Congenital Pseudarthrosis Of The Tibia Research Articles

Comparative study of different extendable intramedullary rods combined with surgery in the treatment of congenital pseudarthrosis of the tibia

BackgroundWhen using traditional extensible intramedullary rods to treat congenital pseudarthrosis of the tibia (CPT), there were cases of re-fracture and internal fixation fracture. Therefore, the authors propose a research hypothesis that a thicker distal extensible intramedullary rod can better protect the tibia and reduce the incidence of refracturePurposeTo investigate the clinical efficacy of new and traditional extensible intramedullary rods in the treatment of CPT in childrenMethodsFrom January 2017 to December 2021, the clinical data of 49 children with CPT who were treated with traditional extensible intramedullary rod combined surgery (group A) and new extensible intramedullary rod combined surgery (group B) in our hospital were collected. Inclusive criteria: ① Crawford type IV CPT children; ② The operation was performed by the same team. Exclusion criteria: patients with multiple tibial angulation. During follow-up, the initial healing, proximal tibial valgus, tibial length, ankle valgus, refracture and intramedullary rod displacement of CPT children in the two groups were evaluatedResultsIt was a retrospective investigation. In group A, 26 cases met the inclusion criteria, 24 cases achieved primary healing, with an primary healing rate of 92%, including 1 case of nonunion due to osteomyelitis complications after surgery, and 1 case of delayed healing, with an average healing time of 4.7 ± 0.8 months. 17 cases (68%) had unequal tibia length, with an average difference of 1.6 ± 0.8 cm. Ankle valgus occurred in 10 cases (40%) with an average of 14.4°±4.8°; Proximal tibial valgus occurred in 6 cases (24%) with an average of 7 °± 1.8 °. 20 cases (80%) had tip of the rod migration.10 cases (40%) had re-fracture; The average follow-up time was 2.4 ± 0.4 years. In group B, 22 patients achieved primary healing, and the primary healing rate was 95%, including 1 case with delayed healing. The average healing time was 4.7 ± 1.7months. 14 cases (61%) had unequal tibia length, with an average difference of 1 ± 0.5 cm. Ankle valgus occurred in 4 cases (17%) with an average of 12.3 °±4.9°; The proximal tibia valgus occurred in 9 cases (39%), with an average of 7.7 °±2.5 °. 14 cases (61%) had new type of intramedullary rod displacement. 3 cases (13%) had re-fracture; The average follow-up time was 2.3 ± 0.6yearsConclusionCompared with the traditional extended intramedullary rod combined operation, the new type of extended intramedullary rod combined operation has a lower incidence of re-fracture after CPT, but it still needs to be verified by large sample and multi-center research

Is Using a Ring External Fixator in the Treatment of Congenital Pseudarthrosis of the Tibia Associated With Better Results or Using a Locking Plate?

Congenital pseudarthrosis of the tibia (CPT) is a rare disease. CPT is often unilateral and occurs between the middle and distal third of the tibia. Concurrent involvement of the fibula is present in more than half of cases. histologic studies indicate the presence of fibrous hamartoma tissue and a sick periosteum, which leads to recalcitrant bone fracture and, eventually, pseudoarthrosis. Although there are various surgical techniques, we intend to compare the 2 methods of external fixation versus internal plating. Demographic data were collected from 26 patients with frank pseudoarthrosis. After exclusion criteria, patients were compared in groups A (12 patients) and B (11 patients). Resection of hamartoma and sclerotic bone, intramedullary rodding and autologous bone, and periosteal grafting were performed for all patients. In group A, we used a ring external fixator for compression and rotational stability, but in group B, a locking plate was used for these purposes. Plating takes less time to use during surgery. In group A, the primary bony union was obtained in 67% of patients, while in group B, 82% of patients had a primary union. Meanwhile, the average time till the final union in group A was 6 months, while in group B, this time was 3.5 months. Positive union mass was obtained in 58% of the patients in group A and 82% of group B. In addition, plating prevented ankle valgus deformity in group B. Permanent intramedullary rodding is a surgical requirement for correction of deformity and refracture prevention, but additional stability can be achieved with the use of a ring external fixator or internal plate. Cross union and positive union mass are 2 important factors in the treatment of pseudoarthrosis; these results are achieved to a greater extent and in a shorter period of time using the plate. level IV - case series.

