NASS COVERAGE POLICY RECOMMENDATIONS

Recombinant
Human Bone
Morphogenetic
Protein (rhBMP-2)
DEFINING APPROPRIATE
COVERAGE POSITIONS

North American Spine Society 7075 Veterans Blvd. Burr Ridge, IL 60527

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 rhBMP-2

12/04/2014

Introduction
North American Spine Society (NASS) coverage policy recommendations are intended to assist payers
and members by proactively defining appropriate coverage positions. Historically, NASS has provided
comment on payer coverage policy upon request. However, in considering coverage policies received by
the organization, NASS believes proactively examining medical evidence and recommending credible
and reasonable positions may be to the benefit of both payers and members in helping achieve
consensus on coverage before it becomes a matter of controversy.
Methodology
The coverage policies put forth by NASS use an evidence-based approach to spinal care when possible.
In the absence of strict evidence-based criteria, policies reflect the multidisciplinary and non-conflicted
experience and expertise of the authors in order to reflect reasonable standard practice indications in
the United States.
To prepare this coverage policy, an extensive literature search of the PubMed, EMBASE, Web of Science,
and Cochrane databases were reviewed.
NASS Coverage Policy Methodology
Scope and Clinical Indications
This coverage policy document addresses the scope and clinical indications for Recombinant human
bone morphogenetic protein-2 (rhBMP-2) in spinal fusion surgeries only. There are other indications for
its use in the appendicular skeleton (e.g. tibial fracture nonunion repair surgery). Those indications are
not addressed in this document.
Based on the available evidence, rhBMP is indicated as an adjunct to spinal fusion in cases in which
other alternatives are either not available or are not likely to lead to successful fusion.
As a clearer picture of the risks and potential for adverse events after rhBMP implantation emerges, a
reassessment of the risk-benefit calculus is required. This will likely be an ongoing process in the future.
For the purpose of determining coverage at the current time, this calculation can be generalized in
several anatomic areas and clinical scenarios in which rhBMP should NOT be used. These include
patients very likely to fuse without rhBMP, most pediatric patients, healthy patients undergoing one
level lumbar fusion procedures, and routine anterior and posterior cervical fusions.

Page 1 of 33
NASS coverage recommendations should not be construed as including all proper methods of care or excluding other acceptable methods of
care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by
the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or
institution. The coverage recommendations do not represent a “standard of care,” nor are they intended as a fixed treatment protocol. It is
anticipated that there will be patients who will require less or more treatment than the average. It is also acknowledged that in atypical cases,
treatment falling outside these criteria will sometimes be necessary. This document should not be seen as prescribing the type, frequency or
duration of intervention. Treatment and accompanying payment should be based on this information in addition to an individual patient’s
needs as well as the doctor’s professional judgment and experience. This document is designed to function as a guide and should not be used
as the sole reason for denial of treatment and services. It is not intended to supersede applicable ethical standards or provisions of law. This is
not a legal document.
© 2014 North American Spine Society. All rights reserved.

 rhBMP-2

12/04/2014

On the other hand, as detailed below, the evidence for continued utilization of rhBMP for spinal fusion
surgery in well-selected patients is supportive. The strength of this evidence varies from level I to level
IV. Specific patient groups likely to benefit from the availability of rhBMP include: patients undergoing
revision fusion for pseudarthrosis; fusion surgery in a compromised graft bed (e.g. prior radiation
therapy); multilevel thoracolumbar fusions, especially long fusions to the sacrum in adult patients
undergoing correction or stabilization of spinal deformity; patients with metabolic or other conditions
increasing their risk for failure with traditional, autogenous bone grafting (e.g. smokers, diabetics,
hypertensive patients, and the elderly); patients in whom autogenous bone is either not available or
simply of too poor quality to be useful (e.g. rheumatoid arthritis patients).
Coverage Recommendation(s)
rhBMP-2 may be considered as an adjunct to spinal fusion for the following diagnoses with qualifying
criteria, when appropriate.
1. Stand-Alone Anterior Lumbar Interbody Fusion (ALIF): in all patient groups except males with a
strong reproductive priority.
2. Posterolateral Lumbar Fusion: in patients at high risk for nonunion with autogenous bone graft
or in those with inadequate or poor quality autogenous bone available. This group includes:
• Revision Posterior Fusion
• Patients with poor quality or unavailable iliac crest autograft (trauma patients
with concomitant pelvic injury, rheumatoid patients, etc.)
• Multilevel surgeries (> 3 levels), particularly those extending to the sacrum or
pelvis
• Elderly patients with osteoporosis
• Previous radiation or other insult to the fusion bed
• Metabolic factors that are likely to interfere with proper autograft
incorporation, such as: smokers, diabetics, patients with hypertension
3. Posterior Lumbar Interbody Fusion (PLIF and TLIF): in patients at high risk for nonunion with
autogenous bone graft or in those with inadequate or poor quality autogenous bone available.
This group includes:
• Revision Posterior Fusion
• Patients with poor quality or unavailable iliac crest autograft (trauma patients
with concomitant pelvic injury, rheumatoid patients, etc.)
• Multilevel surgeries (> 3 levels), particularly those extending to the sacrum or
pelvis
• Elderly patients with osteoporosis
Page 2 of 33
NASS coverage recommendations should not be construed as including all proper methods of care or excluding other acceptable methods of
care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by
the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or
institution. The coverage recommendations do not represent a “standard of care,” nor are they intended as a fixed treatment protocol. It is
anticipated that there will be patients who will require less or more treatment than the average. It is also acknowledged that in atypical cases,
treatment falling outside these criteria will sometimes be necessary. This document should not be seen as prescribing the type, frequency or
duration of intervention. Treatment and accompanying payment should be based on this information in addition to an individual patient’s
needs as well as the doctor’s professional judgment and experience. This document is designed to function as a guide and should not be used
as the sole reason for denial of treatment and services. It is not intended to supersede applicable ethical standards or provisions of law. This is
not a legal document.
© 2014 North American Spine Society. All rights reserved.

 rhBMP-2

12/04/2014

•
•

Previous radiation or other insult to the fusion bed
Metabolic factors that are likely to interfere with proper autograft
incorporation, such as: smokers, diabetics, patients with hypertension

4. Posterior Cervical or Thoracic Fusions
• in pediatric patients at very high risk for fusion failure (e.g. neuromuscular scoliosis,
occipitocervical pathology
• in adult patients at high risk for nonunion, for example, revision surgery
5. Anterior cervical fusion: in patients at high risk for nonunion, for example revision surgery
rhBMP-2 should NOT be considered in cases that do not fulfill the above criteria. Of note, rhBMP-2 is not
indicated in the following scenarios:
•
•
•

Routine anterior and posterior cervical fusion procedures
Single level posterior/posterolateral fusions in healthy adults
Routine pediatric spine fusion procedures (e.g. adolescent idiopathic scoliosis)

Rationale
Background of rhBMP and other Graft Sources: Recombinant human bone morphogenic protein-2
(rhBMP-2) was first identified in 1965 by Marshall Urist and colleagues at UCLA.1 As part of the
transforming growth factor-β (TGF-beta) superfamily of proteins, rhBMPs bind to cell-surface receptors
where they initiate signals that control cell growth, differentiation, and migration. These effects can
powerful induce bone formation.
It took 30 years of careful work with rhBMP dosing and carriers before rhBMP-2 was FDA approved for
use in ALIF surgery. In 2008, it received FDA approval for use in posterolateral spine fusion surgery to
repair pseudarthrosis. That same year, the FDA issued a Public Health notification regarding life
threatening complications associated with anterior cervical implantation of rhBMP. During that time,
competing products such as rhBMP-7 (at one time marketed by Stryker Biotech as OP-1) were also
studied. These agents are no longer commonly available in North America.
The initial studies, now roughly 10 year old, suggested that rhBMP-2 could reliably induce bone
formation with few, if any, device-related adverse events. More recently, a series of potential rhBMPrelated complications have been reported. These complications, in turn, led to a reassessment of the
original data from the Medtronic-sponsored, prospective, randomized FDA Clinical trials.
Page 3 of 33
NASS coverage recommendations should not be construed as including all proper methods of care or excluding other acceptable methods of
care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by
the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or
institution. The coverage recommendations do not represent a “standard of care,” nor are they intended as a fixed treatment protocol. It is
anticipated that there will be patients who will require less or more treatment than the average. It is also acknowledged that in atypical cases,
treatment falling outside these criteria will sometimes be necessary. This document should not be seen as prescribing the type, frequency or
duration of intervention. Treatment and accompanying payment should be based on this information in addition to an individual patient’s
needs as well as the doctor’s professional judgment and experience. This document is designed to function as a guide and should not be used
as the sole reason for denial of treatment and services. It is not intended to supersede applicable ethical standards or provisions of law. This is
not a legal document.
© 2014 North American Spine Society. All rights reserved.

 rhBMP-2

12/04/2014

The June, 2011 special issue of The Spine Journal and the more recent, June 2013, publication of the
YODA studies in the Annals of Internal Medicine have prompted surgeons to reassess their use of
rhBMP-2 in spine fusion procedures. Certainly, the data reveal a number of potential complications and
adverse effects possibly related to rhBMP implantation. On the other hand, in the words of Professors
Eugene Carragee and Daniel Riew, rhBMP is “the most powerful inducer of bone formation available
commercially.” They went on to say that rhBMP “should remain an option for surgeons and wellinformed patients.”2 The real question that remains is in which clinical situations do the potential
benefits of rhBMP outweigh its risks?
To answer this question, a few words about comparable options are required. As a substrate for fusion,
autogenous bone from the iliac crest (ICBG) remains the gold standard. However, while the morbidity of
bone graft harvest continues to be debated, this procedure carries its own risks and post-operative
morbidity.3,4 In their review, Carragee and coworkers concluded that study design features in the
industry sponsored rhBMP trials may have biased results against iliac crest and favored rhBMP.5 In the
YODA trials, this issue is addressed in detail by Fu et al6 and less so by Simmonds et al.7
Sasso and others studied the impact of bone graft harvest in the control patients of the 208 control
patients from the FDA rhBMP ALIF trials.8 These grafts were typically obtained from separate incisions.
At 24 months, 31% of patients still had donor site pain. A fair or poor appearance to the graft site was
noted in 16%. On the other hand, Radcliff and others recently analyzed data from the SPORT Trial
comparing 108 patients fused with ICBG and 246 fused without as part of management of degenerative
spondylolisthesis with stenosis.9 While OR time was higher in the ICBG group, this group also included
more multilevel and lumbosacral fusions. Blood loss, post-operative complications and re-operation
rates were statistically similar. No significant differences in SF-36, ODI, Stenosis Bothersomeness Index,
Low Back Pain Bothersomeness Scale or patient satisfaction were recorded. The authors concluded “our
results are consistent with previous studies that have found no long-term morbidity or worsening in
outcome after iliac crest bone-graft harvest.”
Additionally, there are large patient populations, typically excluded from prospective, randomized
clinical trials, in which autograft volumes are inadequate or are associated with unacceptable healing
rates.10-13 Examples of high risk cases and those cases in which no other, reasonable options exist are:
• No or inadequate volume or poor quality of iliac crest
• Patients at high risk for post-harvest iliac crest fracture
• High pseudarthrosis risk
o Current surgery to treat pseudarthrosis
o Smokers
Page 4 of 33
NASS coverage recommendations should not be construed as including all proper methods of care or excluding other acceptable methods of
care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by
the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or
institution. The coverage recommendations do not represent a “standard of care,” nor are they intended as a fixed treatment protocol. It is
anticipated that there will be patients who will require less or more treatment than the average. It is also acknowledged that in atypical cases,
treatment falling outside these criteria will sometimes be necessary. This document should not be seen as prescribing the type, frequency or
duration of intervention. Treatment and accompanying payment should be based on this information in addition to an individual patient’s
needs as well as the doctor’s professional judgment and experience. This document is designed to function as a guide and should not be used
as the sole reason for denial of treatment and services. It is not intended to supersede applicable ethical standards or provisions of law. This is
not a legal document.
© 2014 North American Spine Society. All rights reserved.

