups showed that POST-INT L and AVE consumed less oxycodone (L: P =0.002; AVE: P <0.001). Also, the overall POST-INT cohort had fewer mean days of oxycodone use (5.6 vs. 8.9, P <0.001) and doses used in the first week (14 vs. 23, P <0.001) compared with the PRE-INT cohort. Subanalysis showed fewer study participants requested and received an opioid refill [3/49 patients (6%)] compared with eligible patients who declined to participate, withdrew, or missed enrollment [8/35 patients (23%)] ( P =0.045)., Conclusions: Preoperative patient education and smaller prescription quantity successfully reduced opioid use while maintaining excellent pain control after PSF for AIS. Setting expectations regarding postoperative pain management is critical, as nonstudy participants were significantly more likely to request an opioid refill., Level of Evidence: Level II-therapeutic., Competing Interests: M.S.C. is currently receiving a grant from the NIH, is the treasurer of the Pediatric Orthopaedic Society of North America, and is on the editorial board of the Journal of Pediatric Orthopaedics. Y.L. is currently receiving a grant from the Scoliosis Research Society, has received consulting fees from Medtronic, has received support for travel from Zimmer Biomet, is the Chair of the Scoliosis Research Society’s Morbidity and Mortality Committee, and is the Chair of the Pediatric Orthopaedic Society of North America’s Membership Committee. The remaining authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Epidemiologic evidence documenting the incidence of fracture and subsequent fractures among adults with cerebral palsy (CP) is lacking, which could inform fracture prevention efforts. The objective was to characterize the 5-year rate of initial and subsequent fragility fractures among adults with CP., Methods: This retrospective cohort study used Medicare claims from 01/01/2008-12/31/2019 from adults ≥18 years old with CP ( n  = 44,239) and elderly ≥65 years old without CP ( n  = 2,176,463) as a comparison. The incidence rate (IR), IR ratio (IRR), and site distribution were estimated for the initial and subsequent fragility fractures over 5-years by sex and age., Results: The IR of fragility fracture at any site over the 5-year follow-up was similar for 18-30-year-old men with CP (IR = 5.2; 95%CI = 4.4-5.9) and 30-34-year-old women with CP (IR = 6.3; 95%CI = 5.3-7.2) compared to the same sex youngest-old (65-74 years old) without CP (IRR = 1.09 and 0.94, respectively, both P  > 0.05), and increased with older age for those with CP. The number of fragility fractures and IR of subsequent fragility fractures was similar for young men and middle-aged women with CP compared to elderly without CP, and increased with older age for those with CP. The proportion of fragility fracture at the tibia/fibula decreased while the vertebral column and multiple simultaneous sites (most involved hip/lower extremities) increased with older age., Conclusion: Young and middle-aged adults with CP had similar-to-worse initial and subsequent fragility fracture profiles compared to the general elderly population- a well characterized group for bone fragility. Findings emphasize the need for fracture prevention efforts at younger ages for CP, possibly by ~5 decades younger., Competing Interests: None., (© 2022 The Authors.)

Purpose: To evaluate clinically relevant fracture characteristics by age, sex, and ambulatory status among individuals with cerebral palsy., Methods: Fracture location, energy of fracture, and activities that lead to a fracture were assessed among a clinic-based sample of children (0-17 years; n  = 57) and adults (18-70 years; n  = 58) with cerebral palsy that sustained a fracture by sex and gross motor function classification system (GMFCS) I-III vs. IV/V., Results: Proportion of fractures that were low-energy was 67-99% for children and 69-84% for adults. ∼2/3rds of fractures were at the lower extremities, with the distal femur being the most common site for children (44%) and the foot/ankle for adults (40%); however, there were age, sex, and ambulatory effects, such that 43% of adults GMFCS IV/V and 32% of women had a distal femur fracture. GMFCS I-III were more likely to fracture from functionally complex activities, while GMFCS IV/V were more likely to fracture from wheelchair/transfers/limb-stuck and incidental findings., Conclusions: The majority of fractures were low-energy and occurred in the lower extremities, with effects by age, sex, and GMFCS. Activities that led to a fracture also differed by age and GMFCS, which can be used to design fracture prevention interventions in addition to bolstering skeletal mass and architecture.Implications for rehabilitationSkeletal fragility is a major problem for individuals with cerebral palsy (CP) across the lifespan leading to an increased risk of fragility fractures.Rehabilitation is a prime clinical intervention to prevent fractures from occurring and improving post-fracture healing and function; yet, effective rehabilitation interventions require knowledge of fracture characteristics, such as where fractures are occurring and the activities that lead to the fracture event specific to individuals with CP.Using a clinic-based sample of 0-70 year olds with CP, we describe salient fracture characteristics based on age, sex, and ambulatory status to enhance translation into clinical and rehabilitation practice.

Aim: To determine (1) frequency of resident research projects being in the same orthopaedic subspecialty that they ultimately choose for fellowship and practice; (2) percentage of research projects that were published., Methods: Resident Thesis Day programs were independently assessed by two reviewers from 2010 to 2020. Reviewers classified projects based on orthopaedic subspecialty: Spine, Joints, Trauma, Hand, Foot and Ankle, Sports, Pediatrics, Oncology, and Shoulder Elbow. Presenting residents' fellowship subspecialty, current practice specialty, and geographic state of current practice were collected using internet searches. Correlation of residents who completed a thesis day project in the same subspecialty as their fellowship and current practice was calculated., Results: A total of 81 resident physicians, 11 (13.6%) female, were included. In the entire cohort, 50.6% did a thesis day project in a different field than their current or projected subspecialty. Of those who completed, or are currently completing fellowship, 33 (52.4%) did their thesis day project in the same subspecialty as their fellowship. Of the current residents who have matched into fellowship, 46.7% did a thesis day project in the same subspecialty. A total of 51 (63.0%) projects were published., Conclusion: The majority of resident research projects were published, and about 50% of orthopaedic residents went on to complete a fellowship and practice in the same subspecialty as their research project. As residents often spend a considerable amount of time and effort on their projects, these findings may help tailor resident education and research curriculums to focus more on research principles than specific orthopedic content., (© 2022. The Author(s) under exclusive licence to SICOT aisbl.)

