Publications by authors named "Michelle S Caird"

95 Publications

Critical periods of bone health across the lifespan for individuals with cerebral palsy: Informing clinical guidelines for fracture prevention and monitoring.

Bone 2021 Sep 18;150:116009. Epub 2021 May 18.

Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA.

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.
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http://dx.doi.org/10.1016/j.bone.2021.116009DOI Listing
September 2021

Fracture characteristics by age, sex, and ambulatory status among individuals with cerebral palsy: a descriptive study.

Disabil Rehabil 2021 May 7:1-7. Epub 2021 May 7.

Department of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor, MI, USA.

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;  = 57) and adults (18-70 years;  = 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.
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http://dx.doi.org/10.1080/09638288.2021.1921860DOI Listing
May 2021

The effect of age when initiating anti-seizure medication therapy on fragility fracture risk for children with epilepsy.

Bone 2021 Aug 5;149:115996. Epub 2021 May 5.

Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA.

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.
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http://dx.doi.org/10.1016/j.bone.2021.115996DOI Listing
August 2021

Higher pedicle screw density does not improve curve correction in Lenke 2 adolescent idiopathic scoliosis.

J Orthop Surg Res 2021 Apr 21;16(1):276. Epub 2021 Apr 21.

C.S. Mott Children's Hospital, University of Michigan Health System, Ann Arbor, MI, USA.

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.
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http://dx.doi.org/10.1186/s13018-021-02415-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061215PMC
April 2021

The Effect of Osteoporosis Medication on Risk Attenuation of Non-Trauma Fracture Among Adults with Cerebral Palsy: A Propensity Score-Matched Observational Study.

Clin Epidemiol 2021 12;13:91-102. Epub 2021 Feb 12.

Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA.

Purpose: 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 (CP) and without CP with Meds (non-CP; reflects "background" population) served as controls and were matched (6:1 ratio) to adults with CP with Meds (CP; 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 CP (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.
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http://dx.doi.org/10.2147/CLEP.S294202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886102PMC
February 2021

Use of the Behavior Assessment Tool in 18 Pilot Residency Programs.

JB JS Open Access 2020 Oct-Dec;5(4). Epub 2020 Nov 23.

Department of Orthopaedic Surgery, University of Minnesota, Minneapolis, Minnesota.

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 (
Level Of Evidence: Level II.
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http://dx.doi.org/10.2106/JBJS.OA.20.00103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682982PMC
November 2020

The respiratory disease burden of non-traumatic fractures for adults with cerebral palsy.

Bone Rep 2020 Dec 27;13:100730. Epub 2020 Oct 27.

Department of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor, MI, USA.

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  < 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  < 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.
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http://dx.doi.org/10.1016/j.bonr.2020.100730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645631PMC
December 2020

Test-Retest Reliability and Correlates of Vertebral Bone Marrow Lipid Composition by Lipidomics Among Children With Varying Degrees of Bone Fragility.

JBMR Plus 2020 Oct 8;4(10):e10400. Epub 2020 Sep 8.

Department of Orthopaedic Surgery University of Michigan Ann Arbor MI USA.

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 ( = 13) or neuromuscular scoliosis and cerebral palsy ( = 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 ( = 0.36; = 0.014) and negatively correlated with the polyunsaturated index ( = 0.26; = 0.043); there was no difference in index measures by sex ( > 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. published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbm4.10400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574707PMC
October 2020

Pattern of bone marrow lipid composition measures along the vertebral column: A descriptive study of adolescents with idiopathic scoliosis.

Bone 2021 01 21;142:115702. Epub 2020 Oct 21.

Department of Orthopaedic Surgery, University of Michigan, A. Alfred Taubman Biomedical Sciences Research Building, Room 2009, Ann Arbor, MI 48109, United States of America.

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.
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http://dx.doi.org/10.1016/j.bone.2020.115702DOI Listing
January 2021

The mortality burden of non-trauma fracture for adults with cerebral palsy.