 rhBMP-2

12/04/2014

o
o
o
o

Elderly
Multilevel surgery
Previous radiation
Metabolic disturbance

Aside from autologous bone and rhBMP-2, other materials are commercially available as fusion
substrates. These include allograft bone, demineralized bone matrix (DBM), silicates, and bone marrow
aspirate. Unfortunately, the evidence base for these materials remains limited.14 Currently, there is
endorsed as ICBG or rhBMP extenders rather than as primary fusion substrates.
For example, demineralized bone matrix (DBM) is produced by acid extraction of the mineral
component allograft bone. With the mineral component removed, Type I collagen, non-collagenous
proteins, and rhBMPs are left. This material is thought to be both osteoconductive and, varyingly,
osteoinductive.15,16 While this material is widely available and avoids donor site morbidity, significant
variation in rhBMP concentrations and osteoinduction potential have been demonstrated between
products and various lots of the same product.17-19 At the current time, there is little data supporting
DBM as a stand-alone graft material.20 More typically, the material is used as a graft extender.
In 2011, Abdullah and others performed a review of the literature on the available lumbar fusion
extenders.21 They found that calcium phosphate was most supported and that other adjuncts are either
“supported by smaller bodies of evidence” (e.g. DBM and rhBMP) or “not conclusively or consistently
supported by available clinical studies” (e.g. most others). Previous reviews have found similar, poor
levels of evidence to support graft alternatives and extenders other than rhBMP.22
Below, we review the rhBMP literature by first focusing on the recent YODA studies. Reasonable people
can reach, and have reached, different conclusions. Even the YODA teams from Oregon Health Sciences
University and the University of York reached somewhat different conclusions while examining the same
data sets. Nonetheless, the YODA process has been quite helpful, but is not definitive. These authors
could only analyze the data they had. The initial FDA trial data are also, on average, 10 years old. A
number of more recent studies have reported results of large groups of rhBMP patients with very
different results.
At this point though, the thoughtful surgeon is rebalancing his or her risk benefit calculus in making
recommendations to patients regarding bone graft options in general, and rhBMP implantation in
particular. However, it is the general message of the current coverage recommendation that the most
Page 5 of 33
NASS coverage recommendations should not be construed as including all proper methods of care or excluding other acceptable methods of
care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by
the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or
institution. The coverage recommendations do not represent a “standard of care,” nor are they intended as a fixed treatment protocol. It is
anticipated that there will be patients who will require less or more treatment than the average. It is also acknowledged that in atypical cases,
treatment falling outside these criteria will sometimes be necessary. This document should not be seen as prescribing the type, frequency or
duration of intervention. Treatment and accompanying payment should be based on this information in addition to an individual patient’s
needs as well as the doctor’s professional judgment and experience. This document is designed to function as a guide and should not be used
as the sole reason for denial of treatment and services. It is not intended to supersede applicable ethical standards or provisions of law. This is
not a legal document.
© 2014 North American Spine Society. All rights reserved.

 rhBMP-2

12/04/2014

powerful inducer of bone formation, rhBMP-2, should remain available to surgeons for appropriate
cases.
The YODA Studies: Increasing reports of complications associated with rhBMP utilization in spine led
Eugene Carragee and coworkers to dedicate an entire issue of The Spine Journal to the question about
the relative risks and benefits of this molecule. A “critical review” paper excited a great deal of
attention and debate.5 These questions spurred rhBMP-2’s manufacturer, Medtronic, and it’s COO
Omar Ishrak, to commission Harlan Krumholz, MD and colleagues at the Yale Open Data Access Project
to independently reassess the individual patient data from the original FDA rhBMP trials.
YODA, in turn, commissioned two independent groups of researchers from the University of York in the
UK and the Oregon Health Sciences University to examine the data. Reports from the YODA process
were published in the summer of 2013 in the Annals of Internal Medicine along with a number of
editorials to assist readers in interpreting the data.6,7 Later, North American Spine Society executive
committee members Christopher Bono and Todd Wetzel provided an excellent, neutral review of the
YODA studies.23 This “meta-meta-analysis” has been endorsed by the Board of Directors of the North
American Spine Society.
In comparing methodology, both YODA Groups6,7 utilized individual patient data (IPD) from the
Medtronic sponsored clinical trials. Each also performed a comprehensive systematic review of
published literature using recognized sources (e.g. MEDLINE, EMBASE, Cochrane Library). Their metaanalyses combined data from multiple studies, when statistically appropriate to analyze a larger group
of data than reported in any original single study. The goal of this meta-analysis was to increase the
probability of finding significant differences not apparent in smaller studies. This approach could also
"wash out" erroneous differences, created by small, heterogeneous patient cohorts detected in smaller
studies. Fu et al6 also incorporated internal reports from Medtronic and data from the FDA website.
This group, from Oregon Health Sciences University performed separate meta-analyses for the different
surgical approaches. Simmonds and colleagues combined the data for a single meta-analysis.
These and other data have been reviewed extensively in order to form reasonable conclusions about the
prudent use of and indications for rhBMP-2 for a variety of different spinal procedures. These are
discussed per procedure below. Numbering corresponds to those listed in the “Coverage
Recommendations” section above.
Item 1: Anterior Lumbar Interbody Fusion
Carragee and colleagues5 described a number of adverse events associated with the use of rhBMP-2 in
anterior lumbar interbody fusion (ALIF) surgeries. Specific concerns included osteolysis, device
Page 6 of 33
NASS coverage recommendations should not be construed as including all proper methods of care or excluding other acceptable methods of
care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by
the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or
institution. The coverage recommendations do not represent a “standard of care,” nor are they intended as a fixed treatment protocol. It is
anticipated that there will be patients who will require less or more treatment than the average. It is also acknowledged that in atypical cases,
treatment falling outside these criteria will sometimes be necessary. This document should not be seen as prescribing the type, frequency or
duration of intervention. Treatment and accompanying payment should be based on this information in addition to an individual patient’s
needs as well as the doctor’s professional judgment and experience. This document is designed to function as a guide and should not be used
as the sole reason for denial of treatment and services. It is not intended to supersede applicable ethical standards or provisions of law. This is
not a legal document.
© 2014 North American Spine Society. All rights reserved.

 rhBMP-2

12/04/2014

subsidence, reoperation rates, incidence of retrograde ejaculation and urinary retention, and infections.
As noted in the posterolateral fusion section, the meta-analysis performed by Simmonds et al7 did not
separately analyze adverse events by surgical approach. They concluded that the risk for implantrelated events, retrograde ejaculation, and wound complications were increased by at least 50% in
rhBMP group at or shortly after surgery. Infections, urogenital events, and implant-related adverse
events were also higher in rhBMP group. By 2-years post-operatively, these same adverse events
remained somewhat higher in the rhBMP group. They reported that the risk of retrograde ejaculation
was substantially higher in rhBMP group (odds ratio 4.76).
Fu et al6 did analyze ALIF data independently and noted that, by 4 weeks, the overall risk of adverse
events was lower in the rhBMP group versus ICBG (38% and 45%, respectively). They did find that
retrograde ejaculation, subsidence, and urogenital problems were more common with rhBMP (both at 4
weeks and 24 month follow-up), but the differences were not statistically different (with wide and
overlapping confidence intervals). Fu’s group calculated the relative risk for retrograde ejaculation to be
4.36 at 2 years, a value similar to that reported by Simmonds et al.7
Bono and Wetzel concluded that Simmonds et al7 agree with Carragee et al5 regarding concerns of
retrograde ejaculation, urogenital complications, subsidence, infections, and implant-related adverse
events (if this can be used as a proxy for osteolysis). Fu et al6, though not statistically significant, seem
to corroborate these concerns. Both reviews reported similar relative risks for retrograde ejaculation.
They could offer no resolution on the issue of reoperation rates, as these were not reported in the
YODA reviews.23
While YODA and Carragee analyzed the initial FDA trial data, longer follow-up was reported later from
the same patient cohorts. In 2009, Burkus and others published their 6 year experience with rhBMP-2 in
ALIF surgery.42 As part of an FDA multicenter RCT, 277 patients were enrolled and received either
rhBMP-2 or ICBG. At 6 years, fusion rates were 98% in the rhBMP group. Significant improvements in
ODI and SF-26 scores were achieved by 6 weeks and were sustained at 6 years. A similar author group
had reported good results using rhBMP-2 and allograft bone dowels in ALIF surgery in 79 investigational
patients when compared with 52 patients receiving ICBG.43 That same year, Pradhan and others warned
that the osteolysis associated with allograft interbody grafts was associated with graft resorption,
instability and eventual nonunion.44
When specifically studying the risk of retrograde ejaculation (RE), disparate results have been reported.
Some groups report identical RE rates between stand-alone ALIF with rhBMP and their control groups,
such as artificial disc replacement. For example, one group compared RE rates in 54 patients
Page 7 of 33
NASS coverage recommendations should not be construed as including all proper methods of care or excluding other acceptable methods of
care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by
the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or
institution. The coverage recommendations do not represent a “standard of care,” nor are they intended as a fixed treatment protocol. It is
anticipated that there will be patients who will require less or more treatment than the average. It is also acknowledged that in atypical cases,
treatment falling outside these criteria will sometimes be necessary. This document should not be seen as prescribing the type, frequency or
duration of intervention. Treatment and accompanying payment should be based on this information in addition to an individual patient’s
needs as well as the doctor’s professional judgment and experience. This document is designed to function as a guide and should not be used
as the sole reason for denial of treatment and services. It is not intended to supersede applicable ethical standards or provisions of law. This is
not a legal document.
© 2014 North American Spine Society. All rights reserved.

 rhBMP-2

12/04/2014

undergoing ALIF with rhBMP and 41 patients undergoing ADR.45 The rate was high, but statistically
similar in both groups at 7.4% and 9.8%, respectively. Recently, Lubelski et al examined the rate of
urogenital complications in 110 male patients undergoing ALIF with or without use of rhBMP.46 The
overall rate of complications was similar (22% vs. 20%, p = 1.0) as was the risk of retrograde ejaculation
(8% vs. 8%, respectively; p = 1.0).
In a prospective study evaluating the incidence of RE after ALIF, Tepper and others compared 21
patients treated with rhBMP to 20 patients treated without.47 In the first study of its kind, the authors
utilized not only a standardized questionnaire, but also pre- and post-operative semen and urine
analysis. The rate of RE was not significantly different between groups.
Risks were compared between 207 males undergoing stand-alone ALIF with rhBMP2 versus 301
undergoing the same procedure with iliac crest autograft or a disc arthroplasty.48 Patients had been
enrolled in one of five FDA approved RCTs with a minimum of 2 years of follow-up. RE rates dropped as
trials progressed. In the RE earliest trial, the RE rate was 4.1% versus 0 to 2.1% in the latest trials.
Overall, the RE rate in patients receiving rhBMP was 3.4% versus 1.7% in the non-BMP group. This
difference was not significant (p = 0.242). RE rate was far lower in patients undergoing a retroperitoneal
approach versus those undergoing the transperitoneal approach. This difference was significant (p =
0.007).
The risk of RE was studied retrospectively using a 10 year prospectively gathered outcomes database
from a busy university spine practice.49 All male patients without baseline sexual incapacity and having
ALIF for lumbar spondylosis or spondylolisthesis of the lowest one or two lumbar levels with and
without rhBMP-2, from 2002 through 2011 were divided into one of 4 cohorts based on the use of
rhBMP. Of 239 patients with exposure to rhBMP-2, RE was diagnosed in 15 subjects (6.3%), compared
with an RE diagnosis rate of two of 233 control patients without rhBMP-2 exposure (0.9%; p=.0012).
Urinary retention after bladder catheter removal was also more frequently observed in patients exposed
to rhBMP-2 (9.7%) compared with control patients (4.6%; p=.043). Patients with previous treatment for
prostatic hypertrophy were found to be at increased risk of RE after ALIF with rhBMP. Some studies
reported no RE among their male patients undergoing ALIF with rhBMP.38
At this point, ALIF remains the single, FDA-approved indication for rhBMP-2. While the YODA and other
recent data must be considered when weighing the risks and benefits of this material in a given patient,
rhBMP should remain available to physicians and well-informed patients.
Item 2: Posterolateral Fusion
Page 8 of 33
NASS coverage recommendations should not be construed as including all proper methods of care or excluding other acceptable methods of
care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by
the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or
institution. The coverage recommendations do not represent a “standard of care,” nor are they intended as a fixed treatment protocol. It is
anticipated that there will be patients who will require less or more treatment than the average. It is also acknowledged that in atypical cases,
treatment falling outside these criteria will sometimes be necessary. This document should not be seen as prescribing the type, frequency or
duration of intervention. Treatment and accompanying payment should be based on this information in addition to an individual patient’s
needs as well as the doctor’s professional judgment and experience. This document is designed to function as a guide and should not be used
as the sole reason for denial of treatment and services. It is not intended to supersede applicable ethical standards or provisions of law. This is
not a legal document.
© 2014 North American Spine Society. All rights reserved.

