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Papers by Maegen Wallace

Osteology, Jan 4, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Springer eBooks, 2020

Osteogenesis imperfecta (OI) has a wide range of presentations and oftentimes presents with recur... more Osteogenesis imperfecta (OI) has a wide range of presentations and oftentimes presents with recurrent femur fractures and/or significant femoral bowing. The concern with femoral bowing is that as children begin to pull to stand, weight bear, cruise, and walk, they are at an increased risk of femur fractures as there are significant tension stresses across the bowed area. Femur fractures, no matter the age or underlying diagnosis, are extremely painful, and in our opinion, avoiding these significantly painful and potentially traumatic experiences is one of the main goals of surgical treatment for patients with OI, as well as decreasing the need for post-fracture immobilization, which causes further osteoporosis, weakness, and stiffness.

Children

Osteogenesis Imperfecta (OI) is a rare genetic disorder in Type I collagen characterized by bone ... more Osteogenesis Imperfecta (OI) is a rare genetic disorder in Type I collagen characterized by bone fractures, fragility, and deformity. Current treatments are focused on decreasing fracture rates, improving bone strength, and improving overall global function. Recent research has focused primarily on fracture fixation and outcomes of intramedullary rodding of long bones. While surgical techniques continue to evolve, recent trends in OI research are focusing on patient quality of life and patient-reported outcomes. We created a 12-question survey seeking information regarding aspects of orthopedic care that OI patients and families feel are the most pressing to improve. The survey was electronically administered, and 341 individuals participated. A total of 75% of respondents who answered the age question (254/335) were adults. Regarding surgical intervention for long bones, only 16% of respondents recall being told they could not have surgery because they were too young. Of the 16%, 3...

Journal of Clinical Investigation, 2022

Osteogenesis imperfecta (OI) is a genetically and phenotypically heterogeneous Mendelian disorder... more Osteogenesis imperfecta (OI) is a genetically and phenotypically heterogeneous Mendelian disorder of connective tissue that has an estimated prevalence of 1 in 10,000 to 20,000 births. Skeletal manifestations of OI include low bone mass, bone fragility, recurrent fractures, scoliosis, and bone deformities. Extraskeletal manifestations include decreased muscle mass, muscle weakness, articular hyperlaxity, dentinogenesis imperfecta, hearing loss, and pulmonary disease (1-5). The management of OI typically involves a multidisciplinary approach that includes pharmacologic therapy to increase bone density, physical medicine and rehabilitation services to optimize function and mobility, audiology evaluations and hearing aids, dental and oral surgery for treatment of dentinogenesis imperfecta and malocclusion, screening for cardiovascular and pulmonary complications, and surgery for treatment of fractures, scoliosis, and bone deformities. Medical therapy for treatment of bone fragility is limited to repurposing of medications that BACKGROUND. Currently, there is no disease-specific therapy for osteogenesis imperfecta (OI). Preclinical studies demonstrate that excessive TGF-β signaling is a pathogenic mechanism in OI. Here, we evaluated TGF-β signaling in children with OI and conducted a phase I clinical trial of TGF-β inhibition in adults with OI. METHODS. Histology and RNA-Seq were performed on bones obtained from children. Gene Ontology (GO) enrichment assay, gene set enrichment analysis (GSEA), and Ingenuity Pathway Analysis (IPA) were used to identify dysregulated pathways. Reverse-phase protein array, Western blot, and IHC were performed to evaluate protein expression. A phase I study of fresolimumab, a TGF-β neutralizing antibody, was conducted in 8 adults with OI. Safety and effects on bone remodeling markers and lumbar spine areal bone mineral density (LS aBMD) were assessed. RESULTS. OI bone demonstrated woven structure, increased osteocytes, high turnover, and reduced maturation. SMAD phosphorylation was the most significantly upregulated GO molecular event. GSEA identified the TGF-β pathway as the top activated signaling pathway, and IPA showed that TGF-β1 was the most significant activated upstream regulator mediating the global changes identified in OI bone. Treatment with fresolimumab was well-tolerated and associated with increases in LS aBMD in participants with OI type IV, whereas participants with OI type III and VIII had unchanged or decreased LS aBMD. CONCLUSION. Increased TGF-β signaling is a driver pathogenic mechanism in OI. Anti-TGF-β therapy could be a potential disease-specific therapy, with dose-dependent effects on bone mass and turnover. TRIAL REGISTRATION. ClinicalTrials.gov NCT03064074. FUNDING. Brittle Bone Disorders Consortium (U54AR068069),

