Although great advances have been made in fracture care, treatment failures are not uncommon. High-energy injuries that result in bone devitalization, or open fractures that are associated with bone loss, can be followed by postoperative infection or, if treated with inadequate methods, may result in the development of a pseudarthrosis. These complex problems require much care before healing can occur. Since the development and use of stainless steel in orthopaedics in the 1920s, surgeons have tried to use advances in metallurgy and implant design to assist fracture-healing. Nails were improved with locking technology, while simple plates were transformed into blade plates, compression plates, and now locking plates. External fixation was revolutionized by G. Ilizarov with the development of distraction osteogenesis. Stainless steel itself was altered to create vanadium, Vitallium, and now titanium alloys. While all of these techniques have decreased the rate of nonunion, they have not completely solved the problem because there are limits to what metal can do to affect the biology of fracture-healing.
Although the biologic approach to fracture-healing seems intuitive, surgeons have had limited options for decades. An ideal bone-graft substitute must provide scaffolding for osteoconduction, growth factors for osteoinduction, and progenitor cells for osteogenesis. Autologous bone-grafting was described by Fred Albee in 19151. Bone-grafting requires additional surgery, can be painful, and is not without complications. Although Albee also described the use of calcium phosphates as an alternative to bone in the 1920s, it was not until 1965, when Marshall Urist identified “bone formation by autoinduction”2, that new options unfolded. Twenty-three years later, Wozney et al.3 and Luyten et al.4 discovered the proteins responsible for this phenomenon, BMPs-2, 3, and 4. Today these proteins can be harvested from a variety of bone sources or synthesized through recombinant gene therapy, and they are available to the practicing orthopaedist.
There has been an explosion of commercial products for the orthopaedic surgeon to choose from. Calcium phosphate ceramics, calcium sulfate, bioactive glass, biodegradable polymers, and recombinant human BMPs (OP-1 and BMP-2) are all offered as solutions to the problem of bone-healing. While the actions of each product can be confusing, suggested combination therapy can be simply baffling, especially when there are few objective scientific data. Hospital administrators are equally perplexed, particularly by the costs of these products, and in many cases they refuse to allow the surgeon to use them even though they are thought to be useful.
This issue is of critical importance to the orthopaedic surgeon involved in fracture care and treatment of nonunions. As the leaders in fracture care in North America, the Orthopaedic Trauma Association has responded by charging a committee under the leadership of Dr. William De Long to generate a white paper to more clearly identify the issues surrounding these products and their use. This initial report was expanded into the Current Concepts Review5 in this issue of The Journal to offer the information to the general orthopaedic community. It is hoped that, after reading this review, surgeons will be better able to make decisions based on sound scientific principles and to understand the limitations as well as the benefits of these commercially available bone-graft substitutes. In the end, it is the responsibility of the physician to prescribe the correct treatment for the patient, and that decision must be made on the basis of fact, not fiction.
Disclosure: The author did not receive any outside funding or grants in support of his research for or preparation of this work. Neither he nor a member of his immediate family received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the author, or a member of his immediate family, is affiliated or associated.
1. Albee FH. Bone graft surgery. Philadelphia: W.B. Saunders; 1915.
2. Urist MR. Bone: formation by autoinduction. Science. 1965;150: 893-9.
3. Wozney JM, Rosen V, Celeste AJ, Mitsock LM, Whitters MJ, Kriz RW, Hewick RM, Wang EA. Novel regulators of bone formation: molecular clones and activities. Science. 1988;242: 1528-34.
4. Luyten FP, Cunningham NS, Ma S, Muthukumaran N, Hammonds RG, Nevins WB, Woods WI, Reddi AH. Purification and partial amino acid sequence of osteogenin, a protein initiating bone differentiation. J Biol Chem. 1989;264: 13377-80.
5. De Long WG Jr, Einhorn TA, Koval K, McKee M, Smith W, Sanders R, Watson T. Current concepts review. Bone grafts and bone graft substitutes in orthopaedic trauma surgery. A critical analysis. J Bone Joint Surg Am. 2007;89: 649-58.