NEW: The use of BMP in spinal fusion surgery

[Guest guest]

I just learned yesterday that I am going to be having a spinal fusion of my

L4L5 and L5S1 and my doctor is going to be using something new called BMP

instead of my own hip bone or that of a cadaver. Here is some information on

this

wonderful new alternative to bone grafting. The fourth article listed below

defines all the types of procedures used for spinal fusion. Casey

http://www.healthcare.ucla.edu/vitalsigns/spine.htm

Protein Promotes Bone Growth in Spine

-Winter 2003-

A protein that stimulates bone growth in the body has been approved for use

in spinal fusion surgery, providing a quicker, less painful recovery and better

results for patients.

The Food and Drug Administration (FDA) recently approved the use of bone

morphogenetic protein (BMP) for certain spinal fusion surgeries, and researchers

are studying other potential applications. The protein was discovered in the

1960s by the late UCLA orthopaedic surgeon Marshall Urist, M.D. “BMP is a

protein that is present in the body naturally in very small amounts. The

genetically

produced version of the protein-recombinant human bone morphogenetic

protein-2, or rhBMP-2-has the ability to stimulate the patient’s own cells to

make

more bone,†explains Wang, M.D., co-director of the UCLA Spine Center.

Spinal fusion surgery is used to treat spinal disorders such as

spondylolisthesis, scoliosis, severe disc degeneration and spinal fractures,

only after

conservative therapies to reduce pain have failed. The surgery joins-or

fuses-one or

more vertebrae to reduce pain and stabilize the spine. The traditional

surgery takes a graft from the patient’s pelvic bone and transplants it to the

spine

to help fuse vertebrae together. The risks of harvesting a bone graft from

the patient’s own body can include increased blood loss and infection, a

longer

hospital stay, and post-operative pain at the grafting site.

“Spinal fusion surgery using rhBMP-2 avoids the need for bone grafts, thereby

making the surgery less invasive. Studies also show that BMP forms fusions

just as well as the patients’ own bone can and with a higher overall success

rate,†notes Nick Shamie, M.D., orthopaedic surgeon at the UCLA Spine Center.

“

The protein is implanted onto the spine on a sponge contained in a special

carrier. The rhBMP-2 directs nearby stem cells to lay down bone and fuses the

spine together. The sponge degrades over time. Since patients do not require

bone

grafting from their pelvises, their hospital stays are shorter and their

post-surgical pain is less.†The FDA approved the use of BMP for a specific

type of

spinal fusion surgery: anterior lumbar interbody fusion surgery. UCLA

researchers are studying the use of BMP to treat osteonecrosis of the hip and

knee,

fracture nonunions (fractures that do not heal), and bone loss associated with

total hip replacements.

http://www.spineuniverse.com

 BMP: Fusion Made Better

<A HREF= " http://www.spineuniverse.com/authorbio.php?authorID=146 " > C.

Wang, M.D.</A>

Chief, Spine Service

UCLA Department of Orthopaedic Surgery

Los Angeles, CA, U.S.A.

Ms. Walsh

SpineUniverse Staff Writer

Bone morphogenetic protein, or BMP, may be the most exciting development in

spine surgery in the past decade. Finally, it seems, there may be a better way

to achieve spinal fusion with more success and less complications. Sound too

good to be true? Perhaps, but studies are showing BMP to be very effective and

may forever change the way fusion surgery is done. What is Fusion Surgery?

Spinal fusion surgery is a common treatment for such spinal disorders as

spondylolisthesis, scoliosis, severe disc degeneration or spinal fractures.

Fusion

surgery is usually considered only after conservative therapies to reduce

pain have failed. Spinal fusion surgery involves the joining or fusing of one or

more vertebrae to reduce pain and stabilize the spine. This surgical technique

includes a grafting procedure utilizing autograft. Autograft is when bone

chips from a patient’s pelvic bone are transplanted, or grafted, to the spinal

vertebra to help fuse them together. (When bone is harvested from a bone bank or

other source it is called allograft). However, harvesting bone graft from a

patient’s own body carries with it numerous problems. Grafting prolongs

surgical time and can increase the risks of blood loss and infection. It often

prolongs the length of time a patient has to stay in the hospital. Many patients

also report significant and long-lasting post-operative pain at the grafting

site. In addition, grafting does not always produce successful fusion, even when

used in combination with instrumentation such as screws, cages or dowels or

when attempted for numerous vertebrae. And Along Came BMP

Scientists have searched for years for a better way to promote bone growth

and alleviate the need for grafting. BMP was “discovered†in the 1960s when

Dr.

