Twenty patients who had delayed union were injected with bone marrow nonunion, with a mean of 9.65 months between initial surgery and marrow injection. Of the 20 fractures, 19 achieved clinical and radiological union, on average after 2.95 months (Connolly et al., 1991).
STEM CELLS FOR FRACTURE HEALING
Nonunion occurs when a fracture has failed to heal in the expected time. Because the expected time is hard to define and arbitrary, it is better defined as when further progress in bone healing will not occur without intervention (Bolhofner, 2010). Nonunion of fracture may be caused by uncontrolled movement of the fracture site or by acellular environment. Bone marrow aspirate from the illiac crest has been applied to nonunion sites with limited morbidity (Gomez-Barrena et al., 2011)
Summing up, most of reported studies are uncontrolled case series although there are a few controlled studies. Local implantation of bone marrow aspirate concentration to core decompression tract was most commonly used while some of recent studies used culture-expanded bone marrow stem cells. Scaffolding materials include fibrin glue, platelet rich plasma, β-TCP, autologous bone and tantalum rod. While it is difficult to compare individual studies because of heterogenous methods of application, bone marrow aspirate concentration or bone marrow stem cell seems to have reasonable, if not remarkable, effects in early stage (Ficat I or II) osteonecrosis of femoral head in terms of symptomatic releief and preventing progression of femoral head collapse.
Daltro et al. conducted a phase I/II, non-controlled study to determine the efficacy and safety of bone marrow aspirate concentration implantation using a minimally invasive technique in 89 sickle cell disease patients with osteonecrosis of the femoral head. At the final follow-up (60 months) there was a significant improvement in clinical joint symptoms and pain relief. In addition, radiographic assessment after the bone marrow aspirate concentration implantation procedure showed disease stabilisastion (Daltro et al., 2015)
Stem cell therapy has been also assessed in unusual forms of osteonecrosis, such as sickle cell disease. Hernigou et al. administered allogeneic stem cells by the intravenous route in a patient who had osteonecrosis of the humeral head secondary to sickle-cell disease, leading to a favourable outcome and total repair of the osteonecrosis after a follow-up of 4 years (Hernigou et all., 1997)
In addition to direct cell placement by surgery, one group attempted targeted intra-arterial delivery of bone marrow aspirate concentration in the treatment of osteonecrosis of the femoral head. Sixty-two patients with osteonecrosis of the femoral head were recruited and were treated with bone marrow aspirate concentration perfusion via the medial circumflex femoral artery. After 5 years, 92.31% (72 of 78) of hips achieved a satisfactory clinical results while only 6 hips (7.69%) progressed to clinical failure and require total hip arthroplasty (Mao et al., 2013). The same group performed a randomised controlled clinical trial of combination treatment of biomechanical support (porous tantalum rod implantation) and targeted intra-arterial infusion of peripheral blood stem cells mobilised by granulocyte-colony stimulating factor in osteonecrosis of the femoral head. At 36 months, 9 of the 41 hips (21.95%) in the control group (porous tantalum rod implantation only) progressed to clinical failure and underwent total hip arthroplasty, whereas only 3 of the 48 hips (6.25%) in the combination treatment group required total hip arthroplasty (Mao et al.,2015).
Martin et al. used bone marrow aspirate concentration and platelet rich plasma during minimally invasive decompression of the femoral head in the treatment of osteonecrosis of the femoral head at Ficat stage I or II. Significant pain relief was reported in 86% of patients.