Background: Treatment of segmental bone loss remains a challenge in
skeletal repairs. This study was performed to evaluate the efficacy of the use
of recombinant bone morphogenetic protein-2 (rhBMP-2) delivered in an
injectable calcium phosphate cement (alpha bone substitute material
[a-BSM]) to bridge critical-sized defects in the rabbit radius.
Methods: Unilateral 20-mm mid-diaphyseal defects were created in the
radii of thirty-six skeletally mature New Zealand White rabbits. The defects
in twelve rabbits each were filled with 0.166 mg/mL rhBMP-2/a-BSM
cement, 0.033 mg/mL rhBMP-2/a-BSM cement, or buffer/a-BSM cement.
Six rabbits from each group were killed at four weeks, and six were killed at
eight weeks. Serial radiographs were made to monitor defect-bridging and
residual a-BSM carrier. A semiquantitative histological scoring system
was used to evaluate defect-bridging. Histomorphometry was used to quantify
residual a-BSM; trabecular bone area; trabecular bone volume fraction;
and cortical length, width, and area.
Results: At four weeks, there had been more rapid resorption of
a-BSM and filling of the defects with trabecular bone in the group
treated with 0.166 mg/mL rhBMP-2/a-BSM than in the other two groups.
Histomorphometry confirmed an increased trabecular area and volume fraction in
this group compared with the other two groups. In both
rhBMP-2/a-BSM-treated groups, the majority of the trabecular bone was
formed by a direct process adjacent to the resorbing a-BSM. At eight
weeks, complete cortical bridging and regeneration of the marrow space were
present in all of the defects treated with 0.166 mg/mL rhBMP-2/a-BSM.
That group also had reduced residual a-BSM and trabecular area and
volume, compared with the other two groups, at eight weeks as a result of a
rapid remodeling process.
Conclusions: Treatment of a critical-sized defect in a rabbit radius
with 0.166 mg/mL rhBMP-2/a-BSM injectable cement can result in bridging
with cortical bone and a regenerated bone-marrow space by eight weeks.
Site-specific remodeling appears to be responsible for corticalization and
marrow regeneration.
Clinical Relevance: RhBMP-2 delivered in a calcium phosphate cement
may be useful to achieve bridging of critical-sized defects in patients. Its
injectable properties may allow minimally invasive use. Delayed percutaneous
administration would also be possible when augmentation is desired following
an initial surgical procedure or when soft-tissue injuries preclude adequate
initial treatment.