Circ_0000888 regulates osteogenic differentiation of periosteal mesenchymal stem cells in congenital pseudarthrosis of the tibia

Congenital pseudarthrosis of the tibia (CPT) is a refractory condition characterized by the decreased osteogenic ability in tibial pseudarthrosis repair. Periosteal mesenchymal stem cells (PMSCs) are multipotent cells involved in bone formation regulation. However, the mechanisms underlying its role in CPT remain unclear. In this study, we observed downregulation of circ_0000888 and pleiotrophin (PTN), as well as upregulation of miR-338-3p in CPT derived PMSCs (CPT-dPMSCs). Our results demonstrated that circ_0000888 and PTN likely enhanced the viability, proliferation, and osteogenic ability of PMSCs, while miR-338-3p had the opposite effect. Further analysis confirmed the regulatory relationship circ_0000888 suppressed the activity of miR-338-3p and upregulated the expression of its downstream target PTN by binding to miR-338-3p, consequently promoting the viability and osteogenic differentiation ability of CPT-dPMSCs. Our findings unveil an unexpected link between circ_0000888/miR-338-3p/PTN in promoting osteogenic ability and indicate the potential pathogenic mechanisms of CPT.

LIMBDREAM: THE LIMB RECONSTRUCTION REGISTRY OF EXPERIENCE, ASPIRATION, AND MEASURES

IntroductionPatient-reported outcome measures (PROMs) has gained momentum in the orthopaedic literature. The GOAL-LD (Gait Outcomes Assessment List for Limb Deformity) incorporates the framework of The WHO International Classification of Functioning, Disability and Health and correlates highly with the Paediatric Outcomes Data Collection Instrument (PODCI) when applied in a limb reconstruction setting. The Royal Children's Hospital Melbourne, Australia, supported by The University of Melbourne is designing and implementing a Limb Reconstruction Registry, prospectively enrolling patients with a number of key conditions and provide a mechanism for capturing surgical data and PROMs at regular follow-up intervals. LimbDREAM (The Limb Reconstruction Registry of Experience, Aspiration and Measures) has begun recruiting participants, and this paper serves as a narrative review of our design and implementation process.Materials & MethodsAfter provision of a research grant, audit was conducted to examine local case mix and estimate recruitment based on conditions selected. Literature review was focussed on (i) registries in the paediatric limb reconstruction domain and (ii) use of PROMs across conditions selected. A high-level process-flow chart was constructed in order to inform governance and staffing requirements in addition to REDCap Database structure. Local as well as scalable deployment was considered. Alpha and beta testing was performed by principal and associate investigators prior to participant recruitment.ResultsAudit identified 6 condition streams for inclusion: Congenital limb deficiencies, congenital pseudarthrosis of the tibia, bone dysplasias, bone tumours, amputation, and complex deformity of other etiology. Literature review identified 20 PROMs used across these conditions, with limited validation studies and significant implementation heterogeneity. REDCap database design took longer than anticipated (planned 10 months, actual 18 months) before being recruitment ready, due to the complexity of ensuring data collection logic would work across highly diverse patient journeys. Initial recruitment across all streams has been promising. Email and text message reminders have proved helpful in increasing survey return rates.ConclusionsProspective collection of PROMs as well as surgical data via a standardized dataset will provide the basis for future condition-specific research, with the ability to support nested trials. Implementation requires forethought with regard to time frames and staffing for non-automated steps as well as data integrity review. The next phase of the LimbDREAM project will be to integrate use of the Registry into our weekly Limb Reconstruction Meeting to ensure that operative plans and data are captured close to the point of care.

Is physeal distraction osteogenesis a good choice to treat CPT patients with tibial shortening?