 rhBMP-2

12/04/2014

In their review paper, Carragee et al5 reported a paradoxical effect toward increased leg pain in the
rhBMP-2 group in the early postoperative period. In a small pilot study, when compared to patients
fused with ICBG, the rhBMP groups exhibited higher percentages of ODI failures and leg pain scores. A
higher, 10%, rate of wound complications was also "associated with rhBMP-2 use." In one of the larger
RCTs, Carragee et al concluded that there were "three times as many back and leg pain adverse
events...during the first 3 months."
In their meta-analysis, which was not specific to the posterolateral approach, Simmonds et al7 reported
a mean improvement in leg pain at all-time points. They demonstrate overlapping confidence intervals
for leg pain scores between rhBMP and iliac crest groups. They found that mean back pain scores were
worse in rhBMP group than the iliac crest group in the early postoperative period, with a slightly
overlapping confidence interval. By 3 months, however, back pain was on average better in the rhBMP2 group.
Simmonds et al7 reported that back and leg pain adverse events at or shortly after surgery were
significantly more common with rhBMP than ICBG, with no apparent overlap of the confidence intervals.
Bono and Wetzel note this data seemed “somewhat incongruous” with clinical outcomes data presented
above.23 In their analysis of four key adverse events (implant-related, infection, neurologic, and pain),
over all time periods for all patients, Simmonds and coworkers’ only clear finding increased pain at or
shortly after surgery.
When Fu and coworkers6 reviewed this data, they found no significant difference in overall incidence of
adverse events between rhBMP and iliac crest groups, except in the early postoperative period. Early
after surgery (4 weeks), back and leg pain scores were higher in rhBMP group.
Bono and Wetzel resolved these conclusions by noting that Carragee et al’s concern about leg pain in
the early postop period were substantiated by both YODA reviews.23 The impact of rhBMP on wound
complication rates (which might include infections as reported by Simmonds et al.) remains unclear.7
A number of other studies have examined the role of rhBMP-2 in posterolateral spinal fusion. The
quality of the data varies, but the data is important in that critical patient populations not included in
the Medtronic-sponsored, FDA trials are included.
In a recent, very large study, Glassman and colleagues reported the complication rates from 1037 pts
who underwent posterolateral spine fusion using rhBMP-2.24 Medical and surgical complications were
observed in 190 of the 1037 patients (18.3%). Of those, 81 were major complications (7.8%) and 110
minor complications (10.2%). Of those complications, using a worst case analysis, a 0.6% complication
Page 9 of 33
NASS coverage recommendations should not be construed as including all proper methods of care or excluding other acceptable methods of
care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by
the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or
institution. The coverage recommendations do not represent a “standard of care,” nor are they intended as a fixed treatment protocol. It is
anticipated that there will be patients who will require less or more treatment than the average. It is also acknowledged that in atypical cases,
treatment falling outside these criteria will sometimes be necessary. This document should not be seen as prescribing the type, frequency or
duration of intervention. Treatment and accompanying payment should be based on this information in addition to an individual patient’s
needs as well as the doctor’s professional judgment and experience. This document is designed to function as a guide and should not be used
as the sole reason for denial of treatment and services. It is not intended to supersede applicable ethical standards or provisions of law. This is
not a legal document.
© 2014 North American Spine Society. All rights reserved.

 rhBMP-2

12/04/2014

rate was attributed to rhBMP. Previously, a similar author group reported that rhBMP-2 was a “viable
ICBG replacement” when they compared 52 patients over the age of 60 undergoing posterolateral
lumbar fusion with ICBG with 50 patients undergoing surgery with rhBMP.25 In this series, 16 ICBG and
10 rhBMP patients required revision procedures for persistent symptoms.
Other recent studies have concluded that rhBMP-2 can offer higher fusion rates than autogenous bone
with no or few implant related complications. For example, Park and colleagues compared fusion rates
using ICBG with rhBMP versus rhBMP and local bone in 1 or 2 level posterolateral fusions in 16 and 35
patients, respectively.26 Combining ICBG with rhBMP-2 was associated with a 96.7% fusion rate by 24
months. The fusion rate from local bone with rhBMP was statistically similar. In 2006, Singh and others
compared ICBG alone vs. ICBG with rhBMP in a prospective, case-matched cohort study.27 In their 52
patient study, there were 11 control patients, rhBMP-2 was associated with 30% higher (77 vs. 97%)
fusion rate. No patients exhibited soft tissue ossification, dural ossification or laminar bone regrowth. A
2010 study found that rhBMP2 with allograft and local autograft achieved a 97.2% fusion rate in a
consecutive cohort of 36 patients.9 Acosta and others reported 90% good and excellent satisfaction and
97% fusion rates in a series of 200 consecutive patients undergoing primary lumbar fusion at a mean 2.5
levels.28 The authors concluded that the high patient satisfactions “might be because the morbidity
associated with harvesting ICBG was avoided…”
Dawson and others reported the results of a 56 patient randomized prospective trial comparing ICBG
and rhBMP-2 in single level instrumented posterolateral fusions.29 In this multicenter pilot project,
more than 86% of the enrolled patients completed 24 month follow-up. Significant improvements in
ODI, SF-36 and back and leg VAS pain scores were reported in both groups. There was a trend toward
greater improvement and a higher fusion rate in the rhBMP group. In 2009, Dimar and colleagues
reported the 2 year outcomes of their randomized, prospective study comparing ICBG with rhBMP-2 for
single level posterolateral instrumented lumbar fusions.30 The failure and second surgery rates were
significantly higher (p = 0.011) in the ICBG group because there were 18 nonunions in that group
(compared with 6 in the rhBMP group). In these 463 patients, both groups should similar improvements
in pain and functional outcomes. Use of rhBMP was also associated with shorter OR times and less
blood loss. A subset of these patients had previously been reported with similar results.31
Independent of the merits of rhBMP in one or two level posterolateral fusions in otherwise healthy
patients is the utility of this material in patients at high risk of fusion failure with autogenous bone graft.
Recently, Hoffman et al compared the complications of associated with use of rhBMP2 for posterolateral
spine fusion in younger vs. older patients.32 While older patients had a longer hospital stay, other
complications were similar. Overall, reasonable complication rates were reported: acute seroma
Page 10 of 33
NASS coverage recommendations should not be construed as including all proper methods of care or excluding other acceptable methods of
care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by
the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or
institution. The coverage recommendations do not represent a “standard of care,” nor are they intended as a fixed treatment protocol. It is
anticipated that there will be patients who will require less or more treatment than the average. It is also acknowledged that in atypical cases,
treatment falling outside these criteria will sometimes be necessary. This document should not be seen as prescribing the type, frequency or
duration of intervention. Treatment and accompanying payment should be based on this information in addition to an individual patient’s
needs as well as the doctor’s professional judgment and experience. This document is designed to function as a guide and should not be used
as the sole reason for denial of treatment and services. It is not intended to supersede applicable ethical standards or provisions of law. This is
not a legal document.
© 2014 North American Spine Society. All rights reserved.

 rhBMP-2

12/04/2014

formation requiring decompression, 3.1%, bone overgrowth, 0.8%, infection requiring debridement,
2.3%, and revision fusion for symptomatic nonunion, 3.7%. These same authors had previously
compared rhBMP-2(67.7%), DBM (21.9%) and autograft(10.4%) in 1,398 patients treated over a 7-year
period (2003-2009).33 They reported a statistically similar, but higher incidence of seroma formation in
the rhBMP group (3.2%) than in the DBM or autograft group (2.0 and 1.4%, respectively). Revision
surgery for “clinically significant nonunion” was required in 103 patients (7.4%). These non-unions were
significantly less likely to occur in the rhBMP-2 group, 4.3%, (p<0.001) compared to the DBM or
autograft group (13.1 and 15.2%, respectively).
Lee and colleagues compared fusion rates and time to fusion in patients receiving ICBG versus rhBMP in
posterolateral lumbar fusions.34 They divided their cohort of 195 patients into four groups: ICBG with or
without risk factors for pseudarthrosis and rhBMP2 with or without risk factors. Risk factors included
smoking, hypertension, diabetes, osteoporosis, multilevel surgery, revision surgery and other
comorbidities. With the relatively low per level dose used, rhBMP was associated with more rapid
progression to fusion in all groups. In the no risk factor group, fusion rates were higher in the rhBMP
group while the fusion rate was higher with ICBG in the high risk group. The authors concluded that
“When compared with patients with fusion-related risk factors, the use of rhBMP-2 was comparable
with autograft but was not sufficient to overcome all aspects of the weakened osteoinductive capacity
encountered in patients with these risk factors.”
Glassman and others compared the fusion rates of smokers and non-smokers in single level
posterolateral instrumented fusions.35 Retrospectively analyzing data extracted from the prospective
FDA rhBMP trials, the author reported a fusion rate of 100% in the non-smokers and 95.2% (20 of 21
smokers) using rhBMP-2. They concluded that rhBMP-2 may enhance the fusion rate in smokers.
Clinical outcomes were still adversely affected by smoking, however.
In a group of 55 moderately disabled to bedridden, elderly patients, lumbar decompression and fusion
with rhBMP produced an 85% rate of improved functional and pain scores at a mean 6 months postoperative.36 In this fragile population, no metallic implants were employed, yet an 80% fusion rate was
reported. The initial, pilot study describing the outcomes of rhBMP-2 use for posterolateral fusion
included both instrumented and uninstrumented cases.37 A 100% fusion rate and “Statistically greater
and quicker improvement in patient-derived clinical outcome(s)” were reported.
Another special subgroup of rhBMP fusion cases represents long thoracolumbar fusions, typically
performed for spinal deformity. While a large percentage of these cases are performed as anteriorposterior surgeries, the rhBMP-2 is used posteriorly when adequate volumes of ICBG are not available or
Page 11 of 33
NASS coverage recommendations should not be construed as including all proper methods of care or excluding other acceptable methods of
care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by
the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or
institution. The coverage recommendations do not represent a “standard of care,” nor are they intended as a fixed treatment protocol. It is
anticipated that there will be patients who will require less or more treatment than the average. It is also acknowledged that in atypical cases,
treatment falling outside these criteria will sometimes be necessary. This document should not be seen as prescribing the type, frequency or
duration of intervention. Treatment and accompanying payment should be based on this information in addition to an individual patient’s
needs as well as the doctor’s professional judgment and experience. This document is designed to function as a guide and should not be used
as the sole reason for denial of treatment and services. It is not intended to supersede applicable ethical standards or provisions of law. This is
not a legal document.
© 2014 North American Spine Society. All rights reserved.