Bone Rep 2020 Dec 7;13:100725. Epub 2020 Oct 7.

Department of Orthopaedic Surgery, University of Michigan, 1540 E Hospital Dr., Ann Arbor, MI 48109, United States of America.

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;  = 1777); (2) CP without NTFx (CP w/o NTFx;  = 12,933); (3) without CP and with NTFx (w/o CP + NTFx;  = 433,560); and (4) without CP and without NTFx (w/o CP w/o NTFx;  = 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.
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http://dx.doi.org/10.1016/j.bonr.2020.100725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560646PMC
December 2020

Intersite reliability of vertebral bone marrow lipidomics-derived lipid composition among children with varying degrees of bone fragility undergoing routine orthopedic surgery.

Bone 2021 02 11;143:115633. Epub 2020 Sep 11.

Department of Orthopaedic Surgery, University of Michigan, A. Alfred Taubman Biomedical Sciences Research Building, Room 2009, Ann Arbor, MI 48109, United States of America.

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_n-9) to 0.88 (15:0 and 18:3_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.
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http://dx.doi.org/10.1016/j.bone.2020.115633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770023PMC
February 2021

Gene Expression Profile and Acute Gene Expression Response to Sclerostin Inhibition in Osteogenesis Imperfecta Bone.

JBMR Plus 2020 Aug 4;4(8):e10377. Epub 2020 Jul 4.

Department of Biomedical Engineering University of Michigan Ann Arbor MI USA.

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) from OI patients (OI type III, type III/IV, and type IV, = 7; non-OI control, = 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 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 -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 targets and , and elicited a compensatory response in inhibitors and 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. published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbm4.10377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7422710PMC
August 2020

Elevated Serum Titanium Levels in Children With Early Onset Scoliosis Treated With Growth-friendly Instrumentation.

J Pediatr Orthop 2020 Jul;40(6):e420-e423

Department of Orthopaedic Surgery, C.S. Mott Children's Hospital, Michigan Medicine, Ann Arbor, MI.

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.
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http://dx.doi.org/10.1097/BPO.0000000000001463DOI Listing
July 2020

Osteoporosis Epidemiology Among Adults With Cerebral Palsy: Findings From Private and Public Administrative Claims Data.

JBMR Plus 2019 Nov 7;3(11):e10231. Epub 2019 Oct 7.

Department of Physical Medicine and Rehabilitation, Michigan Medicine University of Michigan Ann Arbor MI USA.

Individuals with cerebral palsy (CP) have an increased risk for the early development of osteoporosis; however, little is known about the epidemiology of osteoporosis for adults with CP, which is vital to inform clinical practice for osteoporosis prevention, treatment, and management. The purpose of this cross-sectional study was to determine sex-stratified prevalence of osteoporosis among adults with CP, as compared with adults without CP. Data from 2016 were extracted from Optum Clinformatics Data Mart (private insurance administrative claims data) and a random 20% sample from the fee-for-service Medicare (public insurance administrative claims data). Diagnostic codes were used to identify CP and osteoporosis diagnoses. Sex-stratified prevalence of osteoporosis was compared between adults with and without CP for the following age groups: 18 to 30, 31 to 40, 41 to 50, 51 to 60, 61 to 70, and >70 years of age. The overall prevalence of osteoporosis was 4.8% for adults without CP ( = 8.7 million), 8.4% for privately insured adults with CP ( = 7,348), and 14.3% for publicly insured adults with CP ( = 21,907). Women and men with CP had a higher prevalence of osteoporosis compared with women and men without CP for all age groups. Finally, publicly insured women and men with CP had a higher prevalence of osteoporosis compared with privately insured women and men with CP for all age groups, except for the similar prevalence among the 18- to 30-year age group. These findings suggest that osteoporosis is more prevalent among adults with CP compared with adults without CP. Study findings highlight the need for earlier screening and preventive medical services for osteoporosis management among adults with CP. © 2019 The Authors. published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbm4.10231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6874176PMC
November 2019

A xenograft model to evaluate the bone forming effects of sclerostin antibody in human bone derived from pediatric osteogenesis imperfecta patients.

