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BMP/2 use, not told prior surgery

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I had back surgery 12 months ago and have now found that the surgen used bmp/2.The surgen did not tell me I had to find this out myself.Should I have been told, I am now facing another operation to have a cyst removed, due to side affects of bmp/2,has this happened to anyone else out there ?
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First Helper TruthSeeker12
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replied February 1st, 2012
Especially eHealthy
indyone,

When you signed you consent form, there was probably a general clause in it that states that the surgeon can do anything during the surgery, that he/she feels is necessary to treat the condition at hand.

Since BMP is a widely used substance in fusion surgeries, it would not need special permission to be used, other than the above mentioned consent form. It, along with any of the other allograft substances, are commonly used in fusions. The patient's autologous bone graft is usually used, but sometimes it is supplemented with allograft materials.

If you did not want any of the allograft materials used, you would have needed to tell the surgeon up front, and that would have been included on the consent, if the surgeon was willing do the surgery with the constraints.


There can be complications with any procedure. With BMP, most of the recent problems that have been noted were due to it being used for off-label reasons. When used properly, it has no higher rate of complication that any other material.


But, again, if you did not want it, specifically, to be used, you would have to have informed the surgeon up front and had that placed on the consent form.


Hope that your current problem can be taken care of successfully. Good luck.
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replied February 1st, 2012
Hi Gaelic,
Thankyou for your reply.My consent form reads as follows.
Main Procedure: L5 S1 Decompression /TLIF/ Fusion.
Prosthetics: Type: Cage, Rods, Screws, Infuse.
1. Death/Strock/Heart Attack.
2. Anaesthetic Complication/s.
3. Bleeding and Tranfusion/Deep vain thrombosis/ pulmonary embolism.
4. Nerve injury resulting in temporary or permenent numbness or weak in leg or foot.
5. Dural tear resulting in headache and need to lie in bed.
6. Epidural haemstoma resulting in pressure on nerves and need for re-vision surgery.
7. Infection (deep or superficial) requiring antibiotics, removal of implants if applicable and/or a wound washout.
All explained and given a 1% chance of any complications.
8. Recurrence of symptoms due to stenosis at other levels of instability.
9. Non-union and/or hardware failure or breakage.
10. Operation preformed at the wrong level due to equipment malfunction/ cervical deformity/ other / Xrays.
Given a 3% chance of any complications.
I have read ,discused and understood these risks ans voluntarily give my consent to undergo this procedure, including all required follow-up interentions.
This is the contract I signed.
The surgen also showed an animated video of the operation, showing the incision, bone chiped away, removal of disc and replaced with artifical disc,placement of screws and plate,then closed.
During this appoitment there was no mention of Infuse or what it was.( I thought the word Infuse ment the fusion of the bones, stupid me).
I was not informed that there was another procedure that could have been preformed,if I was told then I could have had a choice.
I have since found the Infuse was off-lable and the side affects.
The surgeon only mentioned this when we told him that we had done some research ourselves .
He informed me that he will no longer us BMP/2,not sure if this was to make me fill better.
I have readiating pain in both legs and feet.After complaining that my spine felt full and uncomfortable for several weeks my GP ordered a MRI which found the cyst. Still I was not told of the BMP/2,it was six months untill the penny droped and I remembered that the surgeon had sent me a letter asking me to participate in a survey in which I agreed.
The survey was for patients who had bagk surgery where BMP/2 was or was not used. This letter still didnot say for sure that BMP/2 was used on me.
My GP exlpained that the cyst that had formed was due to a substance used in my operation.
This was how I found out about the BMP/2.
Now I an facing another operation and I am trying to find answers.The surgeon said that he had not see this before asd was not sure how to remove the cyst, and that he was consulting with his other colleagues.
Hope to hear from you soon.
Indyonr
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replied February 1st, 2012
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indyone,

Boy, that is a really short consent form. It may be that the ones I am used to seeing are used in a training facility. The ones we use are, at a minimum, 4 pages long and are usually more like 10 to 15 pages long. They go on forever.

