The challenge of the infected pilon tibial non-union: treatment with radical resection, bone transport and ankle arthrodesis.

A significant number of patients with pilon tibial fractures develop complications, the most devastating being a combination of infection and non-union with bone loss. The results of the Ilizarov bone transport technique were retrospectively evaluated in ten patients. All underwent an extensive resection and reconstruction aiming at an ankle arthrodesis. The outcome was registered by clinical and radiographic examination as proposed by Paley's functional and bone results classification. A good healing at the level of the docking site could be obtained in all patients but with a re- intervention in 8 of the 10. In 5 of these patients, re-intervention with a transcalcaneal nailing leaded to the final healing. Other options are debridement of the docking site (2 patients) and a new Ilizarov procedure (1 patient). If patients are prepared to participate in a long-term treatment with the risk of multiple interventions a reconstruction can be performed, resulting in a limb with an acceptable function, allowing all activities of daily life and even a professional occupation. To obtain this final result with a definite union at the docking site a secondary retrograde intramedullary nailing is considered a valuable and safe procedure.

Neurofibromatosis type 1-related pseudarthrosis: Beyond the pseudarthrosis site.

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder affecting approximately 1 in 2,000 newborns. Up to 5% of NF1 patients suffer from pseudarthrosis of a long bone (NF1-PA). Current treatments are often unsatisfactory, potentially leading to amputation. To gain more insight into the pathogenesis we cultured cells from PA tissue and normal-appearing periosteum of the affected bone for NF1 mutation analysis. PA cells were available from 13 individuals with NF1. Biallelic NF1 inactivation was identified in all investigated PA cells obtained during the first surgery. Three of five cases sampled during a later intervention showed biallelic NF1 inactivation. Also, in three individuals, we examined periosteum-derived cells from normal-appearing periosteum proximal and distal to the PA. We identified the same biallelic NF1 inactivation in the periosteal cells outside the PA region. These results indicate that NF1 inactivation is required but not sufficient for the development of NF1-PA. We observed that late-onset NF1-PA occurs and is not always preceded by congenital bowing. Furthermore, the failure to identify biallelic inactivation in two of five later interventions and one reintervention with a known somatic mutation indicates that NF1-PA can persist after the removal of most NF1 negative cells.

Prevalence of neurofibromatosis type 1 in congenital pseudarthrosis of the tibia.

UNLABELLED: A strong relationship between congenital pseudarthrosis of the tibia (CPT) and neurofibromatosis type 1 (NF1) has been suggested, but prevalence varies widely throughout the literature and the criteria used for diagnosis are very heterogeneous. Literature focus is mainly on treatment and no specific review on the prevalence of NF1 has been published. Based on our own observations, we hypothesized the prevalence of NF1 in patients with CPT to be higher than what is previously accepted. We conducted a comprehensive literature review on this topic and compared results with our study population. Twenty-one out of twenty-five patients in the study population matched the NIH diagnostic criteria for NF1 (84.0 %, CI95 = 69.6-98.4 %). These results are higher than the prevalence reported in the literature (55.4 %, CI95 = 50.4-60.4 %). CONCLUSIONS: The prevalence of NF1 in patients with CPT might be higher than what is reported until now because the criteria of NF1 generally appear only after the diagnosis of CPT. We propose a repeat meticulous examination and a multidisciplinary approach with a clinical genetic counseling in all CPT patients. WHAT IS KNOWN: • Congenital pseudarthrosis of the tibia and neurofibromatosis type 1 are closely related. • Literature focus is mainly on treatment and little epidemiologic research is available. What is New: • Prevalence of neurofibromatosis type 1 in patient with congenital pseudarthrosis of the tibia might be higher than what is reported until now. • A multidisciplinary approach with meticulous clinical examination and genetic counseling might lead to an earlier diagnosis of neurofibromatosis type 1 in patients with congenital pseudarthrosis of the tibia.

First metatarsal shortening after hallux valgus surgery: Benefits of treatment with distraction osteogenesis.

