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).

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.

FGFR3 in Periosteal Cells Drives Cartilage-to-Bone Transformation in Bone Repair.

Most organs and tissues in the body, including bone, can repair after an injury due to the activation of endogenous adult stem/progenitor cells to replace the damaged tissue. Inherent dysfunctions of the endogenous stem/progenitor cells in skeletal repair disorders are still poorly understood. Here, we report that Fgfr3Y637C/+ over-activating mutation in Prx1-derived skeletal stem/progenitor cells leads to failure of fracture consolidation. We show that periosteal cells (PCs) carrying the Fgfr3Y637C/+ mutation can engage in osteogenic and chondrogenic lineages, but following transplantation do not undergo terminal chondrocyte hypertrophy and transformation into bone causing pseudarthrosis. Instead, Prx1Cre;Fgfr3Y637C/+ PCs give rise to fibrocartilage and fibrosis. Conversely, wild-type PCs transplanted at the fracture site of Prx1Cre;Fgfr3Y637C/+ mice allow hypertrophic cartilage transition to bone and permit fracture consolidation. The results thus highlight cartilage-to-bone transformation as a necessary step for bone repair and FGFR3 signaling within PCs as a key regulator of this transformation.

Radiologic and Pathological Investigation of Pseudarthrosis in Ankylosing Spondylitis: Distinguishing Between Inflammatory and Traumatic Etiology.

OBJECTIVE: To investigate the pathogenesis of pseudarthrosis in ankylosing spondylitis (AS) based on the pathological analysis of specimens harvested during surgery. METHODS: Radiographic and clinical data for 17 consecutive AS patients with pseudarthrosis were retrospectively analyzed. Meanwhile, the pathological analysis of specimens obtained during surgery was also performed. RESULTS: In total, 18 extensive Andersson lesions were included. Pseudarthrosis located at the apical region were noted in 12 patients. Complete ossified anterior longitudinal ligaments above or below pseudarthrosis and fracture through posterior elements or facet joints were observed in 7 and 6 lesions, respectively. The most definitive pathological characteristic in all cases was proliferating hypovascular edematous fibrous tissue involving disc, bone-disc border, and vertebral body. Fibrinoid necrosis, necrotic bone fragments, hemosiderin deposits, and active subchondral osteogenesis were found, indicating trauma process. Mild perivascular collections of inflammatory cells were detected in only 2 cases. CONCLUSION: AS-related pseudarthrosis is more likely to originate from mechanical trauma than inflammation. The above-mentioned radiological and histological findings showed that multiple mechanisms lead to the formation of pseudarthrosis. These mechanisms include excessive stress, insufficiency fracture, and an acute fracture involving a 3-column structure.

Evaluation of bone marrow-derived mesenchymal stem cell quality from patients with congenital pseudoarthrosis of the tibia.

BACKGROUND: The treatment of congenital pseudoarthrosis of the tibia (CPT) remains challenging in pediatric orthopedics due to the difficulties in bone union, continuous angulation, joint stiffness, and severe limb length discrepancy. Mesenchymal stem cells (MSCs) therapy offers a complementary approach to improve the conventional surgical treatments. Although the autologous MSC treatment shows a promising strategy to promote bone healing in CPT patients, the quality of MSCs from CPT patients has not been well studied. The purpose of this study is to investigate the quality of MSCs isolated from patients with CPT. METHODS: The bone marrow-derived MSCs from the fracture site and iliac crest of six CPT patients were isolated and compared. The cumulative population doubling level (cPDL), phenotype characteristics, and trilineage differentiation potency were observed to assess the quality of both MSCs. RESULTS: There were no significant differences of the MSCs derived from the fracture site and the MSCs from the iliac crest of the subjects, in terms of cPDL, phenotype characteristics, and trilineage differentiation potency (all p > 0.05). However, MSCs from the fracture site had a higher senescence tendency than those from the iliac crest. CONCLUSION: MSC quality is not the main reason for delayed bone regeneration in those with CPT. Thus, autologous MSC is a promising source for treating CPT patients.

Compressão da artéria subclávia por pseudoartrose de clavícula: apresentação na quinta década de vida / Late presentation of critical upper limb ischemia caused by pseudarthrosis of the clavicle

A compressão da artéria subclávia no desfiladeiro torácico é um fenômeno amplamente conhecido. Anormalidades ósseas, como a pseudoartrose da clavícula, podem raramente causar compressão arterial a esse nível. A pseudoartrose pode desenvolver-se em decorrência de um trauma, que é a forma mais comum, ou ser congênita. Os autores descrevem o caso de uma paciente de 44 anos com quadro de isquemia crítica de membro superior direito. Apresentava história de fratura não tratada de clavícula direita aos 9 meses de idade que evoluiu com pseudoartrose e compressão extrínseca com oclusão da artéria subclávia. O segmento da clavicula acometido pela pseudoartrose foi ressecado e realizada uma tromboembolectomia tardia das artérias subclávia, braquial e distais, com boa evolução.