Background: Fractures represent a triple threat to adults with cerebral palsy (CP): common, accumulate early in adulthood, and are consequential to health. An economic evaluation of fractures in CP is needed to highlight priorities for allocating resources to clinical and public health programs aimed at preventing fractures and their disease sequela., Objective: To identify short-term healthcare costs associated with fractures among adults with CP., Methods: A retrospective cohort study was performed using Optum's de-identified Clinformatics® Data Mart Database from 01/01/2011-12/31/2017. The primary cohort included adults ≥ 18 years old with CP with an incident fracture (CP+Fx), and cost estimates were compared with: CP without fractures (CPw/oFx) and without CP+Fx (w/oCP+Fx). A difference-in-difference (DiD) analysis compared the change in pharmacy and medical costs between cohorts from the one-year baseline period through the one-year post-index period in three-month quarters., Results: CP+Fx (n = 855) had higher mean costs in the baseline and follow-up periods compared with CPw/oFx (n = 5667) and w/oCP+Fx (n = 588,042). The first post-index quarter DiD estimate suggests that CP+Fx accumulated an excess $6462 (95%CI = $3810-$9021) compared with w/oCP+Fx and $17,197 (95%CI = $14,418-$19,833) compared with CPw/oFx. The CP+Fx cohort had higher DiD estimates in the other follow-up quarters, but they were not statistically significant compared with CPw/oFx. When stratified by fracture site, vertebral column fractures for CP+Fx vs. w/oCP+Fx accumulated an excess $25,226 (95%CI = $12,639-$37,417)., Conclusions: Fractures, especially of the vertebral column, were associated with high healthcare costs among adults with CP. Studies are needed to identify cost-effective opportunities to utilize available resources to prevent fractures and their costly sequela for CP., Competing Interests: Conflicts of interest All authors declare that there is no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aim: To understand associations among bone mineral density (BMD), bone mineral content (BMC), and bone area, and their association with fractures in adults with cerebral palsy (CP)., Method: This retrospective cohort study included 78 adults with CP with a hip dual energy X-ray absorptiometry (DXA) from 1st December 2012 to 3rd May 2021 performed at the University of Michigan. Data-driven logistic regression techniques identified which, if any, DXA-derived bone traits (e.g. age/sex/ethnicity-based z-scores) were associated with fracture risk by sex and severity of CP. BMC-area associations were examined to study the structural mechanisms of fragility., Results: Femoral neck area was associated with lower age-adjusted odds ratios (ORs) of fracture history (OR 0.72; 95% confidence interval [CI] 0.49-1.06; p=0.098), while higher BMD was associated with higher odds of incident fracture (OR 3.08; 95% CI 1.14-8.33; p=0.027). Females with fracture had lower area than females without fracture but similar BMC, whereas males with fracture had larger area and higher BMC than males without fracture. The paradoxical BMD-fracture association may be due to artificially elevated BMD from BMC-area associations that differed between females and males (sex interaction, p˂0.05): males had higher BMC at lower area values and lower BMC at higher area values compared to females., Interpretation: BMD alone may not be adequate to evaluate bone strength for adults with CP. Further research into associations (or integration) between BMC and area is needed., (© 2021 Mac Keith Press.)

Background: Gabapentin and intravenous patient-controlled analgesia (PCA) can reduce postoperative pain scores, postoperative opioid use, and time to completing physical therapy compared to PCA alone after posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS). Gabapentin combined with intrathecal morphine has not been studied. The primary purpose of this retrospective study was to evaluate whether perioperative gabapentin and intrathecal morphine provide more effective pain control than intrathecal morphine alone after PSF for AIS., Methods: Patients aged 11 to 18 years who underwent PSF for AIS were identified. Patients who received intrathecal morphine only (ITM group) were matched by age and sex to patients who received intrathecal morphine and perioperative gabapentin (ITM+GABA group). The ITM+GABA group received gabapentin preoperatively and for up to 2 days postoperatively. Both groups received oxycodone and the same non-narcotic adjuvant medications., Results: Our final study group consisted of 50 patients (25 ITM, 25 ITM+GABA). The ITM+GABA group had significantly lower mean total oxycodone consumption during the hospitalization (0.798 vs 1.036 mg/kg, P<0.015). While the ITM group had a lower mean pain score between midnight and 8 am on POD 1 (2.4 vs 3.7, P=0.026), pain scores were significantly more consistent throughout the postoperative period in ITM+GABA group. The ITM+GABA group experienced less nausea/vomiting (52% vs 84%, P=0.032) and pruritus (44% vs 72%, P=0.045). Time to physical therapy discharge and length of hospital stay were similar., Conclusion: Addition of gabapentin resulted in reduced oral opioid consumption and more consistent postoperative pain scores after PSF for AIS. The patients who received intrathecal morphine and gabapentin also experienced a lower rate of nausea/vomiting and pruritus., Trial Registration: All data was collected retrospectively from chart review, with institutional IRB approval. Trial registration is not applicable., (© 2021. The Author(s).)