The purpose of this study was to evaluate the healing index and complications of distraction osteogenesis through the physis in children with Congenital pseudarthrosis of the tibia (CPT) using Ilizarov external fixation device. Nine children with CPT who underwent distraction osteogenesis through the physis surgery with an Ilizarov external fixation device between June 2018 and August 2020 were included in the study. The average follow-up time was 36.1 months. X-ray examination was performed 1 month after physis lengthening, and the callus quality was evaluated using the Li classification. Any complications and the quality of the callus after tibial lengthening were followed up. The average age at the time of operation was 9.4 years, and the average follow-up time was 36.1 months. The average lengthening length of children with CPT was 6.6 cm. The incidence of good callus morphology was 100%, and the healing index was 51.1 d/cm. The average fixation time of the external fixation device was 316 days. Needle tract infection occurred in one case, ankle stiffness occurred in one case, ankle plantar flexion 20° deformity occurred in one case, angular deformity of the tibial lengthening segment occurred in one case (7°) and limited movement of knee joint occurred in one case (0-20°-70°). The osteogenic quality of the patients of distraction osteogenesis through the physis with tibial shortening and small diameter of the proximal tibia is good, which provides a choice of operation for the children with CPT.

Differential expression and effect analysis of lncRNA-mRNA in congenital pseudarthrosis of the tibia.

Background: To analyze the lncRNA-mRNA differential expression and co-expression network of periosteal stem cells (PSCs) from congenital pseudarthrosis of the tibia (CPT) and normal patients, and to explore the role of key lncRNAs. Methods: Differentially expressed lncRNAs and mRNAs in PSCs were obtained by sequencing, and biological functions of differentially expressed mRNAs were detected by gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) pathway and protein -protein interaction (PPI) analysis. The co-expression network of lncRNA-mRNA was constructed by correlation analysis of differentially expressed lncRNAs and mRNAs, and the key lncRNAs were screened according to the connectivity degree. After that, the cis-regulated target genes of differential expressed lncRNAs and mRNAs were predicted. Results: A total of 194 differentially expressed lncRNAs were identified, including 73 upregulated and 121 downregulated genes. A total of 822 differentially expressed mRNAs were identified, including 311 upregulated and 511 downregulated genes. GO, KEGG and PPI enrichment analysis showed that the regulatory function of differentially expressed mRNAs were mainly gathered in skeletal system development and tissue morphogenesis. The co-expression network with 226 nodes and 3,390 edges was constructed based on correlation analysis. A total of 10 key lncRNAs, including FAM227B, POM121L9P, AF165147 and AC103702, were screened according to connectivity degree. Prediction of target genes indicated that FAM227B-FGF7 and AC103702-HOXB4/5/6 may play an important role in the pathogenesis of CPT. Conclusion: A total of 10 key lncRNAs, including FAM227B, POM121L9P, AF165147, and AC103702, occupy the core position in the co-expression network, suggesting that these lncRNAs and their target genes may play an important role in the pathogenesis of CPT.

Association between preoperative concurrent fibular pseudarthrosis and risk of postoperative ankle valgus in patients with congenital pseudarthrosis of the tibia

BackgroundThis study evaluated the correlation of preoperative concurrent fibular pseudarthrosis with the risk of ankle valgus deformity in patients with congenital pseudarthrosis of the tibia (CPT) who underwent successful surgical...

Pseudoarthrosis of tibia and fibula.

It can be defined as a disorder of the diaphysis which is revealed by either pseudarthrosis at birth or by a pathological fracture presenting in bone with modifications such as bowing, narrowing of the medullary canal. Congenital pseudarthrosis of the tibia (CPT) is a rare disease in children, with an estimated frequency of 1/150,000 births. Clinical presentations range from simple anterolateral tibial angulation to complete non-union with extensive bone defects. Normally CPT is unilateral, located at the junction of the middle and distal thirds of the tibial segment with no predominance for sex. A 9-year-old male child was brought to the orthopaedics outpatient department (OPD) with complaints of severe pain in his right leg with a history of fall from bed. Immediately after which his mother noticed a deformity in his right leg. X-ray of right leg anteroposterior view (AP) and lateral view was done which showed fracture, cupping of the proximal fragment of bone proximal to the fracture site with narrow appearance of the distal bone.

Lower Extremity Malformations.

Lower Extremity Malformations.

MiR-30a inhibits the osteogenic differentiation of the tibia-derived MSCs in congenital pseudarthrosis via targeting HOXD8.

