RARE DISEASE
Congenital pseudoarthrosis of the tibia
Congenital pseudoarthrosis of the tibia
Congenital pseudoarthrosis of the tibia
Synonyms: Congenital pseudarthrosis of the tibia
Synonyms: Congenital pseudarthrosis of the tibia
Synonyms: Congenital pseudarthrosis of the tibia
Drug discovery
1
drug
With orphan designation
Overview
Congenital pseudoarthrosis of the tibia (CPT) is a rare pediatric bone disorder characterized by anterolateral bowing and spontaneous nonunion of the tibia, often progressing to refractory fractures. Pathogenesis involves abnormal periosteal function, fibrous hamartoma formation, and disrupted bone metabolism, with 50-80% linked to neurofibromatosis type 1. Treatment focuses on achieving bone union while addressing deformities, limb-length discrepancies, and recurrent fractures through multimodal surgical approaches [1][8][15].
Therapies
Surgical: Excision of pseudarthrosis with bone grafting (autograft/vascularized fibular), Ilizarov external fixation [3][15], intramedullary rods [4][13], and cross-union techniques [13].
Adjuncts: Perioperative bisphosphonates, BMP [4][15], and biological augmentation (periosteal grafts [13]).
Salvage: Amputation considered after ≥3 failed surgeries [1][4].
Categories: rare bone diseases, rare developmental anomalies during embryogenesis, rare genetic diseases
Research Papers
372 drug discovery papers about Congenital pseudoarthrosis of the tibia, with 2 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
372 drug discovery papers about Congenital pseudoarthrosis of the tibia, with 2 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-02-05 | Reconstruction With the Contralateral Fibula for Isolated Congenital Pseudarthrosis of the Fibula.
Congenital pseudarthrosis of the tibia (CPT) remains one of the most challenging conditions to manage in pediatric orthopedics. Fibular pseudarthrosis, often associated with CPT, is similarly resistant to treatment. In contrast, isolated congenital pseudarthrosis of the fibula (ICPF) is a rare condition for which no standardized treatment has been established. Here, we report four pediatric cases of ICPF treated with a novel reconstruction technique using the contralateral fibula. All patients achieved bony union at the pseudarthrotic lesion of the affected fibula. The donor sites of the contralateral fibula were reconstructed with β-tricalcium phosphate blocks. No fractures occurred at the reconstructed sites, and no recurrence of pseudarthrosis was observed. At final follow-up, which corresponded to skeletal maturity, all patients demonstrated mild ankle deformity on radiographs but no functional impairment.
2025-09-27 | An Autologous Human Adipose Stem Cell-Derived 3D Osteogenic Implant for Bone Grafting: From Development to First-in-Human Experience.
Background: NVD003 is an autologous, adipose tissue-derived stem cell-based tissue-engineered bone graft substitute with pro-osteogenic, anti-resorptive, and pro-angiogenic properties. Here, we describe highlights from the NVD003 preclinical development program as well as early clinical experience. Methods: NVD003 is produced in a Good Manufacturing Practice-controlled process from adipose stem cells collected during a minimally invasive liposuction procedure. The final implant is a ready-to-use moldable putty with fixed mineral content and predefined physiologic ranges of osteogenic cells and bioactive growth factors. Preclinical pharmacology studies were conducted in nude rats using a paravertebral implantation model, and subsequently, in a femoral critical-sized bone defect (CSBD) model. In a first-in-human Phase 1b/2a study, NVD003 was used for fracture osteosynthesis with classical fixation material in nine adults with recalcitrant lower limb non-union. NVD003 was also used at the discretion of treating physicians in four pediatric patients surgically treated for congenital pseudarthrosis of the tibia (CPT) with the Masquelet technique. Efficacy was evaluated as clinical healing and in terms of bone formation, bone union, and bone remodeling on radiographs and computed tomography using the extended Lane and Sandhu Scale. Results: Preclinical studies indicated that NVD003 requires cellularity for its bioactivity and moreover facilitates bone union when used as a graft material in femoral CSBD. In the clinical study, nine adult participants were successfully grafted with NVD003 and completed study follow-up to 24 months, with extended safety follow-up to 5 years ongoing. No adverse events were considered related to NVD003. Maximal bone formation occurred between 3 and 12 months post-implantation; the mean time to clinical healing was 6 months and the mean time to radiological union was 17 months. Ultimately, 89% (8/9) of patients achieved bone union without refracture. All four pediatric patients with CPT also achieved lasting bone union following grafting with NVD003. No safety signals were observed over a mean follow-up of 62.1 months. Conclusions: NVD003 represents a safe, autologous bone graft substitute product without side effects of heterotopic ossification or bone resorption. NVD003 facilitated bone union in adult and pediatric patients even under severe pathophysiological conditions.