Objective: The objective of this study was to determine whether two commonly prescribed antiseizure medications (ASMs), levetiracetam (LEV) and oxcarbazepine (OXC), were associated with an increased risk of fragility fracture in children with epilepsy when initiating therapy during a crucial period of bone development, namely, pre- and midpuberty., Methods: Claims data from January 1, 2009 to December 31, 2018 were extracted from the Optum Clinformatics Data Mart. Children aged 4-13 years at baseline with at least 5 years of continuous health plan enrollment were included to allow for a 1-year baseline (e.g., pre-ASM exposure) and 4 years of follow-up. Children with epilepsy who were ASM naïve were grouped based on whether ASM treatment initiation included LEV or OXC. The comparison group included children without epilepsy and without ASM exposure. Crude incidence rate (IR; n per 1000 person-years) and IR ratio (IRR; with 95% confidence interval [CI]) were estimated for nontrauma fracture (NTFx), a claims-based proxy for fragility fracture, for up to 4 years of follow-up. Cox proportional hazards regression estimated the hazard ratio (HR; with 95% CI) after adjusting for demographic variables, motor impairment, and baseline fracture., Results: The crude IR (95% CI) of NTFx was 21.5 (21.2-21.8) for non-ASM-users without epilepsy (n = 271 346), 19.8 (12.3-27.2) for LEV (n = 358), and 34.4 (21.1-47.7) for OXC (n = 203). Compared to non-ASM-users, the crude IRR of NTFx was similar for LEV (IRR = .92, 95% CI = .63-1.34) and elevated for OXC (IRR = 1.60, 95% CI = 1.09-2.35); the crude IRR of NTFx was elevated for OXC compared to LEV (IRR = 1.74, 95% CI = 1.02-2.99). The findings were consistent after adjusting for covariates, except when comparing OXC to LEV (HR = 1.71, 95% CI = .99-2.93), which was marginally statistically insignificant (p = .053)., Significance: Initiating OXC, but not LEV, therapy among 4-13-year-olds with epilepsy is associated with an elevated risk of fragility fracture. Studies are needed to determine whether these children could benefit from adjunct bone fragility therapies., (© 2021 International League Against Epilepsy.)

Background: Skeletal fragility is a major burden for individuals with cerebral palsy (CP), but little is known clinically about when to prevent fractures or monitor bone health for this population. Critical periods of bone health (CPBH) are important windows for intervention to augment bone growth or mitigate bone loss. However, CPBH from the general population may not align with the needs or timing of skeletal fragility for individuals with CP. The objective of this study was to identify discrepancies when evaluating individuals with CP using CPBH across the lifespan from the general population, and propose new CP-specific CPBH., Methods: Data from 2016 administrative claims databases were used, including the Optum's De-identified Clinformatics® Data Mart Database and a random 20% sample of the Medicare fee-for-service database from the Centers for Medicare and Medicaid Services. Sex-stratified fracture prevalence was compared between individuals with and without CP across the lifespan starting at 2 years of age using age groups to capture important stages of development and 3-4-year age bands in adulthood (up to >80 years). Sex-specific CPBH from the general population included: rapid bone accrual, peak bone mass, menopause, and elderly., Results: There were 23,861 individuals with CP and 9,976,161 individuals without CP. CPBH from the general population did not align with the timing of skeletal fragility for CP. For example, fractures were rare and decreased throughout the CPBH of peak bone mass for males without CP, but males with CP had a greater relative fracture risk (2.9-5.6-fold higher) and a substantially increased rate of fracture (CP-slope 14× higher than non-CP-slope). For females with CP, fracture risk was increased by 18-21 years, with additional inflection points (e.g., decade before menopause and again by 57-60 years). For males with CP, fracture risk in mid-life exhibited a pattern similar to elderly males without CP., Conclusions: This study identified discrepancies in evaluating fracture risk for individuals with CP if using established CPBH from the general population. We therefore propose new CP- and sex-specific CPBH for fracture monitoring and prevention., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Anti-seizure medication (ASM) is necessary to manage epilepsy and often prescribed to children and adolescents, but can lead to iatrogenic effects, including bone fragility by altering bone metabolism. Disrupting bone metabolism during crucial developmental stages could have a lasting adverse effect on bone health. Therefore, the objective of this propensity score-matched, observational cohort study was to determine if age when initiating ASM therapy across developmental stages (from pre- to post-puberty) for individuals with epilepsy was associated with an increased risk of fragility fracture., Methods: Data from 01/01/2011 to 12/31/2018 were extracted from Optum Clinformatics® Data Mart. Children aged 4-21 years at baseline with at least 5 years of continuous health plan enrollment were included to allow for a 1-year baseline and 4-years of follow-up. The primary group of interest included new ASM users (i.e., treatment naïve) with epilepsy. The comparison group, no ASM users without epilepsy, was matched 1:14 to new ASM users with epilepsy for demographics and baseline fracture. To provide a proxy for developmental stages, age was categorized as 4-6 (pre-puberty), 7-10 (early puberty), 11-13 (mid-puberty), 14-17 (late puberty), and 18-21 (post-puberty). Crude incidence rate (IR; per 1000 person years) and IR ratio (IRR and 95% confidence intervals [CI]) were estimated for non-trauma fracture (NTFx) for up to 4-years of follow-up., Results: Prior to stratifying by age group, the crude NTFx IR (95% CI) of 20.6 (16.5-24.8) for new ASM users with epilepsy (n = 1205) was 34% higher (IRR = 1.34; 95% CI = 1.09-1.66) than the crude NTFx IR (95% CI) of 15.4 (14.4-16.3) for no ASM users without epilepsy. The groups exhibited a different pattern of NTFx incidence with age, with new ASM users showing a more dramatic increase and peaking at 11-13 years, then decreasing with the older age groups. The crude IR and IRR were elevated for new ASM users with epilepsy compared to no ASM users without epilepsy for each age group (10% to 55% higher), but was only statistically significant for 11-13 years (IRR = 1.55; 95% CI = 1.02-2.36)., Conclusions: Children with epilepsy initiating ASM therapy may be vulnerable to fragility fracture, especially when initiating ASM around the time of puberty. Clinicians should be aware of this age-related association and consider age-appropriate adjunct bone fragility therapies., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Higher pedicle screw density posterior spinal fusion (PSF) constructs have not been shown to result in improved curve correction in Lenke 1 and 5 adolescent idiopathic scoliosis (AIS) but do increase cost. The purpose of this study questioned whether higher screw density constructs improved curve correction and maintenance of correction in Lenke 2 AIS. Secondary goals were to identify predictive factors for correction and postoperative magnitude of curves in Lenke 2 AIS., Methods: We identified patients 11 to 17 years old who underwent primary PSF for Lenke 2 AIS between 2007 and 2017 who had minimum follow-up of 2 years. Demographic and radiographic data were collected to perform regression and elimination analysis., Results: Thirty patients (21 females, 9 males) were analyzed. Average age and SD at time of surgery was 14.0 ± 1.8 years (range, 11-17 years), and median follow-up was 2.8 years (IQR 2.1-4.0 years). Implant density did not predict final postoperative curve magnitude. Predictors of final postoperative curve magnitude were sex and preoperative curve magnitude. Predictors of percentage of correction of major curve were sex and age at the time of surgery. Predictors of final postoperative thoracic kyphosis were sex and percent flexibility preop. Females had lower final postoperative major curve magnitude, a higher percent curve correction, and lower postoperative thoracic kyphosis., Conclusions: Increased implant density is not predictive of postoperative curve magnitude in Lenke 2 AIS. Predictors of postoperative curve magnitude are sex and preoperative curve magnitude., Level of Evidence: Level III, retrospective observational.