INTRODUCTION: Iatrogenic shortening and elevation of the first metatarsal (MT1) is a common complication of hallux valgus surgery, inducing metatarsalgia underneath the lesser rays, a reason for patient dissatisfaction. For resolving this problem, different types of revision surgery are described, of which lengthening MT1 by distraction osteogenesis is underreported and therefore undervalued. MATERIALS AND METHODS: We present three cases with iatrogenic shortening after hallux valgus surgery treated by distraction osteogenesis of MT1 using a custom-made frame, made of Ilizarov equipment. To evaluate the amount of lengthening, the length of the first and second metatarsal (MT2) and the parabolic distribution of the metatarsal heads were compared before and after distraction. To evaluate correction in the sagittal plane, Meary's angle was measured pre- and post-lengthening. Pain was noted by a visual analogic score during follow-up. RESULTS: In our series of three cases, lengthening of MT1 between 7 mm and 18 mm, resulted in an improved parabolic distribution of the MT heads. The average difference between the second and first MT-head, relative to the SM4 axis (M2-M1) improved from 9.4 mm (± 0.9 mm) to 2.8 mm (± 0.7 mm) resolving corresponding pain in all patients. Meary's angle was normalized in one case. The average duration of treatment was 116 days (± 9 days). Minimal follow up was 11 years. CONCLUSION: Using Ilizarov equipment for distraction osteogenesis of MT1 is a low-cost and effective method. Over time, this technique has proven its utility in pronounced iatrogenic shortening of MT1. The possibility to lengthen more than 1 cm, to correct in multiple planes, as well as early mobilization and weight bearing are additional advantages, but one must be careful to avoid overcorrection. The need for strict follow-up with multiple radiographs and rigorous patient selection is mandatory.

Humeral lengthening by distraction osteogenesis: a safe procedure?

This study was conducted to assess the safety of humeral lengthening using an Ilizarov frame. We retrospectively reviewed 26 humeral segments in 17 patients that were lengthened at our department between 1993 and 2011. There were varying aetiologies including achondroplasia, epiphyseal dysplasia, Oilier disease, trauma or infection of the proximal humeral growth-plate, unicameral bone cyst and brachial plexus injury. Mean age at start of surgery was 17.05 years (range : 5-40). The mean lengthening achieved was 8.85 (3-13) cm. Mean lengthening percentage was 353% (range : 10-48). Average healing index was 30.56 days/cm (range : 17.46-4232). There was a significant difference in healing index between achondroplasia patients (28.79 days/cm) compared to others (33.41 days/cm). Minor problems included pin tract infection (14 segments). More important obstacles were temporary elbow flexion contracture (7 segments), premature consolidation (6 segments), radial nerve dysaesthesia (6 segments) and loosening of a Schanz screw (1 segment). Complications included one fracture and one progressive bowing after frame removal. One planned lengthening was not completely achieved. Despite a lot of obstacles, humeral lengthening using an Ilizarov frame provided a reliable method to treat the functional or cosmetic problems of upper limb shortening.

The Pentaconcept in skeletal tissue engineering. A combined approach for the repair of bone defects.

Tissue engineering has become a hot topic in modern medicine. Its application in a surgical setting, such as for the treatment of skeletal defects, still has to tackle some problems that might look simple at first sight, but need a well-structured handling combining surgery and science, with in a central position the patient, who is both cell donor and receptor of the tissue engineered end product. To achieve this goal in a clinical setting, a five steps pathway is described and designated as the Pentaconcept, integrating all ingredients for successful reconstructive procedures.

Reduction of treatment time in external ring fixation using the monofix device.

One of the disadvantages of the Ilizarov method is the long treatment time needed for extensive lengthening or complex deformity correction. To minimize the discomfort of the circular frame the authors have introduced a 'frame reduction' technique in which the ring frame is converted towards a unilateral fixator, the 'Monofix'. Both its efficacy and patient satisfaction encouraged the authors to apply this method on a routine basis since 1998 for lower and upper limb corrections. The technique is demonstrated, its indications and potential problems are discussed.

Corrigendum: Consensus Recommendations for the Diagnosis and Management of X-Linked Hypophosphatemia in Belgium.

[This corrects the article DOI: 10.3389/fendo.2021.641543.].

Consensus Recommendations for the Diagnosis and Management of X-Linked Hypophosphatemia in Belgium.