They list all of the required information by the state, then the facility adds on whatever extra that it wants. And, there is always the one clause, in all consent form, no matter what the specialty or procedure, that basically states that the physician or surgeon can do whatever he/she needs to do, if a situation arises during the procedure, to take care of it. This is basically for the situations where the surgeon finds something unexpected and it has to be dealt with.

I believe it says something like this: I voluntarily request the performance of this treatment/procedure(s) and of such additional procedure(s) as are found necessary and desirable in the judgment of the professional staff of this medical facility, during the course of this procedure(s).

Again, I am used to working in a training facility, where the consent process is very long and involved. Also, the state (Texas) that I am in requires an extremely long informed consent. We have gone to computer generated ones, because we have to make sure all of the state requirements are met, in addition to what the hospital requires. When surgeons get out of training, they sometimes shorten things down to the bare minimums. But, still, it is always better to have broad based statements, rather than specific ones, according to the lawyers.

Instead of saying: Placement of 6 holed plate on tibia, use of autologous bone graft, for fixation of tibia fracture; the lawyers say to use: placement of orthopedic fixation devices, with or without bone grafting materials. That covers just about everything.

The more specific the consent, the more limited the physician, usually. But, it is not unheard of for physicians to have to change midstream, during the procedure. And, as long as they use approved materials, in an approved way, they are usually okay.


But, I'm not a lawyer.


BMP-2 and BMP-7 were initially approved for spinal fusion surgery, because they helped the fusion mass consolidate faster and stronger. And, as long as it was used in the approved way, it seemed to do well. But, as usual in orthopedics, if it is good for one area, let's try it for something else. So, there were a lot of cases where it was used for things like acute fractures, treatment of nonunions, treatment of failed total joints, etc. When it was used off-label, that was when the increase in problems started to be noted. A lot of the problems were due to bony overgrowth and ectopic ossification.

As you probably know, there are always known and unknown risks with any procedure and use of any materials.


Again, in our consents, there is a section for patients to place anything they do not want done. This is mostly for Jehovahs Witness patients and blood products, but any patient can put in restrictions.


I am sort of rambling, because I am not sure exactly what you want to know. If you want to bring suit against the surgeon, then you should consult a malpractice lawyer. But, for a physician to be found negligent four things have to be met:
A plaintiff must establish all four elements of the tort of negligence for a successful medical malpractice claim:
1. A duty was owed: a legal duty exists whenever a hospital or health care provider undertakes care or treatment of a patient.
>> This is met.
2. A duty was breached: the provider failed to conform to the relevant standard care.
>> This might be a problem. The use of BMP is an approved material for spinal fusion. It was used in an approved manner. It is considered a standard of care in spine surgery.
3. The breach caused an injury: The breach of duty was a proximate cause of the injury.
>> All procedures and materials carry risks. Did the surgeon actually do something that caused an injury, or it is just one of those acceptable risks?
4. Damages: Without damages (losses which may be pecuniary or emotional), there is no basis for a claim, regardless of whether the medical provider was negligent. Likewise, damages can occur without negligence, for example, when someone dies from a fatal disease.
>> Return to the OR can be considered to be damage. However, if the next surgery is successful, and you have no problems, then it will be hard to claim damages. You might get emotion or financial damages.

Remember, all four have to be met. Again, I am not a lawyer. If you want legal advice, speak with legal counsel.


If there is something in the medical realm that I can help you with (if I can), I will be glad to try.

Wishing you the best. Good luck.
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replied February 2nd, 2012
Hi Gaelic,
I don,t want to take legal action against the surgeon, I just want to know that with the infuse used off-label should he have given me another option. Might be a hard question as I live in Tasmania, different laws maybe.
I am just trying to find answers when I see the surgeon next.
Have you come across cysts that have formed in the spine with off-label infuse,if so how was it treated and or removed. I am worried as the surgeon has stated that he has not had this happen to him before, and said that he was not sure how to treat or remove the cyst. Do you know of any wed sites that I can look up regarding cysts caused by BMP/2?
I really don't want another operation so this is why I am trying to find as much info as I can before I see him again.I need straight answers and I feel he is keeping me in the dark sometimes.
Do you know how long the BMP/2 stays active once it has been place in the body?
Are there any chance of the cyst growing back if it is removed?
What is the success rate of a second operation,for removing cysts and the hardware being removed and also having the exit of the spine made larger at L5 S1 for the nerves?
Once again thankyou for your comments.
Indyone
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replied February 2nd, 2012
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indyone,

In terms of the informed consent, he did put on the form that Infuse could be used. I'm sure you probably know, Infuse is a system where sponges are impregnated with BMP, then the sponges are placed in cages, that are placed between the vertebral bodies.

