Increased p21 expression in chondrocytes of achondroplasic children independently from the presence of the G380R FGFR3 mutation.

BACKGROUND: Achondroplasia (ACH) represents the major cause of dwarfism and is due to mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. The cellular mechanisms involved in the reduced growth have been mainly described for in vitro or in vivo models, but few data have been obtained for humans. METHODS: Thirteen children with ACH were enrolled in the study; the presence of FGFR3 mutations was determined by restriction fragment length polymorphism analysis and sequencing, whereas protein expression in cartilage biopsy was assessed by immunohistochemistry. RESULTS: Chondrocytes in cartilage biopsies of ACH children were characterized by the presence of growth arrest mediated by STAT activation (both STAT1 and STAT5) and increased expression of p21 and cyclin D1, whereas no expression of either p53 or cyclin D3 could be detected. This mechanism was present in ACH children carrying the G380R mutation but also in a patient in whom no mutation could be detected in the entire coding region of the FGFR3 gene. CONCLUSIONS: These data thus demonstrate the presence of a common final mechanism involving p21 and possibly leading to a block in chondrocyte proliferation.

Gradual femoral lengthening with the Albizzia intramedullary nail.

BACKGROUND: Gradual limb lengthening with currently used external fixation techniques can result in less than optimal outcomes, with complications including infection, stiffness of adjacent joints, and secondary axial deviation of the extremity. We describe a totally implantable lengthening device designed to provide results similar to those achieved with external fixation devices, with fewer complications and improved outcomes. METHODS: Between 1993 and 1997, thirty-one patients (forty-one femora) underwent limb lengthening with a new internal fixation technique (Albizzia) to treat a congenitally short extremity (thirteen patients), post-traumatic limb-length inequality (eleven patients), or developmental problems (seven patients). Twenty-one patients (twenty-one femora) underwent unilateral surgery to equalize the limb lengths, and ten (twenty femora) underwent bilateral surgery to correct short stature. The mean age was twenty years and one month (range, twelve to thirty-nine years). After intramedullary corticotomy of the diaphysis of the femur, an intramedullary nail was inserted in an antegrade fashion. Fifteen alternating internal and external rotation maneuvers of the lower limb elongated the nail by 1 mm. The outcomes were assessed clinically and radiographically at a mean of fifty months postoperatively. RESULTS: The gain in femoral length averaged 3.4 cm (range, 2 to 5.5 cm) after the unilateral lengthening procedures and 6.3 cm (range, 4.6 to 8.4 cm) after the bilateral procedures. Patients underwent an average of three operations on each limb; these procedures included, in addition to the nail insertion and nail removal, ratcheting under general anesthesia in thirteen limbs and eleven procedures to treat complications in nine patients. At the time of follow-up, no patient had axial deviation of the limb secondary to lengthening. CONCLUSIONS: Femoral lengthening with use of the minimally invasive Albizzia technique provides a reasonable alternative to external fixation that is well tolerated by patients and results in excellent function with little or no distortion of body image.

An ongoing research for evaluation of treatment with BMPs or AGFs in long bone non-union: protocol description and preliminary results.

Treatment of long bone non-union (NU) continues to be a challenging task for the trauma surgeon often resulting in unsatisfactory results and long-term morbidity. Whilst autologous bone grafting remains the gold standard of treatment of these difficult cases, recently, due to the advances made in tissue engineering techniques, other alternatives have become available. In this study we report our preliminary results of treating long bone non-unions using either bone morphogenetic protein-7 (BMP-7) or platelet rich plasma (PRP) concentrations. Twenty-nine cases have entered this study thus far. Preliminary results indicate that BMP-7 is more efficacious that PRP as there was a significant failure rate of 6.2% versus 38.5% between BMP-7 and PRP, respectively.