 rhBMP-2

12/04/2014

when the presumptive fusion rate with ICBG alone is considered suboptimal. In a group of 502 long
thoracolumbar deformity procedures in which large doses of rhBMP were used, no major radiculopathy
(1%) or seroma (0.6%) problems were noted.38
In 2009, Maeda and colleagues reported compared 32 patients undergoing long thoracolumbar fusion
with ICBG with 23 patients undergoing the same procedure with rhBMP-2 and no ICBG.39 The ICBG
group had a 28.1% pseudarthrosis rate while rhBMP use was associated with a 4.3% pseudarthrosis rate.
Other outcomes were similar between the groups. In 2013, Kim and coworkers compared outcomes
and complications associated with rhBMP2 and ICBG in long thoracolumbar fusions for deformity.12 The
two groups were well matched in terms of age, comorbidities and technical details and included 31
patients received rhBMP while 32 received ICBG. Of note, 8 of the patients in the rhBMP group
underwent posterior only surgery, while all of the patients in the ICBG group underwent formal anteriorposterior surgery. Oswestry Disability Indexes were similar between groups. However, the rhBMP group
demonstrated superior sum composite Scoliosis Research Society scores in pain, self-image and function
domains (P = 0.02). The fusion rates for rhBMP group were 93.5% and 71.9% for the ICBG group.
Previously, Mulconrey and coworkers described a minimum 2 year follow-up of anterior, posterior and
anterior-posterior spine fusions performed with rhBMP-2. They prospectively followed 98 patients who
underwent fusion at a total of 308 levels. The patients were divided into three groups. Their rhBMP
doses ranged from 10mg/level (placed in an anterior titanium mesh cage) to 40mg/level (posterolateral
fusion patients in whom no autologous bone was available. Fusion rates averaged 95% across the
groups with a 100% fusion rate achieved in the posterolateral fusions performed with 40mg
rhBMP/level and no autologous bone.40 Earlier studies from the same center had also shown high fusion
rates with rhBMP-2 in long thoracolumbar deformity surgeries.41
While the YODA and other recent data must be considered when weighing the risks and benefits of this
material in a given patient, rhBMP should remain available to physicians and well-informed patients.
Especially in patients at risk for fusion failure or without adequate volume or quality of autogenous bone
in the iliac crest, rhBMP remains a viable alternative.
Item 3: TLIF and PLIF
In their review, Carragee et al5 cited concerns regarding bone overgrowth into the canal with rhBMP
causing new radiculitis. They reported that, as with ALIF, posterior interbody implantation of rhBMP
could lead to osteolysis with implant subsidence and loss of spinal alignment. Together, these issues
were reported to generate more "clinical failures" when compared to iliac crest bone graft both at 6
weeks and 2 years after surgery. These failures, in turn, led to higher rates of reoperation.
Page 12 of 33
NASS coverage recommendations should not be construed as including all proper methods of care or excluding other acceptable methods of
care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by
the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or
institution. The coverage recommendations do not represent a “standard of care,” nor are they intended as a fixed treatment protocol. It is
anticipated that there will be patients who will require less or more treatment than the average. It is also acknowledged that in atypical cases,
treatment falling outside these criteria will sometimes be necessary. This document should not be seen as prescribing the type, frequency or
duration of intervention. Treatment and accompanying payment should be based on this information in addition to an individual patient’s
needs as well as the doctor’s professional judgment and experience. This document is designed to function as a guide and should not be used
as the sole reason for denial of treatment and services. It is not intended to supersede applicable ethical standards or provisions of law. This is
not a legal document.
© 2014 North American Spine Society. All rights reserved.

 rhBMP-2

12/04/2014

In their assessment of data derived only from published studies and presumably were not specifically
recorded in the IPD or government databases, Simmonds et al7 found limited data concerning other
specific adverse events. In their literature review, on the other hand, heterotopic bone formation and
osteolysis were more common in rhBMP-2 groups in comparative studies.
Fu and colleagues6 did not include a specific meta-analysis of posterior interbody fusion techniques.
They found that no "trial defined radiculitis, and adverse events consistent with possible radiculitis were
variously classified as back and leg pain, neurologic events, or spinal events. Therefore, they were
unable to perform a critical analysis of these complications. In Bono and Wetzel’s assessment, they
noted that, in apparent absence of IPD, Carragee et al5, Simmonds et al7, and Fu et al6 all relied on
limited published data regarding PLIF. The common conclusion, however, was that ectopic bone
formation was much more common when rhBMP is implanted in the disc space from a posterior or
transforaminal approach.23
Other, more recent studies emphasize the evolution in technique and dosing when performing PLIF and
TLIF procedures with rhBMP. Most conclude that complications such as osteolysis and ectopic bone
formation can be minimized by providing a barrier between the rhBMP and the dura, lowering the dose
used and carefully protecting the vertebral endplates. Others have reported excellent results using
rhBMP for MIS and open TLIF/PLIF surgeries.50-52
For example, Crandall and others reviewed their experience using rhBMP-2 in TLIF procedures at 872
levels in 509 consecutive patients.53,54 In a series that include one through four level surgery in patients
with degenerative disease (179), spondylolisthesis (207), and deformity (123), 12% were smokers and
41% had revision surgery. Significant improvements in clinical and functional outcomes were reported
with a 99.08% fusion rate. The authors of this industry-independent study also noted that rhBMPrelated complications (seroma, ectopic bone) were rare.
In 2009, Geibel and others reported a 48 patient series undergoing PLIF procedures with rhBMP-2 at a
total of 59 operative levels.55 In this series with a mean 11.2 month follow-up, thin-slice CT in all
patients demonstrated successful interbody and posterolateral fusion. No canal compromise,
heterotopic bone formation, or adjacent level fusion was reported. Recently, Singh and coworkers
reported retrospectively collected data from a single center’s of minimally invasive transforaminal
lumbar interbody fusion (MIS-TLIF) utilizing rhBMP-2.56 In their series of 573 patients, 1.7% underwent
additional surgery for ectopic bone formation and recalcitrant radiculopathy. The rate of pseudarthrosis
requiring repeat operation was 6.8%.
Page 13 of 33
NASS coverage recommendations should not be construed as including all proper methods of care or excluding other acceptable methods of
care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by
the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or
institution. The coverage recommendations do not represent a “standard of care,” nor are they intended as a fixed treatment protocol. It is
anticipated that there will be patients who will require less or more treatment than the average. It is also acknowledged that in atypical cases,
treatment falling outside these criteria will sometimes be necessary. This document should not be seen as prescribing the type, frequency or
duration of intervention. Treatment and accompanying payment should be based on this information in addition to an individual patient’s
needs as well as the doctor’s professional judgment and experience. This document is designed to function as a guide and should not be used
as the sole reason for denial of treatment and services. It is not intended to supersede applicable ethical standards or provisions of law. This is
not a legal document.
© 2014 North American Spine Society. All rights reserved.

 rhBMP-2

12/04/2014

Others have concluded that the osteolysis and ectopic bone associated with rhBMP use are clinically
silent.57,58 For example, Meisel and others reported osteoclastic activity in a 17 of their patients
undergoing PLIF with 12mg of rhBMP-2 in the cages.59 Despite this, all of the patients fused by 6 months
and there were no cases of cage subsidence or poor clinical outcomes. Others have reported similar
findings.60,61 Similarly, Michielsen and others recently reported the results of a randomized trial in which
20 patients underwent a single level PLIF with rhBMP versus 20 undergoing the same procedure with
autologous bone.62 Clinical outcomes (VAS, ODI, SF-36) were similar between the groups. Osteolysis
and ectopic bone formation were frequently seen in the rhBMP group and were not seen in the
autograft group. That being said, there were no cases of cage subsidence or radiculopathy noted during
the follow-up interval. While fusion rates were ultimately the same, in this study, interestingly, use of
rhBMP2 was associated with slower fusion incorporation.
Other author groups have reached conclusions similar to Carragee et al. For example, Mindea and
coworkers reported an 11.4% rate of new radicular symptoms after TLIF in their 35 MIS TLIF patients in
whom rhBMP had been utilized.63 None of their 8 non-BMP patients exhibited similar symptoms.
Similarly, Rihn and others reported a 14% post-operative radiculitis in their group of 86 patients
undergoing TLIF with rhBMP-2 compared with a 3% risk in their 33 patients undergoing TLIF with ICBG.64
The authors recommended use of a hydrogel sealant which reduced their radiculitis rate to 5.4%. On
the other hand, the autograft group had a higher complication rate (45.5% vs. 29.1%), but the difference
was not statistically significant (p=.09). The non-union rates were 3.0 and 3.5% in the ICBG and rhBMP
groups, respectively. Nearly a third of the ICBG patients had residual donor site pain and there was a
3.1% donor site infection rate.
Recently, Heida et al performed a systematic review of 29 papers meeting their criteria to assess the
impact of different grafting materials on outcomes in TLIF surgery.65 Various types of interbody cages
were assessed as were local autograft, iliac crest autograft, local bone with rhBMP and local with
allograft. Local bone with rhBMP conferred the best Oswestry Disability Index scores and visual pain
scores.
While the YODA and other recent data must be considered when weighing the risks and benefits of this
material in a given patient, rhBMP should remain available to physicians and well informed patients.
Especially in patients at risk for fusion failure or without adequate volume or quality of autogenous bone
in the iliac crest, rhBMP remains a viable alternative.
Item 4: Posterior Cervical or Thoracic Fusions (in adults or children)
Page 14 of 33
NASS coverage recommendations should not be construed as including all proper methods of care or excluding other acceptable methods of
care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by
the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or
institution. The coverage recommendations do not represent a “standard of care,” nor are they intended as a fixed treatment protocol. It is
anticipated that there will be patients who will require less or more treatment than the average. It is also acknowledged that in atypical cases,
treatment falling outside these criteria will sometimes be necessary. This document should not be seen as prescribing the type, frequency or
duration of intervention. Treatment and accompanying payment should be based on this information in addition to an individual patient’s
needs as well as the doctor’s professional judgment and experience. This document is designed to function as a guide and should not be used
as the sole reason for denial of treatment and services. It is not intended to supersede applicable ethical standards or provisions of law. This is
not a legal document.
© 2014 North American Spine Society. All rights reserved.

 rhBMP-2

12/04/2014

There are relatively few high quality studies assessing the risks and benefits of rhBMP-2 utilization in the
posterior cervical spine. In 2012, Hodges and others retrospectively reviewed 29 patients undergoing CT
fusion assessment at least one year after posterior cervical fusion.80 Three (10.3%) of these patients
developed pseudoarthrosis, but none required additional surgery. No adverse events related to rhBMP
use were reported and no evidence of heterotopic bone formation was found. The authors concluded
that rhBMP “can be used safely in posterior cervical spine fusion, but additional larger studies are
recommended.”
In 2009, Crawford et al reported a higher, but not statistically significant, rate of complications
associated with the use of rhBMP-2 for instrumented posterior cervical spine fusions relative to ICBG.81
While the graft material was chosen at the surgeon’s discretion, a consecutive series of 72 patients were
included, of who 41 received rhBMP-2. One patient in the ICBG group required additional surgery at the
bone harvest site. The posterior cervical wound itself required additional surgical management in 14.6%
of the rhBMP and 2.8% of the ICBG patients. Other outcomes were similar between the groups. The
authors concluded that additional studied are needed to clarify the issue and the “determine optimal
dosing and carrier” for usage in the posterior cervical spine. Another study from the same year
evaluated 83 patients undergoing posterior cervical fusion, 67 with ICBG and 16 with rhBMP-2 (dose
1.3mg/level).82 Here, one patient in the rhBMP group had significant neck swelling that improved over 1
week with steroids. The infection rate was 12% in the ICBG group and 0% in the rhBMP group. Other
outcomes were similar.
At this point, NASS feels that the available data do not support routine use of rhBMP-2 in posterior
cervical fusion surgeries.
Use of rhBMP in children remains controversial, and, as with many other uses, off-label. While it would
be easy to decry exposure of this vulnerable patient population to such a potent osteoinductive protein,
there may be occasions in which the benefits outweigh the risks. Certainly, the use of rhBMP for
pediatric spine fusion has increased. In 2013, Jain and others reported a 3.4-fold increase in rhBMP use,
from 2.7% in 2003 to 9.3% in 2009.13 Certain subgroups of patients were more likely to receive rhBMP,
including congenital (versus idiopathic) scoliosis. In 2010, Fahim and others published a 17 month safety
and efficacy study of rhBMP use in children.85 In this relatively small series, CT evaluation and grading of
the fusion was undertaken 3 months after surgery. While no pseudarthroses or loss of correction was
identified, one of 19 patients did exhibit bony overgrowth and restenosis and required reoperation. The
authors concluded that rhBMP-2 safe and efficacious adjunct to posterior spinal fusion in pediatric
patients.
Page 15 of 33
NASS coverage recommendations should not be construed as including all proper methods of care or excluding other acceptable methods of
care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by
the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or
institution. The coverage recommendations do not represent a “standard of care,” nor are they intended as a fixed treatment protocol. It is
anticipated that there will be patients who will require less or more treatment than the average. It is also acknowledged that in atypical cases,
treatment falling outside these criteria will sometimes be necessary. This document should not be seen as prescribing the type, frequency or
duration of intervention. Treatment and accompanying payment should be based on this information in addition to an individual patient’s
needs as well as the doctor’s professional judgment and experience. This document is designed to function as a guide and should not be used
as the sole reason for denial of treatment and services. It is not intended to supersede applicable ethical standards or provisions of law. This is
not a legal document.
© 2014 North American Spine Society. All rights reserved.

