Abstract
Summary
Randomised controlled study evaluating new bone formation in vivo in fracture non-unions by bone marrow derived stromal cells (BMSC). These cells do not show statistically significant new bone formation. Age of the patient during fracture, diabetes and doubling time had been observed to be correlated with fracture healing.
Introduction
Regenerating new bone by cell therapy could provide therapeutic options in many conditions such as fracture non-unions and osteo-chondral defect regeneration in advance OA. In this randomised controlled study we evaluated the efficacy of new bone formation by bone marrow derived stromal cells (BMSC) in patients with non-union.
Methods
An ethically approved and adequately powered single centre randomised control trial recruited 35 patients for treatment of non-unions with BMSC. Bone marrow was harvested and autologous BMSC were culture expanded in autologous serum at our local MHRA-licensed facility (Oscell, Oswestry, UK). Following selection by adherence and in vitro culture expansion using autologous serum, cells in serum and serum alone was randomised for insertion at one of the two fracture sides by StratOs® computer software. Patients and the operating surgeon were blinded to the side of cell insertion. Such method of randomisation created internal controls at the fracture sites- one side receiving the cell (‘test side’) and other, not (‘control’). Serial radiographs extending up to an average of twelve months were evaluated by four independent assessors blinded to side of cell insertion. Callus formation and bridging of fracture was compared for ‘test’ and ‘control’ side. Radiological and clinical outcome at final follow-up was also noted.
Results
Thirty five patients were recruited (21 males, 14 females; mean age 51.2±13.2SD). The mean duration of non-union was 3±2SD years, with a mean 3.5 (range 1–12) surgical interventions prior to BMSC insertion. Five patients had diabetes. New callus formation and fracture bridging was slow, with no significant difference between the cell-insertion and control side although a substantial improvement in fracture bridging/formation of new callus was noted at 9–12 months. Fracture union was achieved in 21 patients at final follow-up with failure to progress to union in 14 patients. Age at accident, having diabetes and cell doubling time during culture predicted union (r2=0.63, p=0.017). There was no reported adverse effects from the trial.
Conclusion
The study concluded that patient biology predicts the final outcome in cases with non-union of fracture. Slower doubling time during in vitro expansion can be significantly correlated with failure to unite in addition to diabetes and age of the patient. BMSC's are safe option for cell therapy in a setting of non-union although it failed to show statistically significant difference of new bone formation or fracture bridging for up to one year.