The system was designed to be used in lumbar spine fusions, which were done from an anterior approach.

So, this is as "On Label" as you can get.

But, the surgeon really should have explained what Infuse was. Anytime a word or abbreviation is placed on any medical form, the surgical cannot assume that the patient will know what it is. So, just for good medical practice, a physician should explain things and not assume that just because the patient does not ask questions, that they totally understand what is going on. But, that's the way I was taught, not all surgeons may have been educated this way.


I found a couple of articles, which do not have the hysterical hype type of information in them, about the potential and actual complications of BMP in spine fusion. There are a lot of articles out there, mainly written by lay press and law firms, that really blow up sensational cases, and these were in cases where the BMP was used off-label.


The main problem with the BMP is the overgrowth of bone, causing ectopic ossifications. However, in the second article, the author did describe the formation of fluid filled cysts within the fusion mass.

And, it is conceivable the cysts could form in the face of zealous bone formation. The bone could grow in a haphazard manner, forming all sorts of holes, nooks, crannies, and really funky looking formations of bone. If you look at the formation of ectopic ossification (also called heterotopic ossification) in places like hip replacements, it can sometimes look like modern art. So, the formation of cysts could easily be understood.



As to how long it will stay active, that is not really a concern. BMP is a naturally occurring protein in the body. If you did not have BMP, your bones would not be able to remodel and turn over with time, nor heal from injury. BMP is also biologically active in many other musculoskeletal tissues, such as articular cartilage. So, it is more of how much was used. Because what was placed there will be used up and broken down by the body in the usual manner. So, once what was placed is broken down, it is gone. The amount is a set amount. It is that which is contained within the kit, which the surgeon used. Which is really not that much, how much it is exactly, I could not find easily. But, you could find that out from the Infuse company. Or maybe from your hospital. The operating room manager, the one who orders the supplies, should have all the product information on everything used in the OR.


As to a second surgery, there are risks with any procedure, and revisions are always more difficult. The chances of the cyst returning, if it was caused by overgrowth from the BMP, would be small, and it should not occur again, if BMP is not used.

If there is stenosis (narrowing) of the neural foramen (the holes through which the nerve roots exit the spine), then they may need to be enlarged. That is something that would be based on your symptoms, imaging studies, and what is found at surgery.

Success is often very subjective. What would be successful (lessening of pain) in one patient, may not be enough in another (who is expecting to be able to play competitive soccer). So, you have to decide what your goals of surgery would be, and then, with discussions with your surgeon, can that be achieved?


Hope that helps. Wishing you the best.

I have included the two short articles I mentioned earlier, if you want to read them:


Medscape News

Bone Morphogenetic Proteins and Spinal Fusion: Potential Complications of Use in Spinal Surgery


Overzealous Bone Formation:

One concern regarding the nonjudicious use of BMP in the clinical setting to induce or augment spinal arthrodesis is the danger of heterotopic bone formation. Overzealous bone formation can potentially result in symptomatic compression of the thecal sac or exiting nerve roots, calcification of the spinal cord or nerve roots, or unintended fusion of adjacent spinal segments. Review of the normal physiology of bone healing suggests how introduction of large amounts of BMP can potentially cause heterotopic bone formation.
Just as the introduction of other rh proteins such as insulin can alter cellular physiology, the introduction of supraphysiological doses of BMP can override the normal autoregulation of osteoinduction. Although local cellular in vivo levels of BMP are in the nanogram range, clinical studies have used milligram amounts of rBMP, six orders of magnitude difference. Expression of BMP-2 is likely self-regulated through negative feedback, and several inhibitory proteins have been identified in the process of BMP-mediated osteoinduction, including BMP-3 and the inhibitory Smad proteins, Smad-6 and Smad-7. Early work suggests that expression of these inhibitory proteins is increased by exposure of the cell to BMP-2, implicating them in a negative feedback system regulating the osteoinductive effects of BMP-2. The introduction of millionfold higher levels of BMP than normally seen at the cellular level unquestionably overrides the normal negative autoregulation and allows unrestricted osteoinduction. Recombinant BMPdriven osteoinduction, in the absence of effective autoregulation, may facilitate unwanted overzealous bone formation.

