‘No better’ healing rates seen with BMPs over autogenous grafts for fractures

Surgeons can avoid harvesting costs, pain and functional restrictions of grafts with BMPs.

Issue: Issue 2 2007

PHOENIX, U.S.A. — Findings from a British study suggest that more orthopaedic surgeons throughout Europe and Asia may be turning to recombinant human bone morphogenic proteins as a way to stimulate bone healing in fracture cases without the donor site morbidity of autogenous bone grafts.

Bone morphogenic proteins (BMPs) produce new bone by stimulating the existing cells to proliferate and differentiate.

“[BMPs] have the most potent osteoinductive property,” said Peter V. Giannoudis, FRCS, who explained the mechanisms of action, clinical applications, and safety and efficacy of these growth factors at the Orthopaedic Trauma Association annual meeting. “They are the most potent available materials to stimulate cell division and cell differentiation.”

Must be dampened

Giannoudis said Medtronic Sofamor Danek’s recombinant human bone morphogenic protein-2 (rhBMP-2) is packaged on a collagen carrier and must be dampened prior to use.

“You need the sponge to be wet for about 15 minutes, and then you’ve got a window of about 2 hours to put it into the body,” he told Orthopaedics Today International. For rhBMP-7 (Stryker Biotech), marketed as OP-1, surgeons must also add 2.5 mg of saline before implanting into a nonunion or defect site.

While rhBMP-2 has gained full approval in the United States for the treatment of acute open tibia fractures with intramedullary nailing, rhBMP-7 has a humanitarian device exemption for long bone nonunions. Yet, Giannoudis noted that rhBMP-7 has gained full license in Europe and Australia, allowing surgeons to use the protein in various clinical applications.

In his own study of 653 cases using rhBMP-7 in different applications, Giannoudis discovered an overall union rate of nearly 82% and found no adverse treatment effects, according to his abstract. The clinical indications included nonunion (60%), arthrodesis (14%), open fracture (9.3%), distraction osteogenesis (8.8%), acetabular reconstruction (3.3%), osteotomies (3.2%), periprosthetic fractures (0.4%) and free fibula graft (0.3%).

Orthopaedists expose the nonunion site prior to implantation of bone morphogenic proteins (BMPs). The proteins stimulate cell division and differentiation.

Surgeons place the BMPs in the nonunion site. Researchers cite systemic effects, extended bone formation, local edema and allergic reaction as common complications, but Giannoudis said that these are rare.

Images: Giannoudis PV

The tibia topped the list of nonunion sites indicated for the implantation of BMP-7, followed by the femur, the forearm and the fibula, Giannoudis said.

The mean time from injury to implantation was 29.7 months, and 74% of the study group also received autogenous bone graft with rhBMP-7, according to the abstract. Surgeons performed 3.5 operations (mean) prior to the rhBMP-7 implantation, and about half the patients in the series had received autogenous bone graft prior to the implantation, he said.

To determine the safety and efficacy of rhBMP-2 and rhBMP-7, Giannoudis conducted a meta-analysis of human studies and results from 10 years of animal research. “My conclusion was that BMPs stimulate bone formation by causing proliferation and differentiation, of mesenchymal stem cells, directing them toward chondrogenesis or osteogenesis,” he said. “BMP should be evaluated in bone defect models, nonunions, open fractures and spinal fusions.”

Nonequivalent comparisons

Giannoudis also found that researchers reported superior results with BMP when they compared the treatment with nonequivalent treatments for long bone fractures. “For instance, [the surgeons] stabilized the tibia fracture with a nail, but nothing else, or with a nail and BMP,” he said.

Yet, he noted that the results did not bear out when investigators compared BMP treatments with comparable methods.

“Although the results show [they are a] little bit better than the results we obtain with autogenous bone graft, this difference is not statistically significant and, therefore, no better rates of healing have been established [with BMPs] than in treatment with autogenous bone grafting,” Giannoudis said.

He also found that investigators cited extended bone formation, local edema, allergic reaction and systemic effects as the most common complications of BMP treatment. “But, in terms of these four, [a complication] is very rare,” Giannoudis said. For example, of the thousands of cases analyzed, researchers only reported 10 instances of side effects.

BMPs still promising

Although the meta-analysis revealed that BMPs have similar healing rates to autogenous bone grafting, surgeons might still find BMPs advantageous, Giannoudis said. Surgeons performing autogenous bone grafting must still consider the amount of available bone, harvesting costs and subsequent pain and decreased function.

“You don’t have these complications if you don’t take the autologous bone graft and you put the BMP in,” Giannoudis said.

For more information:
Giannoudis PV. Symposium V: Enhancement of bone healing: What is the evidence? — BMPs. Presented at the Orthopaedic Trauma Association 22nd Annual Meeting. Oct. 4-7, 2006. Phoenix.
Peter V. Giannoudis, FRCS, professor of trauma and orthopaedic surgery, University of Leeds, St. James’s University Hospital, Beckett Street, Leeds, LS9 7TF, England; +44-113-2066460; pgiannoudi@aol.com. He has received research or institutional support from Stryker Biotech.