2026-08-10 | Favorable aortic remodeling following type B aortic dissection in a patient with osteogenesis imperfecta.
Osteogenesis imperfecta is a heritable type I collagen disorder, with aortic dissection a recognized complication. A 69-year-old man with osteogenesis imperfecta presented with acute uncomplicated type B aortic dissection with a thrombosed false lumen, managed with anti-impulse therapy targeting systolic blood pressure < 120 mm Hg and heart rate < 70 beats/min. Despite an ulcer-like projection and 4.2 cm proximal descending aortic diameter, serial imaging demonstrated complete resolution with optimal medical therapy by 6 months and reduction to 3.2 cm at 12 months. This favorable remodeling is notable given the underlying collagen disorder, where tissue fragility raises concerns about impaired healing and aortic integrity.
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2026-08-06 | Type V Osteogenesis Imperfecta in an Indian Cohort: Phenotypic Variability and Radiological Insights in IFITM5-Related Bone Fragility.
Osteogenesis imperfecta type V is a rare autosomal dominant form of osteogenesis imperfecta caused by the recurrent c.-14C>T mutation in the IFITM5 gene. This mutation affects osteoblast function and mineralization, leading to distinctive skeletal manifestations that differ from classical collagen-related OI. This study describes the clinical, radiological, and genetic characteristics of Indian children with OI type V, and assesses phenotypic variability and treatment outcomes. A retrospective observational study was conducted in six Indian children with genetically confirmed OI type V. Clinical data, fracture history, radiological findings, and treatment response to intravenous pamidronate were analyzed. All six patients harbored the recurrent IFITM5 c.-14C>T variant. The age at first fracture ranged from birth to three years, with variable fracture frequency and progressive skeletal deformities. Hallmark features such as hyperplastic callus formation, ossification of interosseous membranes, and radial head dislocation were consistently observed. Wormian bones were present in five patients. Progressive spinal deformities, including scoliosis and kyphosis, developed in older children. Notably, none of the patients exhibited blue sclerae or dentinogenesis imperfecta. Familial transmission across three generations was observed in one case. All patients received intravenous pamidronate therapy, which resulted in initial improvement in bone mineral density; however, it did not prevent long-term skeletal complications in some individuals. This first Indian cohort highlights significant phenotypic variability in OI type V despite a uniform underlying mutation. Recognition of its distinctive clinical and radiological features is critical for accurate diagnosis, appropriate genetic counselling, and optimized management strategies.
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2026-08-05 | Adolescent locked femoral nail for recurrent femoral fractures in children with osteogenesis Imperfecta: a case report and literature review.
Osteogenesis imperfecta (OI) is a hereditary connective tissue disorder characterized by increased bone fragility and recurrent fractures. The femur is the most frequently fractured site in pediatric OI patients. Traditional internal fixations such as plates and elastic intramedullary nails carry high complication rates. Although extendable intramedullary nails represent the gold standard for children with OI, they show insufficient stability in adolescent patients with large medullary cavities and severe osteoporosis. Adolescent Locked Femoral Nail (ALFN) is a fixation system designed for adolescents, but its specific efficacy in recurrent femoral fractures in adolescent OI patients has been rarely reported. A 13-year-old male patient with a confirmed COL1A1 pathogenic variant (Sillence type III OI) experienced four left femoral fractures within 5 years. The first two fractures were treated with plate fixation at a local primary hospital and both resulted in postoperative refracture; the third fracture was managed with plate fixation in our hospital, which also ended in refracture.For the fourth fracture, closed reduction and titanium alloy ALFN fixation were performed, combined with intravenous zoledronic acid infusion. At the 3-year follow-up, the fracture healed uneventfully without refracture; the lower limb alignment was normal, with a 0.5 cm limb-length discrepancy and satisfactory knee function. ALFN provides central, stable intramedullary fixation, preserves bone blood supply, and matches the anatomical features of the adolescent femur. Combined with anti-osteoporotic medication, ALFN may serve as a valuable option for selected adolescent OI patients with recurrent fractures, wide medullary canals, or failure of previous fixation methods to reduce refracture risk. For adolescents with unexplained recurrent fractures, early genetic testing and individualized surgical planning are critical to improve clinical outcomes.
