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

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 (n = 8.7 million), 8.4% for privately insured adults with CP (n = 7,348), and 14.3% for publicly insured adults with CP (n = 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. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral ResearchPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152612/1/jbm410231_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152612/2/jbm410231.pd

Low Dose of Bisphosphonate Enhances Sclerostin Antibody‐Induced Trabecular Bone Mass Gains in Brtl/+ Osteogenesis Imperfecta Mouse Model

Osteogenesis imperfecta (OI) is a genetic disorder characterized by altered bone quality and imbalanced bone remodeling, leading to skeletal fractures that are most prominent during childhood. Treatments for OI have focused on restoring pediatric bone density and architecture to recover functional strength and consequently reduce fragility. Though antiresorptive agents like bisphosphonates (BPs) are currently the most common intervention for the treatment of OI, a number of studies have shown efficacy of sclerostin antibody (SclAb) in inducing gains in bone mass and reducing fragility in OI mouse models. In this study, the effects of the concurrent use of BP and SclAb were evaluated during bone growth in a mouse harboring an OI‐causing Gly→Cys mutation on col1a1. A single dose of antiresorptive BP facilitated the anabolic action of SclAb by increasing availability of surfaces for new bone formation via retention of primary trabeculae that would otherwise be remodeled. Chronic effects of concurrent administration of BP and SclAb revealed that accumulating cycles conferred synergistic gains in trabecular mass and vertebral stiffness, suggesting a distinct advantage of both therapies combined. Cortical gains in mass and strength occurred through SclAb alone, independent of presence of BP. In conclusion, these preclinical results support the scientific hypothesis that minimal antiresorptive treatment can amplify the effects of SclAb during early stages of skeletal growth to further improve bone structure and rigidity, a beneficial outcome for children with OI. © 2018 American Society for Bone and Mineral Research.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144688/1/jbmr3421.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144688/2/jbmr3421_am.pd

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

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 ResearchPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153136/1/jbmr3831.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153136/2/jbmr3831_am.pd

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

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.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150537/1/jbmr3694_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150537/2/jbmr3694.pd

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

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 mm3) 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.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156449/2/jbm410377_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156449/1/jbm410377.pd

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

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 (r2 = 0.36; p = 0.014) and negatively correlated with the polyunsaturated index (r2 = 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.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163414/2/jbm410400_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163414/1/jbm410400.pd

Use of the Behavior Assessment Tool in 18 Pilot Residency Programs

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\u27s 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 \u3c 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

How installers select and explain domestic heating controls

Though central heating controls have the potential to reduce the energy consumed through domestic space heating, their installation does not guarantee savings. End users do not always understand their controls, or operate them in an energy-efficient way, but there is little appreciation of why this is. Drawing on an ethnographic study, this paper investigates how installers select and explain central heating controls. With reference to the concept of technology scripting, which suggests that the assumptions made about users during the design of devices can influence their eventual use, it shows how heating installers also draw on certain user scripts. Through these means the paper illuminates the significant role that heating installers play in influencing the control products fitted into homes, and how they might be used. Though their use of these scripts is understandable, it is not always conducive to ensuring that central heating systems are operated in the most energy-efficient way. It is suggested that industry and policy-makers might engage with how installers understand users and revise current guidelines to foster better communication between them

Integrated Molecular Meta-Analysis of 1,000 Pediatric High-Grade and Diffuse Intrinsic Pontine Glioma.

We collated data from 157 unpublished cases of pediatric high-grade glioma and diffuse intrinsic pontine glioma and 20 publicly available datasets in an integrated analysis of >1,000 cases. We identified co-segregating mutations in histone-mutant subgroups including loss of FBXW7 in H3.3G34R/V, TOP3A rearrangements in H3.3K27M, and BCOR mutations in H3.1K27M. Histone wild-type subgroups are refined by the presence of key oncogenic events or methylation profiles more closely resembling lower-grade tumors. Genomic aberrations increase with age, highlighting the infant population as biologically and clinically distinct. Uncommon pathway dysregulation is seen in small subsets of tumors, further defining the molecular diversity of the disease, opening up avenues for biological study and providing a basis for functionally defined future treatment stratification

Gabapentin and intrathecal morphine combination therapy results in decreased oral narcotic use and more consistent pain scores after posterior spinal fusion for adolescent idiopathic scoliosis

Abstract 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.http://deepblue.lib.umich.edu/bitstream/2027.42/173829/1/13018_2021_Article_2525.pd