SUPPLEMENT ARTICLE
BMPs: Options, Indications, and Effectiveness
Peter V. Giannoudis, MD, FRCS and Haralampos T. Dinopoulos, MD
Summary: Alteration of the bone healing process with bone
morphogenetic proteins offers a new perspective in orthopaedic
surgery in those adverse situations that necessitate bone grafting.
BMPs have been demonstrated to be effective and safe for human
application and have an efficacy comparable with that of autologous
bone grafting. Nevertheless, clinical trials with level 1 evidence are
still limited in their ability to extrapolate robust and safe clinical
conclusions for the possible indications mentioned in this article.
Future research should refine issues regarding the relative effective-
ness of bone morphogenetic proteins, the interaction between bone
morphogenetic protein subtypes, and their specific effect on various
target cell populations.
Key Words: applications, BMPs, bone morphogenetic proteins,
fracture healing, nonunion
(J Orthop Trauma 2010;24:S9–S16)
INTRODUCTION
Although bone healing is generally regarded as a bi-
ologically optimized procedure, an anticipated 5%–10% of all
fractures develop delayed and/or nonunion, leading to signifi-
cant patient morbidity, psychosocial stress, and economic cost
to society.1–7
Autologous bone grafting (ABG) remains the gold
standard of treatment of these adverse situations. However,
this practice has been shown to be associated with a num-
ber of issues including donor site morbidity, volume con-
straints, infection, and increased hospital stay.8,9 Due to these
limitations of ABG, stimulation of bone formation by other
means (chemical and physical) has received great interest.1,10–13
Bone morphogenetic proteins (BMPs) are naturally
occurring bioactive molecules.14 Following their isolation by
Urist15 and subsequently their commercialization utilizing
DNA recombinant technology and their use in the clinical
setting, they represent an area of vivid discussion and extended
research with a very promising future. Consequently, the
objective of this study was to clarify some of the basic aspects
Accepted for publication December 3, 2009.
From the Academic Department of Trauma and Orthopaedic Surgery,
University of Leeds, Leeds, United Kingdom.
No funding was received for the preparation of this article.
All authors declare that no benefits in any form have been received or will be
received from a commercial party related directly or indirectly to the
preparation of this article. No funds were received in support of this study.
Reprints: Peter V. Giannoudis, MD, FRCS, Academic Orthopaedic Unit, Floor
A Clarendon Wing, Leeds General Infirmary, Great George St, Leeds, LS1
3EX, United Kingdom (e-mail: pgiannoudi@aol.com).
Copyright Ó 2010 by Lippincott Williams & Wilkins
J Orthop Trauma  Volume 24, Number 3 Supplement, March 2010
of BMPs and to evaluate the current data regarding their
options, indications and efficacy of use in the clinical setting.
BONE MORPHOGENETIC PROTEINS
There are numerous essential signaling molecules that
actively participate during the fracture healing process
including cytokines (IL-1, IL-6, tumor necrosis factor alpha),
transforming growth factor b (TGF-b), platelet-derived growth
factor, fibroblast-derived growth factor, insulin-derived growth
factor, metalloproteinases, angiogenic factors (vascular endo-
thelial growth factors and angiopoietins 1 and 2), and BMPs.16
BMPs are a unique group of biologically active autacoids
belonging to the transforming growth factor b superfamily.14,15
Through molecular cloning techniques and recombinant
expression, osteoinductive BMP molecules have been iden-
tified and have been produced in mass quantities in their pure
form.17,18 More than 20 types of BMPs have been recognized,
but only BMP-2, 4, 6, 7, and 9 have been shown to have
significant osteogenic properties.18–23 BMPs are capable of
inducing the formation of bone tissue in ectopic sites and in
critical sized bone defects in several animal models.3,4 BMPs
diffuse through a concentration gradient, and in response to
this stimulus, the cells proliferate and differentiate following
a predefined pattern and spatial arrangement. From a physical
and chemical point of view, BMPs are proteins secreted by
cells that act as ligands for receptors present on the plasma
membrane of different types of cells (autocrine and paracrine
effects), thus establishing cell and tissue organization. Known
target cells of the BMPs include pluripotent mesenchymal
cells, bone marrow stromal cells, osteoblasts, osteoclasts and
their progenitors, myoblasts, fibroblasts, and neural cells.24–31
BMPs also play important roles in cell proliferation, apoptosis,
differentiation, and morphogenesis of the viscera.32 Conse-
quently, their name as ‘‘bone morphogenetic protein’’ is not
illustrative of the functional range of these molecules.33,34
BMP molecules seem to induce bone formation in
a stepwise fashion, with individual BMP molecules function-
ing at different stages of osteoblastic differentiation and
osteogenesis.18,19,21 Temporal and functional characteristics of
BMPs 2, 4, and 7 observed during fracture healing in animal
models can be seen in Table 1.