BackgroundCongenital pseudarthrosis of the tibia (CPT) is an uncommon congenital deformity and a special subtype of bone nonunion. The lower ability of osteogenic differentiation in CPT-derived mesenchymal stem cells (MSCs) could result in progression of CPT, and miR-30a could inhibit osteogenic differentiation. However, the role of miR-30a in CPT-derived MSCs remains unclear.MethodsThe osteogenic differentiation of CPT-derived MSCs treated with the miR-30a inhibitor was tested by Alizarin Red S staining and alkaline phosphatase (ALP) activity. The expression levels of protein and mRNA were assessed by Western blot or quantitative reverse transcription-polymerase chain reaction (RT-qPCR), respectively. The interplay between miR-30a and HOXD8 was investigated by a dual-luciferase reporter assay. Chromatin immunoprecipitation (ChIP) was conducted to assess the binding relationship between HOXD8 and RUNX2 promoter.ResultsCPT-derived MSCs showed a lower ability of osteogenic differentiation than normal MSCs. miR-30a increased in CPT-derived MSCs, and miR-30a downregulation promoted the osteogenic differentiation of CPT-derived MSCs. Meanwhile, HOXD8 is a direct target for miR-30a, and HOXD8 could transcriptionally activate RUNX2. In addition, miR-30a could inhibit the osteogenic differentiation of CPT-derived MSCs by negatively regulating HOXD8.ConclusionmiR-30a inhibits the osteogenic differentiation of CPT-derived MSCs by targeting HOXD8. Thus, this study might supply a novel strategy against CPT.

Clinical characteristics and in silico analysis of congenital pseudarthrosis of the tibia combined with neurofibromatosis type 1 caused by a novel NF1 mutation.

Congenital pseudarthrosis of the tibia (CPT) is a rare congenital bone malformation, which has a strong relationship with Neurofibromatosis type 1 (NF1). NF1 is an autosomal dominant disease leading to multisystem disorders. Here, we presented the genotypic and phenotypic characteristics of one unique case of a five-generation Chinese family. The proband was CPT accompanied with NF1 due to NF1 mutation. The proband developed severe early-onset CPT combined with NF1 after birth. Appearance photos and X-ray images of the left limb of the proband showed significant bone malformation. Slit-lamp examination showed Lisch nodules in both eyes of the proband. Whole-exome sequencing (WES) and Sanger sequencing confirmed the truncation variant of NF1 (c.871G>T, p. E291*). Sequence conservative and evolutionary conservation analysis indicated that the novel mutation (p.E291*) was highly conserved. The truncated mutation led to the loss of functional domains, including CSRD, GRD, TBD, SEC14-PH, CTD, and NLS. It may explain why the mutation led to a severe clinical feature. Our report expands the genotypic spectrum of NF1 mutations and the phenotypic spectrum of CPT combined with NF1.

Design of a New “U”‐shaped Staple and Its Clinical Application in Postoperative Ankle Valgus of Congenital Pseudarthrosis of the Tibia in Children

ObjectiveThere has been a lack of suitable epiphysis blocking materials due to the characteristics of less tissue coverage and narrow epiphysis in children's distal tibial medial malleolus. Therefore, this study is to investigate the clinical efficacy and safety of a new “U”‐shaped staple in the treatment of postoperative ankle valgus of congenital pseudarthrosis of the tibia (CPT).MethodAccording to the inclusion and exclusion criteria, 33 patients with postoperative ankle valgus of CPT were treated with new “U”‐shaped staples from May 2013 to September 2019. The deformity of ankle valgus was gradually corrected by implanting a new “U”‐shaped staple on the medial side of the distal tibia. Clinical indexes such as the operation time, intraoperative bleeding and hospital stay were observed. Tibiotalar angle was selected as the evaluation index of ankle valgus. American Orthopedic Foot & Ankle Society (AOFAS) scale was used for clinical evaluation of ankle function. The tibiotalar angle, deformity correction rate and complications were evaluated by preoperative, postoperative and last follow‐up imaging data. Student's t‐test was used for statistical analysis.ResultsThirty‐three patients, including 12 males and 21 females were included. All the patients were followed up for at least 14 months, with an average of 35 months. The average operation time was 23 (15–40) min, the average amount of intraoperative bleeding was 7.5 (4–10) mL, and the average hospital stay was 4.2 (3–6) days. The intraoperative tibiotalar angles of all patients were 74.2° ± 4.6°, the tibiotalar angle were 86.8° ± 4.9° when internal fixation was removed, and the tibiotalar angles at the last follow‐up were 84.3° ± 5.9°. The average orthopedic rate was 0.68° per month. No patients suffered from serious complications such as screw prolapse, osteomyelitis, wound infection, etc. Postoperative wound pain complications occurred in two patients, which were relieved after conservative treatment. The AOFAS score improved from 46.2 ± 9.4 before the operation to 74.6 ± 5.7 at the last follow‐up (P < 0.01). The ankle movement was good without joint stiffness. There was no epiphyseal plate injury after the removal of internal fixation.ConclusionThe new “U”‐shaped staple is characterized by simple implantation, low notch, lower risk of fixation failure and close fitting with cortical bone. It is a safe and effective internal fixation system for the treatment of ankle valgus in children.

