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“Orthopaedic surgeons must make difficult decisions when doing a reconstruction secondary to trauma, infection, and periprosthetic osteolysis, among other causes,” said Stuart B. Goodman, MD, PhD, moderator of the AAOS/Orthopaedic Research Society symposium Biologic strategies to grow bone in difficult clinical situations, presented at the 2008 Annual Meeting.

AAOS Now

Published 7/1/2008
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Annie Hayashi

Biologic strategies to build bone

Symposium examines clinical applications of bone formation strategies

Stuart B. Goodman, MD, PhD

Restoring lost bone and avoiding complications are just two of the issues they must consider, he pointed out. Although using an autograft is the “gold standard” for rebuilding bone, the supply is limited and harvesting may result in substantial morbidity. Panelists brought the audience up-to-date on the search for novel, safe, and effective methods to regenerate bone—from basic science to applications in treating fractures, total joint replacement, and orthopaedic oncology.

Back to the basics
Panelist Steven A. Goldstein, PhD, set the stage with a discussion of the basics of bone formation and osteoconductive scaffolds. “The process of bone formation is regulated by a cascade of sequentially oriented biologic and mechanic factors,” he explained.

Steven A. Goldstein, PhD

He also reviewed the factors that regulate the particular processes of bone repair and remodeling. “Some of these are clinical factors—the severity of the trauma, the anatomic location, oxygen tension, and vascular supply,” he said. “The extent of soft-tissue damage that occurs during the bone repair process also influences the bone formation pathways.”

Mechanical factors are also important regulators of bone repair. In the presence of large displacements, bone repair will occur by endochondral formation (cartilage formation and calcification followed by remodeling). Low levels of displacement typically result in direct bone formation (no intermediate cartilage template).

Dr. Goldstein pointed out that naturally occurring materials that support the formation of bone are osteogenic. Osteoconductive methods use materials that support the ongrowth of osteoprogenitor cells to their surface, promoting bone formation directly onto the material surface. Materials or factors that promote denovo bone formation, even where bone may not normally form, are osteoinductive.

New technologies for bone restoration

J. Tracy Watson, MD

Calcium ceramics (calcium sulfates and calcium phosphates) are among the current options for treating metaphyseal defects with a simple cancellous void. The calcium sulfates function as void fillers and the calcium phosphates provide structural support. Both provide progressive, active remodeling of a subchondral defect, depending on the surgical indication and the type of ceramic implanted.

Calcium sulfate ceramics provide initial compressive strength that quickly degrades. These materials serve primarily as fillers and have also been used to deliver antibiotics to infected skeletal defects.

The porous phosphate ceramics provide a large surface area for cellular attachment. “These substances are osteointegrated by a cellular-mediated event. Depending on the porosity of the material, they may require longer incorporation times. They do, however, provide more compressive strength than the sulfate ceramics” said Dr. Watson.

“Orthopaedic surgeons must make difficult decisions when doing a reconstruction secondary to trauma, infection, and periprosthetic osteolysis, among other causes,” said Stuart B. Goodman, MD, PhD, moderator of the AAOS/Orthopaedic Research Society symposium Biologic strategies to grow bone in difficult clinical situations, presented at the 2008 Annual Meeting.
(Top left) Preoperative anterior-posterior radiograph shows superior-lateral acetabular bone loss and a loose acetabular component. AP (top right) and lateral views (bottom) obtained following revision with structural acetabular grafting. Reproduced from Long WJ, Trousdale RT: The use of allograft in adult hip and knee reconstruction, in Friedlaender GE, Mankin HJ, Goldberg VM (eds): Bone Grafts and Bone Graft Substitutes. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2006, p 60.
Remodeling begins when osteoclasts target a “resting surface” of bone and resorb it. Bone is then formed by osteoblasts. According to Dr. Goldstein, during the process of repair and regeneration, bone formation—primarily modeling followed by remodeling—is accelerated.
J. Tracy Watson, MD, addressed the impact of the bone formation process on the treatment of complex fractures. “No well-defined indications exist for using a specific type of bone graft substitute or an inductive factor in complex fracture situations,” he said. As a result, clinicians must base their decisions on contemporary fracture management principles and current levels of evidence for use of these materials.
When evaluating bone graft requirements for total joint arthroplasty (TJA), the surgeon needs to determine the extent of the bone loss and the quality of the host bone. “Two questions should be asked before surgery,” he said. “Does the component need to be revised? Is a structural or nonstructural graft necessary?”
Structural allograft products offer the greatest utility for the surgeon to replace large segments of bone. The defects can be reconstructed with bone that closely matches the anatomy that is removed. Slow and unpredictable healing is the major drawback to this versatile mode of reconstruction.

“The new types of phosphate ceramics are usually osteointegrated completely by 18 months and maintain the congruency of the reconstructed joint surface. These materials resist tension poorly and incorporate best in areas of active bone remoldeling,” he added. “Because they are weak when placed under shear stress, they are not indicated for use as a solitary bone graft supplement in a diaphyseal location or for diaphyseal replacement.”

Managing bone loss in TJA
Bone loss represents a clinical continuum, according to Jay R. Lieberman, MD, who discussed bone loss in total joint reconstruction.

Jay R. Lieberman, MD

When a bone defect requires a structural graft, Dr. Lieberman suggested using either cadaver bone (distal femoral or femoral head allograft) or the new porous metal augments. “The porous metals facilitate bone ingrowth into the component,” he explained. “Porous metal augments can actually substitute for a structural graft.”

To treat osteolytic lesions in the pelvis, Dr. Lieberman noted the importance of selecting appropriate graft materials and maximizing the potential for incorporation in each case. The goal is to provide bone stock if the acetabular component has to be removed later.

In the future, he sees the emergence of “bioimplants” that use porous metals as delivery vehicles for stem cells and scaffolds. Coating porous metals with resorbable polymers that deliver both drugs and growth factors to enhance bone ingrowth at the time of a revision may also be possible.

The challenges of bone restoration in oncology
In orthopaedic oncology, however, the options for bone formation are more limited, as panelist Alan W. Yasko, MD, MBA, noted. “We face many obstacles in treating this patient population—cavitary, osteoarticular, segmental intercalary, large type defects,” he explained. “It is sometimes necessary to replace entire bones or to reconstruct sacral and vertebral defects.”

Most oncologic reconstructions are allograft-based to eliminate the harvest-associated morbidity that exists when using autograft. He recommends using particulate allograft for large cavitary defects because graft incorporation is “extremely predictable.”

Alan W. Yasko, MD, MBA

Free fibula grafts are alternatives to allografts, but the indications for their use are more limited. “The primary indications for using a fibular graft,” Dr. Yasko explained, “are augmenting segmental allografts or performing upper extremity osseous reconstructions, pelvic ring reconstitution, or physis-sparing or preservation procedures. They can also be used in radiation-associated fractures because their incorporation is more rapid than allografts due to their preserved viability.”

For more information on the use of biologics to grow bone and a list of resources, refer to the 2008 Proceedings of the Annual Meeting, available in both text and CD-ROM format through the AAOS online store at www.aaos.org/products

Disclosure information on the panelists may be found online at www.aaos.org/disclosure

Annie Hayashi is the senior science writer for AAOS Now. She can be reached at hayashi@aaos.org