Two of these chemical compounds have recently been
approved for limited clinical use: the recombinant human bone
morphogenetic protein-2 (rhBMP-2) (Infuse; Medtronic
Sofamor Danek, Memphis, TN) and the rhBMP-7 or
osteogenic protein-1 (OP-1) (Stryker, Kalamazoo, MI). The
BMP-2 molecule has Food and Drug Administration (FDA)
approval for the treatment of acute open tibial fractures at
increased risk of nonunion,35 and in the spine in anterior
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TABLE 1. Expression and Functional Characteristics of BMPs 2, 4, and 7 Observed During Fracture Healing in Animal Models16
BMP Subtype Time of Expression
BMP-2 Days 1–21 (the earliest gene to be induced and
second elevation during osteogenesis)
BMP-4 Transient increased expression in the surrounding
soft tissues 6 h to day 5
Days 14–21
Through out fracture healing
BMP-7 Days 14–21
From the early stages of fracture healing
MSCs, mesenchymal stem cells.
lumbar interbody fusion with use of rhBMP-2 within a
titanium tapered cage,36,37 whereas the BMP-7 molecule has
been given FDA approval (humanitarian exception) for the
treatment of recalcitrant long-bone (tibial) nonunions.38,39
Clinical applications for BMP use fall into 5 basic
categories including (a) enhancement of fracture healing (ie,
complex fractures, open fractures, delayed unions or non-
unions, and fractures at risk of nonunion), (b) induction of
bone formation (ie, healing of critical size bony defects),
(c) strengthening of implant integration (ie, revision surgery),
(d) augmentation of spinal fusions, and (e) augmentation of
healing in patient groups of known risk where adverse biology
exists (ie, smokers and comorbidities that affect bone biology).
CLINICAL EFFICACY OF BMPS FOR
STIMULATING FRACTURE HEALING
Three studies represent the milestone of BMP use in
enhancement of fracture healing.2,40,41 More recently, a clinical
case–control study on BMP-grafting of fresh distal tibial
fractures was published by Ristiniemi.42 Two groups of distal
tibial fractures were treated with ring external fixators. The
fractures were grafted with recombinant human osteogenic
protein-1/bovine collagen in 20 cases. A similar fracture group
had no grafting at all. The average time to union in the BMP
group was significantly shorter (15.7 vs. 23.5 weeks) without
any secondary operations in contrast to the control group.
Another anatomic area for the application of rhOP-1, the
pelvic ring, was evaluated prospectively by Giannoudis et al.43
The authors used BMP-7 in 9 cases of persistent pelvic ring
instability and finally showed a fusion rate of 89% and 78%
(anterior vs. posterior pelvis). Patients reported excellent or
good subjective functional results at a median follow-up
period of 12 months (range, 12–27 months).
CLINICAL EFFICACY OF BMPS IN THE
TREATMENT OF BONE DEFECTS
AND NONUNIONS
There are extensive preclinical data that have shown the
potential for BMPs to induce healing of critically sized defects
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Specific Responses In Vivo and In Vitro
Recruitment of mesenchymal cells
Chondrogenesis
May initiate the fracture healing
Cascade and regulate the expression of other BMPs
BMP-2, -6, and -9 may be the most potent to induce
osteoblast lineage-specific differentiation of MSCs
Involvement in the formation of callus at a very early
stage in the healing process
In vitro: BMP-3 and -4 stimulate the migration of human
blood monocytes
Regulatory role in both types of ossification
In vitro: stimulation of relatively mature osteoblasts
(defects that cannot heal without exogenous osteogenic
stimulation).3,16,44 In animal models with such segmental
defects, the results of BMP were equivalent to or better than
those of autologous bone grafting, the standard treatment of
bone defects and nonunions in clinical practice.3,44–47 These
findings demonstrated the potential for BMPs to be used as an
alternative to autologous bone grafting.