Background: Lipidomics, a branch of metabolomics, is an attractive technique to characterize bone marrow lipid composition, which may be associated with skeletal acquisition and homeostasis. However, the reliability of lipidomics-derived lipid composition of the bone marrow is unknown, especially for pediatric populations with bone fragility. The purpose of this study was to evaluate the intersite reliability and standard error of measurement (SEM) of vertebral bone marrow lipid composition at the thoracic (T11/T12) and lumbar (L1/L2) spine determined by targeted lipidomics among children with varying degrees of bone fragility undergoing routine orthopedic surgery., Methods: Children aged between 12 and 19 years of age, with a confirmed diagnosis of adolescent idiopathic scoliosis or neuromuscular scoliosis and cerebral palsy, and undergoing routine posterior spinal fusion surgery at our institution were initially included in this study. Transpedicular vertebral body bone marrow samples were taken from thoracic (T) or lumbar (L) vertebrae. Further inclusion criteria involved having bone marrow extracted from both T11 and T12 (n = 24) or L1 and L2 (n = 19). Lipid composition was measured using a targeted lipidomics technique and examined as the saturated, monounsaturated, and polyunsaturated index and as individual fatty acids. Relative and absolute test-retest reliability was assessed using the intraclass correlation coefficient (ICC) and SEM., Results: For the T11/T12 analysis: the ICC and SEM were 0.59 and 1.7% for the saturated index, 0.31 and 6.2% for the monounsaturated index, and 0.44 and 6.1% for the polyunsaturated index; the ICC showed a considerable range for individual fatty acids from 0.07 (fatty acid 20:2) to 0.82 (15:0) with 62.1% of the fatty acids having poor reliability (i.e., ICC < 0.50). For the L1/L2 analysis: the ICC and SEM were 0.50 and 2.4% for the saturated index, -0.12 and 6.0% for the monounsaturated index, and 0.00 and 4.9% for the polyunsaturated index; the ICC showed a considerable range for individual fatty acids from -0.34 (18:1&#95;n-9) to 0.88 (15:0 and 18:3&#95;n-3) with 79.3% of the fatty acids having poor reliability., Conclusions: The intersite test-retest reliability was poor-to-moderate for index measures and generally poor for individual fatty acids for the thoracic and lumbar spine. At this time, it is not recommended to pool bone marrow adipose tissue across vertebral sites for bone marrow adiposity research or clinical monitoring for pediatric populations with bone fragility., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: There is evidence that the extent of vertebral bone marrow adiposity increases caudally along the vertebral column in children and adolescents. However, no studies have examined the lipid composition of bone marrow along the vertebral column, which may uniquely influence bone acquisition and metabolism during growth independent of the amount of bone marrow adipose tissue. The goal of this study was to characterize the pattern of lipid composition index measures from the thoracic to lumbar spine (T11-L4) among a sample of adolescents with idiopathic scoliosis (AIS) undergoing routine orthopedic surgical care for scoliosis correction., Methods: Adolescents between 14 and 18 years of age, with a confirmed diagnosis of AIS, and undergoing routine posterior spinal fusion surgery at our institution were initially included for this descriptive study. The surgery yielded transpedicular vertebral body marrow samples from T11 through L4; 11 participants had bone marrow samples from T11 through L2 and 4 of the 11 participants had marrow samples from T11 through L4. Lipid composition index measures, including the saturated, monounsaturated, and polyunsaturated index, were measured using a targeted lipidomics technique. Linear regression equation for the slope (m) and Pearson correlation coefficient (r) was computed to assess the pattern of lipid composition index measures along the vertebral column from T11 to L2 (n = 11) and extended analysis to L4. Exploratory analyses were performed to examine the association between the pattern of lipid composition measures (individual slopes) and physical characteristics for T11-L2., Results: For T11-L2, the slope of the saturated index was near 0 (r = 0.08; P = 0.92), whereas the slopes of the unsaturated indices were approximately opposite of one another: the monounsaturated index exhibited a -0.55 change (r = 0.58; P = 0.42) per vertebra and the polyunsaturated index exhibited a 0.52 change (r = 0.72; P = 0.28) per vertebra in the caudal direction from T11-L2. For T11-L4, there were modest changes in slope for the saturated (m = 0.12; r = 0.30; P = 0.57) and monounsaturated (m = -0.68; r = 0.74; P = 0.09) indices, while the polyunsaturated index slope remained similar (m = 0.56; r = 0.89; P = 0.02). Age, sex, height, body mass, and BMI were not associated with the pattern of any of the lipid composition index measures., Conclusions: Study findings in this small sample of individuals with AIS suggest that the bone marrow saturated index may be relatively stable across T11-L4, while the monounsaturated index may decrease by 0.55-0.68% per vertebra and the polyunsaturated index may increase by 0.52-0.56% per vertebra in the caudal direction., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to determine the feasibility and evaluate the effectiveness of the American Board of Orthopaedic Surgery Behavior Tool (ABOSBT) for measuring professionalism., Methods: Through collaboration between the American Board of Orthopaedic Surgery and American Orthopaedic Association's Council of Residency Directors, 18 residency programs piloted the use of the ABOSBT. Residents requested assessments from faculty at the end of their clinical rotations, and a 360° request was performed near the end of the academic year. Program Directors (PDs) rated individual resident professionalism (based on historical observation) at the outset of the study, for comparison to the ABOSBT results., Results: Nine thousand eight hundred ninety-two evaluations were completed using the ABOSBT for 449 different residents by 1,012 evaluators. 97.6% of all evaluations were scored level 4 or 5 (high levels of professional behavior) across all of the 5 domains. In total, 2.4% of all evaluations scored level 3 or below reflecting poorer performance. Of 431 residents, the ABOSBT identified 26 of 32 residents who were low performers (2 or more < level 3 scores in a domain) and who also scored "below expectations" by the PD at the start of the pilot project (81% sensitivity and 57% specificity), including 13 of these residents scoring poorly in all 5 domains. Evaluators found the ABOSBT was easy to use (96%) and that it was an effective tool to assess resident professional behavior (81%)., Conclusions: The ABOSBT was able to identify 2.4% low score evaluations (