 rhBMP-2

12/04/2014

In another recent study of 15 children undergoing spinal fusion with rhBMP, Abd-El-Barr and coworkers
reported three complications, none specifically related to rhBMP (e.g. screw malpositioning).86 Of note,
osseous fusion was achieved in each of these patients despite many having “congenital defects that
historically decrease fusion rate.” Other individual cases of use in salvage procedures have been
described.87
At this point, NASS does not support routine use of rhBMP in skeletally immature patients. On the other
hand, this material should be available for compassionate use in very high risk children.
Item 5: Anterior Cervical Fusion
In their review, Carragee et al5 cited complications associated with rhBMP implantation as part of
anterior cervical fusion procedures. These concerns have not been widely contested and, in fact, were
previously noted by an FDA Public Health Notification in 2008. The YODA reviews did include these
data.
The initial series describing use of rhBMP in the anterior cervical spine reported fusion rates consistently
near 100%, few or no complications.66-70 In 2003, Baskin and coworkers compared the use of rhBMP-2
versus IC autograft in a PRCT of anterior cervical discectomy and fusion procedures.66 All 33 patients
from both groups were fused by 6 months. At 24 months, rhBMP-2 group had significantly better
improvement in neck (P < 0.03) and arm (P < 0.03) pain than autograft. No complications attributable to
rhBMP were reported and those patients receiving rhBMP had avoided statistically significant pain (P <
0.007) from the harvest site at 6 weeks. In 2005, Boakye and colleagues reported outcomes of their
retrospective review of 23 patients in whom rhBMP placed in PEEK cages in anterior cervical discectomy
and fusion procedures.67 In this cohort, 1.05 mg/level of rhBMP-2 in PEEK cages induced solid fusion
with good clinical outcomes and no significant morbidity. Ectopic bone formation was observed in 3
early patients who had received twice the rhBMP dose used later.
By 2006, however, case reports and case series reported adverse events related to anterior cervical
implantation of rhBMP, including airway problems and dysphagia.69,71-73 One of the first of these
reports, by Smucker and coworkers, performed a multivariate analysis and found patients receiving
rhBMP-2 to have a 10.1-fold increase in risk for swelling complications compared to those that did not
receive rhBMP-2.71 That same year, Shields and colleagues retrospectively reviewed 151 ACDF with
rhBMP and Plate patients. They found that 23.2% had suffered complications, including hematoma,
swelling, and dysphagia. They noted that the patients in their series had a three and a half times higher
rhBMP dose than that reported in Baskin et al (2.1 mg rhBMP/level vs 0.6 mg/level).
Page 16 of 33
NASS coverage recommendations should not be construed as including all proper methods of care or excluding other acceptable methods of
care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by
the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or
institution. The coverage recommendations do not represent a “standard of care,” nor are they intended as a fixed treatment protocol. It is
anticipated that there will be patients who will require less or more treatment than the average. It is also acknowledged that in atypical cases,
treatment falling outside these criteria will sometimes be necessary. This document should not be seen as prescribing the type, frequency or
duration of intervention. Treatment and accompanying payment should be based on this information in addition to an individual patient’s
needs as well as the doctor’s professional judgment and experience. This document is designed to function as a guide and should not be used
as the sole reason for denial of treatment and services. It is not intended to supersede applicable ethical standards or provisions of law. This is
not a legal document.
© 2014 North American Spine Society. All rights reserved.

 rhBMP-2

12/04/2014

In two separate papers in 2007, Vaidya and coauthors reported higher dysphagia and graft subsidence
rates in patients receiving rhBMP-2 with allograft for cervical fusion.72,73 In 2008, Buttermann reported
the results of a prospective, non-randomized study in which he compared rhBMP-2 with allograft
against IC autograft in ACDF.74 While both groups exhibited similar clinical improvements, at a dose of
0.9 mg rhBMP/level, 50% of rhBMP group suffered dysphagia compared to 14% autograft. Later that
year, the FDA issued a Black Box Warning of “life threatening complications” associated with use in the
anterior cervical spine.75 Use of rhBMP-2 in the anterior cervical spine dropped thereafter.76
Some authors have continued to argue for its occasional use, citing reasonable complication rates when
lower doses are employed. In one recent study, a relatively small series of patients undergoing anteriorposterior cervical spine surgery, rhBMP was not a predictive factor for the development of postoperative dysphagia.77 Lu and colleagues retrospectively compared dysphagia rates in patients
undergoing multilevel ACDF surgery with or without rhBMP in their cohort of 150 patients.78 The
complication rate was statistically significantly higher in the rhBMP group (13% vs. 8%, p < 0.005). While
dysphagia rates were similar, the rhBMP group’s mean dysphagia severity score was higher.
Interestingly, the severity of dysphagia was similar in patients undergoing 3 and 4 level ACDF. Use of
rhBMP was associated with lower pseudarthrosis rates (0% vs. 16%, p < 0.05). The authors concluded
that “the use of rhBMP-2 appears to reduce the risk of pseudarthrosis. This benefit is most pronounced
in patients who undergo 4-level ACDF and are smokers.”
Klimo and Peele reported osteolysis with loss of sagittal alignment and “a high incidence of bone growth
beyond the core of the PEEK spacer” in their series of 22 patients undergoing ACDF with rhBMP filled
cages.79 While they did not report any clinically significant anterior cervical swelling, they recommended
reservation of rhBMP-2 in the anterior cervical spine only “n those patients who are at greatest risk of
pseudoarthrosis.”
Given the potential for life-threatening complications, it is currently recommended that rhBMP-2 be
used in the anterior cervical spine only in occasional, high-risk patients. In a 2012 editorial, Riew and
Carragee wrote: “While rhBMP can cause catastrophic complications, it is also the most powerful
inducer of bone formation available commercially. We believe that judicious use of appropriate doses, in
special cases, should remain an option for surgeons and well-informed patients.”2
Specific Concerns

Page 17 of 33
NASS coverage recommendations should not be construed as including all proper methods of care or excluding other acceptable methods of
care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by
the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or
institution. The coverage recommendations do not represent a “standard of care,” nor are they intended as a fixed treatment protocol. It is
anticipated that there will be patients who will require less or more treatment than the average. It is also acknowledged that in atypical cases,
treatment falling outside these criteria will sometimes be necessary. This document should not be seen as prescribing the type, frequency or
duration of intervention. Treatment and accompanying payment should be based on this information in addition to an individual patient’s
needs as well as the doctor’s professional judgment and experience. This document is designed to function as a guide and should not be used
as the sole reason for denial of treatment and services. It is not intended to supersede applicable ethical standards or provisions of law. This is
not a legal document.
© 2014 North American Spine Society. All rights reserved.

 rhBMP-2

12/04/2014

Cancer Rates: In their 2011 review, Carragee and others associated implantation of high doses of
rhBMP-2 with an increased risk of cancer.5 They reported a 3.8% rate of new cancers in the rhBMP
group compared to 0.89% in the iliac crest group with minimal overlap of confidence intervals calculated
for two groups. As part of the YODA study, Simmonds and others concluded that cancer "was nearly
twice as common in the rhBMP-2 recipients" with a relative risk of 1.98.7 In their report, the 95%
confidence intervals were wide, ranging from 14% lower to 454% higher. They did not identify different
risk levels based on dosage. Fu and others calculated a relative risk for cancer to be 3.45 in the rhBMP
group as compared to the iliac crest group.6 However, while this difference remained statistically
significant at 24 months, it was no longer significant at 4 years follow-up. They concluded that the
numbers were insufficient to determine if cancer risk dose-dependent. In their review of reviews, Bono
and Wetzel23 noted that Fu et al6 found a stronger association than both Carragee et al5 and Simmonds
et al.7
Since then, a number of studies have examined cancer rates in patients that had previously undergone
spinal fusion with rhBMP. Most of these studies have shown low cancer rates. In a series of 502
consecutive patients from a single center, post-operative cancer prevalence was 3.4%, but did not
increase with dose.38 High doses of rhBMP-2 were used, (mean 115 mg (40-351 mg range)). A recent
retrospective cohort study of Medicare beneficiaries undergoing lumbar fusion studied 146,278 subjects
aged 67 and older who underwent surgery in 2003-2008.83 Of that cohort, 15.1% received rhBMP. At
any overall average follow up of 4.7 years, the rate of new cancers in the rhBMP group was 15.4% versus
17% in those undergoing surgery without rhBMP. rhBMP was also found not to relate to any individual
cancer types.
On the other hand, Carragee et al re-analyzed the data from the FDA AMPLIFY trial of 463 patients.84 At
2 years, with 86% follow-up, there were 15 new cancer events in 11 rhBMP pts versus 2 new cancer
events in 2 pts. The authors calculated an incidence rate of new cancer events per 100 person-years.
The rhBMP-2 group this was 3.37 (95% CI, 1.89 to 5.56) versus 0.50 (95% CI, 0.06 to 1.80) in the ICBG
control.
At this point, it appears there may be a small, but significant increase in cancer risk after implantation of
rhBMP-2. Perhaps the material should be avoided in patients at high risk for cancer. In others,
however, the risk of treatment failure after spinal fusion leads us to conclude that the benefits of rhBMP
outweigh this risk.
Economics: A number of studies have examined the costs and benefits of rhBMP-2 implantation from
both medical and societal perspectives. In 2009, Alt and others examined the economic impact of
rhBMP-2 in lumbar fusion surgery in Germany, France, and the United Kingdom.88 They found that,
Page 18 of 33
NASS coverage recommendations should not be construed as including all proper methods of care or excluding other acceptable methods of
care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by
the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or
institution. The coverage recommendations do not represent a “standard of care,” nor are they intended as a fixed treatment protocol. It is
anticipated that there will be patients who will require less or more treatment than the average. It is also acknowledged that in atypical cases,
treatment falling outside these criteria will sometimes be necessary. This document should not be seen as prescribing the type, frequency or
duration of intervention. Treatment and accompanying payment should be based on this information in addition to an individual patient’s
needs as well as the doctor’s professional judgment and experience. This document is designed to function as a guide and should not be used
as the sole reason for denial of treatment and services. It is not intended to supersede applicable ethical standards or provisions of law. This is
not a legal document.
© 2014 North American Spine Society. All rights reserved.