Journal of Pediatric Orthopaedics, 2022

BACKGROUND The mainstay of deformity correction and fracture prevention for patients with osteoge... more BACKGROUND The mainstay of deformity correction and fracture prevention for patients with osteogenesis imperfecta (OI) includes osteotomies and intramedullary rodding. Guided growth, described in the setting of skeletal dysplasias, offers a less invasive means of deformity correction. We report a multicenter case series of guided growth procedures in the setting of OI. METHODS We retrospectively reviewed patients with OI at three institutions from April 2012 to April 2019: 18 patients underwent guided growth for angular deformity correction with minimum 1-year follow-up or full deformity correction and removal of guided growth hardware. Clinical characteristics, deformity measurements, and complications were collected. Distal femoral and proximal tibial hemiepiphysiodesis was performed using figure-of-eight plates and screws, and distal tibial medial hemiepiphysiodesis with cannulated screws. Preoperative and postoperative lateral distal femoral angle, medial proximal tibial angle, and lateral distal tibial angle were measured. Frequency and descriptive statistics were completed. RESULTS Eighteen patients with OI (five-I, four-III, six-IV, three-V) underwent 33 guided growth procedures with mean follow-up of 3.09 years; all received routine bisphosphonate treatment. Preoperative and postoperative mean joint angles were measured. The location for hemiepiphysiodesis included 8 distal femoral medial, 2 distal femoral lateral, 8 proximal tibial medial, 3 proximal tibial lateral, and 12 distal tibial medial. Twelve of the 33 procedures were in patients who had an intramedullary rod; 1 demonstrated backout of the epiphyseal and metaphyseal screws of a distal femoral medial figure-of-eight plate. It was revised to a larger plate with longer screws and removed upon completion of deformity correction. CONCLUSION Guided growth may be used as an effective means of angular deformity correction with dysplastic OI bone. Having an intramedullary rod did not preclude the use of a guided growth technique. One procedure demonstrated screw backout. Given the short stature associated with OI, performing a guided growth procedure at an early enough age to allow time for correction should be considered. LEVEL OF EVIDENCE Level IV-case series.

Graduate Medical Education Research Journal, 2021

Osteogenesis imperfecta (OI) is a rare genetic condition resulting in decreased bone density and ... more Osteogenesis imperfecta (OI) is a rare genetic condition resulting in decreased bone density and bony deformity and a wide variety of extraskeletal manifestations. Acetabular protrusio and constipation are both commonly associated with OI. We present two cases of severe pelvic deformity resulting in mechanical colonic outlet obstruction, which were successfully treated with a colostomy. Colostomy as the definitive treatment of severe constipation in OI has not previously been reported in the literature.

Journal of the Pediatric Orthopaedic Society of North America

Purpose: Osteogenesis Imperfecta (OI) is a rare genetic disorder caused by a mutation in type I c... more Purpose: Osteogenesis Imperfecta (OI) is a rare genetic disorder caused by a mutation in type I collagen, characterized by bone fragility and deformity. Current treatment methods aim to decrease fracture rates and improve bone density and mobility. Recent orthopaedic surgery research has focused primarily on fracture fixation and outcomes of intramedullary rodding procedures. While surgical techniques continue to evolve, recent trends are focusing on patient-reported outcomes measures (PROMs). Methods: The authors created a 12-question survey in conjunction with the OI Foundation (OIF). The survey was titled, “O.I. Wish Orthopaedic Surgeons Had Better Strategies to Help with . . .” and sought to gather information regarding the aspects of orthopaedic care OI patients and families would most like to see improved. The survey was electronically administrated to members of the OIF and the OI Federation Europe (OIFE). 341 individuals completed the survey. The final question of the survey...