Compression of the subclavian artery in the thoracic outlet is a well-known phenomenon. In rare cases, bone abnormalities, such as pseudarthrosis of the clavicle, can cause arterial compression at this level. Pseudarthrosis may develop as a result of trauma, which is the more common form, or it may be congenital. Here, the authors describe the case of a 44-year-old patient with critical ischemia of the right upper limb. She had a history of untreated right clavicle fracture at 9 months of age which had progressed to pseudarthrosis and extrinsic compression of the subclavian artery causing occlusion. The segment of the clavicle involved was resected and late thromboembolectomy of the subclavian, brachial, distal arteries was performed, with good results.

In silico clinical trials for pediatric orphan diseases.

To date poor treatment options are available for patients with congenital pseudarthrosis of the tibia (CPT), a pediatric orphan disease. In this study we have performed an in silico clinical trial on 200 virtual subjects, generated from a previously established model of murine bone regeneration, to tackle the challenges associated with the small, pediatric patient population. Each virtual subject was simulated to receive no treatment and bone morphogenetic protein (BMP) treatment. We have shown that the degree of severity of CPT is significantly reduced with BMP treatment, although the effect is highly subject-specific. Using machine learning techniques we were also able to stratify the virtual subject population in adverse responders, non-responders, responders and asymptomatic. In summary, this study shows the potential of in silico medicine technologies as well as their implications for other orphan diseases.

[Osteosynthesis of rib fractures, unstable chest wall, pseudoarthroses, and acquired defects of the chest wall].

Several patients suffer from rib fractures after traumas, and in severe cases it can be life-threatening. Until recently, attempts to perform surgical fixation in patients with instability have been unsuccessful. Chronic non-union causes persistent pain, disability and loss of quality of life. Implementation of surgical stabilization of rib fractures with tailored plates seems to improve pain relief, especially in cases of non-union but also in patients with instability of the chest wall after severe traumas, where advanced pain treatment (epidural catheter) is insufficient or weaning off fails.

Clinical translation of a mesenchymal stromal cell-based therapy developed in a large animal model and two case studies of the treatment of atrophic pseudoarthrosis.

Pseudoarthrosis is a relatively frequent complication of fractures, in which the lack of mechanical stability and biological stimuli results in the failure of bone union, most frequently in humerus and tibia. Treatment of recalcitrant pseudoarthrosis relies on the achievement of satisfactory mechanical stability combined with adequate local biology. Herein we present two cases of atrophic pseudoarthrosis that received a tissue-engineering product (TEP) composed of autologous bone marrow-derived mesenchymal stromal cells (BM-MSC) combined with deantigenized trabecular bone particles from a tissue bank. The feasibility of the treatment and osteogenic potential of the cell-based medicine was first demonstrated in an ovine model of critical size segmental tibial defect. Clinical-grade autologous BM-MSC were produced following a good manufacturing practice-compliant bioprocess. Results were successful in one case, with pseudoarthrosis resolution, and inconclusive in the other one. The first patient presented atrophic pseudoarthrosis of the humeral diaphysis and was treated with osteosynthesis and TEP resulting in satisfactory consolidation at month 6. The second case presented a recalcitrant pseudoarthrosis of the proximal tibia and the Masquelet technique was followed before filling the defect with the TEP. This patient presented a neuropathic pain syndrome unrelated to the treatment that forced the amputation of the extremity 3 months later. In this case, the histological analysis of the tissue formed at the defect site provided evidence of neovascularization but no overt bone remodelling activity. It is concluded that the use of expanded autologous BM-MSC to treat pseudoarthrosis was demonstrated to be feasible and safe, provided that no clinical complications were reported, and early signs of effectiveness were observed. Copyright © 2016 John Wiley & Sons, Ltd.

Congenital Anatomical Variant of the Clavicle.