2025-05-04 | Pamidronate regulates the osteogenic differentiation of periosteal-derived mesenchymal stem cells in congenital tibial pseudarthrosis via OPG/RANKL.
Congenital pseudarthrosis of the tibia (CPT) is one of the most challenging conditions in orthopedics. Previous research indicates a strong association between CPT and neurofibromatosis type 1 (NF1). The clinical application of pamidronate has demonstrated efficacy in enhancing bone healing and alleviating NF1-associated bone pathology in specific CPT cases. Nevertheless, the precise mechanistic basis for these therapeutic effects remains poorly characterized, warranting further investigation. In this study, mesenchymal stem cells (MSCs) were isolated from patients with congenital pseudarthrosis of the tibia (CPT MSCs) and from patients undergoing corrective osteotomy (control group). We examined cell conditions post-treatment with pamidronate disodium at concentrations of 0 nM, 10 nM, 100 nM, and 1 μM, evaluating proliferation, toxicity, and differentiation potential, while investigating its effects on the OPG/RANKL pathway. Additionally, we analyzed the alterations in mitogen-activated protein kinase signaling and its correlation with the regulatory expression of OPG/RANKL genes. This study demonstrated that the proliferation and osteogenic differentiation of CPT MSCs were significantly lower than those of the control group. Treatment with pamidronate disodium enhanced both proliferation and osteogenic differentiation in CPT MSCs. Furthermore, pamidronate disodium treatment decreased RANKL expression and increased OPG protein levels in CPT MSCs, activating p38 and ERK1/2 signaling pathways. Notably, the co-administration of p38 or ERK1/2 inhibitors significantly diminished the proliferation and osteogenic differentiation of CPT MSCs treated with pamidronate disodium. Pamiphosphonate disodium can promote the proliferation and osteogenic differentiation of CPT MSCs by activating p38 and ERK1/2 signaling.
2025-03-20 | The role of bisphosphonate and bone morphogenetic proteins in congenital pseudoarthrosis of the tibia management: a literature review
Congenital pseudoarthrosis of the tibia (CPT) is a rare medical condition characterized by a congenital absence of union in the tibia, which causes the leg to flex anterolaterally. Despite the use of several surgical techniques for the treatment of CPT, there is still a significant risk of failure with surgical interventions. Recent studies have shown that bisphosphonates (BP) and bone morphogenetic proteins (BMP) can be effective adjuncts to surgical procedures, increasing the success rate of bone union and reducing the chance of re-fracture. This review aimed to evaluate the role of BP and BMP in CPT. In this review, a comprehensive literature evaluation was conducted using the PRISMA method. The databases used to search for information included PubMed, ScienceDirect, and Google Scholar for the past 10 years. Six articles were included in this review. The results showed that using pharmacological agents such as BMP and BP is considered safe for pediatric patients as an adjunctive treatment to surgery. This combination can effectively increase the speed of bone union and prevent re-fractures. The small sample size, different protocols, and different doses may have impacted the study results, which should be thoroughly explained.
2025-02-24 | Vascularized Deep Femoral Periosteal Flap: Anatomical Study and Clinical Application in Congenital Pseudarthrosis of the Tibia in Two Cases.
Vascularized periosteal transplants have proven to be highly effective and rapid in promoting bone healing in biologically complex nonunions in children, with several reported donor sites. This study aimed to assess the feasibility of harvesting a vascularized diaphyseal femoral periosteal flap (VDFPF) from cadavers and evaluate its clinical application in two cases of bilateral congenital pseudarthrosis of the tibia. This study investigated the periosteal branches of the deep femoral vessels (DFV) supplying the femoral diaphysis in 19 previously latex-injected cadavers. The femur was divided into four segments. The distance from the midpoint of the inguinal ligament to the origin of the DFV and the number of periosteal branches were recorded. The vascularized diaphyseal femoral periosteal flap (VDFPF) was used to treat one side in two patients with bilateral congenital pseudarthrosis of the tibia (aged 14 and 2 years). The DFV's origin was located at a mean of 4.2 cm (range 2.8-8.5 cm) distal to the midpoint of the inguinal ligament. In 15 cases, the DFV coursed adjacent to the second and third quarters of the femoral shaft, providing a mean number of 5 (range 4-8) periosteal branches, allowing for the harvesting of a new pure vascularized periosteal flap. Healing of congenital pseudarthrosis of the tibia occurred within 3 months in both patients, with no donor or recipient site complications at the final follow-up of 13 months. The VDFPF may be an effective periosteal transplant and a viable alternative to other large free periosteal transplants used in children for treating complex non-unions, especially when tibial and fibular donors are not available. Bone union was fast compared to other techniques used to treat these challenging cases.