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2026-07-31 | Altering host microenvironment is critical for success of cell therapy for osteogenesis imperfecta
Osteogenesis Imperfecta (OI) is a genetic disorder where mutations in Collagen I gene or other genes associated with defective collagen matrix lead to low bone density, bone brittleness with increased fracture risk. Current pharmacological treatments for OI do not address the underlying defect in collagen production. Cellular therapy represents a strategy to form healthy bone in OI, but systemic stem cell delivery approaches have not been successful. By contrast, locally delivered skeletal stem and progenitor cells (SSPCs) can engraft within OI bone, differentiate into matrix-producing osteoblasts, and generate normal collagen. However, without perturbing the marrow environment, endosteal engraftment is low. Irradiation used as preconditioning significantly enhances engraftment of donor progenitor cells. We aimed to determine what alterations in the bone marrow microenvironment influence donor SSPCs engraftment and their differentiation into mature lineages. Several preconditioning treatments and animal models were used to determine optimal conditions for local cell transplantation. Preconditioning with lethal irradiation (IRR) in osteogenesis imperfecta mice (OIM) exhibited high donor cell engraftment on the endosteal surface. Chemical myeloablation using busulfan and cyclophosphamide (BuCy) significantly increased donor cell engraftment, but the effect was less than that of IRR. Interestingly, BuCy caused similar initial changes in T and B cell composition as IRR, but proportions of NK, monocytes/macrophages and neutrophils were not as significant as with IRR. An additional preconditioning strategy involved ablation of recipient OI osteoblasts using OIM/Col2.3ΔTK/ + mice, but was not sufficient for mesenchymal donor cell engraftment. Finally, we investigated whether IRR affects cell therapy success via increasing bone turnover. We found that by reducing bone resorption with zoledronic acid, OIM mice had decreased donor cell engraftment. We separately observed increased engraftment rates in high bone turnover of OIM mice compared to WT. Lethal irradiation remained the most effective pretreatment for SSPCs engraftment and their differentiation into osteoblasts producing healthy matrix in OIM bone. Results indicate that increased bone turnover in OIM mice positively affect engraftment and differentiation into osteoblasts/osteocytes. Future cell transplantation research should include repurposing of existing treatments that can increase bone turnover.
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2026-07-29 | Histological and molecular characterization of bone integrity in osteogenesis imperfecta: a case series across genetic subtypes.
Osteogenesis imperfecta (OI) is a genetically heterogeneous skeletal disorder characterized by bone fragility and variable clinical severity. However, how molecular defects translate into alterations of bone microstructure and composition across OI subtypes remains incompletely understood. In this case series, we systematically evaluated cortical bone integrity in patients with OI types 1, 3, 4, 6, 8, and 14 using histological and molecular approaches, including Raman spectroscopy, and compared findings with non-OI controls. Histological analyses revealed case-specific disruption of bone architecture across OI cases, where the severity of bone disorganization increased progressively from OI type 1 to types 3, 6, 8, and 14. In addition osteocyte lacunar area (Ot.Lc.Ar) was increased specifically in OI subtypes 1, 6, 8, and 14 bones, while osteocyte lacunar appearance was heterogeneous in size, shape, alignment, and spatial distribution in OI types 3, 6, 8, and 14, underscoring the case-specific alterations. Consistently, polarized light microscopy demonstrated increased green birefringence under polarized light microscopy in OI types 1 and 14 and reduced lamellar thickness in OI types 1, 6, and 8. At the molecular level, Raman spectroscopic analyses showed reduced mineral and organic matrix signals in OI bone, specifically OI type 3, indicating compromised mineralization and altered bone matrix composition. Together, these findings illustrate the potential that OI bone phenotype illustrates potential subtype-specific trends in bone microarchitecture, collagen disorganization, impaired lamellar bone formation, and deficits in bone mineral and matrix composition. This integrative analysis links genetic defects in collagen-related and non-collagen genes to multiscale alterations in bone tissue, providing mechanistic insight into OI pathophysiology and highlighting potential structural targets for individualized therapeutic strategies.
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