Clinical Evaluation of BMPs and Bone Marrow Stromal Cells in Orthopedic Surgery - Engineered Bone: Tissue Engineering Intelligence Unit - page 197

demographics were comparable in the 2 groups. At 9 months, given clinical and radiological
evaluation criteria (bridging on at least 3 views), healing was achieved in 62% of the OP-1
treated group and 74% of the bone autograft group (p=0.158). No serious adverse effects were
observed. While the outcome of both groups was comparable regarding bone healing, 20% of
the autograft patients group had pain at the donor site at 6 months, and bleeding was signifi-
cantly higher (345cc vs 245cc) in this group. Interestingly, the authors reported significantly
less infection at the fracture site (3% vs 21%) when OP-1 was implanted compared to bone
autograft. In a study performed in rats, Chen 21 confirmed the capacity of OP-1 implants to
form new bone in an infected segmental defect in rats, while the implantation of bone au-
tograft led to osteolysis in most of the cases. More study of this important question, and the
potential mechanisms through which OP-1 would reduce the rate of infection is clearly war-
ranted in the future. This first multicenter trial has confirmed the findings in earlier studies 22
of a significant efficacy of OP-1 in the treatment of nonunions, and today more 2500 implan-
tations have been performed worldwide. Based on this study, the US FDA and the EAEMP
have approved the use of OP-1 in the treatment of tibial nonunions.
In severe cases, sometimes affecting other bones than the tibia, and when conventional
treatment has failed, an individual patient usage approval can be obtained to treat separately a
patient. This was performed in 163 consecutive salvage cases between 1997 and 1999 in Aus-
tralia 23 . The indications for OP-1 implantation included 113 nonunions, 18 revision hip sur-
geries, 16 failed arthrodeses, 9 bone defects, 3 peri-prosthetic fractures, 1 elective osteotomy, 1
congenital pseudarthrosis, and 2 osteochondral defects. 35% of the patients had prior au-
tograft procedures, and 28% had pre-existing pathology such as infection, and rheumatoid
arthritis…OP-1 was usually combined with autograft or other osteoconductive material (al-
lograft, hydroxyapatite). At an average follow-up of 15 months, 95% of the patients were
available for clinical and radiological assessment. Bone repair was achieved in 70% of the cases,
and 25% were considered as failures.
Another recent report displayed promising results in the treatment of bone losses around
loosened prostheses in combination with bulk or morcellized allograft. 24 Placed at the host-bone
allograft junction either in the femur or the acetabulum, the OP-1 implant elicited extensive
new bone formation, but no heterotopic bone in surrounding tissues. Although these prelimi-
nary studies suggest some positive effects of the BMPs in other skeletal sites and indications,
these results must be assessed in larger controlled clinical trials comparing this treatment to the
standard of care in each indication.
Acute Treatment of Tibial Fractures
Fractures of the tibia are known to heal twice as slowly than other location. When the
fracture of the tibia is open, it is estimated that 47% of the patients will require further inter-
ventions to achieve bone healing. The use of BMPs is expected here to reduce the rate of bone
delayed union and nonunion. In a pilot study 25 on the use of rh-BMP2 in the healing of 12
open tibial fractures with a Gustilo classification of II or higher, bone healing was achieved in
9 cases without further intervention. These preliminary results on the benefit of rh-BMP2 on
the time course of open fracture healing were recently confirmed in a prospective randomized
evaluation of 450 tibial fractures stabilized with an internal rod. 26 The rh-BMP2 was delivered
on a bovine type 1 collagen sponge at two different doses, 6 and 12 mg of BMP. The control
group was composed of patients treated with internal fixation and an absorbable sponge alone.
The patients were stratified by the severity of the open wound. The period required to achieve
clinical and radiological healing was significantly reduced in the 12mg-rh-BMP2 group (44%
reduction in the risk of failure) and treatment with rh-BMP2 was associated with fewer sec-
ondary invasive interventions, fewer infections, faster wound healing. Minor adverse reactions
were reported including a significant higher rate of headaches in the BMP treated group (11 vs
7%). Despite some interesting results, the use of rh-BMP2 in the treatment of acute tibial
fractures is still under evaluation by the US FDA for pre-market approval. The main issue that