Bone 2020 01 31;130:115118. Epub 2019 Oct 31.

Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.bone.2019.115118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918492PMC
January 2020

Elevated fracture risk for adults with neurodevelopmental disabilities.

Bone 2020 01 24;130:115080. Epub 2019 Oct 24.

Department of Physical Medicine and Rehabilitation, University of Michigan, 325 E. Eisenhower, Ann Arbor, MI 48108, USA; Institute for Healthcare Policy and Innovation, University of Michigan, 2800 Plymouth Rd., Ann Arbor, MI 48109, USA.

Background: Fracture is a high-burden condition that accelerates unhealthful aging and represents a considerable economic burden. Adults with neurodevelopmental disabilities (NDDs) may be susceptible for fracture at younger ages compared to adults without NDDs; and yet, very little is known about the burden of fracture for these underserved populations. The purpose of this study was to determine the sex-stratified prevalence of all-cause fracture among adults with NDDs, as compared to adults without NDDs, and if comorbidity of NDDs is associated with greater risk of fracture.

Methods: Data from 2016 were extracted from Optum Clinformatics® Data Mart (private insurance) and a random 20% sample from Medicare fee-for-service (public insurance). ICD-10-CM diagnosis codes were used to identify adults with NDDs, including intellectual disabilities, autism spectrum disorders, and cerebral palsy. Age-standardized prevalence of any fracture and fracture by anatomical location was compared between adults with and without NDDs, and then for adults with 1 NDD vs. 2 and 3 NDDs.

Results: Adults with intellectual disabilities (n=69,456), autism spectrum disorders (n=21,844), and cerebral palsy (n=29,255) had a higher prevalence of any fracture compared to adults without NDDs (n=8.7 million). For women, it was 8.3%, 8.1%, and 8.5% vs. 3.5%, respectively. For men, it was 6.6%, 5.9%, and 6.7% vs. 3.0%, respectively. Women with NDDs had a higher prevalence of fracture of the head/neck, thoracic, lumbar/pelvis, upper extremities, and lower extremities compared to women without NDDs. A similar pattern was observed for men, except for no difference for lumbar/pelvis for all NDDs and thoracic for autism spectrum disorders. For women and men, increasing comorbidity of NDDs was associated with a higher prevalence of any fracture: 1 NDD (women, 7.7%; men, 5.7%); 2 NDDs (women, 9.4%; men, 7.2%); all 3 NDDs (women, 11.3%; men, 13.7%).

Conclusions: Study findings suggest that adults with NDDs have an elevated prevalence of fracture compared to adults without NDDs, with the fracture risk being higher with greater numbers of comorbid NDD conditions for most anatomical locations. Our study findings indicate a need for earlier screening and preventive services for musculoskeletal frailty for adults with NDDs.
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http://dx.doi.org/10.1016/j.bone.2019.115080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065344PMC
January 2020

Hoverboard injuries in children and adolescents: results of a multicenter study.

J Pediatr Orthop B 2019 Nov;28(6):555-558

St. Christopher Children's Hospital, Philadelphia, Pennsylvania, USA.

With the increasing popularity of hoverboards in recent years, multiple centers have noted associated orthopaedic injuries of riders. We report the results of a multi-center study regarding hoverboard injuries in children and adolescents. who presented with extremity fractures while riding hoverboards to 12 paediatric orthopaedic centers during a 2-month period were included in the study. Circumstances of the injury, location, severity, associated injuries, and the required treatment were recorded and analysed using descriptive analysis to report the most common injuries. Between-group differences in injury location were examined using chi-squared statistics among (1) children versus adolescents and (2) males versus females. Seventy-eight patients (M/F ratio: 1.8) with average age of 11 ± 2.4 years were included in the study. Of the 78 documented injuries, upper extremity fractures were the most common (84.6%) and the most frequent fracture location overall was at the distal radius and ulna (52.6%), while ankle fractures comprised most of the lower extremity fractures (66.6%). Majority of the distal radius fractures (58.3%) and ankle fractures (62.5%) were treated with immobilization only. Seventeen displaced distal radius fractures and three displaced ankle fractures were treated with closed reduction in the majority of cases (94.1% versus 66.7%, respectively). The distal radius and ulna are the most common fracture location. Use of appropriate protective gear such as wrist guards, as well as adult supervision, may help mitigate the injuries associated with the use of this device; however, further studies are necessary to demonstrate the real effectiveness of these preventions.
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http://dx.doi.org/10.1097/BPB.0000000000000653DOI Listing
November 2019