The aim of this study is to present a rare abnormality of the clavicle (Code: SGS01) that was discovered in an ossuary in the Church of San Gaetano (Sulmona, central Italy; XVII-XIX centuries CE). In the middle third, the clavicle had three areas with losses of substance in the form of oval-shaped foramina with maximum diameters of 1-2 cm that were located in the anterior and superior surfaces of the diaphysis. The margins of these foramina were well defined and rounded, and the surfaces of the canal walls were smooth. Additionally, there were no zones of bony activity or reactive changes around the foramina. This new congenital anomaly of the clavicle and blood vessels is consistent with a variant that might have originated during fetal growth in which the subclavian vein or artery remained included during the process of ossification of the clavicle. Anat Rec, 300:1401-1408, 2017. © 2017 Wiley Periodicals, Inc.

Novel phenotypes of NF1 patients from unrelated Chinese families with tibial pseudarthrosis and anemia.

Neurofibromatosis type 1 (NF1) is an autosomal dominant, multi-system, neurocutaneous disorder, manifested with neurofibromas and Cafe´-au-lait spots. Germline mutations in NF1 gene are associated with Neurofibromatosis type 1. NF1 gene encodes neurofibromin, a RAS-specific GTPase activating protein. In our study, we present a clinical molecular study of four Chinese probands with NF1 from four unrelated families, showing extreme phenotypic variation with rare phenotype. In family 1, the proband is a 16 months old girl with multiple café-au-lait spots throughout her whole body. In family 2, the proband is a 6 months old girl with several café-au-lait spots mostly in her trunk and in lower limbs. In family 3, the proband is a 4 months old boy with several café-au-lait spots, tibial pseudarthrosis, and chronic iron deficiency anemia. In family 4, the proband is a 14 years old boy with multiple café-au-lait spots of variable sizes. Targeted exome capture based next generation sequencing and Sanger sequencing identified a novel mutation and three previously reported mutations in these four probands. These four mutations in NF1 gene were causing disease phenotypes in these four probands and was absent in unaffected family members and in healthy controls. According to the variant interpretation guideline of American College of Medical Genetics and Genomics (ACMG), these four mutations, are classified as "likely pathogenic". Our result expands the mutational spectrum of the NF1 gene associated with neurofibromatosis type1.

Symptomatic pseudarthrosis in ochronotic spine: case report.

In this study the authors report the first example of spinal pseudarthrosis in a patient with ochronosis, and they describe the application of posterior-only 360° surgery as an alternative approach to combined anterior-posterior surgery in the management of pseudarthrosis of an ankylosed spine, regardless of its etiology. Spinal involvement in ochronosis produces loss of flexibility and ankylosis of thoracic and lumbar segments. Pseudarthrosis is a serious complication of the diseases that present with ankylosis of the spine. However, its occurrence in ochronotic spine has not been reported previously. Evaluation of progressive paraparesis in a 68-year-old man with ochronosis revealed pseudarthrosis at the T11-12 level. Circumferential dural sac decompression, debridement of the disc space, interbody fusion, and screw-rod fixation were all done via a posterior-only approach. Postoperatively the patient exhibited a marked recovery in terms of pain and neurological status. At the 3-month follow-up, he was able to walk independently. Ochronosis should be included in the etiology of pseudarthrosis. With aggravation of back pain and the appearance of neurological deficits in an already stable patient with any ankylosing disease, pseudarthrosis should be suspected. Furthermore, single-stage, 360°, posterior-only surgery may obviate the need for single-stage or staged anterior-posterior surgical intervention in patients with pseudarthrosis of the thoracic and lumbar spine.

[Implant-associated infections - Diagnostics]. / Implantatassoziierte Infektion - Diagnostik.

The diagnosis of implant-associated infections is challenging as chronic low-grade infections often only manifest as subtle clinical symptoms. Clinical evaluation, patient history, imaging, histopathological and microbiological examinations build the cornerstones of the diagnostics for implant-associated infections. New onset of pain at rest, local symptoms at the surgical site and early loosening of the prosthesis or pseudarthrosis should raise suspicion for an infection and prompt further evaluation. Percutaneous sinus tracts, purulent wound secretions and skin erosions with exposure of the implant are certain signs of implant-associated infections. Elevated C­reactive protein levels in blood support the diagnosis of infection but are neither sufficient sensitive nor specific to confirm or exclude infection. Preoperative antibiotic therapy interferes with the diagnostic evaluation and should be avoided. In periprosthetic joint infections, joint aspiration with determination of the leukocyte count and microbiological examination is a crucial first diagnostic step. Through microbiological and histopathological examinations of intraoperative tissue samples, as well as sonication of explanted implants, the causative pathogen can be identified in most cases. In osteosynthesis-associated infections imaging plays a key role to detect non-union, infection callus, sequester, peri-implant osteolysis and extraosseous and intramedullary pathologies. In prosthetic joint infections imaging provides information about the position and stability of the prosthesis. In case of hematogenic infection seeding from a distant focus, blood cultures should be sampled, followed by a meticulous investigation of potential primary focus of infection, depending on the causative agent.

