New insights into pathogenesis of congenital pseudarthrosis of tibia in children using periosteum proteomics analysis.

RATIONALE: The exact etiology and pathogenesis of congenital pseudarthrosis of tibia (CPT) are not clear. Quantitative proteomics analysis plays a vital role in disease pathology research. Tandem mass tag (TMT)-based proteomics techniques were employed to identify and analyze the differentially expressed proteins (DEP) in the tibia periosteum tissues of CPT patients. METHODS: The samples were divided into three groups: CPT with NF1 group, CPT without NF1 group (non-NF1-CPT), and control group (patients with open tibial fracture). A fold change ≥1.5 or ≤0.66 and P-value <0.05 were used as the thresholds to screen DEPs. Subsequently, bioinformatics resources such as online tools DAVID and String were used to generate gene ontology (GO) annotation, KEGG pathways enrichment, and protein-protein interaction (PPI) network for these DEPs. RESULTS: The results show that a total of 347 proteins were differentially expressed in NF1-CPT groups, 212 of which were upregulated and 135 were downregulated. There were more DEPs in non-NF1-CPT groups; we identified 467 DEPs, including 281 upregulated and 186 downregulated. Among them, NF1-CPT groups and non-NF1-CPT groups shared 231 DEPs, and the remaining 230 DEPs showed the same expression trend in the two disease groups, with 117 upregulated and 113 downregulated. In particular, 116 proteins were altered only in NF1-CPT groups (94 were upregulated and 22 were downregulated), whereas 236 proteins were altered only in non-NF1-CPT groups (164 were upregulated and 72 were downregulated). Finally, compared with non-NF1-CPT groups, 47 proteins changed 1.5-fold and P-value < 0.05 in NF1-CPT groups. CONCLUSIONS: To sum up, we found that common DEPS in periosteum of NF1-CPT and non-NF1-CPT groups are mainly involved in cell matrix assembly, cell adhesion, AKT-PI3K signal pathway activation, and vascular agglutination, which indicate that these are the pathological characteristics of CPT. The osteogenic ability is weak, the osteoclastic ability is strong, the vascular lumen is narrow, the invasive growth and the proliferation of fibroblasts are enhanced in CPT patients.

Hyperactive Ras/MAPK signaling is critical for tibial nonunion fracture in neurofibromin-deficient mice.

Neurofibromatosis type 1 (NF1) is a common genetic disorder affecting 1 in 3500 individuals. Patients with NF1 are predisposed to debilitating skeletal manifestations, including osteopenia/osteoporosis and long bone pseudarthrosis (nonunion fracture). Hyperactivation of the Ras/mitogen-activated protein kinase (MAPK) pathway in NF1 is known to underlie aberrant proliferation and differentiation in cell lineages, including osteoclast progenitors and mesenchymal stem cells (MSCs) also known as osteoblast progenitors (pro-OBLs). Our current study demonstrates the hyper Ras/MAPK as a critical pathway underlying the pathogenesis of NF1-associated fracture repair deficits. Nf1-deficient pro-OBLs exhibit Ras/MAPK hyperactivation. Introduction of the NF1 GTPase activating-related domain (NF1 GAP-related domain) in vitro is sufficient to rescue hyper Ras activity and enhance osteoblast (OBL) differentiation in Nf1(-/-) pro-OBLs and NF1 human (h) MSCs cultured from NF1 patients with skeletal abnormalities, including pseudarthrosis or scoliosis. Pharmacologic inhibition of mitogen-activated protein kinase kinase (MEK) signaling with PD98059 partially rescues aberrant Erk activation while enhancing OBL differentiation and expression of OBL markers, osterix and osteocalcin, in Nf1-deficient murine pro-OBLs. Similarly, MEK inhibition enhances OBL differentiation of hMSCs. In addition, PD98059 rescues aberrant osteoclast maturation in Nf1 haploinsufficient bone marrow mononuclear cells (BMMNCs). Importantly, MEK inhibitor significantly improves fracture healing in an NF1 murine model, Col2.3Cre;Nf1(flox/-). Collectively, these data indicate the Ras/MAPK cascade as a critical pathway in the pathogenesis of bone loss and pseudarthrosis related to NF1 mutations. These studies provide evidence for targeting the MAPK pathway to improve bone mass and treat pseudarthrosis in NF1.

Scaphoid fracture nonunion: correlation of radiographic imaging, proximal fragment histologic viability evaluation, and estimation of viability at surgery: diagnosis of scaphoid pseudarthrosis.