As shown by animal studies and clinical trials, this risk is far from theoretical. Although placement of rhBMP-2 or bovine whole BMP extract in the posterolateral location in an animal laminectomy model did not result in any significant encroachment of bone into the laminectomy defect, undesired bone formation was seen directly over the laminectomy defect with placement of rhBMP-2 or rhBMP-7. Other models have induced spinal stenosis by direct implantation of BMP over the ligamentum flavum. In the setting of dural laceration in animal models, significant intradural bone formation and calcification of the spinal cord was seen with rhBMP-7, but not with rhBMP-2, although the studies were not of similar design.

Only one of the clinical trials in humans demonstrated untoward bone formation. Implantation of rhBMP-2 by using a PLIF approach resulted in heterotopic bone formation into the spinal canal along the insertion tract in a number of patients, although reportedly no patient developed symptoms of spinal stenosis. The trial was halted and rhBMP-2 is not currently approved for use in PLIF. Although no heterotopic bone formation was seen in the rhBMP-2 ALIF, laparoscopic ALIF, or PLIT trials, some heterotopic bone formation was seen anterior to the spinal column in the anterior cervical interbody trial. Although fewer patients have been enrolled in rhBMP-7 clinical trials, no heterotopic bone formation has yet been reported.


Antibody Formation:

While overzealous bone formation constitutes a localized complication of BMP use, antibody formation against implanted BMP may represent a potential systemic complication. Antibody formation by the immune system occurs in response to introduction of external proteins or antigens and is in part related to both the amount of antigen and the duration of exposure. As such, proteins that are cleared quickly from the circulation are less likely to promote an antibody response compared with proteins that have longer clearance times. Early data suggest that rhBMP-2 is rapidly cleared from circulation, whereas rhBMP-7 clearance may be somewhat slower.

Antibody formation to rhBMP-2 has been negligible in the multiple clinical trials in humans. In the largest pivotal study of rhBMP-2 when using the ALIF model in 279 patients, antibody formation to rhBMP-2 was 0.7% in patients receiving rhBMP-2 and 0.8% in controls. In the same study, the incidence of antibody formation to the bovine type I collagen carrier was 13.1% for the investigational group and 12.9% in controls. In the laparoscopic arm of the pivotal study, the rate of antibody formation to rhBMP-2 was also 0.8% in the rhBMP-2 group, whereas 24.8% developed antibodies to the bovine type I collagen carrier. None of the patients in whom antibodies to the bovine collagen carrier were identified developed antibodies to human type I collagen.

Early data suggest a much higher BMP antibody formation in rhBMP-7 trials. Although trials of rhBMP-7 (rhOP-1) are ongoing, early data suggest a 38% antibody formation in patients treated with rhBMP-7 (European Public Assessment Report on Osteogenic Protein 1, from the Committee for Proprietary Medicinal Products, European Agency for the Evaluation of Medicinal Products, 2001). Antibody formation, although in a high number of patients, appears transient, with low titers. Although the reasons for increased antibody formation with rhBMP-7 remain unclear, increased clearance time from the circulation may be responsible.

Although no adverse effects have been yet reported with antibody formation to either rhBMP-2 or rhBMP-7, such antibody formation is worrisome. At a minimum, antibody formation likely limits future treatments with the same BMP subtype in patients in whom antibodies are detected. Subsequent exposure to the same antigen would likely induce a significant immune response. Routine postoperative serological evaluation may be indicated, especially in patients receiving rhBMP-7, if ongoing trials confirm these preliminary findings to prevent further applications in sensitized patients.