Several clinical studies have shown the capacity of
BMPs to promote healing in critical size bone defects and
nonunions.48–56 Ekrol et al57 evaluated whether rhBMP-7 is
an effective alternative to autogenous bone graft in the
healing of metaphyseal defects in the distal radius following
corrective osteotomies for symptomatic malunion after distal
radial fractures. Thirty patients were entered into the study
and were randomized to receive either rhBMP-7 or auto-
genous bone graft harvested from the ipsilateral iliac crest.
Stabilization of the osteotomy was carried out with either the
nonbridging external fixation or the pi-plate. The first 10
patients were treated using nonbridging external fixation of
the osteotomy. Two of the 4 patients treated with rhBMP-7
developed excessive osteolysis around the osteotomy site,
resulting in loss of the corrected position and nonunion of
the osteotomy. The other 2 patients healed at 13 weeks. The 6
patients treated with autogenous bone graft all healed at an
average of 7 weeks, without any complications. It was
postulated that the osteolysis was related to instability of the
osteotomy site, and the use of external fixation was
abandoned and replaced with internal fixation with a dorsal
pi-plate. In the pi-plate group of patients, 10 were treated
with autogenous bone graft and 10 with rhBMP-7. The 10
patients that were treated with autogenous bone graft healed
at 7 weeks compared with 18 weeks for the rhBMP-7
patients, which was statistically significant (P = 0.019). The
patients who received bone graft had complete filling of the
metaphyseal defect radiologically. Five patients treated with
rhBMP-7 healed at the volar cortex with a dorsal defect
remaining at 1 year. Two patients developed nonunion
radiologically. Ten patients (3 in the rhBMP-7 and 7 in the
bone graft groups) required plate removal for soft tissue
complications. The authors concluded that using the
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J Orthop Trauma  Volume 24, Number 3 Supplement, March 2010
rhBMP-7 with a pi-plate resulted in healing of the osteotomy
but at a slower rate than autogenous bone graft.
STRENGTHENING OF IMPLANT INTEGRATION
Although OP-1 has been suggested quite recently for
use in hip and knee arthroplasty, 58,59 there are not any
randomized controlled studies as yet. Zhang et al60 evaluated
the effect of OP-1 carried by peri-apatite on bone healing in the
gap surrounding titanium implants in a rabbit model and
suggested that OP-1 can be loaded on implants through
peri-apatite to enhance the osseointegration of the implant.
Karrholm et al61 published a case–control study of hip revision
arthroplasties. The morselized allograft used in these revisions
was augmented with rhOP-1. A similar number of revised
implants (acetabular cups and femoral stems) were grafted
with morselized allograft, augmented or not with rhOP-1. An
increase in the rate of early loosening in the rhOP-1 group
was noted (especially in the stem revision subgroup). The
authors did not advocate the expansion of morselized allograft
with rhOP-1.
CLINICAL EFFICACY OF BMPS IN
SPINAL FUSION
Currently, there are limited FDA-approved indications in
the United States for use of BMP in spine surgery.36,38 All
other uses in spine are ‘‘off-label.’’62–67 There are enough
preclinical data that BMPs may be able to replace autologous
bone grafting in spine fusions68–74 On the other hand, BMPs
can safely be added as expanders in autologous grafting of
a spine fusion.72,75–77 Nonetheless, nonunion or failure to
achieve a solid bone fusion still occurs in up to 35% of patients
undergoing a spine fusion, showing that there is enough space
for improvement in grafting.12
Several studies have been focused on the application of
BMPs in spinal surgery and have demonstrated the effective-
ness of BMPs in spinal fusion and the potential for eliminating
the harvest of autograft.5,37,77–80 Table 2 contains relevant
studies that have been performed evaluating the overall safety
and efficacy of BMPs in spinal fusion with supporting results
of their use.7,81–88,91–93 In a recent meta-analysis of randomized
controlled trials to evaluate the radiographic and clinical
effectiveness of BMPs within the context of posterolateral
fusion of the lumbar spine, Papakostidis et al89 reported on
7 randomized controlled trials (n = 331 patients) and
1 prospective comparative study (n = 52 patients). BMPs
seemed more efficacious to iliac crest bone graft in achieving
solid fusion (relative risk [RR] = 0.42; 95% confidence
interval [CI] = 0.28–0.61; P , 0.00001) but with significant
heterogeneity (I = 42.5%).