PURPOSE: The purpose of this study was to correlate the pre-operative imaging, vascularity of the proximal pole, and histology of the proximal pole bone of established scaphoid fracture non-union. METHODS: This was a prospective non-controlled experimental study. Patients were evaluated pre-operatively for necrosis of the proximal scaphoid fragment by radiography, computed tomography (CT) and magnetic resonance imaging (MRI). Vascular status of the proximal scaphoid was determined intra-operatively, demonstrating the presence or absence of puncate bone bleeding. Samples were harvested from the proximal scaphoid fragment and sent for pathological examination. We determined the association between the imaging and intra-operative examination and histological findings. RESULTS: We evaluated 19 male patients diagnosed with scaphoid nonunion. CT evaluation showed no correlation to scaphoid proximal fragment necrosis. MRI showed marked low signal intensity on T1-weighted images that confirmed the histological diagnosis of necrosis in the proximal scaphoid fragment in all patients. Intra-operative assessment showed that 90% of bones had absence of intra-operative puncate bone bleeding, which was confirmed necrosis by microscopic examination. CONCLUSIONS: In scaphoid nonunion MRI images with marked low signal intensity on T1-weighted images and the absence of intra-operative puncate bone bleeding are strong indicatives of osteonecrosis of the proximal fragment.

[Improvement of fracture healing with teriparatide: series of 22 cases and review of the literature]. / Accélération de la guérison fracturaire par le tériparatide: série de 22 cas et revue de la littérature.

Pseudoarthrosis is defined as a non healing fracture 9 months after trauma and without radiological progression within the last three months. Osteoporotic fractures have a greater risk of chirurgical complications. The question of giving a medical treatment in the purpose of accelerating fracture healing is an increasing concern. There are data showing that with teriparatide (bone anabolic treatment derived from the parathyroid hormone) bone healing and functional status are improved, with or without surgery, in the case of either typical or atypical fractures. The risks of this treatment are low but health insurance agreement is needed in this indication. We report our experience with the use of this molecule, out of the official indication, in complex situations of non healing fractures.

[Bisegmental anterior interbody spondylodesis, using rigid plates, in surgical treatment of cervical vertebral column traumas and diseases].

Results of surgical treatment of 34 patients, suffering cervical vertebral column traumas and diseases, are analyzed. In all the patients bisegmental anterior interbody spondylodesis was conducted, using cervical rigid plates and vertical cylindrical net implants. The existing and newly obtained information about changes in the radiological indices dynamics while the method application by its authors is presented. The interbody synostosis was achieved in 82.4% patients in 1 yr after the operation. The complications rate while the implants application have constituted 23.3%, and the total rate of complications--29.1%.

Can MRI predict subsequent pseudarthrosis resulting from osteoporotic thoracolumbar vertebral fractures?

PURPOSE: The purpose of this study was to assess the ability of short inversion time inversion-recovery (STIR) in magnetic resonance imaging for predicting the prognosis of osteoporotic vertebral fractures. METHODS: We analyzed 63 vertebrae of 56 patients who had osteoporotic vertebral fracture (Th10-L2) prospectively. Image finding of a homogeneous high signal change on a fractured vertebra was evaluated and all vertebrae were divided into "homogenous high signal change group" or "non-homogenous high signal change group". On the other hand, image finding of linear black signal area was evaluated and all vertebrae were divided into "linear black signal area group" or "non-linear black signal area group". RESULTS: Sixteen and 24 vertebrae were included in the homogenous high signal change group or the linear black signal area group, respectively. The 16 homogenous high signal change cases did not result in non-union, and 47 non-homogenous high signal change cases resulted in 14 non-unions, a significant difference. Twenty-four linear black signal area and 39 non-linear black signal area cases resulted in 10, and 4 non-unions, respectively, also a significant difference. The kyphosis progression rate of the linear black signal area group (mean 35%) was significantly higher than that of non-linear black signal area group (mean 23%). The visual analog scale of back pain of the linear black signal area group (mean 35 mm) was significantly higher than that of the non-linear black signal area group (mean 23 mm). CONCLUSIONS: STIR was useful for predicting bone union, kyphosis, and back pain in patients with osteoporotic vertebral fracture.

Usefulness of an early MRI-based classification system for predicting vertebral collapse and pseudoarthrosis after osteoporotic vertebral fractures.

