Clinical Trials

Congenital pseudarthrosis of the tibia (CPT) is likely to be a primary periosteal disease and secondary bone disease. The primary goal of treatment is to obtain union, correct the diaphyseal deformity, correct any proximal fibular migration and prevent refracture. The pathobiology demonstrates increased osteoclasis by the surrounding fibrous hamartoma and reduced osteogenesis and bone morphogenic protein production by the bone. This leads to a loss of remodelling potential and gradual bowing and atrophy of the bone with eventual fracture of the tibia and or fibula. This recommends the synergistic use of bisphosphonates and bone morphogenic protein. The pathomechanics of CPT implicate the anterolateral bowing, narrow diameter of the atrophic bone ends and proximal fibular migration. These biomechanical factors can be addressed by means of straightening of the deformity, intramedullary support of both bones, stable fixation and reduction of proximal migration of the fibula. A summary of the literature on CPT shows that the mean probability of achieving primary union without refracture, by most treatments is 50% (12% to 80%). Two recent studies have shown a much higher success rate approaching 100%, by creating a cross-union between the tibia and fibula. The cross-union with intramedullary reinforcement of the bone makes refracture unlikely due to the cross-sectional area of union with its two-bar linkage. A new classification to guide such treatment is also proposed. Read More on PubMed

Bone nonunion is a pathological condition in which all bone healing processes have stopped, resulting in abnormal mobility between 2 bone segments. The incidence of bone-related injuries will increase in an aging population, leading to such injuries reaching epidemic proportions. Tissue engineering and cell therapy using mesenchymal stem cells (MSCs) have raised the possibility of implanting living tissue for bone reconstruction. Bone marrow was first proposed as the source of stem cells for bone regeneration. However, as the quantity of MSCs in the bone marrow decreases, the capacity of osteogenic differentiation of bone marrow stem cells is also impaired by the donor's age in terms of reduced MSC replicative capacity; an increased number of apoptotic cells; formation of colonies positive for alkaline phosphatase; and decreases in the availability, growth potential, and temporal mobilization of MSCs for bone formation in case of fracture. Adipose-derived stem cells (ASCs) demonstrate several advantages over those from bone marrow, including a less invasive harvesting procedure, a higher number of stem cell progenitors from an equivalent amount of tissue harvested, increased proliferation and differentiation capacities, and better angiogenic and osteogenic properties in vivo. Subcutaneous native adipose tissue was not affected by the donor's age in terms of cellular senescence and yield of ASC isolation. In addition, a constant mRNA level of osteocalcin and alkaline phosphatase with a similar level of matrix mineralization of ASCs remained unaffected by donor age after osteogenic differentiation. The secretome of ASCs was also unaffected by age when aiming to promote angiogenesis by vascular endothelial growth factor (VEGF) release in hypoxic conditions. Therefore, the use of adipose cells for bone tissue engineering is not limited by the donor's age from the isolation of stem cells up to the manufacturing of a complex osteogenic graft. Read More on PubMed