Background: Individuals with cerebral palsy (CP) are vulnerable to non-trauma fracture (NTFx) and premature mortality due to respiratory disease (RD); however, very little is known about the contribution of NTFx to RD risk among adults with CP. The purpose of this study was to determine if NTFx is a risk factor for incident RD and if NTFx exacerbates RD risk in the adult CP population., Methods: Data from 2011 to 2016 Optum Clinformatics® Data Mart and a random 20% sample Medicare fee-for-service were used for this retrospective cohort study. Diagnosis codes were used to identify adults (18+ years) with and without CP, NTFx, incident RD at 3-, 6-, 12-, and 24-month time points (pneumonia, chronic obstructive pulmonary disease, interstitial/pleura disease), and comorbidities. Crude incidence rates per 100 person years of RD were estimated. Cox regression estimated hazard ratios (HR and 95% confidence interval [CI]) for RD measures, comparing: (1) CP and NTFx (CP + NTFx); (2) CP without NTFx (CP w/o NTFx); (3) without CP and with NTFx (w/o CP + NTFx); and (4) without CP and without NTFx (w/o CP w/o NTFx) after adjusting for demographics and comorbidities., Results: The crude incidence rate was elevated for CP + NTFx vs. CP w/o NTFx and w/o CP + NTFx for each RD measure. After adjustments, the HR was elevated for CP + NTFx vs. CP w/o NTFx for pneumonia and interstitial/pleura disease at all time points (all P  < 0.05), but not chronic obstructive pulmonary disease (e.g., 24-month HR = 1.07; 95%CI = 0.88-1.31). The adjusted HR was elevated for CP + NTFx vs. w/o CP + NTFx for pneumonia at all time points, interstitial/pleura disease at 12- and 24-month time points, and chronic obstructive pulmonary disease at 24-months (all P  < 0.05). There is evidence of a time-dependent effect of NTFx on pneumonia and interstitial/pleura disease for CP + NTFx as compared to CP w/o NTFx., Conclusions: Study findings suggest that NTFx is a risk factor for incident RD, including pneumonia and interstitial/pleura disease, among adults with CP and that NTFx exacerbates RD risk for adults with vs. without CP., Competing Interests: None., (© 2020 The Author(s).)

