Congenital pseudoarthrosis of the tibia (CPT) is a rare, sinister condition that is often associated with neurofibromatosis type 1 (NF1). Even after achieving union, patients frequently present with significant leg length discrepancy (LLD) due to growth disturbance and repeated reconstructive surgeries. Tibial lengthening using distraction osteogenesis is commonly performed, yet outcomes and complications remain poorly understood. To systematically map the available literature on tibial lengthening in CPT, describe surgical techniques, summarize reported outcomes, and identify research gaps. A scoping review was conducted following Arksey and O'Malley's framework and the PRISMA-ScR guidelines. The PubMed, Embase, Scopus, Web of Science and Cochrane Library databases were searched. Eligible studies included those reporting tibial lengthening during CPT. Data on patient demographics, surgical techniques, length achieved, union rates, complications, and follow-up were extracted. Thirty-one studies involving 486 patients were included. All studies were retrospective. The mean age at lengthening ranged from 3.2 to 33.7 years. NF1 was present in 70% of the patients. The Ilizarov external fixator in isolation or with hybrid techniques was the most frequently reported lengthening modality. The mean lengthening achieved was 5.5 cm (range 1.5-10.2 cm). The most common site of lengthening was through proximal tibial osteotomy followed by physeal distraction. Complications such as pin tract infection, regenerate fractures and tibial bowing deformities were commonly encountered. The follow-up period ranged from 1.6 to 24 years. Tibial lengthening is feasible in CPT and can achieve meaningful limb length equalization. However, complication rates remain high, and evidence is limited by the small number of retrospective studies. Standardized outcome reporting and prospective multicenter collaboration are needed to optimize care.

Lane and Sandhu introduced a radiological score to evaluate bone union in animal and human models after experimental bone grafting. We introduce an extension of the Lane and Sandhu Scoring system to serve as a more granular system for robust bone healing assessment in clinical research. We describe the application of this scoring system in the context of an autologous cell-based osteogenic implant (NVD003) designed to improve the rate of bone union. Images from four participants with congenital pseudoarthrosis of the tibia (CPT) and 9 adults with recurrent osseous non-union after conventional surgery were obtained. All participants underwent NVD003 implantation. An extended version of the Lane and Sandhu scoring system (eLSS; range from 0 to 12) was employed to assess bone formation, union, and remodeling by two independent readers longitudinally, with final adjudication in cases of > 1 point disagreement. Interobserver agreement was assessed using quadratic weighted kappa. 206 exams (170 radiographs and 36 CT scans) were studied across the two pathologies (81 scans for participants with CPT and 125 scans for participants with recurrent osseous non-union). Overall agreement between the expert readers was found to be 0.84 (95% CI: 0.79, 0.89), with comparable agreement found per modality (radiographs [0.85] and CT images [0.76]) and per pathology (CPT [0.83] and recurrent osseous non-union [0.84]). These results support that the eLSS has sufficient reliability to warrant further consideration for clinical trial use. Additional studies with a greater number of subjects, raters, and variety of use cases are required to validate and optimize this method. Level of Evidence: III.

Congenital pseudarthrosis of the tibia (CPT, HP:0009736), commonly known as bowing of the tibia, is a rare congenital tibia malformation characterized by spontaneous tibial fractures and difficulty in reunion after tibial fractures during early childhood, with a prevalence between 1/250,000 and 1/140,000. While 80%-84% of CPT cases present with neurofibromatosis type 1, caused by the variations in the NF1 gene, the underlying cause of CPT remains unclear. Considering its congenital nature and the low prevalence, we hypothesized that the rare genomic protein-damaging variations may contribute to CPT. In this study, we conducted whole exome sequencing on 159 patients with CPT and found loss-of-function (LoF) excesses in the 159 patient cases compared to 208 healthy controls from the 1000 Genomes Project. The LoF variant types primarily included stop-gained and frameshift variants, both present in 97% of the 159 patients with CPT, as well as splice-changing variants, which were found in 78% of these patients. Rare LoF variations in osteocyte-related pathways, such as ossification, were identified in 112 of the 159 CPT cases (70.4%). The top seven genes carrying rare protein-damaging variants that might be related to CPT are NF1, GLI3, MRC2, PTH1R, RYR1, NPR2 and ITGA11. These findings shed light on novel genetic mutations and osteocyte transcriptome-related molecular pathways involved in CPT, providing a new framework for understanding the genetic regulation of CPT pathology and suggesting potential directions to further elucidate its pathogenesis.

The periosteum is the main organ responsible for bone regeneration. Vascularized Periosteal Grafts (VPG) have demonstrated exceptional efficacy and speed in facilitating bone union among children with challenging bone healing conditions. Despite their promising results, the overall impact of these interventions has yet to be comprehensively evaluated through systematic review. This systematic review aimed to provide comprehensive insights into bone union outcomes and complications related to the use of VPG in children. MEDLINE/PubMed, Embase, Web of Science, Clinicaltrials.gov, and Cochrane Library were searched from database inception to September 2023 and screened for relevant studies. Data were collected regarding patient demographics, disease, treatment, anatomical location, graft used, donor and receptor vessels, skin paddle monitoring, follow-up duration, time to union, consolidation, and complications. The correlation between age and bone union was assessed using Pearson and Spearman correlation coefficients, as appropriate. Study quality was assessed using the Methodological Index for Non-randomized Studies Criteria. A total of 15 studies involving 135 patients were included. All the studies were classified as Level 4 evidence. The mean MINORS score was 5.1 ± 1. The aim of the VPG was nonunion treatment in 90 patients (67%), nonunion prevention in 35 patients (26%), and bone union acceleration in 10 patients (7%). The origin of the bone union problem was traumatic in 59 cases (44%), congenital pseudoarthrosis of the tibia or fibula in 48 patients (35%), oncologic in 23 patients (17%), and infectious in 5 patients (4%). Nine different sources of periosteal flaps were used to enhance bone union. Bone union rate was 96% with a mean time of 4.2 months (range 1-18 months). Spearman test showed a non-statistically significant negative correlation between age and bone union time (r = -0.3, p = 0.759). VPGs are a safe and reliable treatment for promoting bone union, especially in the context of complex pediatric bone-healing challenges.

Congenital pseudarthrosis of the tibia (CPT) is a rare, dysplastic condition causing significant disability in the lower limbs. A treatment aims to achieve long-lasting union, prevent limb length discrepancies, and prevent soft tissue lesions. Traditional surgery often yields satisfactory results, but amputation may be proposed in failed cases. This report presents a congenital pseudarthrosis of the tibia and fibula, treated with the Paley cross-union protocol. A 15-month-old girl presented with a crooked right lower leg at the age of two months, history of a right lower leg fracture at the age of eight months, and pain when moving her leg. She had undergone an initial surgical procedure to maintain tibia alignment with K-Wire insertion and was cast at a private hospital. The patient's physical examination showed a cast causing limited range of motion, but no tenderness or distal neurovascular issues. The Paley cross-union protocol was performed, involving anterior approach, curettage, and insertion of a titanium intramedullary elastic nail into the tibia. The fracture site area was covered with a meshed periosteum layer and filled with synthetic bone grafts. A long leg cast was performed after the procedure. An imaging examination post-cross-union protocol showed a good result. Cross-union for CPT represents a paradigm shift in the treatment of this horrible child disease. Given the promising result, the cross-union approach has to be regarded as a fresh criterion for treating CPT.