STUDY DESIGN: Retrospective review. OBJECTIVE: To clarify whether an early magnetic resonance imaging-based classification predicts pseudoarthrosis and final vertebral collapse in osteoporotic vertebral fractures. SUMMARY OF BACKGROUND: Initial therapy for osteoporotic vertebral fractures involves bed rest, orthotic use, and plaster casts. However, in some cases, pain persists because of progressive vertebral collapse or pseudoarthrosis. Prediction of these complications immediately after fractures can facilitate early proactive treatment despite the early prognosis being generally poor. METHODS: A total of 109 patients (129 fractured vertebrae, 88 females, 21 males, and average age 79 y) followed up over 6 months after conservative treatment for thoracolumbar vertebral fractures were included. Early midsagittal T1-weighted and T2-weighted magnetic resonance images were analyzed. The incidence of final vertebral body collapse, pseudoarthrosis conversion, and delayed spinal cord paralysis were examined retrospectively for each vertebral fracture type. RESULTS: According to the T1-weighted image-based classification, 74 of the vertebrae (57%) had total-type fractures. The final vertebral body collapse rate was significantly higher in this type than in others. Pseudoarthrosis was observed in 20 total-type fractures in 20 patients (18.3%); pseudoarthrosis conversion rate was significantly higher in these patients than in others. Delayed spinal cord paralysis occurred in only 1 patient (0.9%) with total-type fracture. According to the T2-weighted image-based classification, 69 vertebrae had the hyperintense wide-type fractures, which was the most common fracture type (53%). Hypointense wide-type fractures were associated with a significantly higher incidence of final vertebral body collapse, pseudoarthrosis, and delayed spinal cord paralysis. When total-type fractures of the T1-weighted image-based classification were subclassified according to the T2-weighted image-based classification, a significantly higher pseudoarthrosis conversion rate was observed in hypointense wide-type fractures. CONCLUSIONS: Our results suggest that the radiologic prognosis can be estimated to a limited extent by determining the degree and extent of osteoporotic vertebral fractures using an early magnetic resonance imaging-based classification.

MEK-SHP2 inhibition prevents tibial pseudarthrosis caused by NF1 loss in Schwann cells and skeletal stem/progenitor cells.

Congenital pseudarthrosis of the tibia (CPT) is a severe pathology marked by spontaneous bone fractures that fail to heal, leading to fibrous nonunion. Half of patients with CPT are affected by the multisystemic genetic disorder neurofibromatosis type 1 (NF1) caused by mutations in the NF1 tumor suppressor gene, a negative regulator of RAS-mitogen-activated protein kinase (MAPK) signaling pathway. Here, we analyzed patients with CPT and Prss56-Nf1 knockout mice to elucidate the pathogenic mechanisms of CPT-related fibrous nonunion and explored a pharmacological approach to treat CPT. We identified NF1-deficient Schwann cells and skeletal stem/progenitor cells (SSPCs) in pathological periosteum as affected cell types driving fibrosis. Whereas NF1-deficient SSPCs adopted a fibrotic fate, NF1-deficient Schwann cells produced critical paracrine factors including transforming growth factor-ß and induced fibrotic differentiation of wild-type SSPCs. To counteract the elevated RAS-MAPK signaling in both NF1-deficient Schwann cells and SSPCs, we used MAPK kinase (MEK) and Src homology 2 containing protein tyrosine phosphatase 2 (SHP2) inhibitors. Combined MEK-SHP2 inhibition in vivo prevented fibrous nonunion in the Prss56-Nf1 knockout mouse model, providing a promising therapeutic strategy for the treatment of fibrous nonunion in CPT.

Repair of long-bone pseudoarthrosis with autologous bone marrow mononuclear cells combined with allogenic bone graft.

BACKGROUND AIMS: Long-bone pseudoarthrosis is a major orthopedic concern because of numerous factors such as difficulty of the treatment, high recurrence, high costs and the devastating effects on the patients' quality of life, which sometimes ends in amputation. Although the "gold standard" for the treatment of this pathology is autologous bone grafting, which has high osteogenic, osteoconductive and osteoinductive properties, this treatment presents some restrictions such as the limited amount of bone that can be taken from the patient and donor site morbidity. Bone marrow mononuclear cells (BM-MNCs) comprise progenitor and stem cells with pro-angiogenic and pro-osteogenic properties. Allogenic cancellous bone graft is a natural and biodegradable osteoconductive and osteoinductive scaffold. Combination of these two components could mimic the advantages of autologous bone grafting while avoiding its main limitations. METHODS: Long-bone pseudoarthrosis was treated in seven patients with autologous BM-MNCs from iliac crest combined with frozen allogenic cancellous bone graft obtained from the tissue bank. RESULTS: All patients showed complete bone consolidation 5.3 ± 0.9 months (range, 2-9 months) after cell transplantation. Moreover, limb pain disappeared in all of them. The mean follow-up was 35.8 ± 4.6 months after transplantation (range, 24-51 months) without pseudoarthrosis recurrence or pain reappearing. CONCLUSIONS: Combination of autologous BM-MNCs and allogenic bone graft could constitute an easy, safe, inexpensive and efficacious attempt to treat long-bone pseudoarthrosis and non-union by reproducing the beneficial properties of autologous bone grafting while restricting its disadvantages.