Background: Individuals with cerebral palsy (CP) manifest skeletal fragility problems early in life, are vulnerable to non-trauma fracture (NTFx), and have a high burden of premature mortality. No studies have examined the contribution of NTFx to mortality among adults with CP. The purpose of this study was to determine if NTFx is a risk factor for mortality among adults with CP and if NTFx exacerbates mortality risk compared to adults without CP., Methods: Data from 2011 to 2016 Optum Clinformatics® Data Mart and a random 20% sample Medicare fee-for-service were used for this retrospective cohort study. Diagnosis codes were used to identify adults (18+ years) with and without CP, NTFx, and pre-NTFx comorbidities. Crude mortality rates per 100 person years were estimated. Cox regression estimated hazard ratios (HR and 95% confidence interval [CI]) for mortality, comparing: (1) CP and NTFx (CP + NTFx; n  = 1777); (2) CP without NTFx (CP w/o NTFx; n  = 12,933); (3) without CP and with NTFx (w/o CP + NTFx; n  = 433,560); and (4) without CP and without NTFx (w/o CP w/o NTFx; n  = 6.8 M) after adjusting for demographics and pre-NTFx comorbidities., Results: The 3-, 6-, and 12-month crude mortality rates were highest among CP + NTFx (12-month mortality rate = 6.80), followed by w/o CP + NTFx (12-month mortality rate = 4.91), CP w/o NTFx (12-month mortality rate = 2.15), and w/o CP w/o NTFx (12-month mortality rate = 0.49). After adjustments, the mortality rate was elevated for CP + NTFx for all time points compared to CP w/o NTFx (e.g., 12-month HR = 1.61; 95%CI = 1.29-2.01), w/o CP + NTFx (e.g., 12-month HR = 1.49; 95%CI = 1.24-1.80), and w/o CP w/o NTFx (e.g., 12-month HR = 5.33; 95%CI = 4.42-6.44). There were site-specific effects (vertebral column, lower extremities) on 12-month mortality., Conclusions: NTFx is associated with an increase of 12-month mortality risk among adults with CP and compared to adults without CP. Findings suggest that NTFx may be a robust risk factor for mortality among adults with CP., Competing Interests: None., (© 2020 The Author(s).)

The reliability of lipidomics, an approach to identify the presence and interactions of lipids, to analyze the bone marrow lipid composition among pediatric populations with bone fragility is unknown. The objective of this study was to assess the test-retest reliability, standard error of measurement (SEM), and the minimal detectable change (MDC) of vertebral bone marrow lipid composition determined by targeted lipidomics among children with varying degrees of bone fragility undergoing routine orthopedic surgery. Children aged 10 to 19 years, with a confirmed diagnosis of adolescent idiopathic scoliosis ( n = 13) or neuromuscular scoliosis and cerebral palsy ( n = 3), undergoing posterior spinal fusion surgery at our institution were included in this study. Transpedicular vertebral body bone marrow samples were taken from thoracic vertebrae (T11, 12) or lumbar vertebrae (L1 to L4). Lipid composition was assessed via targeted lipidomics and all samples were analyzed in the same batch. Lipid composition measures were examined as the saturated, monounsaturated, and polyunsaturated index and as individual fatty acids. Relative and absolute test-retest reliability was assessed using the intraclass correlation coefficient (ICC), SEM, and MDC. Associations between demographics and index measures were explored. The ICC, SEM, and MDC were 0.81 (95% CI, 0.55-0.93), 1.6%, and 4.3%, respectively, for the saturated index, 0.66 (95% CI, 0.25-0.87), 3.5%, and 9.7%, respectively, for the monounsaturated index, and 0.60 (95% CI, 0.17-0.84), 3.6%, and 9.9%, respectively, for the polyunsaturated index. For the individual fatty acids, the ICC showed a considerable range from 0.04 (22:2n-6) to 0.97 (18:3n-3). Age was positively correlated with the saturated index ( r 2 = 0.36; p = 0.014) and negatively correlated with the polyunsaturated index ( r 2 = 0.26; p = 0.043); there was no difference in index measures by sex ( p  > 0.58). The test-retest reliability was moderate-to-good for index measures and poor to excellent for individual fatty acids; this information can be used to power research studies and identify measures for clinical or research monitoring. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research., (© 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.)

Sclerostin antibody (SclAb) therapy has been suggested as a novel therapeutic approach toward addressing the fragility phenotypic of osteogenesis imperfecta (OI). Observations of cellular and transcriptional responses to SclAb in OI have been limited to mouse models of the disorder, leaving a paucity of data on the human OI osteoblastic cellular response to the treatment. Here, we explore factors associated with response to SclAb therapy in vitro and in a novel xenograft model using OI bone tissue derived from pediatric patients. Bone isolates (approximately 2 mm 3 ) from OI patients (OI type III, type III/IV, and type IV, n = 7; non-OI control, n = 5) were collected to media, randomly assigned to an untreated (UN), low-dose SclAb (TRL, 2.5 μg/mL), or high-dose SclAb (TRH, 25 μg/mL) group, and maintained in vitro at 37°C. Treatment occurred on days 2 and 4 and was removed on day 5 for TaqMan qPCR analysis of genes related to the Wnt pathway. A subset of bone was implanted s.c. into an athymic mouse, representing our xenograft model, and treated (25 mg/kg s.c. 2×/week for 2/4 weeks). Implanted OI bone was evaluated using μCT and histomorphometry. Expression of Wnt/Wnt -related targets varied among untreated OI bone isolates. When treated with SclAb, OI bone showed an upregulation in osteoblast and osteoblast progenitor markers, which was heterogeneous across tissue. Interestingly, the greatest magnitude of response generally corresponded to samples with low untreated expression of progenitor markers. Conversely, samples with high untreated expression of these markers showed a lower response to treatment. in vivo implanted OI bone showed a bone-forming response to SclAb via μCT, which was corroborated by histomorphometry. SclAb induced downstream Wnt targets WISP1 and TWIST1 , and elicited a compensatory response in Wnt inhibitors SOST and DKK1 in OI bone with the greatest magnitude from OI cortical bone. Understanding patients' genetic, cellular, and morphological bone phenotypes may play an important role in predicting treatment response. This information may aid in clinical decision-making for pharmacological interventions designed to address fragility in OI. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research., (© 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.)