 rhBMP-2

12/04/2014

despite rhBMP’s higher initial price (2,266 to 2,970 Euros) long term costs were 8,483 to 9,191 Euros per
case due to faster return to work time.
Carreon and others performed a cost-utility study comparing rhBMP-2 and ICBG in lumbar fusion
patients over age 60.89 “A dedicated hospital coder and research nurse tracked each patient to
determine direct costs of inpatient care and all postoperative healthcare encounters up to 2 years after
surgery. Preoperative and 2-year-postoperative SF-6D utility scores for each patient were determined.”
The study found that: “The mean total 2-year cost for care (excluding complication and additional spine
treatment costs) was $34,235 in the ICBG group and $36,530 in the rhBMP-2/ACS group. For the entire
group, the mean cost to treat a major complication was $10,888, the cost of revision surgery for
nonunion was $46,852, and additional treatment for spine-related events was $5892. In the ICBG group,
8 patients had complications; 20 had additional interventions, 5 of whom required revision for
nonunion. In the rhBMP-2/ACS group, 6 patients had complications, 10 had additional interventions, and
1 required revision for nonunion. The cost of using rhBMP-2/ACS was $39,967 with a 0.11 mean
improvement in SF-6D; and for ICBG the cost was $42,286 with a mean improvement of 0.10 in SF-6D.”
The authors concluded that the increased rate of complications associated with ICBG actually accounted
for its higher 2 year cost for care over rhBMP-2.
In 2003, Polly and others performed a cost analysis of rhBMP vs ICBG in a single level ALIF.90 Using an
economic model “developed from clinical trial data, peer-reviewed literature, and clinical expert
opinion,” the authors concluded that “the upfront price of bone morphogenetic protein ($3380) is likely
to be offset to a significant extent by reductions in the use of other medical resources, particularly if
costs incurred during the 2 year period following the index hospitalization are taken into account.”
Several less favorable studies have recently been published. One recent study detailed the costs
associated with complications of rhBMP use such as osteolysis and cage migration ($19,224 per patient),
neuroforaminal bone growth $14,785, and pseudarthrosis, $20,267).56 In 2007, Garrison and others
performed a systematic review of existing RCTs to identify the costs per QALY associated with utilization
of rhBMP-2 in various fracture repair and spine fusion surgeries for the British National Health.91 Based
on their estimates and indirect data, the estimated incremental cost per QALY gained was about
£120,390.”
Technical Improvements: It appears that many of the problems reported after rhBMP implantations
arise from two related factors. First, this material is labeled as an implant and surgeons previously use it
that way. In truth, rhBMP is a drug. It is a powerful molecule capable of both strongly inducing bone
formation, but also inducing a strong inflammatory reaction in surrounding tissue, stimulation of
osteolysis and ectopic bone formation.
Page 19 of 33
NASS coverage recommendations should not be construed as including all proper methods of care or excluding other acceptable methods of
care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by
the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or
institution. The coverage recommendations do not represent a “standard of care,” nor are they intended as a fixed treatment protocol. It is
anticipated that there will be patients who will require less or more treatment than the average. It is also acknowledged that in atypical cases,
treatment falling outside these criteria will sometimes be necessary. This document should not be seen as prescribing the type, frequency or
duration of intervention. Treatment and accompanying payment should be based on this information in addition to an individual patient’s
needs as well as the doctor’s professional judgment and experience. This document is designed to function as a guide and should not be used
as the sole reason for denial of treatment and services. It is not intended to supersede applicable ethical standards or provisions of law. This is
not a legal document.
© 2014 North American Spine Society. All rights reserved.

 rhBMP-2

12/04/2014

It’s possible that the few adverse events reported in the initial rhBMP series led to a skewed
understanding of the real risk-benefit ratio of rhBMP. This view, in turn, may have prompted a laissez
faire attitude. As a drug, careful attention to dosing and carrier is required. Unfortunately, the
utilization of rhBMP “off-label” limited the ability of the manufacturer and others to educate surgeons
on proper dosing, containment, and carrier options. This left many surgeons to “reinvent the wheel” in
their own practices.
Since the FDA trials, a number of changes to routine surgeon practices have occurred. These practices,
including modified rhBMP dosing, use of barrier materials between the rhBMP and the dura, careful
endplate preparation, and, perhaps, improved carrier materials are reported to decrease adverse
events.55,91 Even in anterior cervical spine applications, several authors have reported safer
implantation of rhBMP-2 by decreasing the dose to 0.4-0.7mg per level, containing the rhBMP with DBM
putty or fibrin glue, and adding 20–40 mg of methylprednisolone in wound before closure.2,70,92,93
In posterolateral fusions for deformity, on the other hand, the pseudarthrosis rate essentially dropped
to zero when the per-level rhBMP dose was above 5mg. In ALIF surgery, decreased rhBMP dose was
associated with decreased RE rates.48
Crandall and coworkers recently reported lost rhBMP related complications (0.4% seroma, 0.6% ectopic
bone growth and no cases of symptomatic osteolysis or cage subsidence.54 They recommended
backfilling the disc space with local autograft. Mannion et al, reported that very low dose rhBMP (1.4
mg/level) reduced but did not completely eliminate complications of its usage such as perineural cyst
formation and heterotopic ossification.
Typically, rhBMP-2 is implanted in the spine after soaking onto a type I collage sponge. Compression
resistant, often ceramic, matrices have been tested but the failure to gain FDA approval of posterior
applications has limited their marketing for this purpose.94,95 Others have reported new carriers, such as
microbeads, to contain the rhBMP and decrease soft tissue complications.96

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Page 20 of 33

NASS coverage recommendations should not be construed as including all proper methods of care or excluding other acceptable methods of
care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by
the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or
institution. The coverage recommendations do not represent a “standard of care,” nor are they intended as a fixed treatment protocol. It is
anticipated that there will be patients who will require less or more treatment than the average. It is also acknowledged that in atypical cases,
treatment falling outside these criteria will sometimes be necessary. This document should not be seen as prescribing the type, frequency or
duration of intervention. Treatment and accompanying payment should be based on this information in addition to an individual patient’s
needs as well as the doctor’s professional judgment and experience. This document is designed to function as a guide and should not be used
as the sole reason for denial of treatment and services. It is not intended to supersede applicable ethical standards or provisions of law. This is
not a legal document.
© 2014 North American Spine Society. All rights reserved.

 rhBMP-2

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Page 21 of 33

NASS coverage recommendations should not be construed as including all proper methods of care or excluding other acceptable methods of
care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by
the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or
institution. The coverage recommendations do not represent a “standard of care,” nor are they intended as a fixed treatment protocol. It is
anticipated that there will be patients who will require less or more treatment than the average. It is also acknowledged that in atypical cases,
treatment falling outside these criteria will sometimes be necessary. This document should not be seen as prescribing the type, frequency or
duration of intervention. Treatment and accompanying payment should be based on this information in addition to an individual patient’s
needs as well as the doctor’s professional judgment and experience. This document is designed to function as a guide and should not be used
as the sole reason for denial of treatment and services. It is not intended to supersede applicable ethical standards or provisions of law. This is
not a legal document.
© 2014 North American Spine Society. All rights reserved.

 rhBMP-2

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Page 22 of 33

NASS coverage recommendations should not be construed as including all proper methods of care or excluding other acceptable methods of
care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by
the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or
institution. The coverage recommendations do not represent a “standard of care,” nor are they intended as a fixed treatment protocol. It is
anticipated that there will be patients who will require less or more treatment than the average. It is also acknowledged that in atypical cases,
treatment falling outside these criteria will sometimes be necessary. This document should not be seen as prescribing the type, frequency or
duration of intervention. Treatment and accompanying payment should be based on this information in addition to an individual patient’s
needs as well as the doctor’s professional judgment and experience. This document is designed to function as a guide and should not be used
as the sole reason for denial of treatment and services. It is not intended to supersede applicable ethical standards or provisions of law. This is
not a legal document.
© 2014 North American Spine Society. All rights reserved.

 rhBMP-2

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Page 23 of 33

NASS coverage recommendations should not be construed as including all proper methods of care or excluding other acceptable methods of
care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by
the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or
institution. The coverage recommendations do not represent a “standard of care,” nor are they intended as a fixed treatment protocol. It is
anticipated that there will be patients who will require less or more treatment than the average. It is also acknowledged that in atypical cases,
treatment falling outside these criteria will sometimes be necessary. This document should not be seen as prescribing the type, frequency or
duration of intervention. Treatment and accompanying payment should be based on this information in addition to an individual patient’s
needs as well as the doctor’s professional judgment and experience. This document is designed to function as a guide and should not be used
as the sole reason for denial of treatment and services. It is not intended to supersede applicable ethical standards or provisions of law. This is
not a legal document.
© 2014 North American Spine Society. All rights reserved.

 rhBMP-2

42.
43.
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45.
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Burkus JK, Gornet MF, Schuler TC, Kleeman TJ, Zdeblick TA. Six-year outcomes of anterior
lumbar interbody arthrodesis with use of interbody fusion cages and recombinant human bone
morphogenetic protein-2. J Bone Joint Surg Am. May 2009;91(5):1181-1189.
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allograft interbody constructs in comparison with autograft. Spine (Phila Pa 1976). Apr 1
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Pradhan BB, Bae HW, Dawson EG, Patel VV, Delamarter RB. Graft resorption with the use of
bone morphogenetic protein: lessons from anterior lumbar interbody fusion using femoral ring
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Lindley EM, McBeth ZL, Henry SE, et al. Retrograde ejaculation after anterior lumbar spine
surgery. Spine (Phila Pa 1976). Sep 15 2012;37(20):1785-1789.
Lubelski D, Abdullah KG, Nowacki AS, et al. Urological complications following use of
recombinant human bone morphogenetic protein-2 in anterior lumbar interbody fusion:
presented at the 2012 Joint Spine Section Meeting: clinical article. J Neurosurg Spine. Feb
2013;18(2):126-131.
Tepper G, Rabbani R, Yousefzadeh M, Prince D. Quantitative assessment of retrograde
ejaculation using semen analysis, comparison with a standardized qualitative questionnaire, and
investigating the impact of rhBMP-2. Spine (Phila Pa 1976). May 1 2013;38(10):841-845.
Burkus JK, Dryer RF, Peloza JH. Retrograde ejaculation following single-level anterior lumbar
surgery with or without recombinant human bone morphogenetic protein-2 in 5 randomized
controlled trials: clinical article. J Neurosurg Spine. Feb 2013;18(2):112-121.
Comer GC, Smith MW, Hurwitz EL, Mitsunaga KA, Kessler R, Carragee EJ. Retrograde ejaculation
after anterior lumbar interbody fusion with and without bone morphogenetic protein-2
augmentation: a 10-year cohort controlled study. Spine J. Oct 2012;12(10):881-890.
Anand N, Hamilton JF, Perri B, Miraliakbar H, Goldstein T. Cantilever TLIF with structural allograft
and RhBMP2 for correction and maintenance of segmental sagittal lordosis: long-term clinical,
radiographic, and functional outcome. Spine (Phila Pa 1976). Sep 15 2006;31(20):E748-753.
Schwender JD, Holly LT, Rouben DP, Foley KT. Minimally invasive transforaminal lumbar
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recombinant human bone morphogenetic protein type 2 with cylindrical interbody cages. Spine
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Crandall DG, Revella J, Patterson J, Huish E, Chang M, McLemore R. Transforaminal lumbar
interbody fusion with rhBMP-2 in spinal deformity, spondylolisthesis, and degenerative disease-Page 24 of 33

NASS coverage recommendations should not be construed as including all proper methods of care or excluding other acceptable methods of
care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by
the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or
institution. The coverage recommendations do not represent a “standard of care,” nor are they intended as a fixed treatment protocol. It is
anticipated that there will be patients who will require less or more treatment than the average. It is also acknowledged that in atypical cases,
treatment falling outside these criteria will sometimes be necessary. This document should not be seen as prescribing the type, frequency or
duration of intervention. Treatment and accompanying payment should be based on this information in addition to an individual patient’s
needs as well as the doctor’s professional judgment and experience. This document is designed to function as a guide and should not be used
as the sole reason for denial of treatment and services. It is not intended to supersede applicable ethical standards or provisions of law. This is
not a legal document.
© 2014 North American Spine Society. All rights reserved.

 rhBMP-2

54.

55.
56.
57.
58.

59.
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62.
63.
64.

