Masquelet's procedure and bone morphogenetic protein in congenital pseudarthrosis of the tibia in children: A case series and meta-analysis

Abstract

Purpose A type 2 recombinant human bone morphogenetic protein (rhBMP2) and Masquelet's procedure were used in three children presenting with congenital pseudarthrosis of the tibia (CPT). Recent studies on CPT suggested the presence in situ of pathologic tissues promoting pseudarthrosis. The authors hypothesized that large segmental resection of pseudarthrosis could improve prognosis of the CPT. Masquelet's procedure and rhBMP2 have been advocated for the treatment of long bone defect. Method The authors report three cases of CPT in children treated with Masquelet's procedure and application of rhBMP2. They analyzed all published cases of CPT similarly treated. Results In the present study, Masquelet's procedure did not improve the results in the treatment of CPT, but segmental bone reconstruction was possible. Bone healing was obtained in three out of the five applications of rhBMP2. In one case, the patient's parents asked for leg amputation. Analysis of the 33 published cases with the application of BMP in CPT points to a 62 % healing rate in this pathology. Conclusion The authors confirmed that segmental bone reconstruction is possible in CPT using Masquelet's procedure. In the literature, the success rate of the application of rhBMP in CPT appears to be lower than the healing rate usually reported without BMP. Nevertheless, the strict selection of patients, limited number of cases, and their heterogeneity make interpreting the results difficult. However, the theoretical risk which the children are exposed to during the use of BMP makes rigorous selection of the indications necessary. Finally, the interest of rhBMP2 application in Masquelet's procedure remained to be proven.

In silico clinical trials for pediatric orphan diseases

“…The clinical literature reports conflicting evidence about the effectiveness of BMP in treating CPT 13 , 14 , 17 , 18 . It is difficult to compare these clinical studies and draw solid conclusions for various reasons.…”

“…It is difficult to compare these clinical studies and draw solid conclusions for various reasons. First the surgical procedures and fixation methods are very heterogeneous, varying between Ilizarov fixation 17 , intramedullary fixation 14 , autologous grafting 18 , Masquelet technique 13 , or a combination thereof. Second, some clinical studies are performed with rhBMP-7 18 whereas others use rhBMP-2 14 .…”

“…In recent clinical practice, rhBMP-2 or rhBMP-7 (recombinant human bone morphogenetic protein) is used to enhance the surgical outcome. However, the effectiveness of BMP therapies is still highly debated 13 , 14 and the FDA has issued a warning against the use of BMP in skeletally immature patients 15 . As such, the goal of this study is to assess the effect of BMP treatment in an extensive, investigative in silico clinical trial using a previously developed mechanistic model of murine bone regeneration 16 and advanced machine-learning techniques to mine the large set of virtual subject data.…”

Scaffold-free Three-dimensional Graft From Autologous Adipose-derived Stem Cells for Large Bone Defect Reconstruction

“…Pathophysiological conditions and neo-adjuvant chemotherapy cause nonhealing bone in 15% to 55% of patients after allograft or prosthesis reconstruction. 1 – 6 The current gold standard for bone nonunion remains autologous cancellous bone graft from iliac crest (in most cases and in a small bone defect) containing bone marrow mesenchymal stem cells (MSCs), but available quantities are limited and the harvesting procedure is burdened by comorbidities. 7 , 8 The use of osteoinductive materials such as demineralized bone matrix (DBM) and bone morphogenetic proteins (BMPs) to overcome the lack of osteoinduction and osteogenic properties of synthetic or human materials remains relatively prohibitive in the pediatric context.…”

“…The principle of caution is applied for derived bone growth factors because they have been implicated in the tumor process, and specific studies with long-term follow-up for safety are lacking. 6 , 9 – 15 Tissue engineering and cell therapy using MSCs have raised the possibility of implanting living tissue for bone reconstruction. Adipose-derived stem cells (ASCs) demonstrate several advantages over those from bone marrow (considered the gold standard), 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.…”