Osteology

Osteogenesis imperfecta (OI) often results in recurrent fractures and/or progressive bowing of th... more Osteogenesis imperfecta (OI) often results in recurrent fractures and/or progressive bowing of the long bones, including the arms. Upper extremity deformity has been shown to negatively impact function. The objective of this retrospective case series is to assess the ability to correct deformity, improve function and evaluate the complications and revision rates in our patients with OI who have undergone forearm deformity correction. A retrospective study, approved by The University of Nebraska Medical Center Institutional Review Board, was conducted with OI patients who underwent forearm osteotomy and fixation of one or both forearm bones between December 2011 and August 2018. There were no exclusion criteria. The electronic medical records were reviewed for patient demographics, surgical details, revisions and complications. A total of 48 procedures on 27 forearms in 18 patients were performed during the study. Surgery was performed in children with forearm deformity and recurrent...

INTRODUCTION Dental anomalies in Osteogenesis imperfecta (OI), such as tooth discoloration, pulp ... more INTRODUCTION Dental anomalies in Osteogenesis imperfecta (OI), such as tooth discoloration, pulp obliteration (calcified dental pulp space), and taurodontism (enlarged dental pulp space) vary between and within patients. To better understand the associations and variations in these anomalies, a cross-sectional study was designed to analyze the dental phenotype in OI patients at the individual tooth type. METHOD A cohort of 171 individuals with OI type I, III and IV, aged 3-55 years, were recruited and evaluated for tooth discoloration, pulp obliteration, and taurodontism at the individual tooth level, using intraoral photographs and panoramic radiographs. RESULTS Genetic variants were identified in 154 of the participants. Patients with Helical α1 and α2 glycine substitutions presented the highest prevalence of tooth discoloration, while those with α1 Haploinsufficiency had the lowest (<10%). C-propeptide variants did not cause discoloration but resulted in the highest pulp oblit...

Regional Anesthesia & Pain Medicine, 2020

Background and objectives Regional and neuraxial anesthesia techniques have become instrumental i... more Background and objectives Regional and neuraxial anesthesia techniques have become instrumental in the perioperative period yet have not been well described in patients with osteogenesis imperfecta (OI), a congenital connective tissue disorder characterized by skeletal dysplasia and fragility. Patients with skeletal dysplasia present unique perioperative challenges that warrant consideration of these techniques despite their relative contraindication in this population due to reports of increased bleeding with surgery, skeletal fragility concerns with positioning, and risk of spinal cord injury with continuous neuraxial catheters. The aim of this narrative review was to evaluate literature describing the use of regional and neuraxial techniques in patients with OI and any associated clinical outcomes. Methods All available literature from inception to July 2020 was retrieved, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, from MEDLINE...

Pediatric Orthopedic Trauma Case Atlas

Osteogenesis Imperfecta

Osteogenesis imperfecta is a genetic disorder of type I collagen and characterized by bone fragil... more Osteogenesis imperfecta is a genetic disorder of type I collagen and characterized by bone fragility. Although multiple genotypes and phenotypes are associated with osteogenesis imperfecta, approximately 90% of the mutations are in the COL1A1 and COL1A2 genes. Patients typically have multiple fractures or limb deformity; however, the spine can also be affected. Spinal manifestations include scoliosis, kyphosis, craniocervical junction abnormalities, and lumbosacral issues such as spondylolysis and spondylolisthesis. The use of bisphosphonates has been found to decrease the rate of progression of scoliosis in patients with osteogenesis imperfecta. A lateral cervical radiograph is recommended in patients with this condition before age 6 years for surveillance of craniocervical junction abnormalities, such as basilar impression. Intraoperative and anesthetic considerations in patients with osteogenesis imperfecta include challenges related to fracture risk, airway management, ventilati...

