Promising findings, but few studies exist comparing DBM with BMP or autograft

Researchers seek the best materials to create a supercharged demineralized bone matrix.

Issue: February 2007

PHOENIX — In the absence of randomized control trials and standards regarding tissue processing, the jury is still out as to whether demineralized bone matrix produces comparable results to autografts or bone morphogenetic proteins.

While recent research has found that demineralized bone matrix (DBM) may expand autogenous bone graft, its efficacy relies on the fabrication, purification process and type of filler, Joseph M. Lane, MD, told Orthopedics Today.

"The question is, 'Is it comparable to autogenous bone graft?' Well there's a number of studies out here saying possibly and it may be comparable in certain settings to BMPs, [but] they need more real head-to-head comparisons and we don't really have that data."

In a series of histological studies, researchers have found better defect healing in rabbits using DBM compared to autograft, Lane said. In the rabbits that received autografts, the researchers discovered that the animals' cells had to remove the dead bone before generating new growth.

"In theory, there may be an advantage of demineralized bone matrix. So we say that demineralized bone matrix has shown comparable union rates as autogenous bone graft," Lane said. "It has symmetry of mineral and collagen deposition."

Lane presented his review at the annual meeting of the Orthopaedic Trauma Association, here.

Human studies

A human trial by R. Geesink, MD comparing OP-1 [Stryker Biotech] and DBM for fibula osteotomy showed faster healing with OP-1, but greater bone mineral density with DBM at 1-year follow-up.

"It's like the tortoise and the hare," Lane said. "The demineralized bone matrix made a better ultimate product than the OP-1 and ... the union rate was relatively comparable between the two of them, but the density was superior with the demineralized bone matrix. So, yes, BMPs are wonderful, but I wouldn't knock the demineralized bone matrix."

Lane also cited research by Christian Hierholzer, MD, which found similar union rates in patients with humeral nonunions treated with autograft or DBM.

Hierholzer discovered that 100% of the autograft-treated patients united, while 97% of those treated with DBM healed.

"In a sequential cohort study, there was no question that DBM worked equally, at least in that setting," Lane said.

In a study examining posterolateral spine fusions treated with autograft alone or a DBM and autogenous bone graft mix, Frank Cammisa, MD, found fusion rates of 52% and 54%, respectively.

The results, Lane said, suggest "that DBM in the spine fusion model ... can in fact, give you results as an expander equal to autogenous bone graft."

Not created equal

Demineralized bone matrix comes in various forms, and the preparation, cut and type of carrier chosen by the manufacturer can impact the biologic properties of the graft, Lane said.

"They're all grandfathered by the federal government; there's no control over how they do it," he said. "So you're at the mercy of the company that prepares this and they are not equal because there are no standards. There is no national standard for any of these things."

Lane cited a rodent intramuscular study performed by C. Fox, MD, that compared the osteoinductivity of Grafton [Osteotech], Osteofil [Regeneration Technologies], Dynagraft [GenSci] and Allomatrix [Wright].

On a 4-point osteoinductivity scale, Fox found that Grafton (3.6±0.7) and Osteofil (1.2±0.4) had the highest scores, while Dynagraft (0.8±0.2) and Allomatrix (0.5±0.5) produced the lowest scores.

In a similar study examining spine fusion rates, Jeffrey Wang, MD, found that Grafton had a score of 3.52 and Osteofil had a score of 2.27.

Yet, he found no fusion with Dynagraft.

"Even though it had [DBM] material, it didn't function in an application for demineralized bone matrix," Lane said.

Varied efficacy

He added that the product was removed from the market.

"There's some implied suggestion [of efficacy], but the lack of clinical studies really puts you at risk — does it really work [and] how functional is it?" he said.

"The efficacy varies because of the processing and there are some DBMs which have no function," Lane said.

Also, the age and medical condition of donor can also alter the potency of the graft and skew clinical results, he said.

Some researchers are attempting to pinpoint the most potent material to create a "supercharged" demineralized bone matrix, Lane said.

"We're not sure how to identify that material, but there are efforts now to take off the crème de la crème and that material could maybe give BMP a run for the money," he said.

For more information:
Lane JM. Demineralized bone matrix. Presented in Symposium V, Enhancement of bone healing: What is the evidence? Presented at the Orthopaedic Trauma Association 22nd Annual Meeting. Oct. 4-7, 2006. Phoenix.
Joseph M. Lane, MD, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021; 212-772-1061; lanej@hhs.edu. He has received grants of support or consultation fees from Stryker, Osteotech and Wyeth.