AUGMENTATION OF HEALING IN PATIENTS
WHERE ADVERSE BIOLOGY EXISTS
Recently the comparative study of Glassman et al90
addressed the question of the effect of smoking on bone
healing after implanting BMPs. The purpose of this study was
to examine the influence of smoking on fusion rate and
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BMPs
outcome in a large series of patients treated with rhBMP-2 or
iliac crest bone graft as part of a randomized trial for single-
level lumbar fusion. The results suggested that rhBMP-2 might
enhance fusion rates in cigarette smokers undergoing single-
level, instrumented, posterolateral lumbar fusion. Despite the
improvement in fusion rate with rhBMP-2, clinical outcome
measures were still adversely affected in smokers.
In another large multicenter, randomized, clinical trial,
Dimar et al86 evaluated patients treated with instrumented
posterolateral lumbar arthrodesis and grafted with either
rhBMP-2/compression resistant matrix or iliac crest autolo-
gous graft. The authors reported that all the nonsmokers of the
rhBMP-2 group and 94.1% of the iliac crest autograft group
fused, whereas 95.2% of the rhBMP-2 group and only 76.2%
of the iliac crest autograft smokers successfully united their
operated level. The difference in the fusion rate between all
smokers and nonsmokers was significant (P = 0.016).
THE ROLE OF DEMINERALIZED BONE MATRIX
Demineralized bone matrix (DBM) is the biomaterial of
choice for isolation and purification of BMPs.1,12,15,17,94–97 The
efficacy and osteoinductive properties of the existing different
formulations can range widely depending on the type of bone,
the sterilization process, the carrier, the amount of BMPs
present, and the ratios of different BMPs.97 The relative
quantities of BMP-2 and BMP-7 in DBMs are low, in the order
of 1 3 1029 g of BMP per gram of DBM.98
The effectiveness of DBM compared with the iliac crest
autografting has been evaluated.99–101 However, there are no
randomized controlled trials in humans comparing their
efficacy to autologous bone. Overall, no difference has been
shown in terms of efficacy.51,99–103
DISCUSSION
Although several growth factors have been identified,
not all have shown the potency of BMPs for bone repair.96
DBMs do not have any clinical evidence to support their use in
the treatment of acute fractures, and as they are known to
contain a variable degree of BMPs must be regarded as inferior
in strength to them. Nonetheless, there is supporting evidence
that DBMs can be used as graft expanders in certain situations
such as spinal fusion and unicameral cysts.50,97–102
It is surprising that the effects of BMPs on fresh
fractures, potentially the most common clinical indication,
have been studied only to a limited extent. There is enough
data to support BMP use in open fractures based on the results
of the BMP-2 evaluation in surgery for tibial trauma study2
and the study by McKee et al, which reported that 3.5 mg of
OP-1 is effective in reducing the number of secondary
interventions in open tibial fractures treated with intra-
medullary nail fixation and BMP-7.104
Another very interesting aspect of the BMP use in fresh
fractures and nonunions is the finding of reduced rates of
infection after treatment of the fracture/nonunion site with
BMPs. This has been attributed to induction of neoangio-
genesis and the development of a well-vascularized bed.
Studies of animals have also demonstrated the potential of
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TABLE 2. Latest Literature (5 Years) of the Evidence for BMP-2 and -7 Use in Fresh Fractures, Nonunions, Long-Bone Defects and
Spinal Fusions
Author Type of Grafting Anatomic Location Study vs. Control Conclusions/Outcome
42
Ristiniemi et al Fractured healing Tibial distal metaphyseal rhOP-1/bovine collagen I (3.5 mg rhOP-1 was beneficial in fresh pilon
fractures (40) 20 vs. 20 and 1 g collagen I) fractures and safe
vs. no grafting material
Giannoudis et al43 Fractured healing Pelvic instability nonunions (9) rhOP-1/bovine collagen I and ACBG 89% successful fusions; 78% satisfaction