X-linked hypophosphatemia (XLH) is the most common genetic form of hypophosphatemic rickets and osteomalacia. In this disease, mutations in the PHEX gene lead to elevated levels of the hormone fibroblast growth factor 23 (FGF23), resulting in renal phosphate wasting and impaired skeletal and dental mineralization. Recently, international guidelines for the diagnosis and treatment of this condition have been published. However, more specific recommendations are needed to provide guidance at the national level, considering resource availability and health economic aspects. A national multidisciplinary group of Belgian experts convened to discuss translation of international best available evidence into locally feasible consensus recommendations. Patients with XLH may present to a wide array of primary, secondary and tertiary care physicians, among whom awareness of the disease should be raised. XLH has a very broad differential-diagnosis for which clinical features, biochemical and genetic testing in centers of expertise are recommended. Optimal care requires a multidisciplinary approach, guided by an expert in metabolic bone diseases and involving (according to the individual patient's needs) pediatric and adult medical specialties and paramedical caregivers, including but not limited to general practitioners, dentists, radiologists and orthopedic surgeons. In children with severe or refractory symptoms, FGF23 inhibition using burosumab may provide superior outcomes compared to conventional medical therapy with phosphate supplements and active vitamin D analogues. Burosumab has also demonstrated promising results in adults on certain clinical outcomes such as pseudofractures. In summary, this work outlines recommendations for clinicians and policymakers, with a vision for improving the diagnostic and therapeutic landscape for XLH patients in Belgium.

Ilizarov treatment for aseptic delayed union or non-union after reamed intramedullary nailing of the femur.

The authors reviewed eight patients treated with an Ilizarov frame for a non-infected delayed union or non-union after reamed intramedullary nailing of the femoral diaphysis. The hardware was completely removed in all cases but two, in which the distal fragment of a broken nail was left in situ. In five cases without shortening, progressive compression was applied. In the other three patients a simultaneous lengthening was performed using an additional percutaneous osteotomy. All patients achieved a good consolidation, with an average time to healing of 32 weeks and restoration of length and alignment if necessary. Bone grafting was never required, illustrating the sufficient biological potential for repair in non-infected femoral non-union.

Ilizarov treatment for extreme bilateral genu recurvatum in a pseudoachondroplasia patient: a case report.

The history of a 17-year-old female patient with pseudoachondroplasia, with an extreme bilateral genu recurvatum due to tibial growth disturbance, is presented. She was treated by the Ilizarov method over a nine- month period for consecutive bilateral correction of the lower legs, leading to an excellent functional result. The authors advocate the Ilizarov method as the treatment of choice for severe juxtaarticular osseous deformities, where the technical limits of a standard osteotomy with internal fixation are being exceeded.

A cell-based combination product for the repair of large bone defects.

Regenerative cell-based implants using periosteum-derived stem cells were developed for the treatment of large 3 cm fresh and 4.5 centimeter biological compromised bone gaps in a tibial sheep model and compared with an acellular ceramic-collagen void filler. It was hypothesized that the latter is insufficient to heal large skeletal defects due to reduced endogenous biological potency. To this purpose a comparison was made between the ceramic dicalciumphosphate scaffold (CopiOs®) as such, the same ceramic coated with clinical grade Bone Morphogenetic Protein 2 and 6 (BMP) only or a BMP coated cell-seeded combination product. These implants were evaluated in 2 sheep models, a fresh 3 cm critical size tibial defect and a 4.5 cm biologically exhausted tibial defect. For the groups in which growth factors were applied, BMP-6 was chosen at a dose of 344 µg for 3 cm and 1.500 µg or 3.800 µg for 4.5 cm defects. An additional group in the 4.5 cm defect was tested using BMP-2 in a dose of 1.500 µg. For all the cell based implants autologous periosteum-derived cells were used which were cultured in monolayer during 6 weeks. For the fresh defect 408 million cells and for the biologically exhausted tibial defect 612 million cells were drop-seeded on the BMP coated scaffolds. Bone healing was studied during 16 weeks postimplantation, using standard radiographs. While fresh defects responded to all treatments, regardless the use of cells, the biologically hampered defects responded in half of the cases and only if the BMP-cell combination product was used, supporting the concept that cell-based therapies may become attractive in treating defects with a compromised biological status.

Bone morphogenetic protein signaling in the murine distraction osteogenesis model.

A murine distraction osteogenesis model was standardized to allow analysis of the molecular pathways associated with postnatal de novo bone formation. The authors examined the presence and expression of Bone Morphogenetic Proteins (BMPs) -2, -3, -4, -6 and -7, and the BMP receptors Alk3 and Alk6 at different stages. Strong signals were detected for BMP-4 at the end of the distraction period and for BMP-6 during the entire experimental period. Signals for BMP-7 (Osteogenic Protein-1) were very low, suggesting a less important role during the normal process of distraction bone healing. Immunohistochemical staining revealed the presence of BMP-4 in the early chondroblasts, while BMP-6 was detected in the more mature cartilage cells. The data indicate a BMP molecular profile reminiscent of the embryonic maturation process in endochondral bone formation.