Human pseudoarthrosis tissue contains cells with osteogenic potential.

INTRODUCTION: Nonunion is a challenging problem that may occur after certain bone fractures. The treatment of nonunion is closely related to its type. To develop an effective treatment strategy for each type of nonunion, biological analysis of nonunion tissue is essential. Pseudoarthrosis is a distinct pathologic entity of nonunion. To understand the pathology of pseudoarthrosis, we investigated the cellular properties of pseudoarthrosis tissue-derived cells (PCs) in vitro. PATIENTS AND METHODS: PCs were isolated from four patients with pseudoarthrosis and cultured. Cells were evaluated for cell-surface protein expression by using flow cytometry. Osteogenic differentiation capacity was assessed by using Alizarin Red S staining, alkaline phosphatase (ALP) activity assay, and reverse transcription polymerase chain reaction (RT-PCR) after osteogenic induction. Chondrogenic differentiation capacity was assessed via Safranin O staining and RT-PCR after chondrogenic induction. RESULTS: PCs were consistently positive for the mesenchymal stem cell-related markers CD29, CD44, CD105, and CD166, but were negative for the haematopoietic-lineage markers CD31, CD34, CD45, and CD133. Alizarin Red S staining revealed that PCs formed a mineralised matrix that was rich in calcium deposits after osteogenic induction. ALP activity under osteogenic conditions was significantly higher than that under control conditions. Gene expression of ALP, Runx2, osterix, osteocalcin, and bone sialoprotein was observed in PCs cultured under osteogenic conditions. Induced pellets were negatively stained by Safranin O staining. Gene expression of aggrecan, collagen II, collagen X, SOX5, and SOX9 was not observed. CONCLUSION: We have shown for the first time the properties of cells in patients with pseudoarthrosis. Our results indicated that osteogenic cells existed in the pseudoarthrosis tissue. This study might provide insights into understanding the pathology of pseudoarthrosis and improving the treatment for pseudoarthrosis.

Comparison of four different techniques for performing an osteotomy: a biomechanical, radiological and histological study on rabbits tibias.

This animal study compares different methods of performing an osteotomy, including using an Erbium-doped Yttrium Aluminum Garnet laser, histologically, radiologically and biomechanically. A total of 24 New Zealand rabbits were divided into four groups (Group I: multihole-drilling; Group II: Gigli saw; Group III: electrical saw blade and Group IV: laser). A proximal transverse diaphyseal osteotomy was performed on the right tibias of the rabbits after the application of a circular external fixator. The rabbits were killed six weeks after the procedure, the operated tibias were resected and radiographs taken. The specimens were tested biomechanically using three-point bending forces, and four tibias from each group were examined histologically. Outcome parameters were the biomechanical stability of the tibias as assessed by the failure to load and radiographic and histological examination of the osteotomy site. The osteotomies healed in all specimens both radiographically and histologically. The differences in the mean radiographic (p = 0.568) and histological (p = 0.71) scores, and in the mean failure loads (p = 0.180) were not statistically significant between the groups. Different methods of performing an osteotomy give similar quality of union. The laser osteotomy, which is not widely used in orthopaedics is an alternative to the current methods.

Scaffold-free Three-dimensional Graft From Autologous Adipose-derived Stem Cells for Large Bone Defect Reconstruction: Clinical Proof of Concept.