Bone morphogenetic protein has been implicated in many roles other than osteoinduction and may play a key role in multiple cellular processes in many tissues and organs. Accordingly, antibody formation to such intrinsic human proteins becomes more ominous. As the nonosteoinductive roles of BMP become clearer, the negative implications of antibody formation and possible development of an autoimmune response become more troubling.

These potential complications are not mentioned to temper the excitement regarding the development of BMP products, but rather to encourage their judicious and thoughtful use. Not only must the clinician be aware about these potential complications, but the patient should be educated of these possibilities in the process of obtaining informed consent.








J Bone Joint Surg Br 2009 vol. 91-B no. SUPP III: 437

EARLY COMPLICATIONS ASSOCIATED WITH BMP IN LUMBAR INTERBODY FUSIONS
P. Licina


Abstract

Introduction: Bone morphogenetic protein (BMP) has become widely used in the interbody space as part of a lumbar fusion. Complications can occur but are not completely understood or well documented.

Methods: A prospective review of consecutive lumbar interbody fusions performed by a single surgeon was undertaken over a 2-year period. Early complications (defined as occurring within the first six weeks) were noted. The interbody cages (titanium Syncage, Synthes cages for ALIFs and PEEK Capstone, Medtronic cages for TLIFs) were filled with Infuse BMP-collagen sponge. Until early 2007, the amount of Infuse used was not strictly measured but after that time, only enough to fill the cage was used, with the volume assessed according to the manufacturer’s guidelines. Patients were routinely assessed preoperatively and at the six-week postoperative review using a visual analogue scale and the Oswestry disability score. Plain x-ray and MRI were obtained preoperatively, and plain x-ray was obtained postoperatively. In addition, if early problems developed, MRI scan was obtained. The incidence of complications was compared to that seen in similar procedures but where BMP was not used.

Results: 114 patients, including 78 transforaminal inter-body fusions (TLIFs) and 36 anterior lumbar interbody fusions (ALIFs) were available for review. Early complications were noted in 10 of 114 patients. Two (both with TLIF) were not directly linked with BMP use: in the first, the cage migrated posteriorly and in the second, a deep infection developed. The remaining eight were associated with an exaggerated inflammatory response likely related to BMP use. Severe back pain associated with marked vertebral body inflammation seen on MRI was noted in two ALIF patients. The response occurred within 2 weeks of surgery, and settled with conservative treatment. Severe back pain and recurrence of leg pain developed in six TLIF patients. Fluid cyst formation within the spinal canal was seen on MRI in 4 of these. The cyst extended from the region of the posterior aspect of the cage into the canal and toward the area of the excised facet joint, resulting in compression of the exiting nerve root. In one case, the surgical site was re-explored and the cyst removed. In two cases, the cyst was aspirated under CT guidance and injected with steroid. In the final case a course of oral Prednisone was administered. In the remaining two TLIF cases, there was a diffuse inflammatory response in the region of the posterior aspect of the cage and adjacent epidural space but without discrete cyst formation. In one, oral Prednisone was prescribed. The second was treated expectantly. The majority of these complications were noted in 2007, after the dose of BMP was titrated in line with the manufacturer’s guidelines. In contrast, no such complications were seen when a similar technique but without BMP was undertaken in 33 posterior and 41 anterior interbody fusions.

Discussion: The incidence of an exaggerated inflammatory response with BMP in the lumbar spine may be under-recognised. The majority of complications published to date relate to vertebral osteolysis and bony overgrowth, although a number of adverse responses to BMP reported to the FDA relate to fluid cyst formation or inflammation. With the rapid increase in BMP use, it is important that surgeons are aware of potential complications, and possible strategies to prevent and address them.

Footnotes -
Correspondence should be addressed to:
Dr. Owen Williamson,
Editorial Secretary,
Spine Society of Australia,
25 Erin Street,
Richmond, Victoria 3121, Australia.
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replied February 12th, 2013
Hi, reading through these feeds because I also have a problem with bmp2 being used. While I agree with you on most of the things mentioned as far as standard "consent" forms, IF the bmp was used OFF LABEL, that REQUIRES an additional consent informing the patient that it is being used off label and the patient understands and agrees to it. Mine WAS used off label, and I did not sign a consent for it to be used. There are serious problems arising from this stuff being used off label. So, I'd check to see if he had you sign an "Informed consent" specifically saying he was going to, and it was ok, to use the bmp off label.
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replied May 8th, 2012
There are many lawsuits against Medtronic for bmp/2's ("Infuse") usage. There is a class-action lawsuit being formed as well. The cyst 'Indyone' has experienced is one of the horrible side-effects, but male-sterility, cancer (432% increased chance), and permanent nerve damage are among the horrors listed in current reports. The Senate did an inquiry into Medtronic's product and the Dept. of Justice is currently on the case.