no control (4 cases) vs. no control group at 12 mo
Dimitriou et al51 Persistent Tibial, femoral, humeral, ulnar, rhOP-1 (3.5 mg and 1 g collagen I) Clinical union occurred in 93% of cases at
nonunions patellar, claviclle vs. no control group a mean time of 4.2 mo and radiological
union at a mean time of 5.6 mo
Jones et al52 Cortical defect Tibial fractures (30) 15 vs. 15 rhBMP-2 in collagen sponge and Comparable clinical results with those
allograft vs. ACBG of ACBG
Bilic et al53 Fractured healing Scaphoid proximal pole rhOP-1 and ACBG vs. ACBG vs. rhOP-1 minimized the time to union
nonunions (17) 6 vs. 6 vs. 5 rhOP-1/bovine collagen I and
allograft
Calori et al54 Persistent Tibial, femoral, humeral, ulnar, rhBMP-7 vs. group PRP 86.7% rhBMP-7 vs. 68.3% PRP
nonunions and radial
Kanakaris et al55 Tibial nonunions 68 pts aseptic tibial nonunions BMP-7 89.7%, multicenter registry observational
study
Desmyter et al56 Tibial nonunions 62 patients BMP-7 Clinical healing 79.6%, radiological 84.9%
Ekrol et al57 Distal radial defects 30 pts were randomised rhBMP-7 vs. ICAG rhBMP-7 healed at a slower rate
Karrholm et al61 Implant integration Revision THR revisions (61) rhOP-1 vs. morselized allograft OP-1 with morselized allograft did not
improve early fixation
Baskin et al81 Spinal fusion Cervical fusion (33) 18 vs. 15 rhBMP-2 and fibular allograft Fusion rates were 100%, and
vs. ICAG device-related AEs 0%
Vaccaro et al82 Spinal fusion Single-level lumbar fusion (12) rhOP-1 and ICAG vs. no control rhOP-1 is safe with ICAG
no control group group
Mummaneni al7 Spinal fusion Single-level lumbar fusion (40) rhBMP-2 and interbody cage rhBMP-2 was found safe in transforaminal
21 vs. 19 vs. ICAG lumbar interbody fusion and was
associated with more rapid fusion
Vaccaro et al83 Spinal fusion Single-level lumbar fusion (36) rhOP-1 vs. ICAG At 12 mo postoperation there was 86%
24 vs. 12 clinical success in the rhOP-1 group and
73% in the ICAG group
Villavicencio84 Spinal fusion Single-level lumbar fusion (74) rhBMP-2 and interbody cage 100% of fusion at 12 and 24 mo
no control vs. no control
Kanayama85 Spinal fusion Single-level lumbar fusion (20) rhOP-1 vs. harvested autograft Fusion rate: only 57%
10 vs. 10 and CGc
Dimar et al86 Spinal fusion Single-level lumbar fusion (98) rhBMP-2/CRM vs. ICAG Outcomes and fusion rates (90.6% vs.
53 vs. 45 73.3%) similar to those of ICBG
McClellan87 Spinal fusion Interbody lumbar fusion rhBMP-2/collagen I sponge and Bone resorption defects were noted in
(32 levels) no control allograft, interbody cages, 69% of fused levels
autograft/allografts vs. no control
Slosar et al88 Spinal fusion Single- or multilevel interbody rhBMP-2 and FRA vs. FRA Structural allografts with rhBMP-2
fusions (75) 45 vs. 30 resulted in 100% fusion
89
Papakostidis Spinal fusion 7 randomized control trials BMPs (rBMP-2 and rhBMP-7) rBMP-2 was more efficacious,
meta-analysis (n = 331) and 1 prospective vs. ICBG whereas rhBMP-7 equivalent
comparative study (n = 52 pts)
Glassman et al90 Spinal fusion Single-level lumbar fusion (148) rhBMP-2/CRM vs. ICAG Worse in smokers. rhBMP-2 enhanced
76 vs. 72 fusion rates in smokers
ACBG, autologous crest bone graft; AEs, adverse events; CGc, ceramic graft; CRM, compression resistant matrix or carrier of bovine collagen I and tricalcium/hydroxyapatite;
FRA, femoral ring allograft; ICAG, iliac crest autologous graft; n, number of cases; PRP, platelet rich plasma, Pts, patients; rhBMP-2, recombinant human bone morphogenetic protein-2;
THR, total hip replacement; TLIF, transforaminal lumbar interbody fusion.

BMPs to induce bone formation in infected osseous sites, thus
providing increased callus stability. This is important because
instability of the fracture site has been shown to affect the
healing and progression of bone infections.105–107
As per the nonunion scenarios, the clinical trial con-
ducted by Friedlaender et al41 provided level 1 evidence that
OP-1 is as effective as autogenous bone graft in the treatment
of tibial nonunion when used with intramedullary rod fixation.