Level of Experience Does Not Influence the Accuracy of Radiographic and Ultrasound Measurements of Magnetically Controlled Growing Rod Distractions.

J Pediatr Orthop 2020 May/Jun;40(5):e341-e345

Department of Orthopaedic Surgery, C.S. Mott Children's Hospital, Michigan Medicine, Ann Arbor, MI.

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.
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http://dx.doi.org/10.1097/BPO.0000000000001449DOI Listing
September 2020

Sclerostin Antibody-Induced Changes in Bone Mass Are Site Specific in Developing Crania.

J Bone Miner Res 2019 12 7;34(12):2301-2310. Epub 2019 Nov 7.

Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA.

Sclerostin antibody (Scl-Ab) is an anabolic bone agent that has been shown to increase bone mass in clinical trials of adult diseases of low bone mass, such as osteoporosis and osteogenesis imperfecta (OI). Its use to decrease bone fragility in pediatric OI has shown efficacy in several growing mouse models, suggesting translational potential to pediatric disorders of low bone mass. However, the effects of pharmacologic inhibition of sclerostin during periods of rapid growth and development have not yet been described with respect to the cranium, where lifelong deficiency of functioning sclerostin leads to patterns of excessive bone growth, cranial compression, and facial palsy. In the present study, we undertook dimensional and volumetric measurements in the skulls of growing Brtl/+ OI mice treated with Scl-Ab to examine whether therapy-induced phenotypic changes were similar to those observed clinically in patients with sclerosteosis or Van Buchem disorder. Mice treated between 3 and 14 weeks of age with high doses of Scl-Ab show significant calvarial thickening capable of rescuing OI-induced deficiencies in skull thickness. Other changes in cranial morphology, such as lengths and distances between anatomic landmarks, intracranial volume, and suture interdigitation, showed minimal effects of Scl-Ab when compared with growth-induced differences over the treatment duration. Treatment-induced narrowing of foramina was limited to sites of vascular but not neural passage, suggesting patterns of local regulation. Together, these findings reveal a site specificity of Scl-Ab action in the calvaria with no measurable cranial nerve impingement or brainstem compression. This differentiation from the observed outcomes of lifelong sclerostin deficiency complements reports of Scl-Ab treatment efficacy at other skeletal sites with the prospect of minimal cranial secondary complications. © 2019 American Society for Bone and Mineral Research. © 2019 American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbmr.3858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458133PMC
December 2019

Pamidronate Administration During Pregnancy and Lactation Induces Temporal Preservation of Maternal Bone Mass in a Mouse Model of Osteogenesis Imperfecta.

J Bone Miner Res 2019 11 9;34(11):2061-2074. Epub 2019 Oct 9.

Department of Orthopaedic Surgery, University of Michigan, Ann Arbor, MI, USA.