First successful case of non-invasive in-utero treatment of twin reversed arterial perfusion sequence by high-intensity focused ultrasound.

High-intensity focused ultrasound (HIFU) has excellent potential as a non-invasive therapeutic tool in various fields of medicine. We present a case of twin reversed arterial perfusion sequence, in which non-invasive blood flow occlusion in the acardiac fetus was successfully achieved by means of HIFU exposure from outside the maternal abdomen. HIFU was applied to blood vessels of the acardiac fetus at the point at which the umbilical cord entered the body in a series of four procedures at 3-day intervals starting at 13 weeks' gestation, and in a final procedure with higher power at 17 weeks. The HIFU intensity was set at approximately 2300 W/cm(2) for the initial series of procedures and at 4600 W/cm(2) for the final procedure, with exposure periods of 10 s. As color Doppler examination revealed absence of blood flow to the acardiac fetus after the second round of HIFU exposure, we concluded that complete occlusion of target vessels had been achieved. Delivery was by Cesarean section at 37 weeks' gestation. A male neonate (the pump fetus) was born weighing 1903 g with Apgar scores of 8 and 9 at 1 and 5 min, respectively. At the time of writing, the baby was healthy and growing normally, with the exception of congenital pseudarthrosis.

Congenital pseudarthrosis of the clavicle: a rare and challenging diagnosis.

Congenital pseudarthrosis of the clavicle is a rare clinical entity, first described in 1910. We report on a newborn baby girl who presented with a painless lump over mid-portion of right clavicle at her routine newborn examination, which was subsequently diagnosed as a congenital pseudarthrosis. Here we explore its pathogenesis, elaborate on its differential diagnoses in paediatric patients, and comment on its distinct radiological features.

[Optimization of ostheogenesis with the use of vascularized periosteal-cortical autotransplants in patients with false joints of long bones].

The issue analyzes the use of free revascularizable or rotatable periosteal-cortical autotransplants as an additional source of ostheogenesis in patients with false joints of long tubular bones. The experience of treatment of 58 patients was summarized. The terms of fracture consolidation was similar to that after non-complicated fractures of the same localization.

[The frequency of endothelial dysfunction in patients with pseudarthrosis of long bones with hyperhomocysteinemia and associated metabolic disorder].

In article described research of frequency of endothelial dysfunction in 153 patients with pseudarthrosis of long bones and in individuals with consolidated fractures. The reparative regeneration are associated by structural and functional disorders of the central and peripheral vessels as endothelial dysfunction, thickening of the intima-media, prevails at hypoplastic and atrophic types bone nonunion, neurotrofic syndrome and refractures. Endothelial function was significantly dependent on the levels of homocysteine, total cholesterol and interleukin-6 in serum.

[Metabolic status and bone mineral density in patients with pseudarthrosis of long bones in hyperhomocysteinemia].

In article described research of the metabolic status and bone mineral density in 153 patients with with pseudarthrosis of long bones, in individuals with consolidated fractures and healthy people. The violations of reparative osteogenesis at hyperhomocysteinemia are accompanied by disturbances of the functional state of bone tissue, inhibition of biosynthetic and increased destruction processes, reduced bone mineral density in the formation of osteopenia and osteoporosis. The degree and direction of change of bone depends on the type of violation of reparative osteogenesis.

Post-mortem computed tomography (PMCT) and PMCT-angiography after cardiac surgery. Possibilities and limits.