Analysis of related factors of behavioral problems in children with congenital pseudarthrosis of tibia.

SUMMARYOBJECTIVE:This study aimed to investigate the factors associated with behavioral problems in children with congenital pseudarthrosis of the tibia.METHODS:Random sampling is utilized to obtain a sample of 90 patients. The behavioral problems of the patients are detected by Achenbach Children's Behavior Scale. Parental emotional problems are investigated by the Self-Rating Depression Scale and Self-Rating Anxiety Scale.RESULTS:The results demonstrate that the detection rate of behavioral problems in children with congenital pseudarthrosis of the tibia is 53.3% (48/90). Among these behavioral problems, an abnormal rate is higher in the four dimensions: thinking, violation of discipline, social interaction, and aggression. The anxiety and depression scores of caregivers are statistically higher in the abnormal group than in the normal group. The results of the multivariate analysis show that the anxiety degree of the parents had a significant impact on the behavior of the children.CONCLUSIONS:Children with congenital pseudarthrosis of the tibia are facing the issues of high rates of behavioral problems. Parents of children with congenital pseudarthrosis of the tibia had higher levels of anxiety and depression than parents of normal children. The anxiety and depressive state of mind of parents or caregivers had a significant impact on the behavior of children with congenital pseudarthrosis of the tibia.

Analysis of risk factors affecting union and refracture after combined surgery for congenital pseudarthrosis of the tibia: a retrospective study of 255 cases

BackgroundCongenital pseudarthrosis of the tibia (CPT) is a rare disease occurring in children. The aim of this study is to identify the factors affecting bone union and re-fracture after surgery for CPT and to provide reliable evidence for clinics.MethodsWe collected the detailed information of 255 cases with Crawford IV CPT treated by combined surgery in our hospital from 2013 to 2020. Basic characteristics were recorded. Univariate variance and logistic regression analysis were used to compare the correlations between factors and outcomes.Results92.5% of patients achieved primary union, 7.5% of patients had non-union and 13.3% of patients had re-fracture. Logistic regression analysis showed that age at index surgery (Coef. = 0.171, 95%CI 0.015–0.327, P = 0.032), and CPT location (Coef. = − 1.337, 95%CI − 2.218–0.456, P = 0.003) had statistical differences, while no factors had significant correlation with re-fracture. Furthermore, ROC curve showed that the optimal age threshold for first surgery was 2.37 years old.ConclusionsFor patients with Crawford IV CPT treated by combined surgery, the younger the age at index surgery and the closer the CPT location to the distal end, the easier to achieve bone union.

Combination of the Ilizarov Method and Intramedullary Fixation for the Treatment of Congenital Pseudarthrosis of the Tibia in Children: A Retrospective Observational Study