12/04/2014

part 1: Large series diagnosis related outcomes and complications with 2- to 9-year follow-up.
Spine (Phila Pa 1976). Jun 1 2013;38(13):1128-1136.
Crandall DG, Revella J, Patterson J, Huish E, Chang M, McLemore R. Transforaminal lumbar
interbody fusion with rhBMP-2 in spinal deformity, spondylolisthesis, and degenerative disease-part 2: rhBMP dosage-related complications and long-term outcomes in 509 patients. Spine
(Phila Pa 1976). Jun 1 2013;38(13):1137-1145.
Geibel PT, Boyd DL, Slabisak V. The use of recombinant human bone morphogenic protein in
posterior interbody fusions of the lumbar spine: a clinical series. J Spinal Disord Tech. Jul
2009;22(5):315-320.
Singh K, Nandyala SV, Marquez-Lara A, et al. Clinical sequelae after rhBMP-2 use in a minimally
invasive transforaminal lumbar interbody fusion. Spine J. Sep 2013;13(9):1118-1125.
Joseph V, Rampersaud YR. Heterotopic bone formation with the use of rhBMP2 in posterior
minimal access interbody fusion: a CT analysis. Spine (Phila Pa 1976). Dec 1 2007;32(25):28852890.
Mummaneni PV, Pan J, Haid RW, Rodts GE. Contribution of recombinant human bone
morphogenetic protein-2 to the rapid creation of interbody fusion when used in transforaminal
lumbar interbody fusion: a preliminary report. Invited submission from the Joint Section
Meeting on Disorders of the Spine and Peripheral Nerves, March 2004. J Neurosurg Spine. Jul
2004;1(1):19-23.
Meisel HJ, Schnoring M, Hohaus C, et al. Posterior lumbar interbody fusion using rhBMP-2. Eur
Spine J. Dec 2008;17(12):1735-1744.
Lewandrowski KU, Nanson C, Calderon R. Vertebral osteolysis after posterior interbody lumbar
fusion with recombinant human bone morphogenetic protein 2: a report of five cases. Spine J.
Sep-Oct 2007;7(5):609-614.
McClellan JW, Mulconrey DS, Forbes RJ, Fullmer N. Vertebral bone resorption after
transforaminal lumbar interbody fusion with bone morphogenetic protein (rhBMP-2). J Spinal
Disord Tech. Oct 2006;19(7):483-486.
Michielsen J, Sys J, Rigaux A, Bertrand C. The effect of recombinant human bone morphogenetic
protein-2 in single-level posterior lumbar interbody arthrodesis. J Bone Joint Surg Am. May 15
2013;95(10):873-880.
Mindea SA, Shih P, Song JK. Recombinant human bone morphogenetic protein-2-induced
radiculitis in elective minimally invasive transforaminal lumbar interbody fusions: a series
review. Spine (Phila Pa 1976). Jun 15 2009;34(14):1480-1484; discussion 1485.
Rihn JA, Patel R, Makda J, et al. Complications associated with single-level transforaminal lumbar
interbody fusion. Spine J. Aug 2009;9(8):623-629.
Page 25 of 33

NASS coverage recommendations should not be construed as including all proper methods of care or excluding other acceptable methods of
care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by
the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or
institution. The coverage recommendations do not represent a “standard of care,” nor are they intended as a fixed treatment protocol. It is
anticipated that there will be patients who will require less or more treatment than the average. It is also acknowledged that in atypical cases,
treatment falling outside these criteria will sometimes be necessary. This document should not be seen as prescribing the type, frequency or
duration of intervention. Treatment and accompanying payment should be based on this information in addition to an individual patient’s
needs as well as the doctor’s professional judgment and experience. This document is designed to function as a guide and should not be used
as the sole reason for denial of treatment and services. It is not intended to supersede applicable ethical standards or provisions of law. This is
not a legal document.
© 2014 North American Spine Society. All rights reserved.

 rhBMP-2

65.
66.

67.
68.
69.
70.
71.
72.
73.
74.
75.

12/04/2014

Heida K, Jr., Ebraheim M, Siddiqui S, Liu J. Effects on clinical outcomes of grafts and spacers used
in transforaminal lumbar interbody fusion: a critical review. Orthop Surg. Feb 2013;5(1):13-17.
Baskin DS, Ryan P, Sonntag V, Westmark R, Widmayer MA. A prospective, randomized,
controlled cervical fusion study using recombinant human bone morphogenetic protein-2 with
the CORNERSTONE-SR allograft ring and the ATLANTIS anterior cervical plate. Spine (Phila Pa
1976). Jun 15 2003;28(12):1219-1224; discussion 1225.
Boakye M, Mummaneni PV, Garrett M, Rodts G, Haid R. Anterior cervical discectomy and fusion
involving a polyetheretherketone spacer and bone morphogenetic protein. J Neurosurg Spine.
May 2005;2(5):521-525.
Lanman TH, Hopkins TJ. Early findings in a pilot study of anterior cervical interbody fusion in
which recombinant human bone morphogenetic protein-2 was used with poly(L-lactide-co-D,Llactide) bioabsorbable implants. Neurosurg Focus. Mar 15 2004;16(3):E6.
Shields LB, Raque GH, Glassman SD, et al. Adverse effects associated with high-dose
recombinant human bone morphogenetic protein-2 use in anterior cervical spine fusion. Spine
(Phila Pa 1976). Mar 1 2006;31(5):542-547.
Tumialan LM, Pan J, Rodts GE, Mummaneni PV. The safety and efficacy of anterior cervical
discectomy and fusion with polyetheretherketone spacer and recombinant human bone
morphogenetic protein-2: a review of 200 patients. J Neurosurg Spine. Jun 2008;8(6):529-535.
Smucker JD, Rhee JM, Singh K, Yoon ST, Heller JG. Increased swelling complications associated
with off-label usage of rhBMP-2 in the anterior cervical spine. Spine (Phila Pa 1976). Nov 15
2006;31(24):2813-2819.
Vaidya R, Carp J, Sethi A, Bartol S, Craig J, Les CM. Complications of anterior cervical discectomy
and fusion using recombinant human bone morphogenetic protein-2. Eur Spine J. Aug
2007;16(8):1257-1265.
Vaidya R, Weir R, Sethi A, Meisterling S, Hakeos W, Wybo CD. Interbody fusion with allograft and
rhBMP-2 leads to consistent fusion but early subsidence. J Bone Joint Surg Br. Mar
2007;89(3):342-345.
Buttermann GR. Prospective nonrandomized comparison of an allograft with bone morphogenic
protein versus an iliac-crest autograft in anterior cervical discectomy and fusion. Spine J. MayJun 2008;8(3):426-435.
Schultz D. FDA public health notification: Life-threatening complications associated with
recombinant human bone morphogenetic protein in cervical spine fusion. 2008;
http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/PublicHealthNotifications/ucm06
2000.htm. Available at. Accessed October 10, 2013.

Page 26 of 33
NASS coverage recommendations should not be construed as including all proper methods of care or excluding other acceptable methods of
care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by
the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or
institution. The coverage recommendations do not represent a “standard of care,” nor are they intended as a fixed treatment protocol. It is
anticipated that there will be patients who will require less or more treatment than the average. It is also acknowledged that in atypical cases,
treatment falling outside these criteria will sometimes be necessary. This document should not be seen as prescribing the type, frequency or
duration of intervention. Treatment and accompanying payment should be based on this information in addition to an individual patient’s
needs as well as the doctor’s professional judgment and experience. This document is designed to function as a guide and should not be used
as the sole reason for denial of treatment and services. It is not intended to supersede applicable ethical standards or provisions of law. This is
not a legal document.
© 2014 North American Spine Society. All rights reserved.

 rhBMP-2

76.
77.
78.
79.
80.
81.

82.
83.
84.
85.

86.
87.
88.

12/04/2014

Fineberg SJ, Ahmadinia K, Oglesby M, Patel AA, Singh K. Hospital outcomes and complications of
anterior and posterior cervical fusion with bone morphogenetic protein. Spine (Phila Pa 1976).
Jul 1 2013;38(15):1304-1309.
Chen CJ, Saulle D, Fu KM, Smith JS, Shaffrey CI. Dysphagia following combined anterior-posterior
cervical spine surgeries. J Neurosurg Spine. Sep 2013;19(3):279-287.
Lu DC, Tumialan LM, Chou D. Multilevel anterior cervical discectomy and fusion with and
without rhBMP-2: a comparison of dysphagia rates and outcomes in 150 patients. J Neurosurg
Spine. Jan 2013;18(1):43-49.
Klimo P, Jr., Peelle MW. Use of polyetheretherketone spacer and recombinant human bone
morphogenetic protein-2 in the cervical spine: a radiographic analysis. Spine J. Dec
2009;9(12):959-966.
Hodges SD, Eck JC, Newton D. Retrospective study of posterior cervical fusions with rhBMP-2.
Orthopedics. Jun 2012;35(6):e895-898.
Crawford CH, 3rd, Carreon LY, McGinnis MD, Campbell MJ, Glassman SD. Perioperative
complications of recombinant human bone morphogenetic protein-2 on an absorbable collagen
sponge versus iliac crest bone graft for posterior cervical arthrodesis. Spine (Phila Pa 1976). Jun
1 2009;34(13):1390-1394.
Hiremath GK, Steinmetz MP, Krishnaney AA. Is it safe to use recombinant human bone
morphogenetic protein in posterior cervical fusion? Spine (Phila Pa 1976). Apr 20
2009;34(9):885-889.
Cooper GS, Kou TD. Risk of Cancer Following Lumbar Fusion Surgery with Recombinant Human
Bone Morphogenic Protein-2 (rh-BMP-2). Spine (Phila Pa 1976). Jul 23 2013.
Carragee EJ, Chu G, Rohatgi R, et al. Cancer risk after use of recombinant bone morphogenetic
protein-2 for spinal arthrodesis. J Bone Joint Surg Am. Sep 4 2013;95(17):1537-1545.
Fahim DK, Whitehead WE, Curry DJ, Dauser RC, Luerssen TG, Jea A. Routine use of recombinant
human bone morphogenetic protein-2 in posterior fusions of the pediatric spine: safety profile
and efficacy in the early postoperative period. Neurosurgery. Nov 2010;67(5):1195-1204;
discussion 1204.
Abd-El-Barr MM, Cox JB, Antonucci MU, Bennett J, Murad GJ, Pincus DW. Recombinant human
bone morphogenetic protein-2 as an adjunct for spine fusion in a pediatric population. Pediatr
Neurosurg. 2011;47(4):266-271.
Lu DC, Sun PP. Bone morphogenetic protein for salvage fusion in an infant with Down syndrome
and craniovertebral instability. Case report. J Neurosurg. Jun 2007;106(6 Suppl):480-483.
Alt V, Chhabra A, Franke J, Cuche M, Schnettler R, Le Huec JC. An economic analysis of using
rhBMP-2 for lumbar fusion in Germany, France and UK from a societal perspective. Eur Spine J.
Jun 2009;18(6):800-806.
Page 27 of 33

NASS coverage recommendations should not be construed as including all proper methods of care or excluding other acceptable methods of
care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by
the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or
institution. The coverage recommendations do not represent a “standard of care,” nor are they intended as a fixed treatment protocol. It is
anticipated that there will be patients who will require less or more treatment than the average. It is also acknowledged that in atypical cases,
treatment falling outside these criteria will sometimes be necessary. This document should not be seen as prescribing the type, frequency or
duration of intervention. Treatment and accompanying payment should be based on this information in addition to an individual patient’s
needs as well as the doctor’s professional judgment and experience. This document is designed to function as a guide and should not be used
as the sole reason for denial of treatment and services. It is not intended to supersede applicable ethical standards or provisions of law. This is
not a legal document.
© 2014 North American Spine Society. All rights reserved.

 rhBMP-2

89.
90.
91.
92.
93.
94.
95.
96.