Congenital pseudarthrosis of the tibia is a rare pediatric disorder that often presents with ante... more Congenital pseudarthrosis of the tibia is a rare pediatric disorder that often presents with anterolateral bowing of the tibia. Tibial pseudarthrosis occurs in association with neurofibromatosis in 55% of patients, although only 6% of patients with neurofibromatosis have a pseudarthrosis. The pathology of the tissue is described as abnormal, cellular fibrovascular tissue with paucity of vascular ingrowth and is felt to be mainly a disorder of periosteum. Treatment includes fracture prevention; once fracture occurs, surgery is indicated to attempt to achieve bony union and maintain union until skeletal maturity. Principles of operative treatment include removal of the bone and periosteum at the site of the pseudarthrosis, deformity correction, bony correction, and stable fixation. These goals can be achieved with intramedullary nailing, free vascularized fibular grafts, and external ringed fixators. Amputation is an option when union hasn’t been achieved after three surgical attempts...

The review of abstracts and manuscripts for presentation or publication is an important part of t... more The review of abstracts and manuscripts for presentation or publication is an important part of the peer-review process. Many clinicians and scientists are often asked to review abstracts and manuscripts with little formal training in the process of these reviews. The following stresses the importance of abstract and manuscript review, a recommended process to go through to achieve quality reviews and how to give constructive feedback to authors in a concise yet complete and unbiased way.

Lower extremity deformity occurs commonly in patients with moderate to severe osteogenesis imperf... more Lower extremity deformity occurs commonly in patients with moderate to severe osteogenesis imperfecta (OI). Lower extremity deformity increases fracture occurrence and functional difficulties in these patients. Femoral and tibial osteotomies with telescoping intramedullary fixation are reliable and safe options for deformity correction in this patient population. Telescoping rods decrease the need for revision surgery when compared to static intramedullary implants. Deformity correction and medical treatment with bisphosphonate infusions reduce fracture burden in children with OI. Deformity correction often includes closed, percutaneous our open osteotomies depending on the patient's age, brittleness of the bone, and amount of deformity. Multiple lower extremity bones can be treated in the same surgical setting safely and efficiently.

Contributors: Ernestina Schipani, MD, PhD; Henry Kronenberg, MD; Rosa Serra, PhD; Ola Nilsson, MD... more Contributors: Ernestina Schipani, MD, PhD; Henry Kronenberg, MD; Rosa Serra, PhD; Ola Nilsson, MD, PhD; Klane White, MD; Michael Bober, MD; Benjamin Alman, MD; Daniel Hoernschemeyer, MD; Francesco De Luca, MD; Jan-Maarten Wit, MD, PhD; Ken Noonan, MD; Neil Paloian, MD; David Deyle, MD; Shawn Gilbert, MD; Sanjeev Sabharwal, MD; Peter Stevens, MD; Jonathan Schoenecker, MD, PhD; Noelle Larson, MD; Todd Milbrandt, MD; Wan-Ju Li, PhD

Osteogenesis imperfecta (OI) can cause fractures and progressive deformity of the bones of the pe... more Osteogenesis imperfecta (OI) can cause fractures and progressive deformity of the bones of the pelvis and hip joint in addition to fractures of the long bones. In children with moderate to severe forms of the disease, coxa vara and acetabular protrusion occur quite commonly as do upper femoral shaft deformities and femoral neck fractures. A small subset of patients with the C-propeptide mutation will have an increased risk of hip dysplasia and dislocation as well. This chapter describes the clinical presentations, pathophysiology and treatment of coxa vara, acetabular protrusion, developmental hip dislocation, proximal femoral fractures and deformity in children with OI.