BACKGROUND: PMCT is a well-known tool of the forensic pathologist. It is employed worldwide. PMCT-angiography offers additional insights. This paper intends to demonstrate possibilities of both methods after cardiac surgery. MATERIAL AND METHODS: Exemplary cases with typical findings were selected from our own collection. PMCT was performed as whole body CT (1mm slice, pitch 1.5, 130kV, 180-130mAs, 16 slice MDCT). In PMCT-angiography, contrast material (1.2 litres) is injected into the arteries (arterial phase, also documented with a whole body CT). Thereafter, contrast material is injected into the veins (venous phase, also documented with a whole body CT). The final CT is obtained after circulation has been provoked with a special pump (circulatory phase). RESULTS: PMCT visualised pseudoarthrosis and fractures of the sternum, implanted valves (TAVI) encroaching the ostia of the coronary arteries, bleeding and pericardial tamponade. PMCT-angiography showed the sources of the bleeding, vascular stenosis and obstruction and modified vascular supply. With respect to the postoperative care, malposition of tubes, drainages and complication of punctures could be seen. CONCLUSION: PMCT and PMCT-angiography can visualise complications and the cause of death. Such knowledge may allow for prevention of suffering and death. It may also aid in improving valve design and implantation procedures.

Molecular Dissection of Somatic Skeletal Disease in Neurofibromatosis Type 1.

Neurofibromatosis type 1 (NF1) is a tumor predisposition syndrome caused by heterozygous NF1 gene mutations. Patients with NF1 present with pleiotropic somatic secondary manifestations, including development of bone pseudarthrosis after fracture. Somatic NF1 gene mutations were reproducibly identified in patient-derived pseudarthrosis specimens, suggesting a local mosaic cell population including somatic pathologic cells. The somatic cellular pathogenesis of NF1 pseudarthroses remains unclear, though defects in osteogenesis have been posited. Here, we applied time-series single-cell RNA-sequencing (scRNA-seq) to patient-matched control and pseudarthrosis-derived primary bone stromal cells (BSCs). We show that osteogenic specification to an osteoblast progenitor cell population was evident for control bone-derived cells and haploinsufficient pseudarthrosis-derived cells. Similar results were observed for somatic patient fracture-derived NF1-/- cells; however, expression of genetic pathways associated with skeletal mineralization were significantly reduced in NF1-/- cells compared with fracture-derived NF1+/- cells. In mice, we show that Nf1 expressed in bone marrow osteoprogenitors is required for the maintenance of the adult skeleton. Results from our study implicate impaired Clec11a-Itga11-Wnt signaling in the pathogenesis of NF1-associated skeletal disease. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

A regenerative approach for bone repair in congenital pseudarthrosis of the tibia associated or not associated with type 1 neurofibromatosis: correlation between laboratory findings and clinical outcome.

BACKGROUND AND AIMS: Congenital pseudarthrosis of the tibia (CPT) is a rare orthopedic disease presenting spontaneous fractures that do not heal. The treatment of CPT is characterized by repeated surgical procedures that often fail, with the inevitable outcome of severe disability and amputation. We tested the hypothesis that CPT may benefit from regenerative strategies based on mesenchymal stromal cells (MSC) combined with platelet-rich fibrin (PRF) as a source of growth factors. The aim of the study was to verify whether laboratory testing to assess the osteogenic properties of MSC and the osteo-inductive activity of PRF correlated with the clinical outcome. METHODS: Ten patients affected by refractory CPT were treated by using MSC derived from the iliac crest (IC-MSC), PRF and lyophilized bone. In six patients, CPT was associated with type 1 neurofibromatosis (NF1). Biochemical, functional and molecular assays were performed to assess the intrinsic osteogenic potential of IC-MSC (cells cultured with fetal calf serum) and the osteo-inductive properties of PRF (cells cultured with autologous serum). RESULTS: Bone consolidation was obtained in three patients who had CPT and NF1. In these patients, the IC-MSC exposed to autologous serum were able to form mineral nodules in vitro, while the mineralizing ability was totally abrogated in patients with a poor clinical outcome. CONCLUSIONS: Cell therapy may be a useful tool for the treatment of refractory CPT because it increases the opportunity to achieve effective bone tissue regeneration. Our data suggest that the presence of pro-osteogenic growth factors is an essential requirement for bone healing.

Case report: Floating-clavicle from the 17th century: the oldest case?

BACKGROUND: Dislocation of both ends of the clavicle is a rare traumatic lesion and the mechanism of the lesion is usually related to major trauma. The first case was described in 1831. CASE DESCRIPTION: We present the oldest referenced case of this alteration. The skeleton studied belonged to an old woman buried inside the Sant Pere de Madrona Church in Berga (Barcelona/Spain) and its dating indicated it corresponded to the end of the 17th century. There was a pseudarthrosis between the clavicle and coracoid ligament; when the bones were reconstructed by pseudarthrosis both ends of the clavicle appeared dislocated. LITERATURE REVIEW: Bipolar dislocation of both ends of the clavicle, or "floating-clavicle", is a rare injury. Since 1831 when this type of injury was first reported, approximately 40 cases have been published. No archaeological case has been published. CLINICAL RELEVANCE: Despite experiencing bipolar dislocation of both ends of the clavicle, or floating-clavicle, it is possible to have acceptable function of the arm as suggested by the anthropologic parameters analyzed here. The head of the humerus of the affected shoulder shows no abnormalities and the contralateral glenoid cavity shows severe osteochondritis of the anteroinferior side.