Background: A previous study showed significantly higher serum titanium levels in patients with early-onset scoliosis (EOS) treated with traditional growing rods (TGR) and magnetically controlled growing rods (MCGR) compared with controls. Children with vertical expandable prosthetic titanium rib (VEPTR) were not assessed. The purpose of this study was to compare serum titanium levels in EOS patients treated with TGR, MCGR, and VEPTR. We hypothesized that EOS patients treated with all forms of growth-friendly instrumentation (GFI) have elevated serum titanium levels., Methods: This was a prospective cross-sectional case series. Serum titanium levels were collected from patients with GFI who were enrolled in an EOS database. Blood samples were collected at a clinic visit or lengthening/exchange procedure between April and December 2018. The normal range for serum titanium is 0 to 1 ng/mL. Analyses were conducted using analysis of variance and Bonferroni post hoc test., Results: A total of 23 patients (2 TGR, 8 MCGR, 13 VEPTR) were analyzed. There was a significant difference in age at the time of blood sample collection (12.5 vs. 9.8 vs. 7.5 y, P=0.015) and serum titanium level (1.5 vs. 4.5 vs. 7.6 ng/mL, P=0.021) between TGR, MCGR, and VEPTR, respectively. All of the MCGR and VEPTR patients had a serum titanium level ≥2 ng/mL. Binary comparisons showed that VEPTR had a significantly higher serum titanium level than TGR (P=0.046). There was no difference in serum titanium level when MCGR was compared with TGR and VEPTR. Time from implant insertion to blood sample collection, number of rods currently implanted, total number of rods implanted throughout treatment, and number of lengthenings per patient was similar between the groups., Conclusions: Elevated serum titanium levels may be present in EOS patients treated with all forms of GFI. Although our TGR patients had indwelling implants for the longest period of time, they had the lowest serum titanium level. Repetitive chest wall motion during respiration may lead to continued wear and metal ion release with VEPTR., Level of Evidence: Level II-therapeutic.

Background: Magnetically controlled growing rods (MCGR) have become a popular surgical option for the treatment of early-onset scoliosis. Both radiographs and ultrasound are currently used to measure the amount of length achieved when MCGRs are distracted. Previous studies have investigated the intraobserver and interobserver reliability of radiographic and ultrasound measurements of MCGR distraction. Some authors have reported that there is a "learning curve" in measuring MCGR lengthening with ultrasound, suggesting that new users require several months of experience before they can accurately perform the measurements. The goal of this study was to determine whether surgical experience of the rater is associated with the accuracy of radiographic and ultrasound measurements of MCGR distraction., Methods: Six raters evaluated 29 deidentified radiographs and 30 ultrasound images from early-onset scoliosis patients with MCGR. Raters had varying levels of experience, ranging from a senior fellowship-trained pediatric orthopaedic surgeon to a junior orthopaedic surgery resident. Raters measured the amount of rod distraction in 2 sessions spaced 2 weeks apart. All raters were provided with a document demonstrating the radiographic and ultrasound measurement techniques before the first round of measurements. Intraclass correlation coefficients were calculated., Results: Excellent intraobserver and interobserver agreement was achieved for both radiographic and ultrasound measurements of MCGR distraction. Subanalysis based on experience level showed that excellent intraobserver agreement was maintained with no evidence of decreased reliability in raters with less experience., Conclusions: Excellent intraobserver and interobserver agreement was obtained with radiographic and ultrasound measurements of MCGR distraction, regardless of the experience level of the rater. Posting a document with the radiographic and ultrasound measurement techniques in the orthopaedic surgery clinic, and perhaps also the radiology reading room may help avoid inaccurate measurements of distraction length secondary to a learning curve., Level of Evidence: Level III-diagnostic.

Background: The 24-item Early-Onset Scoliosis Questionnaire (EOSQ-24) and 22-item Scoliosis Research Society (SRS-22) questionnaire measure health-related quality of life in patients with scoliosis. The EOSQ-24 has been recently validated in early-onset scoliosis (EOS), including congenital scoliosis (CS). The SRS-22 has been validated in idiopathic scoliosis. The EOSQ-24 is completed by the caregiver and the SRS-22 is completed by the patient. The primary purpose of this study was to compare the EOSQ-24 and SRS-22 in patients with CS. The secondary purpose was to compare scores by age and also in developmentally delayed patients. We hypothesized that the SRS-22 is appropriate for children with EOS from CS who do not have a diagnosis of developmental delay., Methods: This was a prospective comparative study. A prospective institutional CS database was queried to identify patients who had the EOSQ-24 and SRS-22 completed at the same time point. Children without a diagnosis of developmental delay completed both questionnaires if they understood the questions, regardless of age. Otherwise, the caregiver completed both questionnaires. For the analysis, similar questions were matched so that the EOSQ-24 questions fit into the SRS-22 domains of Function, Pain, Mental Health, and Satisfaction. Pearson correlation coefficients (r) were used to compare domain scores, with r≥0.70 indicating a strong relationship., Results: The final study group included 98 patients. The average age at completion of the questionnaires was 9.5 years. A strong correlation was found for all domains except Satisfaction when the patient or caregiver completed both questionnaires. Subanalysis demonstrated the strongest relationship between domains in the age group 0 to 5 years. In developmentally delayed patients, a weak correlation was noted for all domain scores except Pain, which showed a strong correlation. There was a strong correlation for Pain and a weak correlation for Satisfaction domains across all subgroups., Conclusions: The SRS-22 may be appropriate for children with EOS from CS who do not have a diagnosis of developmental delay. Our findings suggest that the results of previous studies that collected the SRS-22 and future studies that collect the EOSQ-24 can be correlated. It remains unclear which questionnaire is more suitable for developmentally delayed patients., Level of Evidence: Level I-diagnostic.