During pregnancy and lactation, the maternal skeleton undergoes significant bone loss through increased resorption to provide the necessary calcium supply to the developing fetus and suckling neonate. This period of skeletal vulnerability has not been clearly associated with increased maternal fracture risk, but these physiological conditions can exacerbate an underlying metabolic bone condition like osteogenesis imperfecta. Although bisphosphonates (BPs) are commonly used in postmenopausal women, there are cases where premenopausal women taking BPs become pregnant. Given BPs' long half-life, there is a need to establish how BPs affect the maternal skeleton during periods of demanding metabolic bone changes that are critical for the skeletal development of their offspring. In the present study, pamidronate- (PAM-) amplified pregnancy-induced bone mass gains and lactation-induced bone loss were prevented. This preservation of bone mass was less robust when PAM was administered at late stages of lactation compared with early pregnancy and first day of lactation. Pregnancy-induced osteocyte osteolysis was also observed and was unaffected with PAM treatment. No negative skeletal effects were observed in offspring from PAM-treated dams despite lactation-induced bone loss prevention. These findings provide important insight into (1) a treatment window for when PAM is most effective in preserving maternal bone mass, and (2) the maternal changes in bone metabolism that maintain calcium homeostasis crucial for fetal and neonatal bone development. © 2019 American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbmr.3831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854294PMC
November 2019

Management of Pediatric Type I Open Fractures in the Emergency Department or Operating Room: A Multicenter Perspective.

J Pediatr Orthop 2019 Aug;39(7):372-376

Children's Hospital of Philadelphia, Philadelphia, PA.

Background: The management of pediatric type I open fractures remains controversial. The aim of this study is to compare outcomes in type I open fractures managed with superficial wound debridement and antibiotics in the emergency department (ED) (nonoperative management) to patients managed with operative debridement and antibiotics (operative management).

Methods: A multicenter retrospective review was performed of all pediatric type I open forearm, wrist, and tibia fractures treated at 4 high volume pediatric centers between 2000 and 2015. Patients with multiple traumatic injuries, immunocompromised patients, or those without final radiographs indicating healing were excluded.

Results: In total, 219 patients met inclusion criteria. A total of 170 fractures were treated operatively (77.6%), 49 fractures were treated nonoperatively (22.4%). There was 1 infection in the nonoperative group (2.0% infection rate), and no infections in the operatively managed group (P=0.062). Cefazolin was the most commonly administered antibiotic (88.1% of patients). Duration of hospital-administered antibiotics was significantly different, with a mean of 10.9 hours in the nonoperative group and 41.6 hours in the operative group (P<0.001). Length of stay averaged 16.3 hours for nonoperative patients and 48.6 hours for the operatively treated patients (P<0.001). In the nonoperative group, 44/49 had documented superficial wound debridement in the ED utilizing, on an average, 1500 mL of irrigant. There were 10 other complications, 9 in the operative group (5.4%) and 2 in the nonoperative group (4.1%, P=0.107), including 2 compartment syndromes and 1 acute carpal tunnel syndrome all requiring immediate surgical release (1.8%) in the operative group.

Conclusions: There was no significant difference in infection rate or complication rate in those managed with antibiotics and operative debridement versus those managed with superficial wound debridement and antibiotics in the ED. Consideration should be given to the similar safety profiles for these 2 treatment modalities when managing pediatric patients with type I open fractures.

Level Of Evidence: Level III.
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http://dx.doi.org/10.1097/BPO.0000000000000972DOI Listing
August 2019

Comparison of EOSQ-24 and SRS-22 Scores in Congenital Scoliosis: A Preliminary Study.

J Pediatr Orthop 2020 Mar;40(3):e182-e185

Department of Orthopaedic Surgery, C.S. Mott Children's Hospital, Michigan Medicine, Ann Arbor, MI.

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.
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http://dx.doi.org/10.1097/BPO.0000000000001412DOI Listing
March 2020

Obese Children Have Different Forearm Fracture Characteristics Compared With Normal-weight Children.

J Pediatr Orthop 2020 Feb;40(2):e127-e130

Department of Orthopaedic Surgery, C.S. Mott Children's Hospital, Michigan Medicine, Ann Arbor, MI.

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.
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http://dx.doi.org/10.1097/BPO.0000000000001402DOI Listing
February 2020

Adults with Cerebral Palsy have Higher Prevalence of Fracture Compared with Adults Without Cerebral Palsy Independent of Osteoporosis and Cardiometabolic Diseases.

J Bone Miner Res 2019 07 6;34(7):1240-1247. Epub 2019 Mar 6.