The major advantage of using OP-1 instead of harvesting
iliac crest autograft is the avoidance of pain and donor-site
morbidity.110 Geesink et al50 provided level 2 evidence that
OP-1 and DBM may be used in segmental bone defects. Two
uncontrolled retrospective studies by Ring (2004) and Wilkins
(2003) have investigated the effectiveness of DBM in

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J Orthop Trauma  Volume 24, Number 3 Supplement, March 2010
nonunion repair and bone defects.108,109 They provided level 4
evidence that DBM is effective in treating long-bone non-
unions. However, the rate of clinical success of DBM in long-
bone nonunions may be less than that for autograft bone.111,112
The positive effect of BMPs in spinal fusions is more
extensive5,37,81 showing that both BMPs are as effective as
autogenous bone graft in stimulating lumbar interbody fusion.
On the other hand, there is level 1 evidence that allograft DBM
is not as effective as autogenous bone graft in anterior cervical
decompression and fusion.113 Contrary to this finding, it has
been shown in a level 1 study that a Grafton DBM gel/
autograft composite in a 2:1 ratio is as effective as autogenous
bone graft in instrumented posterolateral spinal fusion.99 None
of the studies using rhBMP or DBM has documented any
adverse systemic effects.
Another major concern about the use of BMPs to
enhance spinal fusion is the risk of bone overgrowth or
heterotopic ossification leading to spinal or foraminal stenosis.
In an experimental study, Meyer et al74 found no evidence of
abnormal mineralization within the sac or in the spinal cord
after treatment with rhBMP-2. When BMPs are used in spinal
surgery, the key considerations are accurate placement of the
BMP at the fusion site, retention of the BMP by the carrier,
securing hemostasis to prevent dilution of the BMP, and
limiting the exposure of bone beyond the fusion area.
The clinical application of BMPs is constantly expanding.
However, based on the current existing evidence and despite
the fact that they have a powerful osteoinductive property, it
seems that their efficacy is not better than that of autologous
bone graft. Several issues should be considered in this
context, in an attempt to provide possible explanations for
this observation. First, the timing of implantation of BMPs
that is currently practiced, being at the time of open fracture
closure or during the nonunion revision surgery, may not be
ideal. For these molecules to exert their effect, cell
populations locally must already be present. Therefore, are
there enough cells present under these circumstances? There
is no evidence to provide a firm answer to this question. One,
however, has to assume that cell invasion and chemotaxis
from the bone marrow, periosteum, bone, and muscle tissue
would become optimal with time, potentially over the first 10
days to 2 weeks when the local inflammatory process has
matured. Indeed, implantation of BMPs may well be more
appropriate then. Liquid injectable formulations would
support the approach of implanting these bioactive molecules
in the clinic under image intensifier control within the first 2
weeks after surgery, potentially eliminating the need for
further surgery and increased health care costs. Second, the
containment issue of BMPs should be considered as
a potential drawback in their efficacy. Although, for instance,
a massive dose is implanted at the time of an open wound
closure, it is not clear how much of the active molecule
remains at the local environment over the subsequent 24
hours in vivo. Third, there are distinct differences between
the autologous bone graft and the BMPs. Autologous bone
graft does have all the 3 constituents necessary to enhance
the bone healing process: osteoinduction, osteoconduction,
and osteoprogenitor cells.11,16 On the contrary, BMPs pose
only osteoinduction properties. In this context, it might be
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BMPs
more efficacious to implant the BMPs simultaneously with
osteoprogenitor cells. All of the above issues could be
investigated in the near future with level 1 research studies.
The cost of BMPs is another important issue for
consideration. Dahabreh et al.114 evaluated the cost implica-
tions of treatment of 25 persistent fracture nonunions, before
and after application of rhBMP-7. They concluded that
treating fracture nonunions is costly, but this could be reduced
by early BMP-7 administration when a complex or persistent
fracture nonunion is present or anticipated.114 Regarding the
cost of BMP usage in spinal fusions, there have been several
trials to compare the economic burden of it with the traditional
autogenous iliac crest bone grafting, and they have concluded
that the cost is more or less equal.115–117 Similarly, a more
recent study evaluating the cost of treatment of tibial
nonunions with autogenous bone graft and BMPs reported
no statistical significant difference.118
Growth factor therapy with BMPs offers a new
perspective in surgery in those adverse situations that involve
bone grafting procedures or where the bone healing process
needs enhancement. Despite this, it is obvious that the basic
surgical management of the recipient site is still mandatory to
provide the optimum circumstances necessary not only for
bone stability but also for vascularity and soft tissue
coverage.119 Future research must refine issues regarding the
relative effectiveness of BMPs, the interaction between BMP
subtypes, and how to optimize their powerful osteoinductive
potential.
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