Bone Grafts and Bone-Graft Substitutes
Authors’ Preferred Method of Treatment
Autologous Cancellous Bone Graft
Calcium-based Bone graft Substitutes and Calcium Phosphate–Based Cement
Enhancement of Fracture Healing with Biologic Therapies
Mesenchymal Stem Cells and Progenitor Cells
Bone Morphogenetic Proteins
Other Peptide Signaling Molecules
Nonsteroidal Anti-inflammatory Drugs
Systemic Enhancement of Fracture Healing
Growth Hormone and Insulin-like Growth Factor I
Bisphosphonates and Osteoclast Inhibitors
Physical Enhancement of Skeletal Repair
Mechanical and Biophysical Stimulation
Distraction Osteogenesis, Electrical Stimulation, Ultrasound Stimulation
Conclusions and Future Directions
Reprinted with permission from: Finkemeier CG. Bone-grafting and bone graft substitutes. J Bone J Surg Am. 2002;84:454–464.
We prefer the autologous cancellous bone graft to be used for fractures associated with bone loss, nonunions, and small bone defects (e.g., a metaphyseal or mid-diaphyseal cyst that has undergone curettage). Due to its osteoconductive, osteoinductive, and osteogenic properties, autologous graft material has a well-established history of successful augmentation of fracture healing. Up to 12-cm diaphyseal defects can be treated with nonvascularized autografts, while those over 12 cm are successfully augmented with vascularized grafts. However, there are significant complications associated with autograft harvesting, including deep infections and hematomas, neurologic or vascular injury, iatrogenic fractures, nonunions, and persistent postoperative pain. Use of the RIA is a new harvesting technique that has the potential to overcome some of these morbidities, but has not been extensively studied enough for us to make a recommendation.
Regarding allogeneic bone, there is limited information on its use in fresh fractures or nonunions. In combination with autologous graft, we recommend the use of allograft to augment the volume of graft material in the treatment of fractures associated with large volume loss or nonunions. Incorporation of allogeneic strut grafts may also be enhanced by the use of autogenous cancellous bone at the junction with the host bone.
The efficacy of human DBM as a graft material remains unclear. Although widely available and known to contain BMP, we do not believe there is sufficient evidence demonstrating its efficacy when used alone in the treatment of fresh fractures or nonunions or in the reconstruction of bone defects. However, when used in conjunction with autologous cancellous bone, it has tremendous potential. We believe that DBM provides an osteogenic advantage and may enhance the ability of a fixed volume of autologous graft or bone marrow to be effective.
The calcium-based bone-graft substitutes are best used as bone void fillers, especially when supplemented with autologous bone. It is preferable to use them in parts of the skeleton where tensile strains are low or nonexistent, as their compressive strength is comparable to cancellous bone.126 Calcium sulfate, which is much more rapidly resorbed than the other calcium-based materials, must be used in parts of the skeleton where compressive strength is required for only short periods. These materials should not be used to bridge segmental diaphyseal defects or as onlay grafts where the majority of the surface is exposed to soft tissues.
Calcium phosphate–based cement has been tested in several randomized controlled clinical trials. Based on these data, its use to shorten the time in a cast during treatment of distal radius fractures or to shorten the time to loading such as weight bearing in the augmentation of tibial plateau, distal radius, proximal humerus, and calcaneal fractures is supported by clinical evidence, and this is a viable treatment options for these indications. Furthermore, it appears to lower postoperative pain levels when compared to no graft, as well as to decrease the risk of loss of fracture reduction when compared to autograft. It may be useful in other applications such as acetabular fractures and fractures of the hip, but sufficient evidence is not yet available for its use in these settings.
We recommend the use of OP-1 (BMP-7) for the treatment of recalcitrant nonunions of long bones and BMP-2 for the treatment of open tibia fractures and those with large cortical defects. Some of other molecules, including Wnt pathway modulators and FGF-2 have shown promising preclinical and early clinical study results, but there is not enough evidence to recommend for or against their use at this time.
Regarding freshly harvested bone marrow, we believe there is insufficient evidence to support its routine use in traumatic or reconstructive orthopedic surgery. Alternatively, multiple small aspirations from the iliac crest, with centrifuge-mediated concentration (bone marrow aspirate concentrate) has been able to optimize the concentration of the osteoprogenitor cells.148,150 The senior author (TAE) has used this technique with success in several cases of long-bone nonunions.
While the role of NSAIDs in animal models appears to be well established, there is lack of scientifically rigorous clinical data for or against its effects in the acute phases of fracture healing. In addition, if there is an effect of NSAIDs on fracture healing, it appears to be dose-dependent and reversible, as it disappears after 7 to 10 days once the NSAID has been stopped. Therefore, we believe NSAIDs are safe to be used as an analgesic in short durations (10 to 14 days) after fractures or spinal fusions. However, we would recommend caution of their use in patients with comorbidities, such as smoking, glucocorticoid use, and diabetes.
Although the above compounds all show some promise for the systemic enhancement of fracture healing, their lack of FDA approval would require off-label use in the setting of fracture treatment. Because of this, the authors cannot recommend their use at this time.
The use of controlled micromotion to enhance fracture healing, as described by Easley et al.90 has not been widely used and we have no experience with this method. The use of distraction osteogenesis for the treatment of nonunions for surgeons experienced in this technique is appropriate, but there is an established risk of fracture after the removal of external fixators.
There are data to support the use of electrical stimulation for the treatment of nonunions and delayed unions. DC, capacitive coupling, and PEMFs have all shown the potential to stimulate the healing of nonunions. PEMFs can also be used for the treatment of delayed unions. However, methodologic limitations and high between-study heterogeneity leave the impact of electromagnetic stimulation on fracture healing uncertain. There is no evidence that electrical stimulation of any type enhances the healing of fresh fractures.
Ultrasound stimulation can be used for the treatment of fresh closed fractures of the distal radius and tibia when treated in a cast or external fixation device. We have also had good results in the treatment of tibia fractures that show delayed union. While this therapy might not reduce the rate of reoperations, it appears to influence fracture-healing time and union rates. Until there is evidence to support the use of LIPUS in patients treated with fixation devices apart from distraction osteogenesis, we do not recommend the use of ultrasound in the treatment of fractures of patients who have undergone an operation in which fixation devices have been implanted.
ESWT is a relatively new technology whose potential in fracture healing does not have enough evidence to evaluate for or against its use.