Marshall Urist, a pioneer in this field, identified a group of protein

extracts that help bones grow. At that time, Dr.Urist was affiliated with the

Department of Orthopaedic Surgery at UCLA in Los Angeles, California. In the

1980s,

the proteins were individually identified and reproduced. It was strongly felt

that this bone-growing material could be the answer scientists were looking

for. Could this genetically produced synthetic grafting material, that actually

stimulates cells in the body to make more bone, eliminate the need for

grafting? Scientists quickly began to study it. After numerous animal studies

using

BMP, it was used for the first time in 1997 in a clinical trial of patients

undergoing spinal fusion. 10 of the 11 patients enrolled in the study had

successful fusions within 3 months of surgery, all without the unpleasant side

effects of bone grafting. Additional clinical trials investigating the

effectiveness of BMP have been conducted and continue to show its ability to

successfully

stimulate bone fusion. Studies have proven that BMP not only successfully

creates fusion, but it seems to do so more quickly and reliably than autograft.

For example, in a recent study * conducted at The Houston Clinic in Columbus

Georgia, 46 patients underwent anterior lumbar interbody fusion surgery and were

followed for 2 years. The patients who received BMP bone graft (InFUSEâ„¢)

showed higher rates of fusion at 6, 12 and 24 months after surgery than the

patients who received autograft bone. These patients recovered faster and had

less

back and leg pain than patients who received autograft. Furthermore, and most

importantly, these patients were able to return to normal activities faster.

Availability

BMP has not yet been approved for use in the United States. However there are

indications that the Food and Drug Administration (FDA) is close to granting

approval for the use of BMP in spine surgery. It is widely believed that BMP

will eventually be useful in a variety of spinal surgeries, creating less

invasive surgical techniques, shortening recovery time and relieving pain of

millions of back pain sufferers.SpineUniverse will continue to monitor and

report

the use of BMP in spinal fusion surgery. Stay tuned.rhBMP-2 has recently

received clearance from the Food and Drug Administration (FDA) for specific

uses.

Consult your surgeon to learn if you are a candidate.

http://www.spineuniverse.com

 BMP's Use in Spine Surgery Today

 An Interview with Burkus, M.D. <A

HREF= " http://www.spineuniverse.com/authorbio.php?authorID=95 " >J. Burkus,

M.D.</A>

Orthopaedic Surgeon

The Hughston Clinic, P.C.

Columbus, GA, USA

SpineUniverse: Dr. Burkus, currently there is a great deal of interest about

rhBMP-2, or recombinant bone morphogenetic bone protein. What type of cases

are treated using BMP?

> Dr. Burkus: Spinal fusion surgeries involving the cervical spine (neck),

> and the lumbar spine (low back) are currently being studied with the use of

> rhBMP-2 or InFUSEâ„¢ bone graft. The use of rhBMP-2 has been found to be safe

and

> effective as a bone graft replacement in anterior lumbar spinal fusions. This

> technology is being evaluated for additional applications in ongoing

> clinical trials for use in the neck and low back.

SpineUniverse: Before BMP, how would you treat these cases? And what were the

results like? How quickly did patients fuse? Did they all fuse?

> Dr. Burkus: Prior to the Food and Drug Administration's (FDA) approval of

> rhBMP-2, all spinal fusions required the use of autogenous iliac crest bone

> graft. Harvesting bone from the patient represented the gold standard in

spinal

> fusion surgery. Other products are available to help augment the patient's

> own bone graft. However, none of these products worked as well as the

> patient's own bone graft. RhBMP-2 is the first FDA approved product that has

shown

> itself to be superior to autogenous bone graft in spinal fusions.

SpineUniverse: Now that you are using BMP, how is the surgical procedure

different?

> Dr. Burkus: I am using rhBMP-2 in anterior and posterior lumbar spinal

> fusion surgeries. These surgical procedures have been significantly changed.

The

> use of rhBMP-2 enables me as a surgeon to complete the surgery in a shorter

> amount of time and with less blood loss. Patients postoperatively have an

> easier time getting out of bed, ambulating and returning to activities of

daily

> living including returning to work.

SpineUniverse: What have the results been with your BMP patients?

> Dr. Burkus: Patients treated with rhBMP-2 have experienced less blood loss,

> shorter hospital stays and shorter operating room times. No patients

> receiving rhBMP-2 have required a postoperative transfusion. They, of course,

have

> no complaints of bone graft site pain. They are able to return to work

> earlier.

SpineUniverse: Are there any complications or side-effects patients should be

aware of?