The effect of bone morphogenetic protein-7 (OP-1) and demineralized bone matrix (DBM) in the rabbit tibial distraction model.

OP-1 (800 microg) or DBM (1900 mg) were implanted in a rabbit tibial distraction model, and healing was compared to a non treated control group. The limbs were harvested after ten weeks and examined using radiography, computerized axial tomography and histological analysis. Neither of the treatments showed a changed healing pattern. Densities as measured by CT scan were not increased and the only significant finding was an increased area of bone formation in the DBM treated group (65% increase as compared to the OP-1 group). These experimental results do not show an effect of these substances in this model of bone lengthening. They indicate that further studies are warranted to understand the process of bone formation and the working mechanisms of substances that potentially trigger bone healing.

Knee mobility in femoral lengthening using Ilizarov's method.

Muscle contracture and joint stiffness are a major concern during limb lengthening using the Ilizarov method. The aim of this study was to detect factors that may influence the final loss of knee flexion. We retrospectively studied knee movement in 32 patients undergoing femoral lengthening using the Ilizarov method. The pattern of loss of knee movement showed a rapid fall in knee flexion during the latency period between operation and start of distraction, and the flexion loss continued during lengthening. There was a relationship between the worst knee range of motion achieved during lengthening and the final loss of knee flexion. Intensive physical therapy is necessary in the latency period, because there is a rapid decrease in knee flexion, as well as during the whole lengthening procedure, in which flexion loss continues. Despite the flexion loss, patients finally regain good knee function after removal of the external fixator.

Treatment of delayed union or non-union of the tibial shaft with partial fibulectomy and an Ilizarov frame.

We reviewed 28 patients treated with partial fibulectomy combined with an Ilizarov compression frame for a non-infected tibial delayed union or non-union. Patient data, time to referral, type of fracture (open or closed), type of non-union (atrophic or hypertrophic) and period of treatment were recorded. Neither time to referral, type of fracture or type of non-union did adversely affect the duration of treatment. Only smoking was found to have a negative influence on the healing time. There were no major complications associated with the treatment and all fractures united except one. We conclude that partial fibulectomy combined with an Ilizarov frame is a reliable method for the treatment of tibial delayed and non-union.

Warning About the Use of Critical-Size Defects for the Translational Study of Bone Repair: Analysis of a Sheep Tibial Model.

The repair of large long bone defects requires complex surgical procedures as the bone loss cannot simply be replaced by autologous grafts due to an insufficient bone stock of the human body. Tissue engineering strategies and the use of Advanced Therapy Medicinal Products (ATMPs) for these reconstructions remain a considerable challenge, in particular since robust outcomes in well-defined large animal models are lacking. To be suitable as a model for treatment of human sized bone defects, we developed a large animal model in both skeletally immature and mature sheep and made close observations on the spontaneous healing of defects. We warn for the spontaneous repair of large defects in immature animals, which can mask the (in)effectiveness of ATMP therapies, and propose the use of large 4.5 cm defects that are pretreated with a polymethylmethacrylate (PMMA) spacer in skeletally mature animals.

Management of a large post-traumatic skin and bone defect using an Ilizarov frame.

The authors report the case of a 28-year old male who presented with a compound diaphyseal fracture of the tibia, which was treated with intramedullary nailing. Postoperatively he required an extensive fasciotomy for an acute compartment syndrome. The fracture evolved towards post-traumatic osteomyelitis, growing methicillin-resistant Staphylococcus aureus (MRSA), combined with a large overlying soft tissue gap. An Ilizarov frame was used to treat both the bone and the skin defect. The infected fracture was treated by resection and longitudinal bone transport. Meanwhile, the skin was gradually closed using extra rods on the frame, allowing for a transverse 'skin transport'. Both the bone and the soft tissues healed without further complications.

Extraction of the Wichita Fusion Nail after Knee Arthrodesis.

To avoid a new exposition and partial damage of a knee arthrodesis site due to the removal of the Wichita fusion nail (WFN), a new extraction technique was developed, using a femoral osteotomy at the proximal end of the nail. Fixing the osteotomy with an Ilizarov frame offered the possibility to perform an additional correction of length and/or alignment if necessary.