Department of Physical Medicine and Rehabilitation, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA.

Individuals with cerebral palsy (CP) have an increased risk of fracture throughout their lifespan based on an underdeveloped musculoskeletal system, excess body fat, diminished mechanical loading, and early development of noncommunicable diseases. However, the epidemiology of fracture among adults with CP is unknown. The purpose of this cross-sectional study was to determine the prevalence of fracture among a large sample of privately insured adults with CP, as compared with adults without CP. Data were from the Optum Clinformatics Data Mart (Eden Prairie, MN, USA), a deidentified nationwide claims database of beneficiaries from a single private payer. Diagnostic codes were used to identify 18- to 64-year-old beneficiaries with and without CP and any fracture that consisted of osteoporotic pathological fracture as well as any type of fracture of the head/neck, thoracic, lumbar/pelvic, upper extremity, and lower extremity regions. The prevalence of any fracture was compared between adults with (n = 5,555) and without (n = 5.5 million) CP. Multivariable logistic regression was performed with all-cause fracture as the outcome and CP group as the primary exposure. Adults with CP had a higher prevalence of all-cause fracture (6.3% and 2.7%, respectively) and fracture of the head/neck, thoracic, lumbar/pelvic, upper extremity, and lower extremity regions compared with adults without CP (all p < 0.01). After adjusting for sociodemographic and socioeconomic variables, adults with CP had higher odds of all-cause fracture compared with adults without CP (OR 2.5; 95% CI, 2.2 to 2.7). After further adjusting for cardiometabolic diseases, adults with CP had higher odds of all-cause fracture compared with adults without CP (OR 2.2; 95% CI, 2.0 to 2.5). After further adjusting for osteoporosis, adults with CP still had higher odds of all-cause fracture compared with adults without CP (OR 2.0; 95% CI, 1.8 to 2.2). These findings suggest that young and middle-aged adults with CP have an elevated prevalence of all-cause fracture compared with adults without CP, which was present even after accounting for cardiometabolic diseases and osteoporosis. © 2019 American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbmr.3694DOI Listing
July 2019

A cluster of high psychological and somatic symptoms in children with idiopathic scoliosis predicts persistent pain and analgesic use 1 year after spine fusion.

Paediatr Anaesth 2018 10;28(10):873-880

Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan.

Background: Persistent postoperative pain is a significant problem for many children, particularly for those undergoing major surgery such as posterior spine fusion. More than two-thirds report persistent pain after spine fusion, yet factors that may contribute to poorer outcomes remain poorly understood.

Aims: This prospective, longitudinal study examined how psychologic and somatic symptoms cluster together in children aged 10-17 years with idiopathic scoliosis, and tested the hypothesis that a higher psychological and somatic symptom cluster would predict worse pain outcomes 1 year after fusion.

Methods: Otherwise healthy children with idiopathic scoliosis completed preoperative surveys measuring recent pain intensity, pain location(s), somatic symptom severity, painDETECT (neuropathic-type pain symptoms), pain interference, fatigue, depression, anxiety, and pain catastrophizing. Pain outcome data were collected during hospitalization, and at 1 year after surgery.

Results: Ninety-five children completed baseline surveys and a cluster analysis differentiated 28 (30%) with a high symptom profile that included; higher depression, fatigue, pain interference, catastrophizing, and painDETECT scores. High symptom cluster membership independently predicted higher pain interference at 1 year (β 9.92 [95% CI 6.63, 13.2], P < 0.001). Furthermore, children in this high symptom cluster reported significantly higher pain intensity and painDETECT scores, and had a 50% higher probability of continued analgesic use at 1 year compared to those in the Low Symptom Cluster (95% CI 21.3-78.5, P = 0.001).

Conclusion: Findings from this exploratory study suggest a need to comprehensively assess children with scoliosis for preoperative signs and symptoms that may indicate an underlying vulnerability for persistent pain. This, in turn may help guide a comprehensive perioperative treatment strategy to mitigate the potential for long-term pain trajectories.
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http://dx.doi.org/10.1111/pan.13467DOI Listing
October 2018

Age trajectories of musculoskeletal morbidities in adults with cerebral palsy.