2026-02-05 | Reconstruction With the Contralateral Fibula for Isolated Congenital Pseudarthrosis of the Fibula.
Congenital pseudarthrosis of the tibia (CPT) remains one of the most challenging conditions to manage in pediatric orthopedics. Fibular pseudarthrosis, often associated with CPT, is similarly resistant to treatment. In contrast, isolated congenital pseudarthrosis of the fibula (ICPF) is a rare condition for which no standardized treatment has been established. Here, we report four pediatric cases of ICPF treated with a novel reconstruction technique using the contralateral fibula. All patients achieved bony union at the pseudarthrotic lesion of the affected fibula. The donor sites of the contralateral fibula were reconstructed with β-tricalcium phosphate blocks. No fractures occurred at the reconstructed sites, and no recurrence of pseudarthrosis was observed. At final follow-up, which corresponded to skeletal maturity, all patients demonstrated mild ankle deformity on radiographs but no functional impairment.
2025-09-27 | An Autologous Human Adipose Stem Cell-Derived 3D Osteogenic Implant for Bone Grafting: From Development to First-in-Human Experience.
Background: NVD003 is an autologous, adipose tissue-derived stem cell-based tissue-engineered bone graft substitute with pro-osteogenic, anti-resorptive, and pro-angiogenic properties. Here, we describe highlights from the NVD003 preclinical development program as well as early clinical experience. Methods: NVD003 is produced in a Good Manufacturing Practice-controlled process from adipose stem cells collected during a minimally invasive liposuction procedure. The final implant is a ready-to-use moldable putty with fixed mineral content and predefined physiologic ranges of osteogenic cells and bioactive growth factors. Preclinical pharmacology studies were conducted in nude rats using a paravertebral implantation model, and subsequently, in a femoral critical-sized bone defect (CSBD) model. In a first-in-human Phase 1b/2a study, NVD003 was used for fracture osteosynthesis with classical fixation material in nine adults with recalcitrant lower limb non-union. NVD003 was also used at the discretion of treating physicians in four pediatric patients surgically treated for congenital pseudarthrosis of the tibia (CPT) with the Masquelet technique. Efficacy was evaluated as clinical healing and in terms of bone formation, bone union, and bone remodeling on radiographs and computed tomography using the extended Lane and Sandhu Scale. Results: Preclinical studies indicated that NVD003 requires cellularity for its bioactivity and moreover facilitates bone union when used as a graft material in femoral CSBD. In the clinical study, nine adult participants were successfully grafted with NVD003 and completed study follow-up to 24 months, with extended safety follow-up to 5 years ongoing. No adverse events were considered related to NVD003. Maximal bone formation occurred between 3 and 12 months post-implantation; the mean time to clinical healing was 6 months and the mean time to radiological union was 17 months. Ultimately, 89% (8/9) of patients achieved bone union without refracture. All four pediatric patients with CPT also achieved lasting bone union following grafting with NVD003. No safety signals were observed over a mean follow-up of 62.1 months. Conclusions: NVD003 represents a safe, autologous bone graft substitute product without side effects of heterotopic ossification or bone resorption. NVD003 facilitated bone union in adult and pediatric patients even under severe pathophysiological conditions.
2025-05-04 | Pamidronate regulates the osteogenic differentiation of periosteal-derived mesenchymal stem cells in congenital tibial pseudarthrosis via OPG/RANKL.
