Subject: Osteogenic Protein 1 (OP-1)

Date: Tue, 4 Jun 2002 13:24:09 -0700

From: John Ruth

I am interested in the list members experience with OP-1.  I have read the published JBJS tibial nonunion study. As many of you know OP-1 is available for humanitarian use only and has not yet been FDA approved.  I am concerned about the cost, $5000 per use. Is it worth the cost?  Are there payers that will cover this cost? I think it is wrong to expect the hospital to eat this. As surgeons we can usually only bill about half that amount for treatment of the nonunion and are lucky if we get reimbursed half of what we bill. Does anyone find a problem with this.

Reply at: Orthopaedic Trauma Association forum

Date: Wed, 05 Jun 2002 09:30:51 +0000

From: b.meinhard

Third parties will pay with proper documentation, and the company rep will help with paperwork and follow up calls.. Selective use is appropriate... long standing Non union, smoker, multiple failed attempts with autogenous bone grafts, etc. It is probably not for the simple routine case. We are a center permitted to use it for humanitarian purposes and supposedly the company Stryker Biotech, will allow usage for 40,000 cases nationally.


Date: Wed, 05 Jun 2002 08:06:06 -0400

From: William Obremsky


We just got approval to use it and I have used it only once. I would agree w/ Bruce Meinhard on only selective use in "at risk" patients. I used it in a 72yo w/ DM and an open pilon w/ infected nonunion at the metadiaphyseal juct.w/ bone loss, who was close to an amputation. The amount of callus on his 1 month post op xrays was impressive. If this works I am a "believer". The basic science and clinical data have been very good, but so has my clinical use of allograft and Grafton as well as the OTA report (Ziran OTA 2001 paper). The same principles of debridement., stability and coverage still apply. It is expensive. As my chief resident said after we used it, "so we spent $10,000 to stay out of this guys iliac crest." The only other option w/ some of these patients is an Ilizarov and bone transport. Have you looked at that price tag? Stryker is more than willing to help you get approval through your IRB. Is it hot yet in Tucson??


Date: Wed, 05 Jun 2002 11:13:31 -0400

From: J. Tracy Watson

We participated in the OP-1 studies and found that the results were no better than autograft and in fact when the initial study was expanded to include all non-unions our results were not so hot.......3 failures....In light of this data and our experience and the good results we have had using the platelet gel technologies for difficult non-unions. the cost benefit is not there to incur the added expense....and I'm not sure that the insurance co. will cover the additional cost when the data says that it's no better than auto graft...we are taking a wait and see attitude...also the dose response curve of the material is somewhat bothersome with spine reports of HO causing spinal stenosis and soft tissue ossification.....crucial issues that the recombinant materials have yet to give us the precise dosage..... such that you get bone and not uncontrolled bone growth


Date: Wed, 12 Jun 2002 14:08:56 -0400

From: William Obremsky

This is the 70 yo male s/p dedridement and treatment of infected nonunion of plafond fx.

His post op and 2 mos xrays are attached.


2 months post-op

The 2 mos images are encouraging that he is healing.
Is OP-1 worth the cost?
Does a 70 yo has adequate autograft?
Would allograft and another form of BMP worked as well?

These are question I do not have the answer for in this high risk patient.

Any one else have any thoughts?

Bill Obremskey

Date: Thu, 13 Jun 2002 09:37:52 +0000

From: b.meinhard

I have found that there is often enough iliac bone even in an elderly person to provide bone cells, but I have supplemented that autograft with Grafton or equivalent and Allograft to increase the volume. I have used OP 1 in conjunction with the auto graft and also with allograft when the patient has been depleted of his donor sites by previous surgeries. Also especially in elderly patients, it is critical to evaluate their vascular status to be certain that they have adequate perfusion of thel limb to permit adequate oxygenation and healing. Sometimes a vascular procedure can add wonders to our surgical efforts.


Date: Thu, 13 Jun 2002 07:52:06 -0700

From: Chip Routt

Maybe our pilon expert list members/readers can discuss the situation.

Do we like this alignment, rotation, and length?

Any fibular comments?

How did that xray occur? It's like an anti-textbook example. Have we missed a new lecture?

Aren't we supposed to reduce the articular surfaces, stabilize them, then align the limb and stabilize it? Is the talus location OK?

Yeow. Help!

It seems the fracture/clinical situation warrant much more discussion than grafting strategies.

Pilon experts, please share your discussions.

This man has more issues than the price of op-1.



M.L. Chip Routt, Jr.,M.D.
Professor-Orthopedic Surgery
Harborview Medical Center
Seattle, WA 98104-2499

Date: Thu, 13 Jun 2002 11:31:54 -0400

From: James Carr

Chip has made some good observations. If we have proved one thing about pilon fractures, its that its easy to get in trouble, even in the best of hands. One can pick at a number of technical details here - Alignment, joint reduction, fibular reduction. It does appear to be in valgus, and I would think there was interfragmentary opportunity not used. I hope it wasn't a an ex-fix case with suboptimal treatment of the joint initially. Ex fix with optimal joint treatment is OK. I have been referred a number of cases where a "minimal fixation" is performed (crappy joint reduction), and the fracture gets seeded thru an infected pin. Anyway, I would recommend the use of the boneplast (way-over-priced plaster of paris ~500 US dollars per pack). The use is analogous to bone cement beads. These can be loaded with bacteria specific antibiotics, and have done a good job of controlling dead space. And it has formed bone. My initial operative strategy would be to sacrifice some! length for bone apposition, and reduce the dead space. As I read the case, its out a ways and presented as a reconstructive issue of how to deal with the metaphyseal problem.