Background: Current estimates suggest that one third of children and adolescents are overweight and 1 in 5 are obese. Obese children are at increased risk of sustaining more complex fractures, failing nonoperative treatment, and experiencing more complications during treatment. The purpose of this study was to compare forearm fracture characteristics, treatment, and complications in grouped overweight and obese [OW+OB; body mass index-for-age percentile (BMI%) ≥85] pediatric patients compared with normal-weight (NW; BMI%≤84) patients., Methods: This was a retrospective comparative study of patients aged 2 to 17 years old who presented with a forearm fracture resulting from low-energy trauma between January 2010 and September 2017. Patients with incomplete height and weight data; an underlying condition that predisposes to fractures or altered fracture healing; and torus, greenstick, pathologic, and high-energy fractures were excluded. Demographics, fracture characteristics, treatment, and complications were recorded. Descriptive and inferential analyses were conducted., Results: A total of 565 patients (403 NW, 162 OW+OB) met the inclusion criteria. NW children sustained open fractures nearly twice as frequently as the OW+OB children but this was not statistically significant (9.7% vs. 4.9%; P=0.065). Subanalysis showed that NW children were 4.1 times more likely to sustain an open fracture compared with obese (BMI%≥95) children (9.7% vs. 2.4%; P=0.029). A significant relationship was found between BMI% and location of the fracture, the bones involved, and fracture type. The OW+OB children sustained more distal forearm fractures than midshaft and proximal forearm fractures. Isolated radial shaft fractures were more common in the OW+OB group, whereas isolated ulnar shaft fractures were more common in the NW group. There was no difference in associated neurovascular injury, initial nonoperative versus operative management, failure of nonoperative treatment, and treatment complications., Conclusions: OW+OB children have different forearm fracture characteristics compared with their NW peers. The thick soft tissue envelope in obese children may be protective against an open forearm fracture. In contrast to previous studies, obesity was not associated with failure of nonoperative treatment or a higher rate of complications., Level of Evidence: Level III-prognostic.

Osteogenesis imperfecta (OI) is a rare and severe skeletal dysplasia marked by low bone mass and poor bone quality which is especially burdensome during childhood. Since clinical trials for pediatric OI are difficult, there is a widespread reliance on genetically modified murine models to understand the skeletal effects of emerging therapeutics. However a common model does not yet exist to understand how patient-specific genotype may influence treatment efficacy. Recently, sclerostin antibody (SclAb) has been introduced as a novel putative anabolic therapy for diseases of low bone mass, but effects in pediatric patients remain unexplored. In this study, we aim to establish a direct xenograft approach using OI patient-derived bone isolates which retain patient-specific genetic defects and cells residing in their intrinsic extracellular environment to evaluate the bone-forming effects of SclAb as a bridge to clinical trials. OI and age matched non-OI patient bone typically discarded as surgical waste during corrective orthopaedic procedures were collected, trimmed and implanted subcutaneously (s.c.) on the dorsal surface of 4-6-week athymic mice. A subset of implanted mice were evaluated at short (1 week), intermediate (4 week), and long-term (12 week) durations to assess bone cell survival and presence of donor bone cells in order to determine an appropriate treatment duration. Remaining implanted mice were randomly assigned to a two or four-week SclAb-treated (25mg/kg s.c. 2QW) or untreated control group. Immunohistochemistry determined osteocyte and osteoblast donor/host relationship, TRAP staining quantified osteoclast activity, and TUNEL assay was used to understand rates of bone cell apoptosis at each implantation timepoint. Longitudinal changes of in vivo μCT outcomes and dynamic histomorphometry were used to assess treatment response and ex vivo μCT and dynamic histomorphometry of host femora served as a positive internal control to confirm a bone forming response to SclAb. Human-derived osteocytes and lining cells were present up to 12 weeks post-implantation with nominal cell apoptosis in the implant. Sclerostin expression remained donor-derived throughout the study. Osterix expression was primarily donor-derived in treated implants and shifted in favor of the host when implants remained untreated. μCT measures of BMD, TMD, BV/TV and BV increased with treatment but response was variable and impacted by bone implant morphology (trabecular, cortical) which was corroborated by histomorphometry. There was no statistical difference between treated and untreated osteoclast number in the implants. Host femora confirmed a systemic bone forming effect of SclAb. Findings support use of the xenograft model using solid bone isolates to explore the effects of novel bone-targeted therapies. These findings will impact our understanding of SclAb therapy in pediatric OI tissue through establishing the efficacy of this treatment in human cells prior to extension to the clinic., (Copyright © 2019 Elsevier Inc. All rights reserved.)