Bone 2018 09 5;114:285-291. Epub 2018 Jul 5.

Department of Physical Medicine and Rehabilitation, Michigan Medicine, University of Michigan, 325 E. Eisenhower, Ann Arbor, MI 48108, United States. Electronic address:

Background: Individuals with cerebral palsy (CP) are at an increased risk for age-related morbidities due to functional impairments, maladapted growth, and altered body composition. While musculoskeletal (MSK) deficits are present in children, little is understood about MSK morbidity throughout the lifespan in those with CP. The purpose of this study was to examine the age-related trajectories of MSK morbidity and multimorbidity throughout adulthood in those with CP.

Methods: A clinic-based sample of adults with CP (n = 1395; ≥18 years) was examined to determine prevalence of MSK morbidities at the University of Michigan Medical Center. Logistic regression was used to determine the effects of age on individual MSK morbidities and multimorbidity (i.e., ≥2 morbidities) after adjusting for sex, race, weight, and smoking.

Results: With the 18-30 year age group as the reference, the adjusted odds of osteopenia was lower in the 41-50 and >50 year age groups, the odds of osteoporosis and rheumatoid arthritis was higher in 41-50 and >50 year age groups, and the odds of osteoarthritis was higher in 31-40, 41-50, and >50 year age groups. The adjusted odds of MSK multimorbidity increased substantially with increasing age for 31-40 year olds (OR: 1.919; 95% CI 1.05-3.52), 41-50 year olds (OR: 4.30; 95% CI 2.40-7.69), and >50 year olds (OR: 6.05; 95% CI 3.56-10.27).

Conclusions: Adults with CP are at high risk for MSK morbidities across all ages. Future studies are needed to examine the global aging trajectories of MSK health among adults with CP. Study findings highlight the importance of maximizing MSK accretion, and developing programs to assist individuals with CP and their caregivers to maintain MSK mass and function throughout the lifespan.
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http://dx.doi.org/10.1016/j.bone.2018.07.002DOI Listing
September 2018

Bone Marrow Fat Physiology in Relation to Skeletal Metabolism and Cardiometabolic Disease Risk in Children With Cerebral Palsy.

Am J Phys Med Rehabil 2018 12;97(12):911-919

From the Department of Physical Medicine and Rehabilitation, Michigan Medicine, University of Michigan, Ann Arbor, Michigan (DGW, MDP, EAH); Department of Anthropology, University of Michigan, Ann Arbor, Michigan (MJD); Department of Orthopedic Surgery, Michigan Medicine, University of Michigan, Ann Arbor, Michigan (MSC); and Department of Kinesiology, University of Georgia, Athens, Georgia (CMM).

Individuals with cerebral palsy exhibit neuromuscular complications and low physical activity levels. Adults with cerebral palsy exhibit a high prevalence of chronic diseases, which is associated with musculoskeletal deficits. Children with cerebral palsy have poor musculoskeletal accretion accompanied by excess bone marrow fat, which may lead to weaker bones. Mechanistic studies to determine the role of bone marrow fat on skeletal growth and maintenance and how it relates to systemic energy metabolism among individuals with cerebral palsy are lacking. In this review, we highlight the skeletal status in children with cerebral palsy and analyze the existing literature on the interactions among bone marrow fat, skeletal health, and cardiometabolic disease risk in the general population. Clinically vital questions are proposed, including the following: (1) Is the bone marrow fat in children with cerebral palsy metabolically distinct from typically developing children in terms of its lipid and inflammatory composition? (2) Does the bone marrow fat suppress skeletal acquisition? (3) Or, does it accelerate chronic disease development in children with cerebral palsy? (4) If so, what are the mechanisms? In conclusion, although inadequate mechanical loading may initiate poor skeletal development, subsequent expansion of bone marrow fat may further impede skeletal acquisition and increase cardiometabolic disease risk in those with cerebral palsy.
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http://dx.doi.org/10.1097/PHM.0000000000000981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6237626PMC
December 2018

An Analysis of Research Quality and Productivity at Six Academic Orthopaedic Residencies.