Congenital pseudarthrosis of the tibia (CPT) is one of the most challenging conditions in orthopedics. Previous research indicates a strong association between CPT and neurofibromatosis type 1 (NF1). The clinical application of pamidronate has demonstrated efficacy in enhancing bone healing and alleviating NF1-associated bone pathology in specific CPT cases. Nevertheless, the precise mechanistic basis for these therapeutic effects remains poorly characterized, warranting further investigation. In this study, mesenchymal stem cells (MSCs) were isolated from patients with congenital pseudarthrosis of the tibia (CPT MSCs) and from patients undergoing corrective osteotomy (control group). We examined cell conditions post-treatment with pamidronate disodium at concentrations of 0 nM, 10 nM, 100 nM, and 1 μM, evaluating proliferation, toxicity, and differentiation potential, while investigating its effects on the OPG/RANKL pathway. Additionally, we analyzed the alterations in mitogen-activated protein kinase signaling and its correlation with the regulatory expression of OPG/RANKL genes. This study demonstrated that the proliferation and osteogenic differentiation of CPT MSCs were significantly lower than those of the control group. Treatment with pamidronate disodium enhanced both proliferation and osteogenic differentiation in CPT MSCs. Furthermore, pamidronate disodium treatment decreased RANKL expression and increased OPG protein levels in CPT MSCs, activating p38 and ERK1/2 signaling pathways. Notably, the co-administration of p38 or ERK1/2 inhibitors significantly diminished the proliferation and osteogenic differentiation of CPT MSCs treated with pamidronate disodium. Pamiphosphonate disodium can promote the proliferation and osteogenic differentiation of CPT MSCs by activating p38 and ERK1/2 signaling.
2025-03-20 | The role of bisphosphonate and bone morphogenetic proteins in congenital pseudoarthrosis of the tibia management: a literature review
Congenital pseudoarthrosis of the tibia (CPT) is a rare medical condition characterized by a congenital absence of union in the tibia, which causes the leg to flex anterolaterally. Despite the use of several surgical techniques for the treatment of CPT, there is still a significant risk of failure with surgical interventions. Recent studies have shown that bisphosphonates (BP) and bone morphogenetic proteins (BMP) can be effective adjuncts to surgical procedures, increasing the success rate of bone union and reducing the chance of re-fracture. This review aimed to evaluate the role of BP and BMP in CPT. In this review, a comprehensive literature evaluation was conducted using the PRISMA method. The databases used to search for information included PubMed, ScienceDirect, and Google Scholar for the past 10 years. Six articles were included in this review. The results showed that using pharmacological agents such as BMP and BP is considered safe for pediatric patients as an adjunctive treatment to surgery. This combination can effectively increase the speed of bone union and prevent re-fractures. The small sample size, different protocols, and different doses may have impacted the study results, which should be thoroughly explained.
2025-02-24 | Vascularized Deep Femoral Periosteal Flap: Anatomical Study and Clinical Application in Congenital Pseudarthrosis of the Tibia in Two Cases.
Vascularized periosteal transplants have proven to be highly effective and rapid in promoting bone healing in biologically complex nonunions in children, with several reported donor sites. This study aimed to assess the feasibility of harvesting a vascularized diaphyseal femoral periosteal flap (VDFPF) from cadavers and evaluate its clinical application in two cases of bilateral congenital pseudarthrosis of the tibia. This study investigated the periosteal branches of the deep femoral vessels (DFV) supplying the femoral diaphysis in 19 previously latex-injected cadavers. The femur was divided into four segments. The distance from the midpoint of the inguinal ligament to the origin of the DFV and the number of periosteal branches were recorded. The vascularized diaphyseal femoral periosteal flap (VDFPF) was used to treat one side in two patients with bilateral congenital pseudarthrosis of the tibia (aged 14 and 2 years). The DFV's origin was located at a mean of 4.2 cm (range 2.8-8.5 cm) distal to the midpoint of the inguinal ligament. In 15 cases, the DFV coursed adjacent to the second and third quarters of the femoral shaft, providing a mean number of 5 (range 4-8) periosteal branches, allowing for the harvesting of a new pure vascularized periosteal flap. Healing of congenital pseudarthrosis of the tibia occurred within 3 months in both patients, with no donor or recipient site complications at the final follow-up of 13 months. The VDFPF may be an effective periosteal transplant and a viable alternative to other large free periosteal transplants used in children for treating complex non-unions, especially when tibial and fibular donors are not available. Bone union was fast compared to other techniques used to treat these challenging cases.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
1 orphan drug designation for Congenital pseudoarthrosis of the tibia.
1 orphan drug designation for Congenital pseudoarthrosis of the tibia.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
autologous osteogenic cells cultured from adipose tissue derived stem cells embedded in extracellular matrix with demineralized bone matrix. | cell therapies | FDA | 2016-06-30 | — | Novadip Biosciences |
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