PurposeCongenital pseudoarthrosis of the tibia (CPT) is a rare disease in children, and its treatment remains a challenge for orthopedic surgeons. The purpose of this study was to evaluate treatment outcomes of patients with CPT treated by using the Ilizarov method combined with intramedullary fixation.MethodEighteen patients evaluated retrospectively from January 2009 to January 2020 were treated using the Ilizarov method combined with intramedullary fixation. Demographic data, clinical characteristics, and complications were all recorded and investigated during the period of follow-up. Ankle function was evaluated by the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scores at the last follow-up.ResultThe average follow-up was 39.2 months (25–85 months) for all 18 patients. The mean age was 6.2 years (3.5–11.2 years). Fourteen (77.8%) patients had a primary bone union at the site of pseudarthrosis, while four obtained union after secondary surgical intervention. The mean duration of the Ilizarov method was 8.1 months (4.2–13.5 months). Eight (44.4%) patients had a pin-tract infection during treatment. Four (22.2%) patients had proximal tibial valgus with a mean angle of 12.1° (5–25°), while seven (38.9%) patients had ankle valgus deformities with a mean of 10.3° (5–20°). Eleven (61.1%) patients had an average 1.4 cm of limb length discrepancy (LLD) (0.6–3.1 cm) postoperatively. Five (27.8%) patients had refracture and recovered after a secondary surgery. At the last follow-up, the average postoperative AOFAS score was 72 (55–84).ConclusionThe Ilizarov method combined with intramedullary fixation is an effective method for the treatment of CPT, which can facilitate bony union and help to prevent refracture. Management of fibular pseudarthrosis is associated with functional outcomes. It is necessary to follow up until skeletal maturity and evaluate long-term clinical outcomes.

Are Children Suffering From Congenital Pseudarthrosis of the Tibia Associated With Decreased Bone Strength?

Background:Congenital pseudarthrosis of the tibia (CPT) is a rare and difficult-to-treat congenital disease in neonates. Our previous study found that exosomes derived from serum of children with CPT inhibit bone formation. In this study, we used ultrasound bone densitometry to detect the bone strength differences between hospitalized children with CPT and with non-metabolic diseases to determine the bone strength of children with CPT.MethodsA total of 37 children with CPT with a mean age of 3.14 ± 1.81 years and 40 hospitalized children with a mean age of 3.32 ± 2.66 years with supracondylar fracture of the humerus and without a bone metabolic disease (control group) were recruited in our hospital. The ultrasonic bone densitometer was used to examine the bilateral calcaneus of the subjects. We collected the broadband ultrasonic attenuation (BUA), speed of sound (SOS), quantitative ultrasound index (QUI), bone strength index (STI) and bone mineral density estimation (BMDe) values. Multivariable regression was used to examine the associations between quantitative ultrasound measurement differences and age, body mass index (BMI), neurofibromatosis type 1 (NF1) and CPT Crawford type. Intra-class correlation coefficient (ICC) was calculated to estimate intra- and inter-rater agreements.Results74 calcaneus scans were taken from CPT patients (23 boys and 14 girls) and 80 calcaneus scans were taken from the control (24 boys and 16 girls). The CPT patients exhibited significantly lower SOS (1,368.75 ± 136.78 m/s), STI (7.2319 ± 38.6525), QUI (8.2532 ± 56.1720), and BMDe (−0.0241 ± 0.3552 g/cm3) than the control (SOS: 1,416.02 ± 66.15 m/s, STI: 7.96 ± 16.884, QUI: 28.8299 ± 25.461, BMDe: 0.0180 ± 0.1610 g/cm3). Multiple regression revealed that SOS, STI and QUI were statistically significant and negatively correlated with CPT Crawford classification.ConclusionsWe found the incidence of decreased bone strength in CPT group was higher than that in the non-bone metabolic disease group. This phenomenon was not related to NF1 but related to CPT Crawford classification, which suggested that the higher the grade of the CPT Crawford classification, the lower the bone strength and the higher the risk of fracture.