James B. Carr, MD
Palmetto Health Orthopedics

Date: Mon, 17 Jun 2002 13:35:27 -0600

From: Thomas A. DeCoster

The original (indeed all prior treatment) in this case is unclear although we do know he has a plate on his tibia and has had debridement for infected nonunion. These patients typically suffer more from too much dissection (and wound slough, infection...amputation) rather than too little dissection (imperfect joint reduction).


Date: Tue, 18 Jun 2002 14:07:30 -0400

From: William Obremsky


Your criticisms are always observant and accurate.

This is far from a "home run" case. I took over his care at about 2 weeks post injury. In general I am in favor of initial plating of the fibula to reestablish length , alignment, and rotation, as I would prefer to deal w/ potential complications of minor lateral wound problems vs. malunions ( "Is routine plating of the fibula necessary?" Williams, Marsh, Nepola, et al. JOT 12:16-20, 1998) At 2 weeks I plated his segmental fibula fx, left his ex-fix and did limited exposure joint reconstruction w/ screws. This is the only case I can remember that I could not get the entire articular surface back out to length due to either delayed ORIF of fibula, high energy impaction in osteopenic bone or lack of my skills. I elected to take off the fibular plate to allow shortening of the fibula and reconstruct the ankle mortise complex (like many of the plafond fxs in Marsh, Bonar, Nepola, Decoster, Hurwitz JBJS 77A:1498, 1995) .

Anyone else ever have this prob w/ delayed fibula ORIF?

This guy got into problems w/ a late deep infection at his metadiaphyseal region that required debridement and antibiotic beads. His fixator loosened and I revised to the blade.

I am concerned about the increased valgus as well. Dr. Benirske's suggestion of a fibular IMN is good.

Anyone done this w/ a shortened fibula? It would have required a fibulotomy here to pass the IMN.

Dr. B was also concerned that no lag screw was at the MD junct: This seemed to be more of a segmental defect case w/ minimal bony surfaces to lag together. I intended the blade to be strong enough to bridge the gap until consolidation of the graft. The OP-1 may help w/ this.

These difficult cases are worthy of lots of discussion.
To plate or not to plate the fibula?
Temporary ex fix then internal fixation of joint or ex fix to union and limited joint ORIF?
Ex fix: To bridge or not to bridge the joint?

The OTA is a good forum to consider a prospective multicenter study revisiting internal fixation vs ex fix of plafond fxs as the pendulum is swinging again to internal fixation. like the retrospective review of Pugh, Wolinsky, McAndew and Johnson JOT 47:937, 1999.

This web site is also a great forum to discuss problem cases and issues critically and honestly.

I appreciate the comments of Drs. Routt, Carr and Benirshke.

Bill Obremskey

Date: Fri, 28 Jun 2002 14:04:05 -0400

From: Brown, Sharon

Dr. Obremsky,

I wanted to respond to your questions regarding the OP-1 Implant.

1. Is OP-1 worth the cost?

When OP-1 is utilized with difficult to heal patients, the product is very cost effective. The OP-1 treatment group had an average of 5 previous alternative treatments to achieve a union, including autograft and internal fixation. The average nonunion duration was 17 months. There were a variety of risk factors; 74% were smokers, 67% were comminuted, and 58% were open injuries. Even with this challenging patient population, only 5% of the patients required surgical re-treatment. .

Surgeons have treated over 175 patients so far this year with the OP-1 Implant. The majority of these patients have failed at least one previous surgery and/or have critical size defects, atrophic nonunions, unavailable or poor quality autograft, and risk factors that affect fracture healing.

Most surgeons have agreed the utilization of the OP-1 Implant was justified when the patient heals and the clinical episode has ended. Surgeons have not agreed that the product is cost effective if utilized in hypertrophic nonunions or metaphyseal defects because they feel there are other alternative treatments that will yield the same re-surgery rate.

Cost effectiveness must be viewed on a case-by-case basis. If the surgeon feels he/she can get less than a 5% re-surgery rate with a less expensive alternative treatment, OP-1 is probably not the most cost effective choice. However, if the risk factors, type of nonunion, and lack of viable autograft for the intended purpose bring the patient risk above 5% for re-surgery, it is definitely cost effective.

2. Does a 70 year old have adequate autograft?

Aetna has developed a policy for coverage of the OP-1 Implant. This policy defines autograft is not feasible and includes patients over 65 in that description. However, this is also very patient specific. Concurrent medical conditions and comorbidities that increase the risk of autograft are also taken into consideration.

3. Would autograft and another form of BMP work as well?

The OP-1 Implant provides a therapeutic dose of BMP - 7. There is 3.5 mg of BMP-7 in each implant. DBM's provide BMP's in nanograms. This amount of BMP is at or below the amount found in normal bone, which in nonunion patients, did not yield a union. Furthermore, not one of the DBM's have been studied in a randomized prospective controlled clinical trial.

In critical size defects, surgeons are deciding to utilize void fillers and DBM's as an adjunct to the OP-1 Implant. This seems to be yielding a better radiographic outcome than what was observed in the critical size defects in the OP-1 trial. This may be due to the fact that trial patients were limited to the OP-1 Implant as a stand alone device (total volume 4-8 cc).

A large percentage of the patients that received the OP-1 Implant so far this year had previous surgeries including a combination of allograft, autograft and/or a DBM product. When the OP-1 Implant was the only new addition in the revision surgery, a union was achieved. I am confident that OTA members and other fellowship trained trauma surgeons will be very pleased with the results of the OP-1 Implant. As with any new technology, the clinical results will determine the success of the product. So far the implanting surgeons have been impressed with the early healing on x-ray and the patients positive clinical outcome.

Thank you very much for your interest in the OP-1 Implant.

Sharon Brown
Director, US Sales
Stryker Biotech