The masquelet induced membrane technique with BMP and a synthetic scaffold can heal a rat femoral critical size defect.

Long bone defects can be managed by the induced membrane technique together with autologous bone graft. However, graft harvest is associated with donor site morbidity. This study investigates if a tricalcium phosphate hydroxyapatite scaffold can be used alone or in combination with bone active drugs to improve healing. Sprague Dawley rats (n = 40) were randomized into four groups. (A) scaffold, (B) BMP-7, (C) BMP-7 + scaffold, and (D) BMP-7 + scaffold + systemic bisphosphonate at 2 weeks. Locked femoral nailing was followed by 6 mm segment removal and implantation of an epoxy spacer. At 4 weeks, the spacers were removed and the defects grafted. Eleven weeks later, the bones were explanted for evaluation with radiography, manual assessment, micro-CT, histology, and Fourier Transform Infrared spectroscopy (FTIR). Isolated scaffolds (A) did not heal any defects, whereas the other treatments led to healing in 7/10 (B), 10/10 (C), and 9/10 (D) rats. Group D had greater volume of highly mineralized bone (p < 0.01) and higher bone volume fraction (p < 0.01) compared to all other groups. A synthetic scaffold + BMP-7 combined with a bisphosphonate improved the callus properties in a rat femoral critical size defect, compared to both BMP-7 and scaffold alone or the two combined.

The Masquelet technique of induced membrane for healing of bone defects. A review of 8 cases.

BACKGROUND: Segmental defects of long bones are notoriously difficult to treat. This study evaluates eight cases in which the Masquelet technique of induced membranes was used. The primary purpose was to assess the results compared to other types of bone reconstruction and share our tips and tricks to improve the outcome. METHOD: Retrospective study based on patient records and radiographs. Eight patients operated between 2011 and 2014 were included. Three had infected non-unions. Outcome measures were time-to full weight-bearing, time to radiographic consolidation, need for secondary bone grafting procedures and occurrence of complications. RESULTS: Time to full weight bearing seemed shorter in patients treated with nails. In two cases only partial radiographic consolidation was noted at the latest follow up visit. One patient needed secondary bone grafting and two limbs were malaligned. There were no amputations, no persistent infections, and no implant failures. DISCUSSION: The induced membrane technique is a useful tool to substitute bone loss yet consolidation time is somewhat unpredictable and prolonged non-weight bearing is required. CONCLUSION: Nailing seems to improve outcome compared to plating. It shortens treatment time, reduces the amount of bone graft needed, aligns the bone and should be considered when feasible. Further larger scale studies are welcome to throw more light into the efficacy and effectiveness of this technique.

Influence of systemic bisphosphonate treatment on mechanical properties of BMP-induced calluses in a rat fracture model: comparison of three-point bending and twisting test.

The combination of autograft, BMP and bisphosphonate has been shown to produce strong calluses. In this study, without autograft we investigate the effect of bisphosphonate treatment on BMP-induced calluses, both in bending and in rotation. Sprague-Dawley rats (n = 42) underwent femoral osteotomy and BMP-7 treatment. At 2 weeks an injection of saline or bisphosphonate was administered. The animals were sacrificed after 6 weeks. Both femurs were tested in either three-point bending or twisting. All femurs healed. BMP + bisphosphonate-treatment led to larger calluses (p < 0.05) and in three-point bending, higher ultimate force (p < 0.01) and greater stiffness (p < 0.05) than BMP alone. The BMP + bisphosphonate group was nearly 60% stronger than controls, while the BMP group did not reach the strength (p < 0.05) nor stiffness (p < 0.01) of the controls. In the twisting test, similar trends were found but less pronounced. Three-point bending produced transverse callus associated fractures, whereas the twisting test produced spiral fractures, located in the structurally weaker distal femur. BMP + bisphosphonate-treatment produces calluses that are mechanically superior to calluses induced by BMP alone, when tested both in three-point bending and in twisting. For the mechanical evaluation of pharmacologically enhanced calluses with breaking strengths exceeding the native bone, the bending test is recommended.

Investigating the synergistic efficacy of BMP-7 and zoledronate on bone allografts using an open rat osteotomy model.

Bone grafts are well-established in the treatment of fracture non-unions but union is still not always achieved. Harvesting autograft is associated with donor site morbidity and the available amount of bone is limited. Allograft is more easily obtained and available in greater quantities but lacks the osteoinductive characteristics of autograft. We have previously shown a synergistic effect of bone morphogenetic protein (BMP-7), systemic bisphosphonates and autograft. In the present study we hypothesized that the combination of allograft+BMP-7+systemic ZA is more effective than autograft alone, which is currently the most frequently used aid in augmenting fracture and non-union healing. Femoral osteotomies were performed on 82 male Sprague Dawley rats and fixed with intramedullary K-wires. The rats were randomized into 7 groups: (i) saline, (ii) autograft, (iii) allograft, (iv) allograft+BMP-7, (v) autograft+zoledronate (ZA), (vi) allograft+ZA and (vii) allograft+BMP-7+ZA. Autografts were harvested from the contralateral tibia. Allografts were obtained from donor rats and frozen. BMP-7 was administered locally in the form of a putty placed circumferentially around the osteotomy. At 2 weeks, the rats were injected with a single dose of either saline or ZA. The rats were sacrificed at 6 weeks and the femurs were evaluated using radiography, histology, µCT and three-point bending tests. Complete radiological healing was seen in all rats in the BMP-7 groups. The callus volume was larger and the calluses were denser with allograft+BMP-7+ZA than in all other groups (µCT, p<0.001). Mechanical testing yielded a substantially higher peak force with the allograft+BMP-7+ZA combination than all other groups (p<0.01, p<0.001). This was further reinforced in the 59% increase in the peak force observed in the osteotomized femurs of the allograft+BMP-7+ZA group compared to the control femurs (p<0.01), whereas significant decreases of 22-27% were observed in the saline or bone-graft alone groups (p<0.01, p<0.05). Thus our results suggest that allograft combined with the anabolic effect of BMP-7 and the anti-catabolic effect of zoledronate is more efficient than autograft alone.

Augmentation of autologous bone graft by a combination of bone morphogenic protein and bisphosphonate increased both callus volume and strength.

BACKGROUND AND PURPOSE: Bone morphogenic proteins (BMPs) can be used in non-unions to replace autograft. BMPs induce osteoblasts and (less well known) also osteoclasts, which can in turn be controlled by a bisphosphonate. In the present study, our aim was to improve the biological effect of autologous bone graft by adding an anabolic BMP, with or without bisphosphonates, in an open-fracture model prone to non-union. METHODS: Rat femurs were osteotomized and fixed with an intramedullary K-wire. Autograft was placed at the osteotomy, mixed with either saline or BMP-7. After 2 weeks, the rats had a single injection of saline or of a bisphosphonate (zoledronate). The rats were killed after 6 weeks and the femurs were evaluated by radiography, micro-CT, histology, and 3-point bending test. RESULTS: All fractures healed. The callus volume was doubled in the BMP-treated femurs (p < 0.01) and increased almost 4-fold in the femurs treated with both BMP and systemic zoledronate (p < 0.01) compared to autograft. In mechanical testing, the autograft group reached approximately half the strength of the contralateral, non-osteotomized femur (p < 0.001). By adding BMP to the autograft, the strength was doubled (p < 0.001) and with both BMP and systemic zoledronate, the strength was increased 4-fold (p < 0.001) compared to autograft alone. INTERPRETATION: The combination of BMP and bisphosphonate as an adjunct to autograft is superior to autograft alone or combined with BMP. The combination may prove valuable in the treatment of non-unions.