Basic Science of Bone Grafting
Urist described the induction of bone formation when demineralized bone was placed in extraskeletal sites[1]. His work elucidated osteoinduction, the process of mesenchymal cell recruitment and differentiation into bone forming cells, osteoblasts. Successful mesenchymal cell recruitment requires the presence of cytokines, the bone morphogenic proteins, and a trellis or scaffolding onto which these cells migrate. Cell migration is facilitated by the porosity of bone being grafted, cancellous versus cortical, and is induced by the presence of osteoclasts, which drive bone resorption and increase porosity.
It is important to recognize that bone formation through osteoblasts and bone resorption through osteoclasts is coupled, and the function of either type of cell requires the presence of the other. The term osteogenesis describes the ability of harvested bone forming cells to produce bone when placed in the proper environment. When considering these principles for bone grafting, cancellous bone is 8X as metabolically active as cortical bone and cortical bone is 4X as dense as cancellous bone[2]. Bone formation can be characterized as intramembranous (mesenchymal cell differentiation into osteoblast), endochondral/enchondral (mesenchymal cell differentiation into chondroblast to produce a cartilaginous model, and osteoblast), appositional (bone remodeling), and adaptive (bone formation/resorption due to stress shielding).
When bone is fractured, the healing process is initiated through inflammation. Plate fixation provides rigid immobilization and primary bone healing. A strict requirement of primary bone healing is cortical-cortical contact and compression across the fracture site. When cortical bony defects are larger than 2cm (critical sized defect), cortical bone graft must be interposed and included in the fixation construct. Importantly, cortical allograft bone alone lacks sufficient metabolic activity to induce bone formation and must be augmented with autologous bone marrow. Primary bone healing is induced through the elution of BMP (cytokines) from the mineralized matrix, which act locally to stimulate mesenchymal cells to differentiate and produce bone (creeping substitution)[2]. The elution of BMP’s is facilitated by osteoclastic bone resorption and serves to increase the porosity of bone as described above. If cast immobilization (controlled micromotion) is chosen, bony defects must be absent, and sufficient stability must be achieved.
Clinical Application of the Science
In clinical practice the need for a bone graft must be assessed first by determining if fracture union is required or bony fusion. When considering fracture union, the physician must consider the needs of the patient. Specifically, does the operative site need metabolic activity (cancellous bone and/or bone marrow), stability (cortical bone stabilized with internal fixation), or both. When bony defects are within the metaphyseal region of bone, cancellous autograft should be used to fill the defect, as in a tibia plateau fracture or a pilon fracture. Cancellous allograft is a good choice for bony defects in unchallenged soft-tissue environments and the absence of comorbidities that impede fracture healing, as in the removal of a benign tumor. Nonunion of a bone typically occurs in the diaphyseal region. When presented with a deformed unstable nonunion and first ruling out infection, one must determine if the nonunion is atrophic or hypertrophic. Recall that bone formation (osteoblasts) is coupled to bone resorption (osteoclasts), either cellular process does not proceed without the other, and the grafting material must allow these cells to function in a coupled manner[2]. After the needs of the patient are determined, the appropriate graft composite can be chosen, i.e., cancellous autograft for its ability to fill a defect and provide metabolic activity, or cortical autograft for its ability to fill a defect and provide stability. Preparation of the bony edges and soft-tissue bed requires thorough debridement of interposing fibrous tissue.
Bony fusion is a process of new bone formation across a joint or two separate bony segments wherein the first phase of healing, inflammation, is induced by surgical trauma. This soft-tissue environment is substantially different from that of a fracture. In the case of spine, the graft material is easily placed along the transverse processes or within the interbody space. Critical to the success of a fusion is containment of the graft material. An interbody cage may be a good choice, whereas graft placed in the posterolateral region of the spine may be more difficult to contain. Cancellous autograft provides an excellent mass of bone along with coupled bone forming cells having sufficient metabolic activity to achieve fusion. It must be emphasized that metabolic activity is essential for bony fusion.
Harvesting Techniques
Autologous bone is usually obtained from the iliac crest, either anteriorly or posteriorly, and is reported to be associated with significant morbidity, namely, post-operative pain and/or chronic pain, hematoma formation, neurologic injury, and possible gait disturbance. A careful review of some of the techniques described Ebraheim involve dissection of the muscle and periosteum away from the ilium, while the resultant cavity as a result of bone harvesting, encourages hematoma formation.[3,4,5] Nonetheless, the graft obtained provides all the essential elements of new bone formation. Therefore, emphasis should be placed on minimizing the soft-tissue dissection, and recognizing that the associated morbidity may at times be over emphasized.[6] More importantly, the reluctance to obtaining autologous bone graft may be additionally related to harvesting bone with surgical instruments that are not uniformly effective, a gouge and a curette, keeping aside, a substantial amount of bone graft is lost using this technique. There is a limited amount of autologous bone available for grafting purpose, but some of the limitations on quantity are related to poor grafting techniques. What is needed is a grafting procedure that is safe, simple, and efficient. With an understanding of the basic science of bone grafting, the HPS Bone ToolTM was developed (Orthopedic Sciences, Inc., Seal Beach, CA), which is a vacuum assisted bone grafting system. The Bone Tool can easily obtain 40cc of cancellous bone anteriorly along with 90cc or autologous bone marrow, or 60cc of cancellous bone posteriorly with approximately 110cc of autologous bone marrow. Unique to this system is its ability to harvest bone between the inner and outer table of the ilium, thus minimizing the soft-tissue dissection and post-operative morbidity, and a drain is never required.