The Locking Compression Paediatric Hip Plate: technical guide and critical analysis.

PURPOSE: Osteotomies of the proximal femur and stable fixation of displaced femoral neck fractures are demanding operations. An LCP Paediatric Hip Plate was developed to make these operations safer and less demanding. The article focuses on the surgical technique and critically analyses the device. METHODS: Between 2006 and 2008, 30 hips in 22 patients underwent surgery. Patients' demographics, perioperative details, postoperative outcome and complications were retrospectively collected and analysed. RESULTS: Patients' diagnoses included persistent congenital hip dysplasia (n = 4), neuropathic hip dysplasia (n = 9), idiopathic ante/retroversion (n = 8), femoral neck fracture (n = 3), Perthes' disease (n = 2), deformity after slipped capital femoral epiphysis (SCFE), congenital femoral neck pseudarthrosis, deformity after pelvic tumour resection and malunion following proximal femoral fracture (one each). In 21 of 22 patients, the postoperative radiographs showed corrections as planned. Two cases had to be revised for screw loosening. Intraoperative handling using the plate was excellent in all cases. CONCLUSIONS: In our case series of 30 hip operations, the LCP Paediatric Hip Plate was shown to be safe and applicable in the clinical setting with excellent results and a low complication rate. We consider that the LCP Paediatric Hip Plate is a valuable device for correction of pathological conditions of the proximal femur and for fixation of displaced femoral neck fractures in children. Larger studies should be carried out to better quantify the risk of clinically relevant complications.

"4-in-1 osteosynthesis" for atrophic-type congenital pseudarthrosis of the tibia.

BACKGROUND: According to the authors' multi-targeted, fibular status-based algorithmic approach using the Ilizarov technique, ankle stabilization by end-to-end osteosynthesis of the fibula is advocated for mild (type B1), "4-in-1 osteosynthesis" in which all 4 proximal and distal segments of the tibia and fibula are placed in 1 healing mass for moderate (type B2), and distal tibiofibular (TF) fusion for severe (type B3) fibular pseudarthrosis in association with atrophic-type congenital pseudarthrosis of the tibia (CPT). This report describes the indications, operative technique, and outcomes of "4-in-1 osteosynthesis" for atrophic-type CPT associated with type B2 fibular pseudarthrosis. METHODS: Thirteen patients presented with atrophic-type CPT associated with type B2 fibular pseudarthrosis underwent Ilizarov osteosynthesis between 1989 and 2007 for atrophic-type CPT. To validate the efficacy of "4-in-1 osteosynthesis" in these patients, fracture risk and ankle function were compared between 2 groups of type B2 patients, namely, 8 patients (mean age, 6.3 y) who underwent "4-in-1 osteosynthesis" according to our current protocol (Group I), and 5 patients (mean age, 3.2 y) treated by other techniques (3 distal TF fusion, 2 failed end-to-end osteosynthesis) during the learning period (Group II). RESULTS: No refracture occurred in Group I, whereas refracture occurred in all except 1 in Group II. Ankles were eventually stabilized by distal TF fusion in all patients in Group II. The Kaplan-Meier method revealed a refracture-free cumulative survival rate of 100% in Group I, whereas in Group II, it dropped progressively and reached 60% at 1.8 years and 20% at 2.7 years. No significant difference in ankle function was evident between the 2 groups (american orthopaedic foot and ankle society (AOFAS) score, 89.25 ± 7.25 after 7.4 y of follow-up in Group I, and 84.6 ± 9.53 after 13 y of follow-up in Group II). CONCLUSIONS: It is imperative that fibular status be evaluated carefully to enable the planning of the most effective, safe, practical treatment. "4-in-1 osteosynthesis," which is primarily considered for bony union with a large cross-sectional area and ankle stabilization, seems to be a better choice for atrophic-type CPT associated with type B2 fibular pseudarthrosis, in which end-to-end osteosynthesis of the fibula often fails. LEVEL OF EVIDENCE: Level III, Retrospective comparative study.