> Dr. Burkus: No adverse events have been linked to the use of rhBMP-2.

SpineUniverse: In summary, what do you see the main benefits of BMP to be?

> Dr. Burkus: The primary benefits of rhBMP-2 are complete elimination of

> bone graft site harvesting pain and complications, less blood loss during

> surgery and after surgery, shorter hospital stays, earlier mobilization and

return

> normal activities including work.

SpineUniverse: Dr. Burkus, thank you for your time and comments.

> Dr. Burkus: You are welcome.

rhBMP-2 has recently received clearance from the Food and Drug Administration

(FDA) for specific uses. Consult your surgeon to learn if you are a

candidate.

http://www.spineuniverse.com

 Bone Grafts: No Longer Just a Chip Off the Ol' Hip

<A HREF= " http://www.spineuniverse.com/authorbio.php?authorID=146 " > C.

Wang, M.D.</A>

Chief, Spine Service

UCLA Department of Orthopaedic Surgery

Los Angeles, CA, U.S.A.

Ms. Walsh

SpineUniverse Staff Writer

Many spinal conditions that are treated with surgery require a procedure

called spinal fusion. Spinal fusion is the joining or fusing of one or more

vertebrae to reduce pain and stabilize the spine. During a spinal fusion, a wide

variety of implants, screws and cages may be used to enhance the fusion.

However,

the fusion is only considered successful when the bones grow together

biologically and form a solid mass. To help achieve this biological fusion, bone

grafts or other biological products that promote bone growth must be used.

Currently there are many different types of biologics that surgeons can use to

help

attain solid spinal fusion. It is very important for patients and surgeons to

understand all the options and how each of these biologics work. Since the

success of each varies, careful consideration needs to be used when choosing a

graft material.

Autogenous Bone Graft

The gold standard of bone grafting is taking the patient's own bone. This is

called autogenous bone graft. This means that at the time of surgery, the

surgeon makes a separate incision and takes a small piece of bone from an area

of

the body where it is not needed. Typically, autogenous bone grafts are taken

from the pelvis or iliac crest. Autogenous bone grafting has excellent fusion

rates and has become the standard by which all other biologics are measured.

Many surgeons prefer autogenous bone grafts because there is no risk of the body

rejecting the graft since it came from the patient's own body.

There are disadvantages of autogenous bone grafting including the need for an

additional incision, pain and soreness which often last well after the

surgery is healed, as well as possible complications such as increased blood

loss

and prolonged time in the operating room. Complications such as these occur in

about 10%-35% of patients and vary in their severity. Even when using a

patient's own bone, 100% fusion rates are not always achieved, which is why

other

fusion techniques have been developed.

Allograft Bone Graft

In an effort to minimize the problems associated with taking the patient's

own bone, a number of other fusion techniques have been developed that use

biological products as bone graft extenders or as bone graft replacements. One

common source of bone graft replacement or extender is the use of allograft

bone.

An allograft bone graft is bone harvested from cadavers or deceased

individuals who have donated their bone for use in the treatment of living

patients.

This is commonly used in many forms for spinal fusions ranging from cervical

interbody fusions to lumbar interbody fusions and can provide excellent

structural

support.

The disadvantage of allograft structural bone is that it does not promote

bone growth very well and therefore is very weak at stimulating a spinal fusion.

Although it is used successfully for short-level fusions in the cervical

spine, it is not a powerful enough biological stimulant to allow us to

successfully

use this to achieve a spinal fusion in the thoracic or lumbar spine. Studies

have shown that when using allograft bone as the only graft material, the

fusion rates in the thoracic and lumbar spine are extremely poor and the failure

rate is very high.

Demineralized Bone Matrix

Sometimes allograft bone can be demineralized, a process by which some of the

proteins that stimulate bone formation are extracted from the bone. These

proteins are processed and available in various forms. This type of product is

called demineralized bone matrix and can be readily used in place of or as an

extender to the patient's own bone. Although it has successfully fused spines in

animal studies, there is no proof that this is a powerful enough stimulus to

successfully fuse a human spine and is therefore not recommended for use

without the addition of the patient's own bone. It is only recommended as a bone

graft extender and not a replacement.

Other Graft Extenders

There are several substances such as ceramics, calcium phosphates, and other

synthetic materials which have similar biomechanical properties and structure

to that of cadaver bone; however, they are not biologically active and do not

stimulate a spinal fusion by themselves. These products are currently only

recommended for use as bone graft extenders. There has been recent interest in

supercharging these materials by adding bone marrow aspirate. This is a

procedure in which bone marrow cells are taken up in a syringe and soaked onto

the

structural carrier such as the ceramics or cadaver bone. Since by themselves

these products are not biologically active, the addition of the patient's bone

marrow cells can give them more biological activity. This is currently being

tested; however, there are no good long-term studies in humans showing this to

be

efficacious in stimulating spinal fusion. To date, the results have shown this

technique to be inferior to using the patient's own autogenous bone graft.