Indyone - you may have a legal case now. Look into it. The proverbial crap hit the fan last year and now it's a big deal. Not only should your doctor have notified you of the "off-label" use and the risks before surgery, he may even be one of the many surgeons getting a kick-back from Medtronic. Don't simply take my word for it - Google it. You will find plenty of credible info/research on this topic of Infuse (product name), but info from classaction.org (search "Medtronic Infuse Bone Graft") and lawyers representing the many. Sorry you were one the the people injured. Hang in there!

-A Damaged Infuse Patient
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replied May 17th, 2012
hi all
am i new to this forum and to my ctscan diagnosis of lateral recess stenosis L4/5(not sure of all the jargon yet but i expect i will learn quickly) my GP is referring me to neurosurgeon but has said spinal surgery is likely. i was obviously concerned but having read of your experiences indyone well what can i say i am now really concerned. i also live in Tasmania and as you would know our health system is really suffering. from what i have heard with the public system it is a 3 year wait just to get an appointment with a neurosurgeon then another 5 yr wait for the op, not sure how this compares elsewhere, but not good in anyone's books.

firstly to indyone & truthseeker i hope things are getting better for you.

i have been trying to search on the web about recommendations or otherwise for my soon to be neurosurgeon. given that we don't have too many in our lovely state is he the same one as you saw and should i be worried?

does anyone know if there is a way to check the credentials of surgeons/specialists before you go to see them?

thanks for listening and for the great info I'm off for more ct scans tomorrow
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replied August 3rd, 2013
Fevers following 2 level spinal fusion of L4-L5-S1, using rhBMP2
I know someone who has strange fevers whenever she sleeps longer than 5-7 hours and frequently has fevers from short sleeps as well. These started 6 months after her two level spinal fusion with the use of rhBMP-2. These fevers resemble symptoms many report before developing cancer. The fevers are painful and resemble genuine illness, producing genuine heat in the lumbar, where the surgery also was. We would like to know if there is a solution. We would like to know that it is not happening to others???
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replied January 23rd, 2014
BMP2
Medtronic makes the most highly marketed BMP-2, called InFuse Bone Graft. There are many lawsuits, but there is no class action.

Therefore, whoever said that BMP is used frequently is either (a) not knowledgeable or (b) works for Medtronic and/or (c) not providing you with full disclosure.

I say this because InFuse is approved for FDA approval for one very limited use called Anterior Lumbar Interbody Fusion (ALIF).

My reading of the other comment seemed to say that the "frequent use" of BMP is permissible and safe. It is neither. It has not proven to be safe for uses that Medtronic illegally marketed, after gaining Pre-Market Approval in 2002 for a sliver of the back surgery maket.
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replied September 16th, 2014
Let me just start by saying that I too had L5-S1 fusion surgery. My surgeon performed mine via TLIF method using Infuse bmp2. I am 10 months post surgery and I am having multiple complications and may have to have revision surgery. During my recent research, I have discovered that Infuse is ONLY allowed by the FDA for use is PLIF fusions of the lumbar spine and NEVER in TLIF procedures and is an OFF LABEL product which means it is not approved by the FDA. From what a local attorney has told me, the surgeons consent form is worthless if legal procedures established by the FDA are not followed. He is the one in position to do the right thing, the right way and for the right reasons and if they are familiar with current medical regulations, they would know that. I understand that they have discretion to do what they feel is right for each patient and procedure, but they are also responsible for explaining the use of an off label product and allow the patient to make that decision. If you research Medtronic Infuse Complaints, you can read through several individual lawsuits, which from what I have found were settled by Medtronic outside of a trial. I wish you the best!
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