Особенности ортопедической патологии у больных нейрофиброматозом I типа

Introduction Neurofibromatosis type 1 (NF1) is one of the most common hereditary tumor syndromes. The average incidence of NF1 in the world is 1:3000 of the population. The characteristic signs of the disease are neurofibromas and café-au-lait macules on the skin. 60 % of patients with NF1 develop specific skeletal anomalies: scoliosis, chest deformity, pseudarthrosis, requiring surgical treatment and long-term rehabilitation. It is necessary to develop prognostic criteria for the development of severe skeletal anomalies in NF1 and take early measures to prevent their progression. Congenital pseudarthrosis of the tibia is diagnosed in 5 % of children with NF1, accounting for 80 % of all cases of this pathology in the general population. Spinal scoliosis is detected in 60 %, osteoporosis in 50 %, chest deformity in 37.6 %, microgenia in 53 %, increased head circumference in 25 %, sphenoid wing dysplasia in 12 %, facial asymmetry in 10 % of patients with NF1. The aim of the review is to focus on the pathogenesis of skeletal anomalies development in NF1 that result in disorders of the musculoskeletal system in NF1 in order to take early measures for the prevention and treatment of the disease. Materials and method The review is based on numerous studies found in the databases: PubMed, Scopus, Web of Science, published mainly over the past 5 years. The suitable studies were searched by keywords and their combinations «neurofibromatosis type 1» with the words «skeletal abnormalities», «musculoskeletal system», «pseudarthrosis», «scoliosis», «pathogenesis», «deformation», «treatment», «frequency», «prevalence», «genotype-phenotype correlation», « modifier genes». Results and discussion The pathogenesis of skeletal anomalies is due to both the loss of heterozygosity of the NF1 gene in pseudoarthrosis and the effect of neurofibromin deficiency on the development of connective tissue. Currently, the only effective drugs for the treatment of tumor syndrome in NF1 are inhibitors of mitogen-activated kinase (MEK), which suppress the increased activity of Ras oncogenes. A promising issue is the study of the effect of MEK inhibitors on the progression of skeletal anomalies in patients with NF1 in the treatment of tumor syndrome. Therefore, dynamic observation by an orthopedic surgeon with an objective assessment of the observed changes is of great importance in the management of patients. It is necessary to widely introduce molecular genetics methods for confirming the diagnosis of NF1 in the clinic in cases of a combination of skeletal anomalies with individual signs of the disease, since the manifestations of NF1 are steadily progressing with age, even in the presence of erased and atypical forms of the disease. Since the analysis of scientific literature has shown the possible influence of modifier genes on the pathogenesis of NF1, the search for mutations in these genes is promising. Conclusion Most patients with NF1 develop orthopedic pathology, which is associated with the role of the NF1 gene in the development of connective tissue. The increased mutability of this gene causes the loss of heterozygosity in the development of congenital pseudoarthrosis of the tibia. At the same time, NF1 driver mutations are detected in 10 % of sporadic malignant neoplasms. Therefore, the role of somatic mutations in the NF1 gene in the development of skeletal anomalies in the general population is probable. The methods of NF1 therapy that are under investigation may become the basis for the complex treatment of oncological and orthopedic patients.

Does An Osteotomy Performed in Congenital Pseudarthrosis of the Tibia Heal?

Shortening and deformity of the tibia commonly occur during the treatment of congenital pseudarthrosis of the tibia (CPT). The role of osteotomies in lengthening and deformity correction remains controversial in CPT. This study evaluates the approach to and outcome after osteotomy performed in CPT. We performed an IRB approved retrospective review of consecutive patients with CPT treated at our institution from 2010 through 2019. Patients who underwent osteotomies were included in this study. Nine patients (10 osteotomies-5 proximal metaphyseal and 5 diaphyseal) with a median age at osteotomy of 8.9 years (range: 4 to 21 y) were included. Six patients had neurofibromatosis-1, 1 had cleidocranial dysplasia, and 2 patients had idiopathic CPT. Four osteotomies were performed for deformity correction, 3 osteotomies to allow intramedullary instrumentation, and 3 osteotomies for lengthening. Five osteotomies were preceded by zolendronate treatment before surgery. Nine were fixed with a rod supplemented with external fixation (7) or locking plates (2). One osteotomy was stabilized with locked intramedullary nailing alone. Four osteotomies were supplemented with autologous bone graft, and bone morphogenic protein-2 was utilized in 3 osteotomies. Median time to healing was 222.5 days (range: 124 to 323 d). One osteotomy (locked intramedullary nailing) required grafting at 5.5 months and then healed uneventfully. Median healing index for patients undergoing lengthening was 57.9 days/cm (range: 35 to 81 d/cm). All 3 osteotomies performed for lengthening required a second osteotomy for preconsolidation at a mean of 34 days. Other complications included compartment syndrome requiring fasciotomy (n=2), tibial osteomyelitis (n=1), and fracture distal to cross-union (n=1). Contrary to much of the established practice, osteotomies may be safely performed in CPT for various indications. All osteotomies healed with only 1 osteotomy requiring secondary bone grafting. Although time to healing of the osteotomy was generally prolonged, this study suggests, somewhat surprisingly, that preconsolidation can occur frequently in lengthening procedures. Level IV-case series.

Ilizarov bone transport combined with the Masquelet technique for bone defects of various etiologies (preliminary results).