Vascularized Bone Grafting
Free vascularized bone grafting (free vascularized fibula, FVFG) is recognized in the work of Urbaniak in the treatment of osteonecrosis. Urbaniak thoroughly debrides the femoral head and fills the resultant cavity with autologous cancellous bone. The FVFG stabilizes the bone graft, i.e., applying the principles described above. Thorough debridement to a bleeding host bed and bone graft stabilization are basic tenets of successful bone grafting, as demonstrated by the work of Mont[7] and Rosenwasser[8], irrespective of the site being grafted, spine or otherwise. In this regard, the role of a vascularized bone graft in short-segment defects should be questioned. Vascularized fibula grafts have been shown to hypertrophy with increasing mechanical loads, a benefit for long-segment bony defects[9]. Incorporation into the host bed requires viable bone forming cells acting on the grafted bone (creeping substitution), vascularized or otherwise.
Bone graft Substitutes
In view of the reported morbidity of autologous bone grafting, numerous shelf products are available for bone grafting purposes. Several terms describes these shelf products. Demineralized Bone Matrix: Acid dissolved human bone (allograft), in which the residual product is the type I collagen matrix and to a degree BMP’s, i.e., Grafton. Mineral Bone Matrix: Calcium carbonate or calcium phosphate salts, i.e., OsteoSet. It is important to recognize that neither of these types of bone graft substitutes is efficacious without coupled bone forming cells. Further, bone graft substitute is a misnomer, as these materials are bone graft expanders. The volume of graft material is expanded and not extended. Notwithstanding the above, neither graft material provides the full requirement for successful bone formation. Thus, these products should not be used as stand-alones, and must be combined with autologous cancellous bone or bone marrow.
Bone Graft Augmentation
Bone graft formation can be augmented with the application of recombinant bone morphogenic proteins. Two commercially available products include rhBMP2, InfuseTM, and rhBMP7, OP-1. The principal objective of these products is to enhance the metabolic activity of bone formation through cellular migration and differentiation. Importantly, the prohibitive cost of Infuse and OP-1 may indirectly prevent their use in the most efficacious manner, i.e., combined with autologous cancellous bone or bone marrow.
Standard of Care
When deciding to graft a skeletal site, the standard of care is reached through an understanding of the basic science of bone grafting in view of a given patient’s needs, rather than recognizing that the given patient needs a bone graft. Complex surgical procedures require bone grafting, and the use of inefficient tools make bone grafting time consuming and shelf products appealing. However, if one fully understands the metabolic and stability needs of an operative site, the proper bone graft composite will be chosen and the physician (who) will graft the patient (whom) and the standard of care will have been met.
Dr. James K. Brannon is Founder, President, and C.E.O. of Orthopedic Sciences, Inc. www.orthopedicsciences.com.
References
- Urist MM. Bone: Formation by Autoinduction. Science 12 November 1965: Vol. 150. no. 3698, pp. 893 – 899.
- Day SM, Ostrum RF, Chao EYS, Clinton RT, Aro HT, Einhorn TA: Bone injury, regeneration, and repair. In: JA Buckwalter, TA Einhorn, SR Simon editors. Orthopaedic basic sciences: Biology and biomechanics of the musculoskeletal system, 2nd edition. Rosemont, American Academy of Orthopaedic Surgeons, 2000; p. 388.
- Kurz LT, Garfin SR, Booth RE Jr: Harvesting autogenous iliac bone grafts: A review of complications and techniques. Spine 1989;14:1324-1331.
- Rupp RE, Podeszwa D, Ebraheim NA: Danger zones associated with fibular osteotomy. J Orthop Trauma 1994;8:54-58.
- Ebraheim NA, Elgafy H, and Xu R. Bone-Graft Harvesting From Iliac and Fibular Donor Sites: Techniques and Complications. J. Am. Acad. Ortho. Surg., May/June 2001; 9: 210 - 218.
- Ahlmann E, Patzakis M, Roidis N, Shepherd L, and Holtom P. Comparison of Anterior and Posterior Iliac Crest Bone Grafts in Terms of Harvest- Site Morbidity and Functional Outcomes. J. Bone Joint Surg. Am., May 2002; 84: 716 - 720.
- Mont MA, Einhorn TA, Sponseller, PD, Hungerford, DS. The trapdoor procedure using autogenous cortical and cancellous bone grafts for osteonecrosis of the femoral head. J Bone Joint Surg. 1998; 80-B: 56-62.
- Rosenwasser MP, Garino JP, Kiernan HA, Michelsen CB. Long term followup of thorough debridement and cancellous bone grafting of the femoral head for a vascular necrosis. Clin Orthop, 1994; 306: 17-27.
- Jupiter JB, Palumbo MA, Nunley JA, Aulicino PL, and Herzenberg JE. Secondary reconstruction after vascularized fibular transfer. J. Bone Joint Surg. Am., Oct 1993; 75: 1442 - 1450.