J Surg Educ 2018 Nov 6;75(6):1635-1642. Epub 2018 Jun 6.

Womack Army Medical Center, Fort Bragg, North Carolina. Electronic address:

Objective: It remains largely unknown what factors impact the research productivity of residency programs. We hypothesized that dedicated resident research time would not affect the quantity and quality of a program's peer-reviewed publication within orthopedic residencies. These findings may help programs improve structure their residency programs to maximize core competencies.

Design: Three hundred fifty-nine residents and 240 staff from six different US orthopedic residency programs were analyzed. All publications published by residents and faculty at each program from January 2007 to December 2015 were recorded. SCImago Journal Rankings (SJR) were found for each journal.

Results: There were no significant differences in publications by residents at each program (p > 0.05). Faculty with 10+ years of on staff, had significantly more publications than those with less than 10 years (p < 0.01). Programs with increased resident research time did not consistently produce publications with higher SJR than those without dedicated research time.

Conclusions: Increased dedicated resident research time did not increase resident publication rates or lead to publications with higher SJR.
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http://dx.doi.org/10.1016/j.jsurg.2018.04.022DOI Listing
November 2018

Noncommunicable disease and multimorbidity in young adults with cerebral palsy.

Clin Epidemiol 2018 1;10:511-519. Epub 2018 May 1.

Department of Physical Medicine and Rehabilitation, 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.
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http://dx.doi.org/10.2147/CLEP.S159405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5935087PMC
May 2018

Altered corneal biomechanical properties in children with osteogenesis imperfecta.

J AAPOS 2018 06 7;22(3):183-187.e1. Epub 2018 Apr 7.

Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan. Electronic address:

Purpose: To evaluate biomechanical corneal properties in children with osteogenesis imperfecta (OI).

Methods: A prospective, observational, case-control study was conducted on children 6-19 years of age diagnosed with OI. Patients with OI and healthy control subjects underwent complete ophthalmic examinations. Additional tests included Ocular Response Analyzer (ORA) and ultrasonic pachymetry. Primary outcomes were central corneal thickness (CCT), corneal hysteresis (CH), and corneal resistance factor (CRF). Intraocular pressure (IOP) was measured directly by either iCare or Goldmann applanation and indirectly by the ORA (Goldmann-correlated and corneal-compensated IOP). Statistically significant differences between OI and control groups were determined using independent samples t test.

Results: A total of 10 of 18 OI cases (mean age, 13 ± 4.37 years; 8 males) and 30 controls (mean age, 12.76 ± 2.62 years; 16 males) were able to complete the corneal biomechanics and pachymetry testing. Children with OI had decreased CH (8.5 ± 1.0 mm Hg vs 11.6 ± 1.2 mm Hg [P < 0.001]), CRF (9.0 ± 1.9 mm Hg vs 11.5 ± 1.5 [P < 0.001]) and CCT (449.8 ± 30.8 μm vs 568 ± 47.6 μm [P < 0.001]) compared to controls. The corneal-compensated IOP was significantly higher in OI cases (18.8 ± 3.1 mm Hg) than in controls (15.0 ± 1.6 mm Hg, P < 0.004), but there was no significant difference in Goldmann-correlated IOP (16.3 ± 4.2 mm Hg vs 15.8 ± 2.2 mm Hg).

Conclusions: Collagen defects in OI alter corneal structure and biomechanics. Children with OI have decreased CH, CRF, and CCT, resulting in IOPs that are likely higher than measured by tonometry. These corneal alterations are present at a young age in OI. Affected individuals should be routinely screened for glaucoma and corneal pathologies.
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http://dx.doi.org/10.1016/j.jaapos.2017.12.015DOI Listing
June 2018