BACKGROUNDThe Ilizarov bone transport (IBT) and the Masquelet induced membrane technique (IMT) have specific merits and shortcomings, but numerous studies have shown their efficacy in the management of extensive long-bone defects of various etiologies, including congenital deficiencies. Combining their strong benefits seems a promising strategy to enhance bone regeneration and reduce the risk of refractures in the management of post-traumatic and congenital defects and nonunion that failed to respond to other treatments.AIMTo combine IBT and IMT for the management of severe tibial defects and pseudarthrosis, and present preliminary results of this technological solution. METHODSSeven adults with post-traumatic tibial defects (subgroup A) and nine children (subgroup B) with congenital pseudarthrosis of the tibia (CPT) were treated with the combination of IMT and IBT after the failure of previous treatments. The mean number of previous surgeries was 2.0 ± 0.2 in subgroup A and 3.3 ± 0.7 in subgroup B. Step 1 included Ilizarov frame placement and spacer introduction into the defect to generate the induced membrane which remained in the interfragmental gap after spacer removal. Step 2 was an osteotomy and bone transport of the fragment through the tunnel in the induced membrane, its compression and docking for consolidation without grafting. The outcomes were retrospectively studied after a mean follow-up of 20.8 ± 2.7 mo in subgroup A and 25.3 ± 2.3 mo in subgroup B. RESULTSThe “true defect” after resection was 13.3 ± 1.7% in subgroup A and 31.0 ± 3.0% in subgroup B relative to the contralateral limb. Upon completion of treatment, defects were filled by 75.4 ± 10.6% and 34.6 ± 4.2%, respectively. Total duration of external fixation was 397 ± 9.2 and 270.1 ± 16.3 d, including spacer retention time of 42.4 ± 4.5 and 55.8 ± 6.6 d, in subgroups A and B, respectively. Bone infection was not observed. Postoperative complications were several cases of pin-tract infection and regenerate deformity in both subgroups. Ischemic regeneration was observed in two cases of subgroup B. Complications were corrected during the course of treatment. Bone union was achieved in all patients of subgroup A and in seven patients of subgroup B. One non-united CPT case was further treated with the Ilizarov compression method only and achieved union. After a follow-up period of two to three years, refractures occurred in four cases of united CPT. CONCLUSIONThe combination of IMT and IBT provides good outcomes in post-traumatic tibial defects after previous treatment failure but external fixation is longer due to spacer retention. Refractures may occur in severe CPT.

Combination Treatment by Cross-Union of the Tibia and Fibula, Autogenic Iliac Bone Grafting, Reliable Fixation and Bone Morphogenetic Proteins for the Treatment of Refractory Congenital Pseudarthrosis of the Tibia.

Background:The treatment of congenital pseudarthrosis of the tibia (CPT) remains a challenge because of the difficulties of achieving and maintaining bone union, as well as complications of joint deformity and limb-length discrepancy. The purpose of this study was to evaluate the efficacy of cross-union of the tibia and fibula in achieving union and preventing refracture for patients with refractory CPT as a complementary approach to improve upon conventional surgical treatments.Methods:A retrospective study including patients with refractory CPT who attended our department between June 2014 and August 2020. Eighteen CPT patients, who had sustained refracture that required cast immobilization or secondary surgery, and were managed by pseudarthrosis resection, cross-union of the tibia and fibula, bone morphogenetic protein-2 and autogenous iliac bone grafting, were included. Clinical outcomes of the bone union rate and the frequency of refracture after performing cross-union of the tibia and fibula were assessed during the follow-up period.Results:The mean follow-up period was 4.3 years (range: 1.5 to 6.25 y). The mean age of the patients at surgery was 5.4 years (range: 2.6 to 10 y), and all 18 (100%) of the 18 patients had final healing at the site of pseudarthrosis. The average time spent to achieve radiologic bone union of the pseudarthrosis after operation was 2.96 months (range: 2.2 to 4.1 mo). Two (11.1%) patients had an average 2.5 cm limb-length discrepancy, none (0%) sustained refracture which needed cast immobilization or secondary surgery. Patients were all pain-free and move actively.Conclusions:Cross-union of the tibia and fibula is a promising complementary procedure for treating refractory CPT patients.Level of Evidence:Level IV—case series.