12/04/2014

Carreon LY, Glassman SD, Djurasovic M, et al. RhBMP-2 versus iliac crest bone graft for lumbar
spine fusion in patients over 60 years of age: a cost-utility study. Spine (Phila Pa 1976). Feb 1
2009;34(3):238-243.
Polly DW, Jr., Ackerman SJ, Shaffrey CI, et al. A cost analysis of bone morphogenetic protein
versus autogenous iliac crest bone graft in single-level anterior lumbar fusion. Orthopedics. Oct
2003;26(10):1027-1037.
Garrison KR, Donell S, Ryder J, et al. Clinical effectiveness and cost-effectiveness of bone
morphogenetic proteins in the non-healing of fractures and spinal fusion: a systematic review.
Health Technol Assess. Aug 2007;11(30):1-150, iii-iv.
Dickerman RD, Reynolds AS, Morgan BC, Tompkins J, Cattorini J, Bennett M. rh-BMP-2 can be
used safely in the cervical spine: dose and containment are the keys! Spine J. Jul-Aug
2007;7(4):508-509.
Patel VV, Zhao L, Wong P, et al. An in vitro and in vivo analysis of fibrin glue use to control bone
morphogenetic protein diffusion and bone morphogenetic protein-stimulated bone growth.
Spine J. Jul-Aug 2006;6(4):397-403; discussion 404.
Minamide A, Kawakami M, Hashizume H, Sakata R, Tamaki T. Evaluation of carriers of bone
morphogenetic protein for spinal fusion. Spine (Phila Pa 1976). Apr 15 2001;26(8):933-939.
Minamide A, Kawakami M, Hashizume H, Sakata R, Yoshida M, Tamaki T. Experimental study of
carriers of bone morphogenetic protein used for spinal fusion. J Orthop Sci. 2004;9(2):142-151.
Abbah SA, Liu J, Goh JC, Wong HK. Enhanced control of in vivo bone formation with surface
functionalized alginate microbeads incorporating heparin and human bone morphogenetic
protein-2. Tissue Eng Part A. Feb 2013;19(3-4):350-359.

Authors
NASS Coverage Committee
Chair: Christopher Bono, MD
Members:
Jamie Baisden, MD
Ray Baker, MD
Ashok Biyani, MD
Maxwell Boakye, MD
Page 28 of 33
NASS coverage recommendations should not be construed as including all proper methods of care or excluding other acceptable methods of
care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by
the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or
institution. The coverage recommendations do not represent a “standard of care,” nor are they intended as a fixed treatment protocol. It is
anticipated that there will be patients who will require less or more treatment than the average. It is also acknowledged that in atypical cases,
treatment falling outside these criteria will sometimes be necessary. This document should not be seen as prescribing the type, frequency or
duration of intervention. Treatment and accompanying payment should be based on this information in addition to an individual patient’s
needs as well as the doctor’s professional judgment and experience. This document is designed to function as a guide and should not be used
as the sole reason for denial of treatment and services. It is not intended to supersede applicable ethical standards or provisions of law. This is
not a legal document.
© 2014 North American Spine Society. All rights reserved.

 rhBMP-2

12/04/2014

Charles Cho, MD, MBA
Michael DePalma, MD
Donald Dietze, MD
John Easa, MD
Gary Ghiselli, MD
John Glaser, MD
James Harrop, MD
Anthony Lapinsky, MD
Darren Lebl, MD
Paul Matz, MD
David O’Brien, MD
Alpesh Patel, MD, FACS
Mitchell Reiter, MD
Charles Reitman, MD
Lee Riley, MD
Alok Sharan, MD
Jeffrey Summers, MD
William Tontz, MD
John Toton, MD, JD
Scott Tromanhauser, MD, MBA
Eeric Truumees, MD
Allen Villavincencio, MD
Michael Zindrick, MD
Financial Statement
These Coverage Recommendations were developed in their entirety by the North American Spine
Society (NASS). All participating authors have disclosed potential conflicts of interest consistent with
NASS’ disclosure policy.
Author Disclosures
Bono, Christopher: Royalties: Wolters Kluwer (B); Consulting: Harvard Clinical Research Institute
(Financial), United Health Care (B); Board of Directors: North American Spine Society (Nonfinancial)
Other Office: JAAOS (B), The Spine Journal (Nonfinancial)
Baisden, Jamie: Nothing to Disclose.
Page 29 of 33
NASS coverage recommendations should not be construed as including all proper methods of care or excluding other acceptable methods of
care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by
the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or
institution. The coverage recommendations do not represent a “standard of care,” nor are they intended as a fixed treatment protocol. It is
anticipated that there will be patients who will require less or more treatment than the average. It is also acknowledged that in atypical cases,
treatment falling outside these criteria will sometimes be necessary. This document should not be seen as prescribing the type, frequency or
duration of intervention. Treatment and accompanying payment should be based on this information in addition to an individual patient’s
needs as well as the doctor’s professional judgment and experience. This document is designed to function as a guide and should not be used
as the sole reason for denial of treatment and services. It is not intended to supersede applicable ethical standards or provisions of law. This is
not a legal document.
© 2014 North American Spine Society. All rights reserved.

 rhBMP-2

12/04/2014

Biyani, Ashok: Royalties: Globus Medical (E), custom spine (C); Consulting: K2M (B)
Boakye, Maxwell: Nothing to Disclose.
Cho, Charles: Nothing to Disclose.
DePalma, Michael: Consulting: Vertiflex, Inc (Financial); Trips/Travel: Medtronic (Financial); Board of
Directors: International Spine Intervention Society (Financial), Virginia Spine Research Institute, Inc
(Financial); Scientific Advisory Board: Medtronic; Kimberly Clark (Financial); Other Office: Secretary,
International Spine Intervention Society (Financial); Research Support (Investigator Salary): Relievant (B),
SI Bone (B), Mesoblast, Inc (B); Research Support (Staff/Materials): Relievant (B), Mesoblast (B), SI Bone
(B); Relationships Outside the One Year Requirement: AOI Medical (Upcoming Committee Meeting
[Clinical Guidlelines), Stryker Interventional Spine (B), St. Jude Medical (NASS Annual Meeting,
Consulting), Stryker Biotech (NASS Annual Meeting), ATRM (NASS Annual Meeting)
Dietze, Donald: Stock Ownership: Globus Medical Consulting: Globus Medical (Financial); Other: DePuy
Spine (B)
Easa, John: Stock Ownership: Janus Biotherapeutics
Ghiselli, Gary: Private Investments: DiFusion; Consulting: Biomet (C); Speaking and/or teaching
arrangements: Medacta (B); Scientific Advisory Board: DiFusion (Nonfinancial)
Glaser, John A.: Trips/Travel: Depuy Synthes Spine (Nonfinancial, Trip expenses, A); Grants: SI Bone (D,
Research grant funding, Paid directly to institution/employer).
Harrop, James: Consulting: Depuy Spine (B); Board of Directors: Jefferson Medical College Physician
Board (Nonfinancial); Scientific Advisory Board: Axiomed (Nonfinancial); Other Office: Bioventus (B ),
Penn Neurologic Society (Nonfinancial); Research Support (Staff/Materials): NACTN (E); Grants: AO
Spine/ NREF (F)
Lapinsky, Anthony: Royalties: RTI formerly Pioneer (B); Consulting: Orthofix (Financial)
Lebl, Darren: Nothing to Disclose.
Matz, Paul: Speaking and/or teaching arrangements: AO Spine North America (B); Trips/Travel: NASS (A)
O’Brien, David: Speaking and/or teaching arrangements: NASS (B); Trips/Travel: ISIS & AAPMR (B); Other
Office: ISIS & AAPMR (Nonfinancial)
Page 30 of 33
NASS coverage recommendations should not be construed as including all proper methods of care or excluding other acceptable methods of
care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by
the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or
institution. The coverage recommendations do not represent a “standard of care,” nor are they intended as a fixed treatment protocol. It is
anticipated that there will be patients who will require less or more treatment than the average. It is also acknowledged that in atypical cases,
treatment falling outside these criteria will sometimes be necessary. This document should not be seen as prescribing the type, frequency or
duration of intervention. Treatment and accompanying payment should be based on this information in addition to an individual patient’s
needs as well as the doctor’s professional judgment and experience. This document is designed to function as a guide and should not be used
as the sole reason for denial of treatment and services. It is not intended to supersede applicable ethical standards or provisions of law. This is
not a legal document.
© 2014 North American Spine Society. All rights reserved.

 rhBMP-2

12/04/2014

Patel, Alpesh: Royalties: Amedica (B); Stock Ownership: Amedica, Cytonics, Nocimed Vital5; Consulting:
Amedica (B), Stryker (B), Biomet (Financial), Depuy (B); Board of Directors: Lumbar Spine Research
Society (Nonfinancial), Cervical Spine Research Society (Nonfinancial), Indo-American Spine Alliance
(Nonfinancial); Fellowship Support: OREF (D), Omega (B); Other: Amedica (Financial)
Reiter, Mitchell: Private Investments: CreOsso
Reitman, Charles: Trips/Travel: NASS - BOD (Financial), AAOS - Evidence Based Committee (Financial);
Scientific Advisory Board: Clinical Orthopedics And Related Research - Deputy Editor (B)
Riley, Lee: Stock Ownership: Spinal kinetics; Speaking and/or teaching arrangements: AOSNA (B);
Trips/Travel: DePuy Spine (B); Board of Directors: Lifenet Health (C); Other Office: CSRS (A); Grants:
DePuy Spine (B)
Sharan, Alok: Consulting: Paradigm Spine (B); Speaking and/or teaching arrangements: Synthes Spine (B)
Summers, Jeffrey: Stock Ownership: MedWorx ; Private Investments: Morris Innovative (2000 Shares);
Board of Directors: International Spine Intervention Society (ISIS) (Nonfinancial)
Tontz, William: Stock Ownership: Phygen; Consulting: Medtronic (C); Speaking and/or teaching
arrangements: SpineArt (B); Trips/Travel: Medtronic (B); Scientific Advisory Board: Medtronic (Financial)
Toton, John: Nothing to Disclose.
Tromanhauser, Scott: Stock Ownership: Soteira, Inc.; Speaking and/or teaching arrangements: DePuy
Synthes Spine, Inc. (B); Other Office: Best Doctors Occupational Health Institute (E)
Truumees, Eeric: Royalties: Stryker Spine (C); Stock Ownership: Doctor's Research Group (D); Board of
Directors: North American Spine Society (Nonfinancial); Other Office: AAOS Communications Cabinet
(Financial); Research Support (Investigator Salary): Relievant (B) Globus (B); Other: Stryker Biotech
(Nonfinancial)
Villavincencio, Allen: Stock Ownership: Lanx; Board of Directors: Junstin Parker Neurological Institute
(Nonfinancial); Other Office: Boulder Neurosurgical Associates, LLC (Nonfinancial); Research Support
(Investigator Salary): Profibrix, Medtronic (F)
Zindrick, Michael: Royalties: OrthoFix (C), Biomet (B); Stock Ownership: VTI; Scientific Advisory Board:
Orthofix
Page 31 of 33
NASS coverage recommendations should not be construed as including all proper methods of care or excluding other acceptable methods of
care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by
the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or
institution. The coverage recommendations do not represent a “standard of care,” nor are they intended as a fixed treatment protocol. It is
anticipated that there will be patients who will require less or more treatment than the average. It is also acknowledged that in atypical cases,
treatment falling outside these criteria will sometimes be necessary. This document should not be seen as prescribing the type, frequency or
duration of intervention. Treatment and accompanying payment should be based on this information in addition to an individual patient’s
needs as well as the doctor’s professional judgment and experience. This document is designed to function as a guide and should not be used
as the sole reason for denial of treatment and services. It is not intended to supersede applicable ethical standards or provisions of law. This is
not a legal document.
© 2014 North American Spine Society. All rights reserved.

 rhBMP-2

12/04/2014

Comments
Comments regarding the coverage recommendations may be submitted to coverage@spine.org and will
be considered in development of future revisions of the work.

Page 32 of 33
NASS coverage recommendations should not be construed as including all proper methods of care or excluding other acceptable methods of
care reasonably directed to obtaining the same results. The ultimate judgment regarding any specific procedure or treatment is to be made by
the physician and patient in light of all circumstances presented by the patient and the needs and resources particular to the locality or
institution. The coverage recommendations do not represent a “standard of care,” nor are they intended as a fixed treatment protocol. It is
anticipated that there will be patients who will require less or more treatment than the average. It is also acknowledged that in atypical cases,
treatment falling outside these criteria will sometimes be necessary. This document should not be seen as prescribing the type, frequency or
duration of intervention. Treatment and accompanying payment should be based on this information in addition to an individual patient’s
needs as well as the doctor’s professional judgment and experience. This document is designed to function as a guide and should not be used
as the sole reason for denial of treatment and services. It is not intended to supersede applicable ethical standards or provisions of law. This is
not a legal document.
© 2014 North American Spine Society. All rights reserved.