Long bone nonunion in the context of congenital pseudarthrosis or carcinologic resection (with intercalary bone allograft implantation) is one of the most challenging pathologies in pediatric orthopedics. Autologous cancellous bone remains the gold standard in this context of long bone nonunion reconstruction, but with several clinical limitations. We then assessed the feasibility and safety of human autologous scaffold-free osteogenic 3-dimensional (3D) graft (derived from autologous adipose-derived stem cells [ASCs]) to cure a bone nonunion in extreme clinical and pathophysiological conditions. Human ASCs (obtained from subcutaneous adipose tissue of 6 patients and expanded up to passage 4) were incubated in osteogenic media and supplemented with demineralized bone matrix to obtain the scaffold-free 3D osteogenic structure as confirmed in vitro by histomorphometry for osteogenesis and mineralization. The 3D "bone-like" structure was finally transplanted for 3 patients with bone tumor and 3 patients with bone pseudarthrosis (2 congenital, 1 acquired) to assess the clinical feasibility, safety, and efficacy. Although minor clones with structural aberrations (aneuploidies, such as tri or tetraploidies or clonal trisomy 7 in 6%-20% of cells) were detected in the undifferentiated ASCs at passage 4, the osteogenic differentiation significantly reduced these clonal anomalies. The final osteogenic product was stable, did not rupture with forceps manipulation, did not induce donor site morbidity, and was easily implanted directly into the bone defect. No acute (<3 mo) side effects, such as impaired wound healing, pain, inflammatory reaction, and infection, or long-term side effects, such as tumor development, were associated with the graft up to 4 years after transplantation. We report for the first time that autologous ASC can be fully differentiated into a 3D osteogenic-like implant without any scaffold. We demonstrated that this engineered tissue can safely promote osteogenesis in extreme conditions of bone nonunions with minor donor site morbidity and no oncological side effects.

Enrichment of bacteria samples by centrifugation improves the diagnosis of orthopaedics-related infections via real-time PCR amplification of the bacterial methicillin-resistance gene.

BACKGROUND: To effectively treat orthopaedic infections by methicillin-resistant strains, an early diagnosis is necessary. Bacterial cultures and real-time polymerase chain reaction (PCR) have been used to define methicillin-resistant staphylococci. However, even when patients display clinical signs of infections, bacterial culture and real-time PCR often cannot confirm infection. The aim of this study was to prospectively compare the utility of real-time PCR for the mecA gene detection following centrifugation of human samples with suspected orthopaedic infections. RESULTS: In addition to the conventional real-time PCR method, we performed real-time PCR following centrifugation of the sample at 4,830×g for 10 min in a modified real-time PCR (M-PCR) method. We suspended cultured methicillin-resistant Staphylococcus aureus and generated standard dilution series for in vitro experiments. The in vitro detection sensitivity of the M-PCR method was approximately 5.06 times higher than that of the conventional real-time PCR method. We performed bacterial culture, pathological examination, real-time PCR, and M-PCR to examine the infectious fluids and tissues obtained from 36 surgical patients at our hospital. Of these, 20 patients who had undergone primary total hip arthroplasty were enrolled as negative controls. In addition, 15 patients were examined who were clinically confirmed to have an infection, including periprosthetic joint infection (eight patients), pyogenic spondylitis (two patients), infectious pseudoarthrosis (two patients), and after spine surgery (three patients). In one sample from a patient who developed infectious pseudoarthrosis and two samples from surgical site infections after spine surgery, the mecA gene was detected only by the M-PCR method. In one patient with infectious pseudoarthrosis, one patient with infection after arthroplasty, and two patients with purulent spondylitis, the detection sensitivity of the M-PCR method was increased compared with PCR (clinical sample average: 411.6 times). CONCLUSIONS: These findings suggest that the M-PCR method is useful to detect methicillin-resistant strains infections. In addition, the centrifugation process only takes 10 min longer than conventional real-time PCR methods. We believe that the M-PCR method could be clinically useful to detect orthopaedic infections caused by methicillin-resistant strains.

Utilidad de la proteína morfogenética en el tratamiento de la seudoartrosis congénita de la tibia / Utility of morphogenetic protein for the treatment of congenital pseudoarthrosis of the tibia

Objetivo: Reportar la capacidad de la proteína morfogenética de lograr la consolidación ósea en pacientes con seudoartrosis congénita de tibia. Pacientes y métodos: Se realizó en tres pacientes con diagnóstico de seudoartrosis congénita de tibia, se hizo seguimiento durante seis meses a cada uno observando la consolidación y capacidad funcional de la extremidad. Resultados: Se logró consolidación en todos los casos presentándose ésta a los tres meses y medio en promedio. Conclusiones: La proteína morfogenética tiene utilidad como coadyuvante para conseguir la regeneración y consolidación ósea en pacientes con seudoartrosis congénita de tibia.

Objective: To report the ability of bone morphogenetic protein to achieve bone healing in patients with congenital pseudoarthrosis of the tibia. Patients and methods: Three patients with a diagnosis of congenital pseudoarthrosis of the tibia were followed-up for six months. Bone healing and functional capacity of the limb were observed. Results: Bone healing occurred in all cases at a mean of three and half months of treatment. Conclusions: Morphogenetic protein is useful as an adjuvant to achieve bone regeneration and healing in patients with congenital pseudoarthrosis of the tibia.

[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%.

[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.