There are several synthetic carriers being developed which also will need

stimulation with bone marrow cells to have some type of biological activity.

Unfortunately studies have shown that these carriers also fall far short of

using the

patient's own bone.

Blood Products

Another area of biotechnology interest is the use of blood products such as

platelet gels that are taken from the patient's own blood. This gel-like

material is created by isolating a concentration of platelets, which are

important

clotting factors; from the patient's own blood. The platelet gel contains many

growth factors that can help in bone formation and can play a key role in the

formation and maturation of bony spinal fusion. The advantage of using

platelet gels is that they are easily removed from the patient's blood with very

few

complications. The major disadvantage is that they do not contain

osteoinductive proteins, which means they are not powerful enough stimulants to

induce

bone formation. They can be used as graft extenders but not graft replacements.

All of the products discussed above have not shown to be as effective as using

the patient's own autogenous bone for spinal fusion. They are all considered

graft extenders and can supplement the patient's own bone graft but should not

be used in place of the patient's own bone.

Bone-Morphogenetic Proteins

The next category of products is termed growth and differentiation factors.

These are very powerful stimulants for bone formation and can be used as graft

replacements. These proteins play a key role in the body's own natural

bone-forming process and are found naturally at sites of spinal fusion. These

proteins can be produced, concentrated and placed in the body in areas where

bone

formation is needed and are powerful enough to stimulate bone formation without

the need for taking the patient's own bone. These proteins were discovered by

Dr. Marshall Urist, an Orthopaedic Surgeon at the UCLA Department of

Orthopaedic Surgery in Los Angeles, CA. Through his groundbreaking work, he

discovered

these proteins and named them bone-morphogenetic proteins, or BMPs.

There are several different BMPs naturally found in the body and many play a

critical role in bone formation. The most promising proteins are BMP-2 and

BMP-7. These two proteins have been extensively studied in animals and humans

with very promising results. Both proteins have shown to successfully stimulate

spinal fusion equally or even superiorly to autogenous bone graft. They

accomplish this by stimulating " regular " cells to turn into bone forming cells.

This

in turn results in a solid spinal fusion. BMP-2, the most extensively studied

growth factor, has shown to achieve spinal fusions faster and with higher

success rates when used alone as compared to using the patient's autogenous bone

graft. The use of BMP-2 in spinal fusions will eliminate the need for taking

the patient's own bone as well as the side effects and potential complications

of the grafting procedure. BMP-2 has received preliminary FDA approval and will

most likely be the first growth factor available for general use in human

patients for spinal fusion.

rhBMP-2 has recently received clearance from the Food and Drug Administration

(FDA) for specific uses. Consult your surgeon to learn if you are a

candidate.

<A

HREF= " http://www.spineuniverse.com/displayarticle.php/article477.html " >Idiopathi\

c Scoliosis: Graft Harvest for Fusion</A>

<A

HREF= " http://www.spineuniverse.com/displayarticle.php/article2123.html " >Anterior

Cervical Fixation: BMP</A>

<A HREF= " http://www.spineuniverse.com/displayarticle.php/article1544.html " >Bone

Morphogenetic Protein (BMP)</A>

<A

HREF= " http://www.spineuniverse.com/displayarticle.php/article2020.html " >Minimall\

y Invasive Bone Grafts: Requirements, Methods, and Use</A>

<A

HREF= " http://www.spineuniverse.com/displayarticle.php/article2061.html " >Advancem\

ents in Biotechnology</A>

<A

HREF= " http://www.spineuniverse.com/displayarticle.php/article1879.html " >MacroPor\

eOSâ„¢ Reconstruction System - Broad Application</A>

Article written 05/22/2002

Published online 06/27/2002

Last updated 08/29/2003

This article briefly but accurately describes the current status of bone

fusion technology and its application to spinal surgery. Although an extensive

experience with the use of autograft has demonstrated successful results in

achieving a solid spinal fusion, the negative aspects of harvesting the

patient's

own bone has led researchers and clinicians to investigate new and less

invasive ways of achieving similar results. Research in the area of bone

physiology

and biochemistry is progressing rapidly and, as the author points out, may

eventually help minimize the extent of major spinal fusion surgeries in the

future.